Sample records for n2 nodal disease

  1. Preoperative predictors of occult nodal disease in cT1N0 oral cavity squamous cell carcinoma: Review of 2623 cases.

    PubMed

    Zhan, Kevin Y; Morgan, Patrick F; Neskey, David M; Kim, Joanne J; Huang, Andrew T; Garrett-Mayer, Elizabeth; Day, Terry A

    2018-05-14

    Nodal disease predicts survival in oral cavity squamous cell carcinoma (SCC). Currently, no large studies on predictors of occult nodal disease in cT1N0 oral cavity SCC exist. The National Cancer Database (NCDB) review for cT1N0 oral cavity SCC with surgical resection and elective neck dissection (END). The number of patients found with occult nodal disease was 2623 (15.1%). In multivariable regression, female sex and tumor differentiation predict occult nodal disease. Occult nodal disease incidence was 5.9% in well-differentiated tumors, 17.4% in moderately differentiated tumors, and 28.5% in poorly differentiated tumor (P < .001). Women with oral tongue tumors had higher occult nodal disease (19.1%) than men (12%; P = .001). Adjusted odds ratios (aORs) for occult nodal disease in women were: aOR 1.26; 95% confidence interval (CI) 1.01-1.59; P = .045; moderately differentiated aOR 3.52; 95% CI 2.47-5.01; P < .001; and poorly differentiated aOR 6.25; 95% CI 4.17-9.38; P < .001. Sex and tumor differentiation significantly predict occult nodal disease. END is recommended for all moderately and poorly differentiated cT1N0 oral cavity SCC, regardless of the depth of invasion. One can consider not performing END in well-differentiated tumors. © 2018 Wiley Periodicals, Inc.

  2. Occult Nodal Disease Prevalence and Distribution in Recurrent Laryngeal Cancer Requiring Salvage Laryngectomy.

    PubMed

    Birkeland, Andrew C; Rosko, Andrew J; Issa, Mohamad R; Shuman, Andrew G; Prince, Mark E; Wolf, Gregory T; Bradford, Carol R; McHugh, Jonathan B; Brenner, J Chad; Spector, Matthew E

    2016-03-01

    The indications for neck dissection concurrent with salvage laryngectomy in the clinically N0 setting remain unclear. Our goals were to determine the prevalence of occult nodal disease, analyze nodal disease distribution patterns, and identify predictors of occult nodal disease in a salvage laryngectomy cohort. Case series with planned data collection. Tertiary academic center. Patients with persistent or recurrent laryngeal squamous cell carcinoma (LSCC) after radiation/chemoradiation failure undergoing salvage laryngectomy with neck dissection. We analyzed a single-institution retrospective case series of patients between 1997 and 2014 and identified those who had clinically N0 (cN0) necks (n = 203). Clinical and pathologic data, including nodal prevalence and distribution, were collected and statistical analyses performed. Overall, cN0 necks had histologically positive occult nodes in 17% (n = 35) of cases. Univariate predictors of occult nodal positivity included recurrent T4 stage (34% T4 vs 12% non-T4; P = .0003) and supraglottic subsite (28% supraglottic vs 10% nonsupraglottic; P = .0006). Histologically positive nodes associated with supraglottic primaries were most frequently positive in ipsilateral levels II and III (17% and 16%). Positive nodes for glottic LSCC were most frequently positive in the ipsilateral and contralateral paratracheal nodes (11% and 9%). Histologically positive occult nodes are identified in 17% of cN0 patients undergoing salvage laryngectomy with neck dissection. Occult nodal disease varies in frequency and distribution based on tumor subsite. Predictors of high (>20%) occult nodal positivity include T4 tumors and supraglottic subsite. In glottic LSCC, the most frequent sites of occult nodal disease are the paratracheal nodal basins. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  3. Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): Can breast MRI exclude advanced nodal disease?

    PubMed

    Hyun, Su Jeong; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Min Jung

    2016-11-01

    To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease. A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group. The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2-pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039). Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group. • Breast MRI can be used to exclude advanced nodal disease (pN2-3). • Negative MRI allows breast cancer patients to avoid unnecessary axillary surgery (98.2 %). • Negative MRI findings exclude 99.6 % of pN2-pN3 in the no-NAC group. • Negative MRI findings exclude 96.0 % of pN2-pN3 in the NAC group.

  4. Spinless hourglass nodal-line semimetals

    NASA Astrophysics Data System (ADS)

    Takahashi, Ryo; Hirayama, Motoaki; Murakami, Shuichi

    2017-10-01

    Nodal-line semimetals, one of the topological semimetals, have degeneracy along nodal lines where the band gap is closed. In many cases, the nodal lines appear accidentally, and in such cases it is impossible to determine whether the nodal lines appear or not, only from the crystal symmetry and the electron filling. In this paper, for spinless systems, we show that in specific space groups at 4 N +2 fillings (8 N +4 fillings including the spin degree of freedom), presence of the nodal lines is required regardless of the details of the systems. Here, the spinless systems refer to crystals where the spin-orbit coupling is negligible and the spin degree of freedom can be omitted because of the SU(2) spin degeneracy. In this case the shape of the band structure around these nodal lines is like an hourglass, and we call this a spinless hourglass nodal-line semimetal. We construct a model Hamiltonian as an example and we show that it is always in the spinless hourglass nodal-line semimetal phase even when the model parameters are changed without changing the symmetries of the system. We also establish a list of all the centrosymmetric space groups, under which spinless systems always have hourglass nodal lines, and illustrate where the nodal lines are located. We propose that Al3FeSi2 , whose space-group symmetry is Pbcn (No. 60), is one of the nodal-line semimetals arising from this mechanism.

  5. Regional Nodal Irradiation in Early-Stage Breast Cancer.

    PubMed

    Whelan, Timothy J; Olivotto, Ivo A; Parulekar, Wendy R; Ackerman, Ida; Chua, Boon H; Nabid, Abdenour; Vallis, Katherine A; White, Julia R; Rousseau, Pierre; Fortin, Andre; Pierce, Lori J; Manchul, Lee; Chafe, Susan; Nolan, Maureen C; Craighead, Peter; Bowen, Julie; McCready, David R; Pritchard, Kathleen I; Gelmon, Karen; Murray, Yvonne; Chapman, Judy-Anne W; Chen, Bingshu E; Levine, Mark N

    2015-07-23

    Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001). Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).

  6. Potential clinical value of PET/CT in predicting occult nodal metastasis in T1-T2N0M0 lung cancer patients staged by PET/CT

    PubMed Central

    Zhou, Xiang; Chen, Ruohua; Huang, Gang; Liu, Jianjun

    2017-01-01

    We assessed the clinical value of 2-fluoro-2-deoxyglucose (18F-FDG) PET/CT imaging for predicting occult nodal metastasis in non-small cell lung cancer (NSCLC) patients. This retrospective study included 54 patients with T1-2N0M0 NSCLC who had undergone 18F-FDG PET/CT before surgery. Occult nodal metastasis was detected in 25.9% (14/54) of the patients. Immunohistochemical analysis revealed that increased glucose transporter 1 expression was associated with occult nodal metastasis, but hexokinase 2 expression was not. Compared to the negative nodal metastasis group, the positive nodal metastasis group was associated with increased maximum standardized uptake value (SUVmax) and tumor size. Multivariate analysis indicated that SUVmax and tumor size were associated with nodal metastasis. Nodal metastasis could be predicted with a sensitivity of 92.9% and a specificity of 55.0% when the SUVmax cutoff was 4.35. When patients were divided into low-risk (tumor size ≤ 2.5 cm and SUVmax ≤ 4.35), moderate-risk (tumor size ≤ 2.5 cm and SUVmax > 4.35 or tumor size > 2.5 cm and SUVmax ≤ 4.35) and high-risk (tumor size > 2.5 cm and SUVmax > 4.35) groups, the lymph node metastasis rates were 4.3%, 22.7%, and 88.9%, respectively. These results indicate that the combination of SUVmax and tumor size has potential clinical value for predicting occult nodal metastasis in NSCLC patients. PMID:29137276

  7. Role of Nodal-PITX2C signaling pathway in glucose-induced cardiomyocyte hypertrophy.

    PubMed

    Su, Dongmei; Jing, Sun; Guan, Lina; Li, Qian; Zhang, Huiling; Gao, Xiaobo; Ma, Xu

    2014-06-01

    Pathological cardiac hypertrophy is a major cause of morbidity and mortality in cardiovascular disease. Recent studies have shown that cardiomyocytes, in response to high glucose (HG) stimuli, undergo hypertrophic growth. While much work still needs to be done to elucidate this important mechanism of hypertrophy, previous works have showed that some pathways or genes play important roles in hypertrophy. In this study, we showed that sublethal concentrations of glucose (25 mmol/L) could induce cardiomyocyte hypertrophy with an increase in the cellular surface area and the upregulation of the atrial natriuretic peptide (ANP) gene, a hypertrophic marker. High glucose (HG) treatments resulted in the upregulation of the Nodal gene, which is under-expressed in cardiomyocytes. We also determined that the knockdown of the Nodal gene resisted HG-induced cardiomyocyte hypertrophy. The overexpression of Nodal was able to induce hypertrophy in cardiomyocytes, which was associated with the upregulation of the PITX2C gene. We also showed that increases in the PITX2C expression, in response to Nodal, were mediated by the Smad4 signaling pathway. This study is highly relevant to the understanding of the effects of the Nodal-PITX2C pathway on HG-induced cardiomyocyte hypertrophy, as well as the related molecular mechanisms.

  8. Mapping of nodal disease in locally advanced prostate cancer: Rethinking the clinical target volume for pelvic nodal irradiation based on vascular rather than bony anatomy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shih, Helen A.; Harisinghani, Mukesh; Zietman, Anthony L.

    2005-11-15

    Purpose: Toxicity from pelvic irradiation could be reduced if fields were limited to likely areas of nodal involvement rather than using the standard 'four-field box.' We employed a novel magnetic resonance lymphangiographic technique to highlight the likely sites of occult nodal metastasis from prostate cancer. Methods and Materials: Eighteen prostate cancer patients with pathologically confirmed node-positive disease had a total of 69 pathologic nodes identifiable by lymphotropic nanoparticle-enhanced MRI and semiquantitative nodal analysis. Fourteen of these nodes were in the para-aortic region, and 55 were in the pelvis. The position of each of these malignant nodes was mapped to amore » common template based on its relation to skeletal or vascular anatomy. Results: Relative to skeletal anatomy, nodes covered a diffuse volume from the mid lumbar spine to the superior pubic ramus and along the sacrum and pelvic side walls. In contrast, the nodal metastases mapped much more tightly relative to the large pelvic vessels. A proposed pelvic clinical target volume to encompass the region at greatest risk of containing occult nodal metastases would include a 2.0-cm radial expansion volume around the distal common iliac and proximal external and internal iliac vessels that would encompass 94.5% of the pelvic nodes at risk as defined by our node-positive prostate cancer patient cohort. Conclusions: Nodal metastases from prostate cancer are largely localized along the major pelvic vasculature. Defining nodal radiation treatment portals based on vascular rather than bony anatomy may allow for a significant decrease in normal pelvic tissue irradiation and its associated toxicities.« less

  9. High VEGF-D and Low MMP-2 Serum Levels Predict Nodal-Positive Disease in Invasive Bladder Cancer

    PubMed Central

    Benoit, Tobias; Keller, Etienne X.; Wolfsgruber, Pirmin; Hermanns, Thomas; Günthart, Michele; Banzola, Irina; Sulser, Tullio; Provenzano, Maurizio; Poyet, Cédric

    2015-01-01

    Background To investigate stromal variables including angiogenesis, lymphangiogenesis, and matrix metalloproteinase (MMP) in the serum of patients with urothelial carcinoma of the bladder (UCB) and to evaluate their association with histopathological characteristics and clinical outcome. Material/Methods Protein levels of vascular endothelial growth factors-A, -C, -D (VEGF-A/-C/-D), their receptors- VEGF-R2 and -R3 (VEGF-R2/-R3), and matrix metalloproteinases 2, -3, and -7 (MMP-2, MMP-3, MMP-7) were quantified in the blood serum samples of 71 patients with UCB before radical cystectomy (RC). Samples of patients with non-invasive UCB or no history of UCB were investigated as controls (n=20). Protein levels in the serum were measured using a flow cytometric cytokine assay. Results A positive association for VEGF-D (p<0.001) and an inverse association for MMP-2 (p=0.017) were observed in patients with positive lymph node (LN) status at the time of RC. VEGF-A (p<0.001), VEGF-C (p<0.001), MMP-2 (p<0.001), and MMP-7 (p=0.005) serum levels were different in serum of patients with invasive UCB compared with non-invasive UCB or healthy individuals. None of the serum markers were associated with disease progression. Conclusions High VEGF-D and low MMP-2 serum levels predict LN metastasis in patients with UCB at the time of RC. VEGF-A, VEGF-C, MMP-2, and MMP-7 serum levels varied significantly between invasive and non-invasive disease as well as in comparison with healthy individuals. Clinical implementation of these marker serum measurements may be valuable to select high-risk patients with more invasive or nodal-positive disease. PMID:26241709

  10. Risk of Nodal Metastasis in Major Salivary Gland Adenoid Cystic Carcinoma.

    PubMed

    Megwalu, Uchechukwu C; Sirjani, Davud

    2017-04-01

    Objective To determine the risk of nodal metastasis, examine risk factors for nodal metastasis, and evaluate the impact of nodal metastasis on survival in patients with major salivary gland adenoid cystic carcinoma. Study Design Retrospective cohort study from a large population- based cancer database. Methods Data were extracted from the SEER 18 database (Surveillance, Epidemiology, and End Results) of the National Cancer Institute. The study cohort included 720 patients diagnosed with major salivary gland adenoid cystic carcinoma between 1988 and 2013. Results The overall rate of lymph node metastasis was 17%. T3 disease (odds ratio, 4.74) and T4 disease (odds ratio, 9.24) were associated with increased risk of nodal metastasis. Age, sex, and site were not associated with nodal metastasis. Nodal metastasis was associated with worse overall survival (hazard ratio, 2.56) and disease-specific survival (hazard ratio, 3.27), after adjusting for T stage, presence of distant metastasis, site, surgical resection, radiotherapy, neck dissection, age, sex, race, marital status, and year of diagnosis. Conclusion Major salivary gland adenoid cystic carcinoma carries significant risk of nodal metastasis. Advanced T stage is associated with increased risk of nodal metastasis. Nodal metastasis is associated with worse survival.

  11. Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson's Disease.

    PubMed

    Koshimori, Yuko; Cho, Sang-Soo; Criaud, Marion; Christopher, Leigh; Jacobs, Mark; Ghadery, Christine; Coakeley, Sarah; Harris, Madeleine; Mizrahi, Romina; Hamani, Clement; Lang, Anthony E; Houle, Sylvain; Strafella, Antonio P

    2016-01-01

    The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson's disease (PD). This study aimed to investigate functional changes in sensorimotor and cognitive networks in Parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls (HCs) and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the HC and patient groups. We found nodal and hub changes in patients compared with HCs, including the right pre-supplementary motor area (SMA), left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex (DLPFC), and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e., right pre-SMA and right mid-insula) displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral DLPFC possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of PD.

  12. Reappraisal of nodal Epstein-Barr Virus-negative cytotoxic T-cell lymphoma: identification of indolent CD5+ diseases.

    PubMed

    Yamashita, Daisuke; Shimada, Kazuyuki; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Kohno, Kei; Satou, Akira; Sakakibara, Ayako; Nakamura, Shigeo; Asano, Naoko; Kato, Seiichi

    2018-05-29

    Nodal cytotoxic molecule (CM)-positive peripheral T-cell lymphoma (CTL) has recently been recognized as a clinicopathologically distinct disease. To further characterize this disease, here we compared 58 patients with Epstein-Barr virus (EBV)-negative CTL to 48 patients with EBV-positive CTL. The two groups did not differ in histopathology, T-cell receptor (TCR) expression or rearrangement incidences, or survival curves. However, patients with EBV-negative CTL less frequently showed hepatic involvement (P = 0.007), B symptoms (P = 0.020), hemophagocytosis (P = 0.024), and detectable CD4 (P = 0.002) and CD5 (P = 0.009). Univariate and multivariate analyses identified three factors that independently predicted favorable survival, onset age <60 years (P = 0.002), CD5 expression (P = 0.002), and mixed morphology (P = 0.013), TCRαβ was not an independent predictor (P = 0.30), but was strongly linked with long survivorship among patients younger than 60 years old. A prognostic model incorporating these factors worked well for prognostic delineation, independently of the International Prognostic Index (P = 0.007 vs. P = 0.082) and Prognostic Index for PTCL (P = 0.020 vs. P = 0.15). Moreover, this constellation of findings indicated two nodal indolent diseases: CD5 + TCRαβ (n = 13), and CD5 + NK-cell type lacking TCR expression or clonal TCRγ rearrangement (n = 4). The survival curves for these two groups were significantly superior to others (n = 29, P < 0.001). These diseases appear to be unique in their indolent clinical behavior, and should be managed differently from other diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Occult nodal metastasis in solid carcinomata

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moloy, P.J.; Nicolson, G.L.

    1987-01-01

    This book contains 23 selections. Some of the titles are: Rationale for radiotherapy in subclinical nodal disease; rationale of chemotherapy for nodal disease: The stabilization of topoisomerase II-DNA complexes as a mechanism of antineoplastic drug action; magnetic resonance imaging of malignant cervical adenopathy; and local and regional immune function in cancer patients.

  14. Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson’s Disease

    PubMed Central

    Koshimori, Yuko; Cho, Sang-Soo; Criaud, Marion; Christopher, Leigh; Jacobs, Mark; Ghadery, Christine; Coakeley, Sarah; Harris, Madeleine; Mizrahi, Romina; Hamani, Clement; Lang, Anthony E.; Houle, Sylvain; Strafella, Antonio P.

    2016-01-01

    The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson’s disease (PD). This study aimed to investigate functional changes in sensorimotor and cognitive networks in Parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls (HCs) and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the HC and patient groups. We found nodal and hub changes in patients compared with HCs, including the right pre-supplementary motor area (SMA), left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex (DLPFC), and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e., right pre-SMA and right mid-insula) displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral DLPFC possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of PD. PMID:27891090

  15. The role of elective-nodal irradiation for esthesioneuroblastoma patients with clinically negative neck

    PubMed Central

    Jiang, Wen; Mohamed, Abdallah Sherif; Fuller, Clifton David; Kim, Betty Y.S.; Tang, Chad; Gunn, G. Brandon; Hanna, Ehab Y.; Frank, Steven J.; Su, Shirley Y.; Diaz, Eduardo; Kupferman, Michael E.; Beadle, Beth M.; Morrison, William H.; Skinner, Heath; Lai, Stephen Y.; El-Naggar, Adel K.; DeMonte, Franco; Rosenthal, David I.; Garden, Adam S.; Phan, Jack

    2017-01-01

    Purpose Although adjuvant radiation to the tumor bed has been reported to improve the clinic outcomes of esthesioneuroblastoma (ENB) patients, the role of elective neck irradiation (ENI) in clinically node negative (N0) patients remains controversial. Here, we evaluated the effects of ENI on neck nodal relapse risk in ENB patients treated with radiotherapy as a component of multi-modality treatment. Methods and Materials Seventy-one N0 ENB patients irradiated at XXXXXXXXX between 1970 and 2013 were identified. ENI was performed on 22 of these patients (31%). Survival analysis was performed with focus on comparative outcomes of those patients who did and did not receive ENI. Results The median follow up time for our cohort is 80.8 months (range 6 – 350 month). Among N0 patients, 13 (18.3%) developed neck nodal relapses, with a median time to progression of 62.5 months. None of these 13 patients received prophylactic neck irradiation. ENI was associated with significantly improved regional nodal control at 5-year (regional control rate of 100% for ENI vs 82%, p < 0.001), but not overall survival or disease-free survival. Eleven patients without ENI developed isolated neck recurrences. All had further treatment for their neck disease, including neck dissection (n=10), radiation (n=10), or chemotherapy (n=5). Six of these 11 patients (54.5%) demonstrated no evidence of further recurrence with a median follow up of 55.5 month. Conclusion ENI significantly reduces the risk of cervical nodal recurrence in ENB patients with clinically N0 neck but this did not translate to a survival benefit. Multimodality treatment for isolated neck recurrence provides a reasonable salvage rate. The greatest benefit for ENI appeared to be among younger patients who presented with Kadish C disease. Further studies are needed to confirm these findings. PMID:26979544

  16. Observation of a nodal chain with Dirac surface states in Ti B2

    NASA Astrophysics Data System (ADS)

    Yi, C.-J.; Lv, B. Q.; Wu, Q. S.; Fu, B.-B.; Gao, X.; Yang, M.; Peng, X.-L.; Li, M.; Huang, Y.-B.; Richard, P.; Shi, M.; Li, G.; Yazyev, Oleg V.; Shi, Y.-G.; Qian, T.; Ding, H.

    2018-05-01

    Topological nodal-line semimetals (TNLSMs) are characterized by symmetry-protected band crossings extending along one-dimensional lines in momentum space. The nodal lines exhibit a variety of possible configurations, such as nodal ring, nodal link, nodal chain, and nodal knot. Here, using angle-resolved photoemission spectroscopy, we observe nodal rings on the orthogonal kz=0 and kx=0 planes of the Brillouin zone in Ti B2 . The nodal rings connect with each other on the intersecting line Γ-K of the orthogonal planes forming a remarkable nodal-chain structure. Furthermore, we observe surface states (SSs) on the (001) cleaved surface, which are consistent with the calculated SSs considering the contribution from both Ti and B terminations. The calculated SSs have novel Dirac-cone-like band structures, which are distinct from the usual drumhead SSs with a single flatband proposed in other TNLSMs.

  17. Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Varlotto, John M., E-mail: john.varlotto@umassmemorial.org; Yao, Aaron N.; DeCamp, Malcolm M.

    Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy.more » Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum. Conclusions: Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence

  18. Role of Ultrasonography of Regional Nodal Basins in Staging Triple-Negative Breast Cancer and Implications For Local-Regional Treatment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shaitelman, Simona F., E-mail: sfshaitelman@mdanderson.org; Tereffe, Welela; Dogan, Basak E.

    2015-09-01

    Purpose: We sought to determine the rate at which regional nodal ultrasonography would increase the nodal disease stage in patients with triple-negative breast cancer (TNBC) beyond the clinical stage determined by physical examination and mammography alone, and significantly affect the treatments delivered to these patients. Methods and Materials: We retrospectively reviewed the charts of women with stages I to III TNBC who underwent physical examination, mammography, breast and regional nodal ultrasonography with needle biopsy of abnormal nodes, and definitive local-regional treatment at our institution between 2004 and 2011. The stages of these patients' disease with and without ultrasonography of the regionalmore » nodal basins were compared using the Pearson χ{sup 2} test. Definitive treatments of patients whose nodal disease was upstaged on the basis of ultrasonographic findings were compared to those of patients whose disease stage remained the same. Results: A total of 572 women met the study requirements. In 111 (19.4%) of these patients, regional nodal ultrasonography with needle biopsy resulted in an increase in disease stage from the original stage by physical examination and mammography alone. Significantly higher percentages of patients whose nodal disease was upstaged by ultrasonographic findings compared to that in patients whose disease was not upstaged underwent neoadjuvant systemic therapy (91.9% and 51.2%, respectively; P<.0001), axillary lymph node dissection (99.1% and 34.5%, respectively; P<.0001), and radiation to the regional nodal basins (88.2% and 29.1%, respectively; P<.0001). Conclusions: Regional nodal ultrasonography in TNBC frequently changes the initial clinical stage and plays an important role in treatment planning.« less

  19. The role of elective nodal irradiation for esthesioneuroblastoma patients with clinically negative neck.

    PubMed

    Jiang, Wen; Mohamed, Abdallah S R; Fuller, Clifton David; Kim, Betty Y S; Tang, Chad; Gunn, G Brandon; Hanna, Ehab Y; Frank, Steven J; Su, Shirley Y; Diaz, Eduardo; Kupferman, Michael E; Beadle, Beth M; Morrison, William H; Skinner, Heath; Lai, Stephen Y; El-Naggar, Adel K; DeMonte, Franco; Rosenthal, David I; Garden, Adam S; Phan, Jack

    2016-01-01

    Although adjuvant radiation to the tumor bed has been reported to improve the clinic outcomes of esthesioneuroblastoma (ENB) patients, the role of elective neck irradiation (ENI) in clinically node-negative (N0) patients remains controversial. Here, we evaluated the effects of ENI on neck nodal relapse risk in ENB patients treated with radiation therapy as a component of multimodality treatment. Seventy-one N0 ENB patients irradiated at the University of Texas MD Anderson Cancer Center between 1970 and 2013 were identified. ENI was performed on 22 of these patients (31%). Survival analysis was performed with focus on comparative outcomes of those patients who did and did not receive ENI. The median follow-up time for our cohort is 80.8 months (range, 6-350 months). Among N0 patients, 13 (18.3%) developed neck nodal relapses, with a median time to progression of 62.5 months. None of these 13 patients received prophylactic neck irradiation. ENI was associated with significantly improved regional nodal control at 5 years (regional control rate of 100% for ENI vs 82%, P < .001), but not overall survival or disease-free survival. Eleven patients without ENI developed isolated neck recurrences. All had further treatment for their neck disease, including neck dissection (n = 10), radiation (n = 10), or chemotherapy (n = 5). Six of these 11 patients (54.5%) demonstrated no evidence of further recurrence with a median follow-up of 55.5 months. ENI significantly reduces the risk of cervical nodal recurrence in ENB patients with clinically N0 neck, but this did not translate to a survival benefit. Multimodality treatment for isolated neck recurrence provides a reasonable salvage rate. The greatest benefit for ENI appeared to be among younger patients who presented with Kadish C disease. Further studies are needed to confirm these findings. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  20. Topological nodal-line fermions in spin-orbit metal PbTaSe2

    DOE PAGES

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; ...

    2016-02-02

    Here we discuss how topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe 2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe 2 are not only protected by the reflection symmetry butmore » also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems.« less

  1. Topological nodal-line fermions in spin-orbit metal PbTaSe2

    PubMed Central

    Bian, Guang; Chang, Tay-Rong; Sankar, Raman; Xu, Su-Yang; Zheng, Hao; Neupert, Titus; Chiu, Ching-Kai; Huang, Shin-Ming; Chang, Guoqing; Belopolski, Ilya; Sanchez, Daniel S.; Neupane, Madhab; Alidoust, Nasser; Liu, Chang; Wang, BaoKai; Lee, Chi-Cheng; Jeng, Horng-Tay; Zhang, Chenglong; Yuan, Zhujun; Jia, Shuang; Bansil, Arun; Chou, Fangcheng; Lin, Hsin; Hasan, M. Zahid

    2016-01-01

    Topological semimetals can support one-dimensional Fermi lines or zero-dimensional Weyl points in momentum space, where the valence and conduction bands touch. While the degeneracy points in Weyl semimetals are robust against any perturbation that preserves translational symmetry, nodal lines require protection by additional crystalline symmetries such as mirror reflection. Here we report, based on a systematic theoretical study and a detailed experimental characterization, the existence of topological nodal-line states in the non-centrosymmetric compound PbTaSe2 with strong spin-orbit coupling. Remarkably, the spin-orbit nodal lines in PbTaSe2 are not only protected by the reflection symmetry but also characterized by an integer topological invariant. Our detailed angle-resolved photoemission measurements, first-principles simulations and theoretical topological analysis illustrate the physical mechanism underlying the formation of the topological nodal-line states and associated surface states for the first time, thus paving the way towards exploring the exotic properties of the topological nodal-line fermions in condensed matter systems. PMID:26829889

  2. Risk of isolated nodal failure for non-small cell lung cancer (NSCLC) treated with the elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) techniques--a retrospective analysis.

    PubMed

    Kepka, Lucyna; Bujko, Krzysztof; Zolciak-Siwinska, Agnieszka

    2008-01-01

    To estimate retrospectively the rate of isolated nodal failures (INF) in NSCLC patients treated with the elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT). One hundred and eighty-five patients with I-IIIB stage treated with 3D-CRT in consecutive clinical trials differing in an extent of the ENI were analyzed. According to the extent of the ENI, two groups were distinguished: extended (n = 124) and limited (n = 61) ENI. INF was defined as regional nodal failure occurring without local progression. Cumulative Incidence of INF (CIINF) was evaluated by univariate and multivariate analysis with regard to prognostic factors. With a median follow up of 30 months, the two-year actuarial overall survival was 35%. The two-year CIINF rate was 12%. There were 16 (9%) INF, eight (6%) for extended and eight (13%) for limited ENI. In the univariate analysis bulky mediastinal disease (BMD), left side, higher N stage, and partial response to RT had a significant negative impact on the CIINF. BMD was the only independent predictor of the risk of incidence of the INF (p = 0.001). INF is more likely to occur in case of more advanced nodal status.

  3. Face Centered Cubic SnSe as a Z2 Trivial Dirac Nodal Line Material

    NASA Astrophysics Data System (ADS)

    Tateishi, Ikuma; Matsuura, Hiroyasu

    2018-07-01

    The presence of a Dirac nodal line in a time-reversal and inversion symmetric system is dictated by the Z2 index when spin-orbit interaction is absent. In a first principles calculation, we show that a Dirac nodal line can emerge in Z2 trivial material by calculating the band structure of SnSe in a face centered cubic lattice as an example. We qualitatively show that it becomes a topological crystalline insulator when spin-orbit interaction is taken into account. We clarify the origin of the Dirac nodal line by obtaining irreducible representations corresponding to bands and explain the triviality of the Z2 index. We construct an effective model representing the Dirac nodal line using the k · p method, and discuss the Berry phase and a surface state expected from the Dirac nodal line.

  4. pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Karam, Irene; Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC; Lesperance, Maria F.

    Purpose: To examine treatment patterns, recurrence, and survival outcomes in patients with pN0(i+) breast cancer. Methods and Materials: Subjects were 5999 women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between 2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had pNmic (micrometastases >0.2 mm to ≤2 mm), and 1212 (20%) had pN1a (1-3 positive macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and overall survival were compared between nodal subgroups. Multivariable analysis was performed using Cox regression modeling. A 1:3 case-match analysis examinedmore » outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor and treatment characteristics. Results: Median follow-up was 4.8 years. Adjuvant systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0, pN0(i+), pNmic, and pN1a disease, respectively (P<.001). Nodal radiation therapy (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in pNmic, and 63% in pN1a cohorts (P<.001). Five-year Kaplan-Meier outcomes in pN0 versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20), RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RR events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+) was not associated with worse locoregional control or survival. On case-match analysis, LRR and overall survival were similar between pN0(i+) and matched pN0 counterparts. Conclusions: Nodal involvement with isolated tumor cells is not a significant prognostic factor for LRR or survival in this study's multivariable and case-match analyses. These data do not support the routine use of nodal RT in the setting of pN0(i+) disease. Prospective studies are needed to define

  5. A Prospective Study of Level IIB Nodal Metastasis (Supraretrospinal) in Clinically N0 Oral Squamous Cell Carcinoma in Indian Population.

    PubMed

    Chheda, Yogen P; Pillai, Sundaram K; Parikh, Devendra G; Dipayan, Nandy; Shah, Shakuntala V; Alaknanda, Gupta

    2017-06-01

    Oral cavity carcinoma is the most common cancer in Indian population. Metastatic nodal disease is the most important prognostic factor for oral cancers. In head and neck cancers with clinically N0 neck, standard selective neck dissection is performed by protecting the spinal accessory nerve to remove level IIA & IIB lymph nodes. The purpose of this study was to analyze the significance of level IIB dissection in patients of oral cavity cancer who underwent primary surgery with functional neck dissection. Two hundred ten patients with clinically N0 neck underwent neck dissection, where level IIB lymph nodes were dissected, labelled and processed separately. Among 210 patients of clinically N0 neck, 168 patients were pathologically N0 (80 %). Out of remaining 42 (20 %), 36 (17.14 %) were pN1 and 6 (2.86 %) were pN2. Among those with pN1 (36), level IB was involved in 24 patients (66.67 %) and level IIA was involved in 12 patients (33.33 %). Only 2 patients had involvement of level IIB lymph nodes. Among 6 patients of pN2 disease, 4 patients had simultaneous involvement of level IB and level IIA lymph nodes. Remaining 2 patients had isolated involvement of level III lymph nodes. Thus only 2 patients (< 1 %) out of 210 clinically N0 oral squamous cell carcinoma showed level IIB lymph node involvement. Thus we conclude that a frozen section of level 2a is advisable to decide the need for level 2b node dissection in clinically N0 neck as the sensitivity of clinical evaluation is extremely low.

  6. Experimental discovery of nodal chains

    NASA Astrophysics Data System (ADS)

    Yan, Qinghui; Liu, Rongjuan; Yan, Zhongbo; Liu, Boyuan; Chen, Hongsheng; Wang, Zhong; Lu, Ling

    2018-05-01

    Three-dimensional Weyl and Dirac nodal points1 have attracted widespread interest across multiple disciplines and in many platforms but allow for few structural variations. In contrast, nodal lines2-4 can have numerous topological configurations in momentum space, forming nodal rings5-9, nodal chains10-15, nodal links16-20 and nodal knots21,22. However, nodal lines are much less explored because of the lack of an ideal experimental realization23-25. For example, in condensed-matter systems, nodal lines are often fragile to spin-orbit coupling, located away from the Fermi level, coexist with energy-degenerate trivial bands or have a degeneracy line that disperses strongly in energy. Here, overcoming all these difficulties, we theoretically predict and experimentally observe nodal chains in a metallic-mesh photonic crystal having frequency-isolated linear band-touching rings chained across the entire Brillouin zone. These nodal chains are protected by mirror symmetry and have a frequency variation of less than 1%. We use angle-resolved transmission measurements to probe the projected bulk dispersion and perform Fourier-transformed field scans to map out the dispersion of the drumhead surface state. Our results establish an ideal nodal-line material for further study of topological line degeneracies with non-trivial connectivity and consequent wave dynamics that are richer than those in Weyl and Dirac materials.

  7. TGF-β promotes glioma cell growth via activating Nodal expression through Smad and ERK1/2 pathways

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sun, Jing; Liu, Su-zhi; Lin, Yan

    Highlights: •TGF-β promoted Nodal expression in glioma cells. •TGF-β promoted Nodal expression via activating Smad and ERK1/2 pathways. •TGF-β promotes glioma cell growth via activating Nodal expression. -- Abstract: While there were certain studies focusing on the mechanism of TGF-β promoting the growth of glioma cells, the present work revealed another novel mechanism that TGF-β may promote glioma cell growth via enhancing Nodal expression. Our results showed that Nodal expression was significantly upregulated in glioma cells when TGF-β was added, whereas the TGF-β-induced Nodal expression was evidently inhibited by transfection Smad2 or Smad3 siRNAs, and the suppression was especially significantmore » when the Smad3 was downregulated. Another, the attenuation of TGF-β-induced Nodal expression was observed with blockade of the ERK1/2 pathway also. Further detection of the proliferation, apoptosis, and invasion of glioma cells indicated that Nodal overexpression promoted the proliferation and invasion of tumor cells and inhibited their apoptosis, resembling the effect of TGF-β addition. Downregulation of Nodal expression via transfection Nodal-specific siRNA in the presence of TGF-β weakened the promoting effect of the latter on glioma cells growth, and transfecting Nodal siRNA alone in the absence of exogenous TGF-β more profoundly inhibited the growth of glioma cells. These results demonstrated that while both TGF-β and Nodal promoted glioma cells growth, the former might exert such effect by enhancing Nodal expression, which may form a new target for glioma therapy.« less

  8. The accuracy of preoperative axillary nodal staging in primary breast cancer by ultrasound is modified by nodal metastatic load and tumor biology

    PubMed Central

    Dihge, Looket; Grabau, Dorthe A.; Rasmussen, Rogvi W.; Bendahl, Pär-Ola; Rydén, Lisa

    2016-01-01

    Abstract Background The outcome of axillary ultrasound (AUS) with fine-needle aspiration biopsy (FNAB) in the diagnostic work-up of primary breast cancer has an impact on therapy decisions. We hypothesize that the accuracy of AUS is modified by nodal metastatic burden and clinico-pathological characteristics. Material and methods The performance of AUS and AUS-guided FNAB for predicting nodal metastases was assessed in a prospective breast cancer cohort subjected for surgery during 2009–2012. Predictors of accuracy were included in multivariate analysis. Results AUS had a sensitivity of 23% and a specificity of 95%, while AUS-guided FNAB obtained 73% and 100%, respectively. AUS-FNAB exclusively detected macro-metastases (median four metastases) and identified patients with more extensive nodal metastatic burden in comparison with sentinel node biopsy. The accuracy of AUS was affected by metastatic size (OR 1.11), obesity (OR 2.46), histological grade (OR 4.43), and HER2-status (OR 3.66); metastatic size and histological grade were significant in the multivariate analysis. Conclusions The clinical utility of AUS in low-risk breast cancer deserves further evaluation as the accuracy decreased with a low nodal metastatic burden. The diagnostic performance is modified by tumor and clinical characteristics. Patients with nodal disease detected by AUS-FNAB represent a group for whom neoadjuvant therapy should be considered. PMID:27050668

  9. Outcomes of surgically treated human papillomavirus-related oropharyngeal squamous cell carcinoma with N3 disease.

    PubMed

    Zenga, Joseph; Haughey, Bruce H; Jackson, Ryan S; Adkins, Douglas R; Aranake-Chrisinger, John; Bhatt, Neel; Gay, Hiram A; Kallogjeri, Dorina; Martin, Eliot J; Moore, Eric J; Paniello, Randal C; Rich, Jason T; Thorstad, Wade L; Nussenbaum, Brian

    2017-09-01

    To evaluate outcomes for patients with pathological N3 (pN3) neck disease from human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and determine variables predictive of survival. Retrospective case series with chart review. This study was conducted between 1998 and 2013 and included patients with HPV-related OPSCC treated with surgery with or without adjuvant therapy and who had pN3 nodal disease. The primary outcome was disease-specific survival (DSS). Secondary outcomes included overall survival (OS), disease-free survival (DFS), adverse events, and gastrostomy tube rates. Thirty-nine patients were included, of whom 36 (90%) underwent adjuvant therapy. Median follow-up was 39 months (range, 2-147 months). Mean age was 56 years, and 87% were male. Seventeen patients (44%) underwent selective neck dissection, whereas six (15%) underwent radical (n = 2) or extended radical (n = 4) neck dissection. Ninety-two percent had extracapsular extension. Five-year Kaplan-Meier estimated DSS, OS, and DFS were 89% (95% confidence interval [CI]: 79%-99%), 87% (95% CI: 75%-99%), and 84% (95% CI: 72%-96%), respectively. The disease recurrence rate was 10% (5% regional, 5% distant metastasis). Patients with less than 5 pathologically positive lymph nodes (P = .041) had improved DFS. Patients with HPV-related OPSCC and pN3 nodal disease treated with surgery and adjuvant therapy have very favorable long-term survival and regional control. Patients with five or more pathologically positive lymph nodes may be at higher risk for recurrence. 4. Laryngoscope, 127:2033-2037, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Nodal surface semimetals: Theory and material realization

    NASA Astrophysics Data System (ADS)

    Wu, Weikang; Liu, Ying; Li, Si; Zhong, Chengyong; Yu, Zhi-Ming; Sheng, Xian-Lei; Zhao, Y. X.; Yang, Shengyuan A.

    2018-03-01

    We theoretically study the three-dimensional topological semimetals with nodal surfaces protected by crystalline symmetries. Different from the well-known nodal-point and nodal-line semimetals, in these materials, the conduction and valence bands cross on closed nodal surfaces in the Brillouin zone. We propose different classes of nodal surfaces, both in the absence and in the presence of spin-orbit coupling (SOC). In the absence of SOC, a class of nodal surfaces can be protected by space-time inversion symmetry and sublattice symmetry and characterized by a Z2 index, while another class of nodal surfaces are guaranteed by a combination of nonsymmorphic twofold screw-rotational symmetry and time-reversal symmetry. We show that the inclusion of SOC will destroy the former class of nodal surfaces but may preserve the latter provided that the inversion symmetry is broken. We further generalize the result to magnetically ordered systems and show that protected nodal surfaces can also exist in magnetic materials without and with SOC, given that certain magnetic group symmetry requirements are satisfied. Several concrete nodal-surface material examples are predicted via the first-principles calculations. The possibility of multi-nodal-surface materials is discussed.

  11. Dirac Magnon Nodal Loops in Quasi-2D Quantum Magnets.

    PubMed

    Owerre, S A

    2017-07-31

    In this report, we propose a new concept of one-dimensional (1D) closed lines of Dirac magnon nodes in two-dimensional (2D) momentum space of quasi-2D quantum magnetic systems. They are termed "2D Dirac magnon nodal-line loops". We utilize the bilayer honeycomb ferromagnets with intralayer coupling J and interlayer coupling J L , which is realizable in the honeycomb chromium compounds CrX 3 (X ≡ Br, Cl, and I). However, our results can also exist in other layered quasi-2D quantum magnetic systems. Here, we show that the magnon bands of the bilayer honeycomb ferromagnets overlap for J L  ≠ 0 and form 1D closed lines of Dirac magnon nodes in 2D momentum space. The 2D Dirac magnon nodal-line loops are topologically protected by inversion and time-reversal symmetry. Furthermore, we show that they are robust against weak Dzyaloshinskii-Moriya interaction Δ DM  < J L and possess chiral magnon edge modes.

  12. Bcl-2 and BLIMP-1 expression predict worse prognosis in gastric diffuse large B cell lymphoma (DLCBL) while other markers for nodal DLBCL are not useful.

    PubMed

    Martin-Arruti, Maialen; Vaquero, Manuel; Díaz de Otazu, Ramón; Zabalza, Iñaki; Ballesteros, Javier; Roncador, Giovanna; García-Orad, Africa

    2012-04-01

    Previous studies have identified clinicopathological and immunohistochemical differences among diffuse large B cell lymphomas (DLBCL) as a function of disease location. Nevertheless, there is a continuing tendency to generalize the prognostic value of various identified markers without taking into account tumour site. Accordingly, we analysed the prognostic value of several of the immunohistochemical markers that have been proposed for nodal DLBCL in a group of patients with gastric DLBCL. Using histochemical methods, CD10, Bcl-6, Gcet1, MUM-1, Bcl-2 and BLIMP-1 expression was investigated in 43 cases of gastric DBLCL. As in nodal DLBCLs, expression of BLIMP-1, and of Bcl-2 in non-germinal centre B cell-like (non-GCB) patients, was associated with a worse prognosis. However, unlike nodal DBLCL, there was no significant association of prognosis with expression of CD10, Bcl-6, Gcet1 or MUM-1, or with categorization according to Hans or Muris algorithms. Although most markers of prognosis in nodal DLBCL are not useful indicators for gastric DLBCL, Bcl-2 or BLIMP-1 expression does correlate with worse prognosis. These data support the notion that clinicopathological features in DLBCL vary according to the disease location. © 2012 Blackwell Publishing Ltd.

  13. Nodal gap detection through polar angle-resolved density of states measurements in uniaxial superconductors

    NASA Astrophysics Data System (ADS)

    Tsutsumi, Yasumasa; Nomoto, Takuya; Ikeda, Hiroaki; Machida, Kazushige

    2016-12-01

    We propose a spectroscopic method to identify the nodal gap structure in unconventional superconductors. This method is best suited for locating the horizontal line node and for pinpointing the isolated point nodes by measuring polar angle (θ ) resolved zero-energy density of states N (θ ) . This is measured by specific heat or thermal conductivity at low temperatures under a magnetic field. We examine a variety of uniaxially symmetric nodal structures, including point and/or line nodes with linear and quadratic dispersions, by solving the Eilenberger equation in vortex states. It is found that (a) the maxima of N (θ ) continuously shift from the antinodal to the nodal direction (θn) as a field increases accompanying the oscillation pattern reversal at low and high fields. Furthermore, (b) local minima emerge next to θn on both sides, except for the case of the linear point node. These features are robust and detectable experimentally. Experimental results of N (θ ) performed on several superconductors, UPd2Al3,URu2Si2,CuxBi2Se3 , and UPt3, are examined and commented on in light of the present theory.

  14. Cryopreservation of in vitro grown nodal segments of Rauvolfia serpentina by PVS2 vitrification.

    PubMed

    Ray, Avik; Bhattacharya, Sabita

    2008-01-01

    This paper describes the cryopreservation by PVS2 vitrification of Rauvolfia serpentina (L.) Benth ex kurz, an important tropical medicinal plant. The effects of type and size of explants, sucrose preculture (duration and concentration) and vitrification treatment were tested. Preliminary experiments with PVS1, 2 and 3 produced shoot growth only for PVS2. When optimizing the PVS2 vitrification of nodal segments, those of 0.31 - 0.39 cm in size were better than other nodal sizes and or apices. Sucrose preculture had a positive role in survival and subsequent regrowth of the cryopreserved explants. Seven days on 0.5 M sucrose solution significantly improved the viability of nodal segments. PVS2 incubation for 45 minutes combined with a 7-day preculture gave the optimum result of 66 percent. Plantlets derived after cryopreservation resumed growth and regenerated normally.

  15. Robust doubly charged nodal lines and nodal surfaces in centrosymmetric systems

    NASA Astrophysics Data System (ADS)

    Bzdušek, Tomáš; Sigrist, Manfred

    2017-10-01

    Weyl points in three spatial dimensions are characterized by a Z -valued charge—the Chern number—which makes them stable against a wide range of perturbations. A set of Weyl points can mutually annihilate only if their net charge vanishes, a property we refer to as robustness. While nodal loops are usually not robust in this sense, it has recently been shown using homotopy arguments that in the centrosymmetric extension of the AI symmetry class they nevertheless develop a Z2 charge analogous to the Chern number. Nodal loops carrying a nontrivial value of this Z2 charge are robust, i.e., they can be gapped out only by a pairwise annihilation and not on their own. As this is an additional charge independent of the Berry π -phase flowing along the band degeneracy, such nodal loops are, in fact, doubly charged. In this manuscript, we generalize the homotopy discussion to the centrosymmetric extensions of all Atland-Zirnbauer classes. We develop a tailored mathematical framework dubbed the AZ +I classification and show that in three spatial dimensions such robust and multiply charged nodes appear in four of such centrosymmetric extensions, namely, AZ +I classes CI and AI lead to doubly charged nodal lines, while D and BDI support doubly charged nodal surfaces. We remark that no further crystalline symmetries apart from the spatial inversion are necessary for their stability. We provide a description of the corresponding topological charges, and develop simple tight-binding models of various semimetallic and superconducting phases that exhibit these nodes. We also indicate how the concept of robust and multiply charged nodes generalizes to other spatial dimensions.

  16. A Variational Nodal Approach to 2D/1D Pin Resolved Neutron Transport for Pressurized Water Reactors

    DOE PAGES

    Zhang, Tengfei; Lewis, E. E.; Smith, M. A.; ...

    2017-04-18

    A two-dimensional/one-dimensional (2D/1D) variational nodal approach is presented for pressurized water reactor core calculations without fuel-moderator homogenization. A 2D/1D approximation to the within-group neutron transport equation is derived and converted to an even-parity form. The corresponding nodal functional is presented and discretized to obtain response matrix equations. Within the nodes, finite elements in the x-y plane and orthogonal functions in z are used to approximate the spatial flux distribution. On the radial interfaces, orthogonal polynomials are employed; on the axial interfaces, piecewise constants corresponding to the finite elements eliminate the interface homogenization that has been a challenge for method ofmore » characteristics (MOC)-based 2D/1D approximations. The angular discretization utilizes an even-parity integral method within the nodes, and low-order spherical harmonics (P N) on the axial interfaces. The x-y surfaces are treated with high-order P N combined with quasi-reflected interface conditions. Furthermore, the method is applied to the C5G7 benchmark problems and compared to Monte Carlo reference calculations.« less

  17. A Variational Nodal Approach to 2D/1D Pin Resolved Neutron Transport for Pressurized Water Reactors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Tengfei; Lewis, E. E.; Smith, M. A.

    A two-dimensional/one-dimensional (2D/1D) variational nodal approach is presented for pressurized water reactor core calculations without fuel-moderator homogenization. A 2D/1D approximation to the within-group neutron transport equation is derived and converted to an even-parity form. The corresponding nodal functional is presented and discretized to obtain response matrix equations. Within the nodes, finite elements in the x-y plane and orthogonal functions in z are used to approximate the spatial flux distribution. On the radial interfaces, orthogonal polynomials are employed; on the axial interfaces, piecewise constants corresponding to the finite elements eliminate the interface homogenization that has been a challenge for method ofmore » characteristics (MOC)-based 2D/1D approximations. The angular discretization utilizes an even-parity integral method within the nodes, and low-order spherical harmonics (P N) on the axial interfaces. The x-y surfaces are treated with high-order P N combined with quasi-reflected interface conditions. Furthermore, the method is applied to the C5G7 benchmark problems and compared to Monte Carlo reference calculations.« less

  18. Human papillomavirus reduces the prognostic value of nodal involvement in tonsillar squamous cell carcinomas.

    PubMed

    Straetmans, Jos M J A A; Olthof, Nadine; Mooren, Jeroen J; de Jong, Jos; Speel, Ernst-Jan M; Kremer, Bernd

    2009-10-01

    Assessment of the prognostic value of nodal status in relation to human papillomavirus (HPV) status and the various treatment modalities in tonsillar squamous cell carcinomas (TSCC). Retrospective 5-year survival analysis. A 5-year follow-up of disease-free, disease-specific, and overall survival in a group of 81 patients with TSCC was conducted. The nodal status and integration of HPV-DNA in the genome (detected with fluorescence in situ hybridization) as prognostic indicators were examined while correcting for other clinical parameters (smoking habits, alcohol consumption, treatment modality, differentiation, TNM classification). Of TSCCs, 41% were positive for HPV type 16. In these TSCCs, the primary tumor was significantly smaller when compared to HVP-negative TSCCs (P = .04), whereas the percentage of cases with cervical metastases was identical. In the total population, it was not nodal involvement, but rather HPV manifestation, which was related to patient prognosis. Within the treatment modalities (surgery combined with radiotherapy and radiotherapy alone), neither nodal status nor HPV were prognostic indicators. Since a substantial percentage of TSCCs are HPV-positive and metastasizes to cervical lymph nodes in less advanced primary tumors, the N status is an unreliable prognostic indicator in TSCCs. HPV is only prognostically relevant in the total tumor population, but loses its value within patient groups receiving a single treatment modality. The value of HPV for prognosis of patients with TSCC requires further study.

  19. Pressure-induced organic topological nodal-line semimetal in the three-dimensional molecular crystal Pd (dddt) 2

    NASA Astrophysics Data System (ADS)

    Liu, Zhao; Wang, Haidi; Wang, Z. F.; Yang, Jinlong; Liu, Feng

    2018-04-01

    The nodal-line semimetal represents a class of topological materials characterized with highest band degeneracy. It is usually found in inorganic materials of high crystal symmetry or a minimum symmetry of inversion aided with accidental band degeneracy [Phys. Rev. Lett. 118, 176402 (2017), 10.1103/PhysRevLett.118.176402]. Based on first-principles band structure, Wannier charge center, and topological surface state calculations, here we predict a pressure-induced topological nodal-line semimetal in the absence of spin-orbit coupling (SOC) in the synthesized single-component 3D molecular crystal Pd (dddt) 2 . We show a Γ -centered single nodal line undulating within a narrow energy window across the Fermi level. This intriguing nodal line is generated by pressure-induced accidental band degeneracy, without protection from any crystal symmetry. When SOC is included, the fourfold degenerated nodal line is gapped and Pd (dddt) 2 becomes a strong 3D topological metal with an Z2 index of (1;000). However, the tiny SOC gap makes it still possible to detect the nodal-line properties experimentally. Our findings afford an attractive route for designing and realizing topological states in 3D molecular crystals, as they are weakly bonded through van der Waals forces with a low crystal symmetry so that their electronic structures can be easily tuned by pressure.

  20. Management of recurrent/persistent nodal disease in patients with differentiated thyroid cancer: a critical review of the risks and benefits of surgical intervention versus active surveillance.

    PubMed

    Tufano, Ralph P; Clayman, Gary; Heller, Keith S; Inabnet, William B; Kebebew, Electron; Shaha, Ashok; Steward, David L; Tuttle, R Michael

    2015-01-01

    The primary goals of this interdisciplinary consensus statement are to define the eligibility criteria for management of recurrent and persistent cervical nodal disease in patients with differentiated thyroid cancer (DTC) and to review the risks and benefits of surgical intervention versus active surveillance. A writing group was convened by the Surgical Affairs Committee of the American Thyroid Association and was tasked with identifying the important clinical elements to consider when managing recurrent/persistent nodal disease in patients with DTC based on the available evidence in the literature and the group's collective experience. The decision on how best to manage individual patients with suspected recurrent/persistent nodal disease is challenging and requires the consideration of a significant number of variables outlined by the members of the interdisciplinary team. Here we report on the consensus opinions that were reached by the writing group regarding the technical and clinical issues encountered in this patient population. Identification of recurrent/persistent disease requires a team decision-making process that includes the patient and physicians as to what, if any, intervention should be performed to best control the disease while minimizing morbidity. Several management principles and variables involved in the decision making for surgery versus active surveillance were developed that should be taken into account when deciding how best to manage a patient with DTC and suspected recurrent or persistent cervical nodal disease.

  1. Prognostic impact of the level of nodal involvement: retrospective analysis of patients with advanced oral squamous cell carcinoma.

    PubMed

    Murakami, R; Nakayama, H; Semba, A; Hiraki, A; Nagata, M; Kawahara, K; Shiraishi, S; Hirai, T; Uozumi, H; Yamashita, Y

    2017-01-01

    We retrospectively evaluated the prognostic impact of the level of nodal involvement in patients with advanced oral squamous cell carcinoma (SCC). Between 2005 and 2010, 105 patients with clinical stage III or IV oral SCC had chemoradiotherapy preoperatively. Clinical (cN) and pathological nodal (pN) involvement was primarily at levels Ib and II. We defined nodal involvement at levels Ia and III-V as anterior and inferior extensions, respectively, and recorded such findings as extensive. With respect to pretreatment variables (age, clinical stage, clinical findings of the primary tumour, and nodal findings), univariate analysis showed that extensive cN was the only significant factor for overall survival (hazard ratio [HR], 3.27; 95% CI 1.50 to 7.13; p=0.001). Univariate analysis showed that all pN findings, including the nodal classification (invaded nodes, multiple, and contralateral) and extensive involvement were significant, and multivariate analysis confirmed that extensive pN (HR 4.71; 95% CI 1.85 to 11.97; p=0.001) and multiple pN (HR 2.59; 95% CI 1.10 to 6.09; p=0.029) were independent predictors of overall survival. Assessment based on the level of invaded neck nodes may be a better predictor of survival than the current nodal classification. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. PET-NECK: a multicentre randomised Phase III non-inferiority trial comparing a positron emission tomography-computerised tomography-guided watch-and-wait policy with planned neck dissection in the management of locally advanced (N2/N3) nodal metastases in patients with squamous cell head and neck cancer.

    PubMed

    Mehanna, Hisham; McConkey, Chris C; Rahman, Joy K; Wong, Wai-Lup; Smith, Alison F; Nutting, Chris; Hartley, Andrew Gj; Hall, Peter; Hulme, Claire; Patel, Dharmesh K; Zeidler, Sandra Ventorin von; Robinson, Max; Sanghera, Bal; Fresco, Lydia; Dunn, Janet A

    2017-04-01

    CRT and fit for ND were recruited. Patients randomised to planned ND before or after CRT (control), or CRT followed by fludeoxyglucose PET-CT 10-12 weeks post CRT with ND only if PET-CT showed incomplete or equivocal response of nodal disease (intervention). Balanced by centre, planned ND timing, CRT schedule, disease site and the tumour, node, metastasis stage. In total, 564 patients were recruited (ND arm, n  = 282; and surveillance arm, n  = 282; 17% N2a, 61% N2b, 18% N2c and 3% N3). Eighty-four per cent had oropharyngeal cancer. Seventy-five per cent of tested cases were p16 positive. The median time to follow-up was 36 months. The HR for OS was 0.92 [95% confidence interval (CI) 0.65 to 1.32], indicating non-inferiority. The upper limit of the non-inferiority HR margin of 1.50, which was informed by patient advisors to the project, lies at the 99.6 percentile of this estimate ( p  = 0.004). There were no differences in this result by p16 status. There were 54 NDs performed in the surveillance arm, with 22 surgical complications, and 221 NDs in the ND arm, with 85 complications. Quality-of-life scores were slightly better in the surveillance arm. Compared with planned ND, PET-CT surveillance produced an incremental net health benefit of 0.16 QALYs (95% CI 0.03 to 0.28 QALYs) over the trial period and 0.21 QALYs (95% CI -0.41 to 0.85 QALYs) over the modelled lifetime horizon. Pragmatic randomised controlled trial with a 36-month median follow-up. PET-CT-guided active surveillance showed similar survival outcomes to ND but resulted in considerably fewer NDs, fewer complications and lower costs, supporting its use in routine practice. PET-CT surveillance is cost-effective in the short term, and long-term cost-effectiveness could be addressed in future work. Current Controlled Trials ISRCTN13735240. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health

  3. Clinical Usefulness of [(18)F]Fluoro-2-Deoxy-D-Glucose Uptake in 178 Head-and-Neck Cancer Patients With Nodal Metastasis Treated With Definitive Chemoradiotherapy: Consideration of Its Prognostic Value and Ability to Provide Guidance for Optimal Selection of Patients for Planned Neck Dissection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Inokuchi, Haruo, E-mail: h.inokuchi@scchr.j; Kodaira, Takeshi; Tachibana, Hiroyuki

    2011-03-01

    Purpose: To evaluate the clinical effectiveness of pretreatment [(18)F]fluoro-2-deoxy-D-glucose-positron emission tomography for head-and-neck squamous cell carcinoma patients with nodal metastasis treated with chemoradiotherapy. Methods and Materials: Between March 2002 and December 2006, 178 patients with head-and-neck squamous cell carcinoma and nodal metastasis underwent fluoro-2-deoxy-D-glucose positron emission tomography before chemoradiotherapy. Fluoro-2-deoxy-D-glucose uptake by both the primary lesion and the neck node was measured using the standard uptake value (SUV). The overall survival, disease-free survival, local control, nodal progression-free survival, and distant metastasis-free survival rates were calculated, and several prognostic factors were evaluated. Results: The patients with a nodal SUV {>=}6.00 hadmore » a significantly lower 3-year disease-free survival rate than those with a lower SUV (44% vs. 69%, p = .004). On multivariate analysis, a high SUV of nodal disease also proved to be a significantly unfavorable factor for disease-free survival (p = .04, 95% confidence interval [CI], 1.02-3.23), nodal progression-free survival (p = .05; 95% CI, 1.00-4.15), and distant metastasis-free survival (p = .016; 95% CI, 1.25-8.92). Among the patients with a greater nodal SUV ({>=}6.00), those treated with planned neck dissection had better nodal progression-free survival than those in the observation group (p = .04, hazard ratio, 2.36; 95% CI, 1.00-5.85). Conclusion: Among head-and-neck squamous cell carcinoma patients treated with chemoradiotherapy, the pretreatment SUV of nodal disease was one of the strongest prognostic factors and also provided important information for the selection of patients suitable for planned neck dissection.« less

  4. Nodal domains of a non-separable problem—the right-angled isosceles triangle

    NASA Astrophysics Data System (ADS)

    Aronovitch, Amit; Band, Ram; Fajman, David; Gnutzmann, Sven

    2012-03-01

    We study the nodal set of eigenfunctions of the Laplace operator on the right-angled isosceles triangle. A local analysis of the nodal pattern provides an algorithm for computing the number νn of nodal domains for any eigenfunction. In addition, an exact recursive formula for the number of nodal domains is found to reproduce all existing data. Eventually, we use the recursion formula to analyse a large sequence of nodal counts statistically. Our analysis shows that the distribution of nodal counts for this triangular shape has a much richer structure than the known cases of regular separable shapes or completely irregular shapes. Furthermore, we demonstrate that the nodal count sequence contains information about the periodic orbits of the corresponding classical ray dynamics.

  5. Counting nodal domains on surfaces of revolution

    NASA Astrophysics Data System (ADS)

    Karageorge, Panos D.; Smilansky, Uzy

    2008-05-01

    We consider eigenfunctions of the Laplace-Beltrami operator on special surfaces of revolution. For this separable system, the nodal domains of the (real) eigenfunctions form a checkerboard pattern, and their number νn is proportional to the product of the angular and the 'surface' quantum numbers. Arranging the wavefunctions by increasing values of the Laplace-Beltrami spectrum, we obtain the nodal sequence, whose statistical properties we study. In particular, we investigate the distribution of the normalized counts \\frac{\

  6. From cluster structures to nuclear molecules: The role of nodal structure of the single-particle wave functions

    NASA Astrophysics Data System (ADS)

    Afanasjev, A. V.; Abusara, H.

    2018-02-01

    The nodal structure of the density distributions of the single-particle states occupied in rod-shaped, hyper- and megadeformed structures of nonrotating and rotating N ˜Z nuclei has been investigated in detail. The single-particle states with the Nilsson quantum numbers of the [N N 0 ]1 /2 (with N from 0 to 5) and [N ,N -1 ,1 ]Ω (with N from 1 to 3 and Ω =1 /2 , 3/2) types are considered. These states are building blocks of extremely deformed shapes in the nuclei with mass numbers A ≤50 . Because of (near) axial symmetry and large elongation of such structures, the wave functions of the single-particle states occupied are dominated by a single basis state in cylindrical basis. This basis state defines the nodal structure of the single-particle density distribution. The nodal structure of the single-particle density distributions allows us to understand in a relatively simple way the necessary conditions for α clusterization and the suppression of the α clusterization with the increase of mass number. It also explains in a natural way the coexistence of ellipsoidal mean-field-type structures and nuclear molecules at similar excitation energies and the features of particle-hole excitations connecting these two types of the structures. Our analysis of the nodal structure of the single-particle density distributions does not support the existence of quantum liquid phase for the deformations and nuclei under study.

  7. Assessment of nodal involvement in non-small-cell lung cancer with 18F-FDG-PET/CT: mediastinal blood pool cut-off has the highest sensitivity and tumour SUVmax/2 has the highest specificity.

    PubMed

    Mallorie, Amy; Goldring, James; Patel, Anant; Lim, Eric; Wagner, Thomas

    2017-08-01

    Lymph node involvement in non-small-cell lung cancer (NSCLC) is a major factor in determining management and prognosis. We aimed to evaluate the accuracy of fluorine-18-fluorodeoxyglucose-PET/computed tomography (CT) for the assessment of nodal involvement in patients with NSCLC. In this retrospective study, we included 61 patients with suspected or confirmed resectable NSCLC over a 2-year period from April 2013 to April 2015. 221 nodes with pathological staging from surgery or endobronchial ultrasound-guided transbronchial needle aspiration were assessed using a nodal station-based analysis with original clinical reports and three different cut-offs: mediastinal blood pool (MBP), liver background and tumour standardized uptake value maximal (SUVmax)/2. Using nodal station-based analysis for activity more than tumour SUVmax/2, the sensitivity was 45%, the specificity was 89% and the negative predictive value (NPV) was 87%. For activity more than MBP, the sensitivity was 93%, the specificity was 72% and NPV was 98%. For activity more than liver background, the sensitivity was 83%, the specificity was 84% and NPV was 96%. Using a nodal staging-based analysis for accuracy at detecting N2/3 disease, for activity more than tumour SUVmax/2, the sensitivity was 59%, the specificity was 85% and NPV was 80%. For activity more than MBP, the sensitivity was 95%, the specificity was 61% and NPV was 96%. For activity more than liver background, the sensitivity was 86%, the specificity was 81% and NPV was 92%. Receiver-operating characteristic analysis showed the optimal nodal SUVmax to be more than 6.4 with a sensitivity of 45% and a specificity of 95%, with an area under the curve of 0.85. Activity more than MBP was the most sensitive cut-off with the highest sensitivity and NPV. Activity more than primary tumour SUVmax/2 was the most specific cut-off. Nodal SUVmax more than 6.4 has a high specificity of 95%.

  8. Two highly-related regulatory subunits of PP2A exert opposite effects on TGF-β/Activin/Nodal signalling

    PubMed Central

    Batut, Julie; Schmierer, Bernhard; Cao, Jing; Raftery, Laurel A.; Hill, Caroline S.; Howell, Michael

    2016-01-01

    Summary We identify Bα (PPP2R2A) and Bδ (PPP2R2D), two highly-related members of the B family of regulatory subunits of the protein phosphatase PP2A, as important modulators of TGF-β/Activin/Nodal signalling, which affect the pathway in opposite ways. Knockdown of Bα in Xenopus embryos or mammalian tissue culture cells suppresses TGF-β/Activin/Nodal-dependent responses, whereas knockdown of Bδ enhances these responses. Moreover, in Drosophila, overexpression of Smad2 rescues a severe wing phenotype caused by overexpression of the single Drosophila PP2A B subunit, Twins. We show that in vertebrates Bα enhances TGF-β/Activin/Nodal signalling by stabilising the basal levels of type I receptor, whereas Bδ negatively modulates these pathways by restricting receptor activity. Thus, these highly-related members of the same subfamily of PP2A regulatory subunits differentially regulate TGF-β/Activin/Nodal signalling to elicit opposing biological outcomes. PMID:18697906

  9. Theoretical and experimental evidence for a nodal energy gap in MgB2

    NASA Astrophysics Data System (ADS)

    Agassi, Y. Dan; Oates, Daniel E.

    2017-11-01

    We present a phenomenological model that strongly suggests that the smaller of the two energy gaps in MgB2, the so-called π gap, contains nodal lines with a six-fold symmetry (i-wave). The model also indicates that the larger gap, the so-called σ gap, is conventional s-wave. The model is an extension of the BCS gap equation that accounts for the elastic anisotropy in MgB2 and the Coulomb repulsion. It is based on a phononic pairing mechanism and assumes no coupling between the two energy gaps in MgB2 at zero temperature. All of the parameters of the model, such as sound velocities and masses, are independently determined material constants. The results agree with a previous ad-hoc hypothesis that the π energy gap has six nodal lines. That hypothesis was motivated by low-temperature measurements of the surface impedance and intermodulation distortion in high-quality thin films. We briefly review experimental evidence in the literature that is relevant to the energy-gap symmetry. We find that the evidence from the literature for s-wave is inconclusive. Our finding is that the π gap has six nodal lines.

  10. Long-term results of high-dose conformal radiotherapy for patients with medically inoperable T1-3N0 non-small-cell lung cancer: is low incidence of regional failure due to incidental nodal irradiation?

    PubMed

    Chen, Ming; Hayman, James A; Ten Haken, Randall K; Tatro, Daniel; Fernando, Shaneli; Kong, Feng-Ming

    2006-01-01

    To report the results of high-dose conformal irradiation and examine incidental nodal irradiation and nodal failure in patients with inoperable early-stage non-small-cell lung cancer (NSCLC). This analysis included patients with inoperable CT-staged T1-3N0M0 NSCLC treated on our prospective dose-escalation trial. Patients were treated with radiation alone (total dose, 63-102.9 Gy in 2.1-Gy daily fractions) with a three-dimensional conformal technique without intentional nodal irradiation. Bilateral highest mediastinal and upper/lower paratracheal, prevascular and retrotracheal, sub- and para-aortic, subcarinal, paraesophageal, and ipsilateral hilar regions were delineated individually. Nodal failure and doses of incidental irradiation were studied. The potential median follow-up was 104 months. For patients who completed protocol treatment, median survival was 31 months. The actuarial overall survival rate was 86%, 61%, 43%, and 21% and the cause-specific survival rate was 89%, 70%, 53%, and 35% at 1, 2, 3, and 5 years, respectively. Weight loss (p = 0.008) and radiation dose in Gy (p = 0.013) were significantly associated with overall survival. In only 22% and 13% of patients examined did ipsilateral hilar and paratracheal (and subaortic for left-sided tumor) nodal regions receive a dose of > or = 40 Gy, respectively. Less than 10% of all other nodal regions received a dose of > or = 40 Gy. No patients failed initially at nodal sites. Radiation dose is positively associated with overall survival in patients with medically inoperable T1-3N0 NSCLC, though long-term results remain poor. The nodal failure rate is low and does not seem to be due to high-dose incidental irradiation.

  11. A Planned Neck Dissection Is Not Necessary in All Patients With N2-3 Head-and-Neck Cancer After Sequential Chemoradiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Soltys, Scott G., E-mail: sgsoltys@stanford.edu; Choi, Clara Y.H.; Fee, Willard E.

    2012-07-01

    Purpose: To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease. Methods and Materials: We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed. Results: The median follow-up durations for livingmore » and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR{yields}pCR, and cPR{yields}pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR{yields}pCR, and cPR{yields}pPR groups were 53%, 75%, and 42%, respectively (p = 0.04). Conclusion: In our series, patients with N2-N3 neck disease achieving a cCR in the neck, PND would have benefited only 4% and, therefore, is not recommended. Patients with a cPR should be treated with PND. Residual tumor in the PND specimens was associated with poor outcomes; therefore, aggressive therapy is recommended. Studies using novel imaging modalities are needed to better assess treatment response.« less

  12. A predictive index of axillary nodal involvement in operable breast cancer.

    PubMed Central

    De Laurentiis, M.; Gallo, C.; De Placido, S.; Perrone, F.; Pettinato, G.; Petrella, G.; Carlomagno, C.; Panico, L.; Delrio, P.; Bianco, A. R.

    1996-01-01

    We investigated the association between pathological characteristics of primary breast cancer and degree of axillary nodal involvement and obtained a predictive index of the latter from the former. In 2076 cases, 17 histological features, including primary tumour and local invasion variables, were recorded. The whole sample was randomly split in a training (75% of cases) and a test sample. Simple and multiple correspondence analysis were used to select the variables to enter in a multinomial logit model to build an index predictive of the degree of nodal involvement. The response variable was axillary nodal status coded in four classes (N0, N1-3, N4-9, N > or = 10). The predictive index was then evaluated by testing goodness-of-fit and classification accuracy. Covariates significantly associated with nodal status were tumour size (P < 0.0001), tumour type (P < 0.0001), type of border (P = 0.048), multicentricity (P = 0.003), invasion of lymphatic and blood vessels (P < 0.0001) and nipple invasion (P = 0.006). Goodness-of-fit was validated by high concordance between observed and expected number of cases in each decile of predicted probability in both training and test samples. Classification accuracy analysis showed that true node-positive cases were well recognised (84.5%), but there was no clear distinction among the classes of node-positive cases. However, 10 year survival analysis showed a superimposible prognostic behaviour between predicted and observed nodal classes. Moreover, misclassified node-negative patients (i.e. those who are predicted positive) showed an outcome closer to patients with 1-3 metastatic nodes than to node-negative ones. In conclusion, the index cannot completely substitute for axillary node information, but it is a predictor of prognosis as accurate as nodal involvement and identifies a subgroup of node-negative patients with unfavourable prognosis. PMID:8630286

  13. Outcomes of Patients With Head-and-Neck Cancer of Unknown Primary Origin Treated With Intensity-Modulated Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shoushtari, Asal; Saylor, Drew; Kerr, Kara-Lynne

    2011-11-01

    Purpose: To analyze survival, failure patterns, and toxicity in patients with head-and-neck carcinoma of unknown primary origin (HNCUP) treated with intensity-modulated radiotherapy (IMRT). Methods and materials: Records from 27 patients with HNCUP treated during the period 2002-2008 with IMRT were reviewed retrospectively. Nodal staging ranged from N1 to N3. The mean preoperative dose to gross or suspected disease, Waldeyer's ring, and uninvolved bilateral cervical nodes was 59.4, 53.5, and 51.0 Gy, respectively. Sixteen patients underwent neck dissection after radiation and 4 patients before radiation. Eight patients with advanced nodal disease (N2b-c, N3) or extracapsular extension received chemotherapy. Results: With amore » median follow-up of 41.9 months (range, 25.3-93.9 months) for nondeceased patients, the 5-year actuarial overall survival, disease-free survival, and nodal control rates were 70.9%, 85.2%, and 88.5%, respectively. Actuarial disease-free survival rates for N1, N2, and N3 disease were 100%, 94.1%, and 50.0%, respectively, at 5 years. When stratified by nonadvanced (N1, N2a nodal disease without extracapsular spread) vs. advanced nodal disease (N2b, N2c, N3), the 5-year actuarial disease-free survival rate for the nonadvanced nodal disease group was 100%, whereas for the advanced nodal disease group it was significantly lower at 66.7% (p = 0.017). Three nodal recurrences were observed: in 1 patient with bulky N2b disease and 2 in patients with N3 disease. No nodal failures occurred in patients with N1 or N2a disease who received only radiation and surgery. Conclusion: Definitive IMRT to 50-56 Gy followed by neck dissection results in excellent nodal control and overall and disease-free survival, with acceptable toxicity for patients with T0N1 or nonbulky T0N2a disease without extracapsular spread. Patients with extracapsular spread, advanced N2 disease, or N3 disease may benefit from concurrent chemotherapy, targeted therapeutic agents, or

  14. Nodal Lymphangiogenesis and Metastasis

    PubMed Central

    Hirakawa, Satoshi; Detmar, Michael; Kerjaschki, Dontscho; Nagamatsu, Shogo; Matsuo, Keitaro; Tanemura, Atsushi; Kamata, Nobuyuki; Higashikawa, Koichiro; Okazaki, Hidenori; Kameda, Kenji; Nishida-Fukuda, Hisayo; Mori, Hideki; Hanakawa, Yasushi; Sayama, Koji; Shirakata, Yuji; Tohyama, Mikiko; Tokumaru, Sho; Katayama, Ichiro; Hashimoto, Koji

    2009-01-01

    Nodal lymphangiogenesis promotes distant lymph node (LN) metastasis in experimental cancer models. However, the role of nodal lymphangiogenesis in distant metastasis and in the overall survival of cancer patients remains unknown. Therefore, we investigated mechanisms that might facilitate regional and distant LN metastasis in extramammary Paget’s disease (EMPD). We retrospectively analyzed the impact of tumor-induced lymphatic vessel activation on the survival of 116 patients, the largest cohort with EMPD studied to date. Nodal lymphangiogenesis was significantly increased in metastatic, compared with tumor-free, LNs (P = 0.022). Increased lymphatic invasion within regional LNs was significantly associated with distant metastasis in LN (P = 0.047) and organs (P = 0.003). Thus, invasion within regional LNs is a powerful indicator of systemic tumor spread and reduced patient survival in EMPD (P = 0.0004). Lymphatic vessels associated with tumors expressed stromal cell-derived factor-1 (SDF-1), whereas CXCR4 was expressed on invasive Paget cells undergoing epithelial-mesenchymal transition (EMT)-like process. A431 cells overexpressing Snail expressed increased levels of CXCR4 in the presence of transforming growth factor-β1. Haptotactic migration assays confirmed that Snail-induced EMT-like process promotes tumor cell motility via the CXCR4-SDF-1 axis. Sinusoidal lymphatic endothelial cells and macrophages expressed SDF-1 in subcapsular sinuses of lymph nodes before Paget cell arrival. Our findings reveal that EMT-related features likely promote lymphatic metastasis of EMPD by activating the CXCR4-SDF-1 axis. PMID:19815713

  15. Unusual presentation of Warthin variant of Papillary thyroid carcinoma with lymph nodal metastases in a patient of Graves' disease.

    PubMed

    Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga; Arun, B R

    2015-01-01

    Warthin-like Papillary thyroid carcinoma (WPTC) is a rare variant of papillary carcinoma of thyroid, PTC which derives its name by closely resembling Warthin's tumor of salivary gland. Hallmark histological feature of this variant is papillary folding lined by oncocytic neoplastic cells with clear nuclei and nuclear pseudoinclusions, accompanied by prominent lymphocytic infiltrate in the papillary stalks. It is thought to be one of those differentiated thyroid cancers with favorable prognosis. We report a case of Graves' disease with a cold nodule harboring WPTC with initial presentation of lymph nodal metastases. It is important to identify this peculiar variant of PTC as 5 to 10% of them undergo dedifferentiation and 30% have the lymph nodal metastases and extra thyroidal extension.

  16. HDAC1/2-Dependent P0 Expression Maintains Paranodal and Nodal Integrity Independently of Myelin Stability through Interactions with Neurofascins.

    PubMed

    Brügger, Valérie; Engler, Stefanie; Pereira, Jorge A; Ruff, Sophie; Horn, Michael; Welzl, Hans; Münger, Emmanuelle; Vaquié, Adrien; Sidiropoulos, Páris N M; Egger, Boris; Yotovski, Peter; Filgueira, Luis; Somandin, Christian; Lühmann, Tessa C; D'Antonio, Maurizio; Yamaguchi, Teppei; Matthias, Patrick; Suter, Ueli; Jacob, Claire

    2015-01-01

    The pathogenesis of peripheral neuropathies in adults is linked to maintenance mechanisms that are not well understood. Here, we elucidate a novel critical maintenance mechanism for Schwann cell (SC)-axon interaction. Using mouse genetics, ablation of the transcriptional regulators histone deacetylases 1 and 2 (HDAC1/2) in adult SCs severely affected paranodal and nodal integrity and led to demyelination/remyelination. Expression levels of the HDAC1/2 target gene myelin protein zero (P0) were reduced by half, accompanied by altered localization and stability of neurofascin (NFasc)155, NFasc186, and loss of Caspr and septate-like junctions. We identify P0 as a novel binding partner of NFasc155 and NFasc186, both in vivo and by in vitro adhesion assay. Furthermore, we demonstrate that HDAC1/2-dependent P0 expression is crucial for the maintenance of paranodal/nodal integrity and axonal function through interaction of P0 with neurofascins. In addition, we show that the latter mechanism is impaired by some P0 mutations that lead to late onset Charcot-Marie-Tooth disease.

  17. HDAC1/2-Dependent P0 Expression Maintains Paranodal and Nodal Integrity Independently of Myelin Stability through Interactions with Neurofascins

    PubMed Central

    Brügger, Valérie; Engler, Stefanie; Pereira, Jorge A.; Ruff, Sophie; Horn, Michael; Welzl, Hans; Münger, Emmanuelle; Vaquié, Adrien; Sidiropoulos, Páris N. M.; Egger, Boris; Yotovski, Peter; Filgueira, Luis; Somandin, Christian; Lühmann, Tessa C.; D’Antonio, Maurizio; Yamaguchi, Teppei; Matthias, Patrick; Suter, Ueli; Jacob, Claire

    2015-01-01

    The pathogenesis of peripheral neuropathies in adults is linked to maintenance mechanisms that are not well understood. Here, we elucidate a novel critical maintenance mechanism for Schwann cell (SC)–axon interaction. Using mouse genetics, ablation of the transcriptional regulators histone deacetylases 1 and 2 (HDAC1/2) in adult SCs severely affected paranodal and nodal integrity and led to demyelination/remyelination. Expression levels of the HDAC1/2 target gene myelin protein zero (P0) were reduced by half, accompanied by altered localization and stability of neurofascin (NFasc)155, NFasc186, and loss of Caspr and septate-like junctions. We identify P0 as a novel binding partner of NFasc155 and NFasc186, both in vivo and by in vitro adhesion assay. Furthermore, we demonstrate that HDAC1/2-dependent P0 expression is crucial for the maintenance of paranodal/nodal integrity and axonal function through interaction of P0 with neurofascins. In addition, we show that the latter mechanism is impaired by some P0 mutations that lead to late onset Charcot-Marie-Tooth disease. PMID:26406915

  18. Lymphovascular Invasion Increases the Risk of Nodal and Distant Recurrence in Node-Negative Stage I-IIA Non-Small-Cell Lung Cancer.

    PubMed

    Sung, Soo Yoon; Kwak, Yoo-Kang; Lee, Sea-Won; Jo, In Young; Park, Jae Kil; Kim, Kyung Soo; Lee, Kyo Young; Kim, Yeon-Sil

    2018-05-30

    Despite complete surgical resection, 30-40% of patients with stage I-IIA non-small-cell lung cancer (NSCLC) have recurrences. We aimed to elucidate the effect of lymphovascular invasion (LVI) on the prognosis and patterns of recurrence in patients with pathologically confirmed T1-2N0 NSCLC. We evaluated 381 patients who underwent complete resection and were diagnosed with pathologic T1-2N0 NSCLC between March 2000 and January 2012. Local recurrence, nodal recurrence, and distant metastasis were defined and analyzed. LVI was present in 72 patients (18.9%). The 5-year disease-free survival (DFS) for all patients was 69.9%. Patients with LVI showed a significant decrease in 5-year DFS (47.3 vs. 74.4%, p < 0.001). LVI was a significant prognostic predictor in multivariate analysis (p = 0.003). The patients with LVI showed a significantly increased 5-year cumulative incidence of nodal recurrence (22.5 vs. 8.7%, p < 0.001) and distant metastasis (30.4 vs. 14.9%, p = 0.004). However, no difference was shown between the two groups in the 5-year cumulative incidence of local recurrence (p = 0.416). LVI is a negative prognostic factor in patients with stage I-IIA NSCLC. The presence of LVI significantly increases the risk of nodal and distant recurrence. © 2018 S. Karger AG, Basel.

  19. Rules for Phase Shifts of Quantum Oscillations in Topological Nodal-Line Semimetals

    NASA Astrophysics Data System (ADS)

    Li, Cequn; Wang, C. M.; Wan, Bo; Wan, Xiangang; Lu, Hai-Zhou; Xie, X. C.

    2018-04-01

    Nodal-line semimetals are topological semimetals in which band touchings form nodal lines or rings. Around a loop that encloses a nodal line, an electron can accumulate a nontrivial π Berry phase, so the phase shift in the Shubnikov-de Haas (SdH) oscillation may give a transport signature for the nodal-line semimetals. However, different experiments have reported contradictory phase shifts, in particular, in the WHM nodal-line semimetals (W =Zr /Hf , H =Si /Ge , M =S /Se /Te ). For a generic model of nodal-line semimetals, we present a systematic calculation for the SdH oscillation of resistivity under a magnetic field normal to the nodal-line plane. From the analytical result of the resistivity, we extract general rules to determine the phase shifts for arbitrary cases and apply them to ZrSiS and Cu3 PdN systems. Depending on the magnetic field directions, carrier types, and cross sections of the Fermi surface, the phase shift shows rich results, quite different from those for normal electrons and Weyl fermions. Our results may help explore transport signatures of topological nodal-line semimetals and can be generalized to other topological phases of matter.

  20. PITX2 and NODAL expression during axis formation in the early rabbit embryo.

    PubMed

    Plöger, Ruben; Viebahn, Christoph

    2018-04-26

    Attaining molecular and morphological axial polarity during gastrulation is a fundamental early requirement for normal development of the embryo. In mammals, the first morphological sign of the anterior-posterior axis appears anteriorly in the form of the anterior marginal crescent (or anterior visceral endoderm) while in the avian the first such sign is the Koller's sickle at the posterior pole of the embryonic disc. Despite this inverse mode of axis formation many genes and molecular pathways involved in various steps of this process seem to be evolutionary conserved amongst amniotes, the nodal gene being a well-known example with its functional involvement prior and during gastrulation. The pitx2 gene, however, is a new candidate described in the chick as an early marker for anterior-posterior polarity and as regulator of axis formation including twinning. To find out whether pitx2 has retained its inductive and early marker function during the evolution of mammals, this study analyzes pitx2 and nodal expression at parallel stages during formation of the anterior-posterior polarity in the early rabbit embryo using whole-mount in situ hybridization and serial light-microscopical sections. At a late pre-gastrulation stage a localized reduction of nodal expression presages the position of the anterior pole of the embryonic disc and thus serves as the earliest molecular marker of anterior-posterior polarity known so far. pitx2 is expressed in a polarized manner in the anterior marginal crescent and in the posterior half of the embryonic disc during further development only while nodal expression in the anterior segment of the posterior pitx2 expression domain helps to define the so-called anterior streak domain (ASD), a novel progenitor region of the anterior half of the primitive streak. The expression patterns of both genes thus serve as signs of a conserved involvement in early axis formation in amniotes and, possibly, in twinning in mammals as well. Copyright

  1. Radiotherapy for esthesioneuroblastoma: is elective nodal irradiation warranted in the multimodality treatment approach?

    PubMed

    Noh, O Kyu; Lee, Sang-wook; Yoon, Sang Min; Kim, Sung Bae; Kim, Sang Yoon; Kim, Chang Jin; Jo, Kyung Ja; Choi, Eun Kyung; Song, Si Yeol; Kim, Jong Hoon; Ahn, Seung Do

    2011-02-01

    The role of elective nodal irradiation (ENI) in radiotherapy for esthesioneuroblastoma (ENB) has not been clearly defined. We analyzed treatment outcomes of patients with ENB and the frequency of cervical nodal failure in the absence of ENI. Between August 1996 and December 2007, we consulted with 19 patients with ENB regarding radiotherapy. Initial treatment consisted of surgery alone in 2 patients; surgery and postoperative radiotherapy in 4; surgery and adjuvant chemotherapy in 1; surgery, postoperative radiotherapy, and chemotherapy in 3; and chemotherapy followed by radiotherapy or concurrent chemoradiotherapy in 5. Five patients did not receive planned radiotherapy because of disease progression. Including 2 patients who received salvage radiotherapy, 14 patients were treated with radiotherapy. Elective nodal irradiation was performed in 4 patients with high-risk factors, including 3 with cervical lymph node metastasis at presentation. Fourteen patients were analyzable, with a median follow-up of 27 months (range, 7-64 months). The overall 3-year survival rate was 73.4%. Local failure occurred in 3 patients (21.4%), regional cervical failure in 3 (21.4%), and distant failure in 2 (14.3%). No cervical nodal failure occurred in patients treated with combined systemic chemotherapy regardless of ENI. Three cervical failures occurred in the 4 patients treated with ENI or neck dissection (75%), none of whom received systemic chemotherapy. ENI during radiotherapy for ENB seems to play a limited role in preventing cervical nodal failure. Omitting ENI may be an option if patients are treated with a combination of radiotherapy and chemotherapy. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey.

    PubMed

    Belkacemi, Y; Kaidar-Person, O; Poortmans, P; Ozsahin, M; Valli, M-C; Russell, N; Kunkler, I; Hermans, J; Kuten, A; van Tienhoven, G; Westenberg, H

    2015-03-01

    Predicting outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is an area of uncertainty. It influences the decision-making for regional nodal irradiation (RNI). The aim of the NORA (NOdal RAdiotherapy) survey was to examine the patterns of RNI. A web-questionnaire, including several clinical scenarios, was distributed to 88 EORTC-affiliated centers. Responses were received between July 2013 and January 2014. A total of 84 responses were analyzed. While three-dimensional (3D) radiotherapy (RT) planning is carried out in 81 (96%) centers, nodal areas are delineated in only 51 (61%) centers. Only 14 (17%) centers routinely link internal mammary chain (IMC) and supraclavicular node (SCN) RT indications. In patients undergoing total mastectomy (TM) with ALND, SCN-RT is recommend by 5 (6%), 53 (63%) and 51 (61%) centers for patients with pN0(i+), pN(mi) and pN1, respectively. Extra-capsular extension (ECE) is the main factor influencing decision-making RNI after breast conserving surgery (BCS) and TM. After primary systemic therapy (PST), 49 (58%) centers take into account nodal fibrotic changes in ypN0 patients for RNI indications. In ypN0 patients with inner/central tumors, 23 (27%) centers indicate SCN-RT and IMC-RT. In ypN1 patients, SCN-RT is delivered by less than half of the centers in patients with ypN(i+) and ypN(mi). Twenty-one (25%) of the centers recommend ALN-RT in patients with ypN(mi) or 1-2N+ after ALND. Seventy-five (90%) centers state that age is not considered a limiting factor for RNI. The NORA survey is unique in evaluating the impact of SLNB/ALND status on adjuvant RNI decision-making and volumes after BCS/TM with or without PST. ALN-RT is often indicated in pN1 patients, particularly in the case of ECE. Besides the ongoing NSABP-B51/RTOG and ALLIANCE trials, NORA could help to design future specific RNI trials in the SLNB era without ALND in patients receiving or not PST.

  3. Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05).

    PubMed

    Noh, J M; Park, W; Suh, C-O; Keum, K C; Kim, Y B; Shin, K H; Kim, K; Chie, E K; Ha, S W; Kim, S S; Ahn, S D; Shin, H S; Kim, J H; Lee, H-S; Lee, N K; Huh, S J; Choi, D H

    2014-03-18

    To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

  4. Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II–III breast cancer? A multicentre retrospective study (KROG 12-05)

    PubMed Central

    Noh, J M; Park, W; Suh, C-O; Keum, K C; Kim, Y B; Shin, K H; Kim, K; Chie, E K; Ha, S W; Kim, S S; Ahn, S D; Shin, H S; Kim, J H; Lee, H-S; Lee, N K; Huh, S J; Choi, D H

    2014-01-01

    Background: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II–III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). Methods: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. Results: After a median follow-up period of 66.2 months (range, 15.6–127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0−is vs 1 vs 2–4) and the number of LNs sampled (<13 vs ⩾13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. Conclusions: ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials. PMID:24481403

  5. Utility of PET-CT in detecting nodal metastasis in cN0 early stage oral cavity squamous cell carcinoma.

    PubMed

    Zhang, Han; Seikaly, Hadi; Biron, Vincent L; Jeffery, Caroline C

    2018-05-01

    Management of the clinically node-negative neck (cN0) in patients with early stage oral cavity squamous cell carcinoma (OCSCC) is challenging. Accurate imaging alternatives to elective neck dissections would help reduce surgical morbidity. While pooled studies suggest that imaging modalities have similar accuracy in predicting occult nodal disease, no study has examined the utility of PET-CT in this specific population of low-volume, clinically T1 and T2 OCSCC patients. A retrospective review of patients in the Alberta Cancer Registry who were diagnosed with cT1 or T2N0M0 OCSCC who underwent elective unilateral or bilateral neck dissections was performed. Pre-operative PET-CT and CT necks were reviewed for number of radiographically suspicious lymph nodes. Surgical pathology reports were reviewed to obtain the total number of nodes sampled and number of malignant nodes. Between 2009 and 2013, 148 patients were diagnosed with cT1 or T2N0M0 OCSCC. Of these, 96 patients underwent elective neck dissections. All patients underwent preoperative CT of the neck with 32 patients having undergone additional preoperative PET-CT. Based on finally surgical pathology, the overall rate of occult metastasis was 13.5% (13/96). The overall sensitivity and specificity of PET-CT in this cohort was 21.4% and 98.4%, respectively with a negative predictive value of 99.1%. Although sensitivity improved in patients with tumors ≥2 cm and depth ≥4 mm, specificity remained unchanged. In patients with cT1 and T2N0 OCSCC, PET-CT has high negative predictive value. These patients can be considered for treatment with single modality surgical resection and elective neck dissection. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Zebrafish hhex, nk2.1a, and pax2.1 regulate thyroid growth and differentiation downstream of Nodal-dependent transcription factors.

    PubMed

    Elsalini, Osama A; von Gartzen, Julia; Cramer, Matthias; Rohr, Klaus B

    2003-11-01

    During zebrafish development, the thyroid primordium initiates expression of molecular markers such as hhex and nk2.1a in the endoderm prior to pharynx formation. As expected for an endodermally derived organ, initiation of thyroid development depends on Nodal signalling. We find that it also depends on three downstream effectors of Nodal activity, casanova (cas), bonnie and clyde (bon), and faust (fau)/gata5. Despite their early Nodal-dependent expression in the endoderm, both hhex and nk2.1a are only required relatively late during thyroid development. In hhex and nk2.1a loss-of-function phenotypes, thyroid development is initiated and arrests only after the primordium has evaginated from the pharyngeal epithelium. Thus, like pax2.1, both hhex and nk2.1a have similarly late roles in differentiation or growth of thyroid follicular cells, and here, we show that all three genes act in parallel rather than in a single pathway. Our functional analysis suggests that these genes have similar roles as in mammalian thyroid development, albeit in a different temporal mode of organogenesis.

  7. Incidence of isolated nodal failure in non-small cell lung cancer patients included in a prospective study of the value of PET-CT.

    PubMed

    Kolodziejczyk, Milena; Bujko, Krzysztof; Michalski, Wojciech; Kepka, Lucyna

    2012-07-01

    Elective nodal irradiation (ENI) is not recommended in PET-CT-based radiotherapy for NSCLC despite a low level of evidence to support such guidelines. The aim of this investigation is to find out whether omitting ENI is safe. Sixty-seven patients treated within a frame of a previously published prospective trial of the value of PET-CT were included in the analysis. Seventeen (25%) patients received ENI due to higher initial nodal involvement and in the remaining 50 patients (75%) with N0-N1 or single N2 disease ENI was omitted. Isolated nodal failure (INF) was recorded if relapse occurred in the initially uninvolved regional lymph node without previous or simultaneous local recurrence regardless of the status of distant metastases. With a median follow-up of 32 months, the estimated 3-year overall survival was 42%, local progression-free interval was 55%, and distant metastases-free interval was 62%. Three patients developed INF; all had ENI omitted from treatment, giving a final result of three INFs in 50 (6%) patients treated without ENI. In this group of patients, the 3-year cause-specific cumulative incidence of INF was 6.4% (95% confidence interval: 0-17%). The omission of ENI appears to be not as safe as suggested by current recommendations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  8. Limitations of PET/CT in the Detection of Occult N1 Metastasis in Clinical Stage I(T1-2aN0) Non-Small Cell Lung Cancer for Staging Prior to Stereotactic Body Radiotherapy.

    PubMed

    Akthar, Adil S; Ferguson, Mark K; Koshy, Matthew; Vigneswaran, Wickii T; Malik, Renuka

    2017-02-01

    Patients receiving stereotactic body radiotherapy for stage I non-small cell lung cancer are typically staged clinically with positron emission tomography-computed tomography. Currently, limited data exist for the detection of occult hilar/peribronchial (N1) disease. We hypothesize that positron emission tomography-computed tomography underestimates spread of cancer to N1 lymph nodes and that future stereotactic body radiotherapy patients may benefit from increased pathologic evaluation of N1 nodal stations in addition to N2 nodes. A retrospective study was performed of all patients with clinical stage I (T1-2aN0) non-small cell lung cancer (American Joint Committee on Cancer, 7th edition) by positron emission tomography-computed tomography at our institution from 2003 to 2011, with subsequent surgical resection and lymph node staging. Findings on positron emission tomography-computed tomography were compared to pathologic nodal involvement to determine the negative predictive value of positron emission tomography-computed tomography for the detection of N1 nodal disease. An analysis was conducted to identify predictors of occult spread. A total of 105 patients with clinical stage I non-small cell lung cancer were included in this study, of which 8 (7.6%) patients were found to have occult N1 metastasis on pathologic review yielding a negative predictive value for N1 disease of 92.4%. No patients had occult mediastinal nodes. The negative predictive value for positron emission tomography-computed tomography in patients with clinical stage T1 versus T2 tumors was 72 (96%) of 75 versus 25 (83%) of 30, respectively ( P = .03), and for peripheral versus central tumor location was 77 (98%) of 78 versus 20 (74%) of 27, respectively ( P = .0001). The negative predictive values for peripheral T1 and T2 tumors were 98% and 100%, respectively; while for central T1 and T2 tumors, the rates were 85% and 64%, respectively. Occult lymph node involvement was not associated with

  9. Limitations of PET/CT in the Detection of Occult N1 Metastasis in Clinical Stage I(T1-2aN0) Non-Small Cell Lung Cancer for Staging Prior to Stereotactic Body Radiotherapy

    PubMed Central

    Akthar, Adil S.; Ferguson, Mark K.; Koshy, Matthew; Vigneswaran, Wickii T.

    2016-01-01

    Purpose/Objectives: Patients receiving stereotactic body radiotherapy for stage I non-small cell lung cancer are typically staged clinically with positron emission tomography–computed tomography. Currently, limited data exist for the detection of occult hilar/peribronchial (N1) disease. We hypothesize that positron emission tomography–computed tomography underestimates spread of cancer to N1 lymph nodes and that future stereotactic body radiotherapy patients may benefit from increased pathologic evaluation of N1 nodal stations in addition to N2 nodes. Materials/Methods: A retrospective study was performed of all patients with clinical stage I (T1-2aN0) non-small cell lung cancer (American Joint Committee on Cancer, 7th edition) by positron emission tomography–computed tomography at our institution from 2003 to 2011, with subsequent surgical resection and lymph node staging. Findings on positron emission tomography–computed tomography were compared to pathologic nodal involvement to determine the negative predictive value of positron emission tomography–computed tomography for the detection of N1 nodal disease. An analysis was conducted to identify predictors of occult spread. Results: A total of 105 patients with clinical stage I non-small cell lung cancer were included in this study, of which 8 (7.6%) patients were found to have occult N1 metastasis on pathologic review yielding a negative predictive value for N1 disease of 92.4%. No patients had occult mediastinal nodes. The negative predictive value for positron emission tomography–computed tomography in patients with clinical stage T1 versus T2 tumors was 72 (96%) of 75 versus 25 (83%) of 30, respectively (P = .03), and for peripheral versus central tumor location was 77 (98%) of 78 versus 20 (74%) of 27, respectively (P = .0001). The negative predictive values for peripheral T1 and T2 tumors were 98% and 100%, respectively; while for central T1 and T2 tumors, the rates were 85% and 64

  10. F18 FDG positron emission tomography revelation of primary testicular lymphoma with concurrent multiple extra nodal involvement

    PubMed Central

    Vamsy, Mohana; Dattatreya, PS; Parakh, Megha; Dayal, Monal; Rao, VVS Prabhakar

    2013-01-01

    Primary testicular lymphoma (PTL) a relatively rare disease of non-Hodgkin's lymphomas occurring with a lesser incidence of 1-2% has a propensity to occur at later ages above 50 years. PTL spreads to extra nodal sites due to deficiency of extra cellular adhesion molecules. We present detection of multiple sites of extra nodal involvement of PTL by F-18 positron emission tomography/computed tomography study aiding early detection of the dissemination thus aiding in staging and management. PMID:24019676

  11. Nodal variations and long-term changes in the main tides on the coasts of China

    NASA Astrophysics Data System (ADS)

    Feng, Xiangbo; Tsimplis, Michael N.; Woodworth, Philip L.

    2015-02-01

    The long-term changes in the main tidal constituents (O1, K1, M2, N2, and S2) along the coasts of China and in adjacent seas are investigated based on 17 tide-gauge records covering the period 1954-2012. The observed 18.61 year nodal modulations of the diurnal constituents O1 and K1 are in agreement with the equilibrium tidal theory, except in the South China Sea. The observed modulations of the M2 and N2 amplitudes are smaller than theoretically predicted at the northern stations and larger at the southern stations. The discrepancies between the theoretically predicted nodal variations and the observations are discussed. The 8.85 year perigean cycle is identifiable in the N2 parameters at most stations, except those in the South China Sea. The radiational component of S2 contributes on average 16% of the observed S2 except in the Gulf of Tonkin, on the south coast, where it accounts for up to 65%. We confirmed the existence of nodal modulation in S2, which is stronger on the north coast. The semidiurnal tidal parameters show significant secular trends in the Bohai and Yellow Seas, on the north coast, and in the Taiwan Strait. The largest increase is found for M2 for which the amplitude increases by 4-7 mm/yr in the Yellow Sea. The potential causes for the linear trends in tidal constants are discussed. This article was corrected on 13 MAR 2015. See the end of the full text for details.

  12. Omitting elective nodal irradiation during thoracic irradiation in limited-stage small cell lung cancer--evidence from a phase II trial.

    PubMed

    Colaco, Rovel; Sheikh, Hamid; Lorigan, Paul; Blackhall, Fiona; Hulse, Paul; Califano, Raffaele; Ashcroft, Linda; Taylor, Paul; Thatcher, Nicholas; Faivre-Finn, Corinne

    2012-04-01

    Omitting elective nodal irradiation (ENI) in limited-stage disease small cell lung cancer (LD-SCLC) is expected to result in smaller radiation fields. We report on data from a randomised phase II trial that omitted ENI in patients receiving concurrent chemo-radiotherapy for LD-SCLC. 38 patients with LD-SCLC were randomised to receive once-daily (66 Gy in 33 fractions) or twice-daily (45 Gy in 30 fractions) radiotherapy (RT). 3D-conformal RT was given concurrently with cisplatin and etoposide starting with the second cycle of a total of four cycles. The gross tumour volume was defined as primary tumour with involved lymph nodes (nodes ≥1 cm in short axis) identifiable with CT imaging. ENI was not used. Six recurrence patterns were identified: recurrence within planning target volume (PTV) only, recurrence within PTV+regional nodal recurrence and/or distant recurrence, isolated nodal recurrence outside PTV, nodal recurrence outside PTV+distant recurrence, distant metastases only and no recurrence. At median follow-up 16.9 months, 31/38 patients were evaluable and 14/31 patients had relapsed. There were no isolated nodal recurrences. Eight patients relapsed with intra-thoracic disease: 2 within PTV only, 4 within PTV and distantly and 2 with nodal recurrence outside PTV plus distant metastases. Rates of grade 3+ acute oesophagitis and pneumonitis in the 31 evaluable patients were 23 and 3% respectively. In our study of LD-SCLC, omitting ENI based on CT imaging was not associated with a high risk of isolated nodal recurrence, although further prospective studies are needed to confirm this. Routine ENI omission will be further evaluated prospectively in the ongoing phase III CONVERT trial (NCT00433563). Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  13. An Interesting Case of Retropharyngeal Lymph Nodal Metastases in a Case of Iodine-Refractory Thyroid Cancer.

    PubMed

    Harisankar, Chidambaram Natrajan Balasubramanian; Vijayabhaskar, Ramakrishnan

    2018-01-01

    Metastases to cervical lymph node are fairly common in differentiated thyroid cancer. In iodine-refractory disease, the disease may persist in the thyroid bed, cervical lymph nodes, lungs, or the bones commonly. Retropharyngeal lymph nodal involvement in thyroid cancer is unusual and may even be the presenting complaint. We represent a case of iodine-refractory thyroid cancer with retropharyngeal lymph nodal involvement in addition to lung metastases.

  14. Topological transport in Dirac nodal-line semimetals

    NASA Astrophysics Data System (ADS)

    Rui, W. B.; Zhao, Y. X.; Schnyder, Andreas P.

    2018-04-01

    Topological nodal-line semimetals are characterized by one-dimensional Dirac nodal rings that are protected by the combined symmetry of inversion P and time-reversal T . The stability of these Dirac rings is guaranteed by a quantized ±π Berry phase and their low-energy physics is described by a one-parameter family of (2+1)-dimensional quantum field theories exhibiting the parity anomaly. Here we study the Berry-phase supported topological transport of P T -invariant nodal-line semimetals. We find that small inversion breaking allows for an electric-field-induced anomalous transverse current, whose universal component originates from the parity anomaly. Due to this Hall-like current, carriers at opposite sides of the Dirac nodal ring flow to opposite surfaces when an electric field is applied. To detect the topological currents, we propose a dumbbell device, which uses surface states to filter charges based on their momenta. Suggestions for experiments and device applications are discussed.

  15. Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ahmed, Faisal; Loma Linda University Medical Center, Department of Radiation Oncology, Loma Linda, CA; Sarkar, Vikren

    Purpose: To evaluate radiation dose delivered to pelvic lymph nodes, if daily Image Guided Radiation Therapy (IGRT) was implemented with treatment shifts based on the primary site (primary clinical target volume [CTV]). Our secondary goal was to compare dosimetric coverage with patient outcomes. Materials and methods: A total of 10 female patients with gynecologic malignancies were evaluated retrospectively after completion of definitive intensity-modulated radiation therapy (IMRT) to their pelvic lymph nodes and primary tumor site. IGRT consisted of daily kilovoltage computed tomography (CT)-on-rails imaging fused with initial planning scans for position verification. The initial plan was created using Varian's Eclipsemore » treatment planning software. Patients were treated with a median radiation dose of 45 Gy (range: 37.5 to 50 Gy) to the primary volume and 45 Gy (range: 45 to 64.8 Gy) to nodal structures. One IGRT scan per week was randomly selected from each patient's treatment course and re-planned on the Eclipse treatment planning station. CTVs were recreated by fusion on the IGRT image series, and the patient's treatment plan was applied to the new image set to calculate delivered dose. We evaluated the minimum, maximum, and 95% dose coverage for primary and nodal structures. Reconstructed primary tumor volumes were recreated within 4.7% of initial planning volume (0.9% to 8.6%), and reconstructed nodal volumes were recreated to within 2.9% of initial planning volume (0.01% to 5.5%). Results: Dosimetric parameters averaged less than 10% (range: 1% to 9%) of the original planned dose (45 Gy) for primary and nodal volumes on all patients (n = 10). For all patients, ≥99.3% of the primary tumor volume received ≥ 95% the prescribed dose (V95%) and the average minimum dose was 96.1% of the prescribed dose. In evaluating nodal CTV coverage, ≥ 99.8% of the volume received ≥ 95% the prescribed dose and the average minimum dose was 93%. In evaluating

  16. MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers.

    PubMed

    Laghi, Luigi; Bianchi, Paolo; Delconte, Gabriele; Celesti, Giuseppe; Di Caro, Giuseppe; Pedroni, Monica; Chiaravalli, Anna Maria; Jung, Barbara; Capella, Carlo; de Leon, Maurizio Ponz; Malesci, Alberto

    2012-06-01

    Patients with colorectal cancers (CRC) and high microsatellite instability (MSI) have a better outcome than their chromosome-unstable counterpart. Given the heterogeneity of microsatellite-unstable CRCs, we wanted to see whether any MSI-associated molecular features are specifically associated with prognosis. One hundred and nine MSI-high CRCs were typed for primary mismatch repair (MMR) defect and for secondary loss of MMR proteins. Frameshifts at seven target genes, mutations in the RAS pathway, and methylation at MLH1/CDKN2A promoters were also searched. The interplay of molecular findings with clinicopathologic features and patient survival was analyzed. Of 84 MLH1-deficient CRCs, 31 (36.9%) had MSH3 and 11 (13.1%) had MSH6 loss (P < 0.001), biallelic frameshift mutations at mononucleotide repeats accounting for most (78%) MSH3 losses. As compared with MSH3-retaining cancers, MLH1-deficient tumors with MSH3 loss showed a higher number of mutated target genes (3.94 ± 1.56 vs. 2.79 ± 1.75; P = 0.001), absence of nodal involvement at pathology [N0; OR, 0.11; 95% confidence interval (CI), 0.04-0.43, P < 0.001], and better disease-free survival (P = 0.06). No prognostic value was observed for KRAS status and for MLH1/CDKN2A promoter methylation. The association between MSH3 loss and N0 was confirmed in an independent cohort of 71 MLH1-deficient CRCs (OR, 0.23; 95% CI, 0.06-0.83, P = 0.02). MLH1-deficient CRCs not expressing MSH3 have a more severe MSI, a lower rate of nodal involvement, and a better postsurgical outcome.

  17. Patterns of nodal relapse after surgery and postoperative radiation therapy for carcinomas of the major and minor salivary glands: What is the role of elective neck irradiation?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Allen M.; Garcia, Joaquin; Lee, Nancy Y.

    2007-03-15

    Purpose: To evaluate the incidence of nodal relapses from carcinomas of the salivary glands among patients with clinically negative necks in an attempt to determine the potential utility of elective neck irradiation (ENI). Methods and Materials: Between 1960 and 2004, 251 patients with clinically N0 carcinomas of the salivary glands were treated with surgery and postoperative radiation therapy. None of the patients had undergone previous neck dissection. Histology was: adenoid cystic (84 patients), mucoepidermoid (60 patients), adenocarcinoma (58 patients), acinic cell (21 patients), undifferentiated (11 patients), carcinoma ex pleomorphic adenoma (7 patients), squamous cell (7 patients), and salivary duct carcinomamore » (3 patients); 131 patients (52%) had ENI. Median follow-up was 62 months (range, 3-267 months). Results: The 5- and 10-year actuarial estimates of nodal relapse were 11% and 13%, respectively. The 10-year actuarial rates of nodal failure were 7%, 5%, 12%, and 16%, for patients with T1, T2, T3, and T4 disease, respectively (p = 0.11). The use of ENI reduced the 10-year nodal failure rate from 26% to 0% (p = 0.0001). The highest crude rates of nodal relapse among those treated without ENI were found in patients with squamous cell carcinoma (67%), undifferentiated carcinoma (50%), adenocarcinoma (34%), and mucoepidermoid carcinoma (29%). There were no nodal failures observed among patients with adenoid cystic or acinic cell histology. Conclusion: ENI effectively prevents nodal relapses and should be used for select patients at high risk for regional failure.« less

  18. Hopf-link topological nodal-loop semimetals

    NASA Astrophysics Data System (ADS)

    Zhou, Yao; Xiong, Feng; Wan, Xiangang; An, Jin

    2018-04-01

    We construct a generic two-band model which can describe topological semimetals with multiple closed nodal loops. All the existing multi-nodal-loop semimetals, including the nodal-net, nodal-chain, and Hopf-link states, can be examined within the same framework. Based on a two-nodal-loop model, the corresponding drumhead surface states for these topologically different bulk states are studied and compared with each other. The connection of our model with Hopf insulators is also discussed. Furthermore, to identify experimentally these topologically different semimetal states, especially to distinguish the Hopf-link from unlinked ones, we also investigate their Landau levels. It is found that the Hopf-link state can be characterized by the existence of a quadruply degenerate zero-energy Landau band, regardless of the direction of the magnetic field.

  19. Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes.

    PubMed

    Fernandes, Annemarie T; Shen, Jason; Finlay, Jarod; Mitra, Nandita; Evans, Tracey; Stevenson, James; Langer, Corey; Lin, Lilie; Hahn, Stephen; Glatstein, Eli; Rengan, Ramesh

    2010-05-01

    Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  20. Nodal enhances the activity of FoxO3a and its synergistic interaction with Smads to regulate cyclin G2 transcription in ovarian cancer cells.

    PubMed

    Fu, G; Peng, C

    2011-09-15

    Nodal, a member of the transforming growth factor-β superfamily, has been recently shown to suppress cell proliferation and to stimulate the expression of cyclin G2 (CCNG2) in human epithelial ovarian cancer cells. However, the precise mechanisms underlying these events are not fully understood. In this study, we investigated the transcriptional regulation of CCNG2 by the Nodal signaling pathway. In ovarian cancer cells, overexpression of Nodal or its receptors, activin receptor-like kinase 7 (ALK7) or ALK4, resulted in an increase in the CCNG2 promoter activity. Several putative Forkhead box class O (FoxO)3a-binding sites are present in the human CCNG2 promoter and overexpression of FoxO3a enhanced the CCNG2 promoter activity. The functional FoxO3a-binding element (FBE) was mapped to a proximal region located between -398 and -380 bp (FBE1) through deletion and mutation analyses, as well as chromatin immunoprecipitation (IP) assay. Interestingly, mutation of the FBE1 not only abolished the effect of FoxO3a, but also blocked Nodal-induced CCNG2 transcription. Nodal stimulated FoxO3a mRNA and protein expression through the canonical Smad pathway and suppressed FoxO3a inactivation by inhibiting AKT activity. Silencing of FoxO3a using small interfering RNA significantly reduced the effect of Nodal on the CCNG2 promoter activity. On the other hand, overexpression of Smad2 and Smad3 enhanced the FoxO3a-induced CCNG2 promoter activity whereas knockdown of Smad4 blocked the activity of FoxO3a. Furthermore, IP assays revealed that FoxO3a formed complexes with Smad proteins and that Nodal enhanced the binding of FoxO3a to the CCNG2 promoter. Finally, silencing of FoxO3a reversed the inhibitory effect of Nodal on cell proliferation. Taken together, these findings demonstrated that Nodal signaling promotes CCNG2 transcription by upregulating FoxO3a expression, inhibiting FoxO3a phosphorylation and enhancing its synergistic interaction with Smads. These results also suggest

  1. Nodal-chain metals.

    PubMed

    Bzdušek, Tomáš; Wu, QuanSheng; Rüegg, Andreas; Sigrist, Manfred; Soluyanov, Alexey A

    2016-10-06

    The band theory of solids is arguably the most successful theory of condensed-matter physics, providing a description of the electronic energy levels in various materials. Electronic wavefunctions obtained from the band theory enable a topological characterization of metals for which the electronic spectrum may host robust, topologically protected, fermionic quasiparticles. Many of these quasiparticles are analogues of the elementary particles of the Standard Model, but others do not have a counterpart in relativistic high-energy theories. A complete list of possible quasiparticles in solids is lacking, even in the non-interacting case. Here we describe the possible existence of a hitherto unrecognized type of fermionic excitation in metals. This excitation forms a nodal chain-a chain of connected loops in momentum space-along which conduction and valence bands touch. We prove that the nodal chain is topologically distinct from previously reported excitations. We discuss the symmetry requirements for the appearance of this excitation and predict that it is realized in an existing material, iridium tetrafluoride (IrF 4 ), as well as in other compounds of this class of materials. Using IrF 4 as an example, we provide a discussion of the topological surface states associated with the nodal chain. We argue that the presence of the nodal-chain fermions will result in anomalous magnetotransport properties, distinct from those of materials exhibiting previously known excitations.

  2. Patterns of failure after the reduced volume approach for elective nodal irradiation in nasopharyngeal carcinoma.

    PubMed

    Seol, Ki Ho; Lee, Jeong Eun

    2016-03-01

    To evaluate the patterns of nodal failure after radiotherapy (RT) with the reduced volume approach for elective neck nodal irradiation (ENI) in nasopharyngeal carcinoma (NPC). Fifty-six NPC patients who underwent definitive chemoradiotherapy with the reduced volume approach for ENI were reviewed. The ENI included retropharyngeal and level II lymph nodes, and only encompassed the echelon inferior to the involved level to eliminate the entire neck irradiation. Patients received either moderate hypofractionated intensity-modulated RT for a total of 72.6 Gy (49.5 Gy to elective nodal areas) or a conventional fractionated three-dimensional conformal RT for a total of 68.4-72 Gy (39.6-45 Gy to elective nodal areas). Patterns of failure, locoregional control, and survival were analyzed. The median follow-up was 38 months (range, 3 to 80 months). The out-of-field nodal failure when omitting ENI was none. Three patients developed neck recurrences (one in-field recurrence in the 72.6 Gy irradiated nodal area and two in the elective irradiated region of 39.6 Gy). Overall disease failure at any site developed in 11 patients (19.6%). Among these, there were six local failures (10.7%), three regional failures (5.4%), and five distant metastases (8.9%). The 3-year locoregional control rate was 87.1%, and the distant failure-free rate was 90.4%; disease-free survival and overall survival at 3 years was 80% and 86.8%, respectively. No patient developed nodal failure in the omitted ENI site. Our investigation has demonstrated that the reduced volume approach for ENI appears to be a safe treatment approach in NPC.

  3. Patterns of failure after the reduced volume approach for elective nodal irradiation in nasopharyngeal carcinoma

    PubMed Central

    Seol, Ki Ho

    2016-01-01

    Purpose To evaluate the patterns of nodal failure after radiotherapy (RT) with the reduced volume approach for elective neck nodal irradiation (ENI) in nasopharyngeal carcinoma (NPC). Materials and Methods Fifty-six NPC patients who underwent definitive chemoradiotherapy with the reduced volume approach for ENI were reviewed. The ENI included retropharyngeal and level II lymph nodes, and only encompassed the echelon inferior to the involved level to eliminate the entire neck irradiation. Patients received either moderate hypofractionated intensity-modulated RT for a total of 72.6 Gy (49.5 Gy to elective nodal areas) or a conventional fractionated three-dimensional conformal RT for a total of 68.4–72 Gy (39.6–45 Gy to elective nodal areas). Patterns of failure, locoregional control, and survival were analyzed. Results The median follow-up was 38 months (range, 3 to 80 months). The out-of-field nodal failure when omitting ENI was none. Three patients developed neck recurrences (one in-field recurrence in the 72.6 Gy irradiated nodal area and two in the elective irradiated region of 39.6 Gy). Overall disease failure at any site developed in 11 patients (19.6%). Among these, there were six local failures (10.7%), three regional failures (5.4%), and five distant metastases (8.9%). The 3-year locoregional control rate was 87.1%, and the distant failure-free rate was 90.4%; disease-free survival and overall survival at 3 years was 80% and 86.8%, respectively. Conclusion No patient developed nodal failure in the omitted ENI site. Our investigation has demonstrated that the reduced volume approach for ENI appears to be a safe treatment approach in NPC. PMID:27104162

  4. Association of Nodal Metastasis and Mortality With Vermilion vs Cutaneous Lip Location in Cutaneous Squamous Cell Carcinoma of the Lip.

    PubMed

    Wang, David M; Kraft, Stefan; Rohani, Pooyan; Murphy, George F; Besaw, Robert J; Karia, Pritesh S; Morgan, Frederick C; Schmults, Chrysalyne D

    2018-06-01

    Although the lip is considered a high-risk location in cutaneous squamous cell carcinoma (cSCC), it has not been established whether this risk stems from vermilion or cutaneous locations or both. To compare differences in risks of recurrence, metastasis, and death from cSCCs on the vermilion vs cutaneous lip. Retrospective cohort study of 303 patients with 310 primary cSCCs of the lip (138 cutaneous, 172 vermilion) diagnosed between 2000 and 2015 at 2 academic tertiary care centers in Boston, Massachusetts. Development of local recurrence, nodal metastasis, distant metastasis, disease-specific death, and all-cause death. Of the 303 study participants with 310 SCCs of the lip, 153 (50.5%) were men, and 150 (49.5%) were women; median age at diagnosis, 68 years (range, 27-93 years). Outcomes were as follows for vermilion vs cutaneous locations: local recurrence, 6.4% (11 of 172) vs 2.9% (4 of 138); nodal metastasis, 7.6% (13 of 172) vs 1.5% (2 of 138); distant metastasis, 0.6% (1 of 172) vs 0.7% (1 of 138); disease-specific death, 3.5% (6 of 172) vs 2.9% (4 of 138); and all-cause death, 26.7% (46 of 172) vs 29.0% (40 of 138). The difference was statistically significant for nodal metastasis (P = .01). In multivariable analysis, nodal metastasis was associated with vermilion lip location (subhazard ratio, 5.0; 95% CI, 1.1-23.8) and invasion beyond fat (fascia or beyond for vermilion lip) (subhazard ratio, 4.4; 95% CI, 1.3-14.9). The risk of nodal metastasis is 5-fold greater for cSCCs on the vermilion lip compared with those on the cutaneous lip. Squamous cell carcinomas of the cutaneous lip have a nodal metastasis risk similar to cSCCs in general (1.5%). Thus, vermilion involvement appears responsible for the increased risk associated with cSCC of lip. Vermilion involvement may merit radiologic nodal staging and inclusion in future tumor staging, since it was independently associated with higher-risk cSCC of the lip region.

  5. Temporal Nodal Regression and Regional Control After Primary Radiation Therapy for N2-N3 Head-and-Neck Cancer Stratified by HPV Status

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Huang, Shao Hui; O'Sullivan, Brian; Xu, Wei

    Purpose: To compare the temporal lymph node (LN) regression and regional control (RC) after primary chemoradiation therapy/radiation therapy in human papillomavirus-related [HPV(+)] versus human papillomavirus-unrelated [HPV(−)] head-and-neck cancer (HNC). Methods and Materials: All cases of N2-N3 HNC treated with radiation therapy/chemoradiation therapy between 2003 and 2009 were reviewed. Human papillomavirus status was ascertained by p16 staining on all available oropharyngeal cancers. Larynx/hypopharynx cancers were considered HPV(−). Initial radiologic complete nodal response (CR) (≤1.0 cm 8-12 weeks after treatment), ultimate LN resolution, and RC were compared between HPV(+) and HPV(−) HNC. Multivariate analysis identified outcome predictors. Results: A total of 257more » HPV(+) and 236 HPV(−) HNCs were identified. The initial LN size was larger (mean, 2.9 cm vs 2.5 cm; P<.01) with a higher proportion of cystic LNs (38% vs 6%, P<.01) in HPV(+) versus HPV(−) HNC. CR was achieved is 125 HPV(+) HNCs (49%) and 129 HPV(−) HNCs (55%) (P=.18). The mean post treatment largest LN was 36% of the original size in the HPV(+) group and 41% in the HPV(−) group (P<.01). The actuarial LN resolution was similar in the HPV(+) and HPV(−) groups at 12 weeks (42% and 43%, respectively), but it was higher in the HPV(+) group than in the HPV(−) group at 36 weeks (90% vs 77%, P<.01). The median follow-up period was 3.6 years. The 3-year RC rate was higher in the HPV(−) CR cases versus non-CR cases (92% vs 63%, P<.01) but was not different in the HPV(+) CR cases versus non-CR cases (98% vs 92%, P=.14). On multivariate analysis, HPV(+) status predicted ultimate LN resolution (odds ratio, 1.4 [95% confidence interval, 1.1-1.7]; P<.01) and RC (hazard ratio, 0.3 [95% confidence interval 0.2-0.6]; P<.01). Conclusions: HPV(+) LNs involute more quickly than HPV(−) LNs but undergo a more prolonged process to eventual CR beyond the time of initial assessment at 8 to

  6. Nonfunctional pancreatic neuroendocrine tumors <2 cm on preoperative imaging are associated with a low incidence of nodal metastasis and an excellent overall survival.

    PubMed

    Toste, Paul A; Kadera, Brian E; Tatishchev, Sergei F; Dawson, David W; Clerkin, Barbara M; Muthusamy, Raman; Watson, Rabindra; Tomlinson, James S; Hines, Oscar J; Reber, Howard A; Donahue, Timothy R

    2013-12-01

    The optimal surgical management of small nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) remains controversial. We sought to identify (1) clinicopathologic factors associated with survival in NF-PNETs and (2) preoperative tumor characteristics that can be used to determine which lesions require resection and lymph node (LN) harvest. The records of all 116 patients who underwent resection for NF-PNETs between 1989 and 2012 were reviewed retrospectively. Preoperative factors, operative data, pathology, surgical morbidity, and survival were analyzed. The overall 5- and 10-year survival rates were 83.9 and 72.8 %, respectively. Negative LNs (p = 0.005), G1 or G2 histology (p = 0.033), and age <60 years (p = 0.002) correlated with better survival on multivariate analysis. The 10-year survival rate was 86.6 % for LN-negative patients (n = 73) and 34.1 % for LN-positive patients (n = 32). Tumor size ≥2 cm on preoperative imaging predicted nodal positivity with a sensitivity of 93.8 %. Positive LNs were found in 38.5 % of tumors ≥2 cm compared to only 7.4 % of tumors <2 cm. LN status, a marker of systemic disease, was a highly significant predictor of survival in this series. Tumor size on preoperative imaging was predictive of nodal disease. Thus, it is reasonable to consider parenchyma-sparing resection or even close observation for NF-PNETs <2 cm.

  7. Proton beam radiotherapy as part of comprehensive regional nodal irradiation for locally advanced breast cancer.

    PubMed

    Verma, Vivek; Iftekaruddin, Zaid; Badar, Nida; Hartsell, William; Han-Chih Chang, John; Gondi, Vinai; Pankuch, Mark; Gao, Ming; Schmidt, Stacey; Kaplan, Darren; McGee, Lisa

    2017-05-01

    This study evaluates acute toxicity outcomes in breast cancer patients treated with adjuvant proton beam therapy (PBT). From 2011 to 2016, 91 patients (93 cancers) were treated with adjuvant PBT targeting the intact breast/chest wall and comprehensive regional nodes including the axilla, supraclavicular fossa, and internal mammary lymph nodes. Toxicity was recorded weekly during treatment, one month following treatment, and then every 6months according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Charts were retrospectively reviewed to verify toxicities, patient parameters, disease and treatment characteristics, and disease-related outcomes. Median follow-up was 15.5months. Median PBT dose was 50.4 Gray relative biological effectiveness (GyRBE), with subsequent boost as clinically indicated (N=61, median 10 GyRBE). Chemotherapy, when administered, was given adjuvantly (N=42) or neoadjuvantly (N=46). Grades 1, 2, and 3 dermatitis occurred in 23%, 72%, and 5%, respectively. Eight percent required treatment breaks owing to dermatitis. Median time to resolution of dermatitis was 32days. Grades 1, 2, and 3 esophagitis developed in 31%, 33%, and 0%, respectively. PBT displays acceptable toxicity in the setting of comprehensive regional nodal irradiation. Copyright © 2017. Published by Elsevier B.V.

  8. Three-dimensional conformal radiation for esophageal squamous cell carcinoma with involved-field irradiation may deliver considerable doses of incidental nodal irradiation.

    PubMed

    Ji, Kai; Zhao, Lujun; Yang, Chengwen; Meng, Maobin; Wang, Ping

    2012-11-27

    To quantify the incidental irradiation dose to esophageal lymph node stations when irradiating T1-4N0M0 thoracic esophageal squamous cell carcinoma (ESCC) patients with a dose of 60 Gy/30f. Thirty-nine patients with medically inoperable T1-4N0M0 thoracic ESCC were treated with three-dimensional conformal radiation (3DCRT) with involved-field radiation (IFI). The conformal clinical target volume (CTV) was re-created using a 3-cm margin in the proximal and distal direction beyond the barium esophagogram, endoscopic examination and CT scan defined the gross tumor volume (GTV) and a 0.5-cm margin in the lateral and anteroposterior directions of the CT scan-defined GTV. The PTV encompassed 1-cm proximal and distal margins and 0.5-cm radial margin based on the CTV. Nodal regions were delineated using the Japanese Society for Esophageal Diseases (JSED) guidelines and an EORTC-ROG expert opinion. The equivalent uniform dose (EUD) and other dosimetric parameters were calculated for each nodal station. Nodal regions with a metastasis rate greater than 5% were considered a high-risk lymph node subgroup. Under a 60 Gy dosage, the median D mean and EUD was greater than 40 Gy in most high-risk nodal regions except for regions of 104, 106tb-R in upper-thoracic ESCC and 101, 104-R, 105, 106rec-L, 2, 3&7 in middle-thoracic ESCC and 107, 3&7 in lower-thoracic ESCC. In the regions with an EUD less than 40 Gy, most incidental irradiation doses were significantly associated with esophageal tumor length and location. Lymph node stations near ESCC receive considerable incidental irradiation doses with involved-field irradiation that may contribute to the elimination of subclinical lesions.

  9. Three-dimensional conformal radiation for esophageal squamous cell carcinoma with involved-field irradiation may deliver considerable doses of incidental nodal irradiation

    PubMed Central

    2012-01-01

    Background To quantify the incidental irradiation dose to esophageal lymph node stations when irradiating T1-4N0M0 thoracic esophageal squamous cell carcinoma (ESCC) patients with a dose of 60 Gy/30f. Methods Thirty-nine patients with medically inoperable T1–4N0M0 thoracic ESCC were treated with three-dimensional conformal radiation (3DCRT) with involved-field radiation (IFI). The conformal clinical target volume (CTV) was re-created using a 3-cm margin in the proximal and distal direction beyond the barium esophagogram, endoscopic examination and CT scan defined the gross tumor volume (GTV) and a 0.5-cm margin in the lateral and anteroposterior directions of the CT scan-defined GTV. The PTV encompassed 1-cm proximal and distal margins and 0.5-cm radial margin based on the CTV. Nodal regions were delineated using the Japanese Society for Esophageal Diseases (JSED) guidelines and an EORTC-ROG expert opinion. The equivalent uniform dose (EUD) and other dosimetric parameters were calculated for each nodal station. Nodal regions with a metastasis rate greater than 5% were considered a high-risk lymph node subgroup. Results Under a 60 Gy dosage, the median Dmean and EUD was greater than 40 Gy in most high-risk nodal regions except for regions of 104, 106tb-R in upper-thoracic ESCC and 101, 104-R, 105, 106rec-L, 2, 3&7 in middle-thoracic ESCC and 107, 3&7 in lower-thoracic ESCC. In the regions with an EUD less than 40Gy, most incidental irradiation doses were significantly associated with esophageal tumor length and location. Conclusions Lymph node stations near ESCC receive considerable incidental irradiation doses with involved-field irradiation that may contribute to the elimination of subclinical lesions. PMID:23186308

  10. Prognostic Modeling in Pathologic N1 Breast Cancer Without Elective Nodal Irradiation After Current Standard Systemic Management.

    PubMed

    Yu, Jeong Il; Park, Won; Choi, Doo Ho; Huh, Seung Jae; Nam, Seok Jin; Kim, Seok Won; Lee, Jeong Eon; Kil, Won Ho; Im, Young-Hyuck; Ahn, Jin Seok; Park, Yeon Hee; Cho, Eun Yoon

    2015-08-01

    This study was conducted to establish a prognostic model in patients with pathologic N1 (pN1) breast cancer who have not undergone elective nodal irradiation (ENI) under the current standard management and to suggest possible indications for ENI. We performed a retrospective study with patients with pN1 breast cancer who received the standard local and preferred adjuvant chemotherapy treatment without neoadjuvant chemotherapy and ENI from January 2005 to June 2011. Most of the indicated patients received endocrine and trastuzumab therapy. In 735 enrolled patients, the median follow-up period was 58.4 months (range, 7.2-111.3 months). Overall, 55 recurrences (7.4%) developed, and locoregional recurrence was present in 27 patients (3.8%). Recurrence-free survival was significantly related to lymphovascular invasion (P = .04, hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.03-2.88), histologic grade (P = .03, HR, 2.57; 95% CI, 1.05-6.26), and nonluminal A subtype (P = .02, HR, 3.04; 95% CI, 1.23-7.49) in multivariate analysis. The prognostic model was established by these 3 prognostic factors. Recurrence-free survival was less than 90% at 5 years in cases with 2 or 3 factors. The prognostic model has stratified risk groups in pN1 breast cancer without ENI. Patients with 2 or more factors should be considered for ENI. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. On the Nodal Lines of Eisenstein Series on Schottky Surfaces

    NASA Astrophysics Data System (ADS)

    Jakobson, Dmitry; Naud, Frédéric

    2017-04-01

    On convex co-compact hyperbolic surfaces {X=Γ backslash H2}, we investigate the behavior of nodal curves of real valued Eisenstein series {F_λ(z,ξ)}, where {λ} is the spectral parameter, {ξ} the direction at infinity. Eisenstein series are (non-{L^2}) eigenfunctions of the Laplacian {Δ_X} satisfying {Δ_X F_λ=(1/4+λ^2)F_λ}. As {λ} goes to infinity (the high energy limit), we show that, for generic {ξ}, the number of intersections of nodal lines with any compact segment of geodesic grows like {λ}, up to multiplicative constants. Applications to the number of nodal domains inside the convex core of the surface are then derived.

  12. Additional Nodal Disease Prediction in Breast Cancer with Sentinel Lymph Node Metastasis Based on Clinicopathological Features.

    PubMed

    Orsaria, Paolo; Caredda, Emanuele; Genova, Federica; Materazzo, Marco; Capuano, Ilaria; Vanni, Gianluca; Granai, Alessandra Vittoria; DE Majo, Adriano; Portarena, Ilaria; Sileri, Pierpaolo; Petrella, Giuseppe; Palombi, Leonardo; Buonomo, Oreste Claudio

    2018-04-01

    The standard-of-care in breast cancer (BC) with positive sentinel lymph node (SLN) metastasis includes complete axillary lymph node dissection (ALND); however, almost half of such cases have no further tumor burden. This study aimed to assess the clinicopathological factors that predict non-SLN metastasis to define subgroups of SLN-positive patients in whom the axilla may be staged by SLN biopsy alone, while avoiding unnecessary overtreatment. The records of 191 patients with histologically-proven primary BC who underwent a positive (SLN) biopsy between 2005 and 2017 were reviewed. Patients with at least one tumor-involved SLN who underwent completion ALND were enrolled. Demographic and clinicopathological characteristics, including age, primary tumor size and histological grade, lymphovascular invasion, ratio of positive SLNs to the harvested SLNs, SLN metastasis size, and molecular subtype classification according to immunohistochemical biomarker status [estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)], were evaluated. Data were collected retrospectively and analyzed using the Mann-Whitney and Chi-square tests (statistical significance: p<0.05). The incidence of non-SLN metastasis associated with positive SLN was 48.6% (93/191). The risk of additional nodal spread correlated with high sentinel nodal ratio >0.67 [odds ratio (OR)=2.55, p=0.032], luminal BC subtype (OR=2.67, p=0.06), HER2 overexpression (OR=0.4, p=0.016), and ER + PR - HER2 - profile (OR=2.95, p=0.027). There was a tendency (statistically insignificant; p>0.05) toward higher incidence of non SLN metastasis with increasing age and histological grade, which could be attributed to the small sample size. According to this study, sentinel nodal ratio and BC subtypes as per ER, PR, and HER2 status significantly predicted the likelihood of additional lymphatic involvement. Validation of these parameters in prospective studies is indicated, and may

  13. Quantum oscillations in nodal line systems

    NASA Astrophysics Data System (ADS)

    Yang, Hui; Moessner, Roderich; Lim, Lih-King

    2018-04-01

    We study signatures of magnetic quantum oscillations in three-dimensional nodal line semimetals at zero temperature. The extended nature of the degenerate bands can result in a Fermi surface geometry with topological genus one, as well as a Fermi surface of electron and hole pockets encapsulating the nodal line. Moreover, the underlying two-band model to describe a nodal line is not unique, in that there are two classes of Hamiltonian with distinct band topology giving rise to the same Fermi-surface geometry. After identifying the extremal cyclotron orbits in various magnetic field directions, we study their concomitant Landau levels and resulting quantum oscillation signatures. By Landau-fan-diagram analyses, we extract the nontrivial π Berry phase signature for extremal orbits linking the nodal line.

  14. A contemporary view of atrioventricular nodal physiology.

    PubMed

    Markowitz, Steven M; Lerman, Bruce B

    2018-06-16

    In delaying transmission of the cardiac impulse from the atria to the ventricles, the atrioventricular (AV) node serves a critical function in augmenting ventricular filling during diastole and limiting the ventricular response during atrial tachyarrhythmias. The complex structure of the nodal region, however, also provides the substrate for reentrant rhythms. Recent discoveries have elucidated the cellular basis and anatomical determinants of slow conduction in the node. Based on analysis of gap junction proteins, distinct structural components of the AV node have been defined, including the compact node, right and left inferior nodal extensions, the lower nodal bundle, and transitional tissue. Emerging evidence supports the role of the inferior nodal extensions in mediating slow pathway conduction. The most common form of reentry involving the node, slow-fast AV nodal reentrant tachycardia (AVNRT), utilizes the inferior nodal extensions for anterograde slow pathway conduction; the structures responsible for retrograde fast pathway activation in the superior septum are less well defined and likely heterogeneous. Atypical forms of AVNRT arise from circuits that activate at least one of the inferior extensions in the retrograde direction.

  15. SU-E-J-179: Prediction of Pelvic Nodal Coverage Using Mutual Information Between Cone-Beam and Planning CTs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jani, S; Kishan, A; O'Connell, D

    2014-06-01

    Purpose: To investigate if pelvic nodal coverage for prostate patients undergoing intensity modulated radiotherapy (IMRT) can be predicted using mutual image information computed between planning and cone-beam CTs (CBCTs). Methods: Four patients with high-risk prostate adenocarcinoma were treated with IMRT on a Varian TrueBeam. Plans were designed such that 95% of the nodal planning target volume (PTV) received the prescription dose of 45 Gy (N=1) or 50.4 Gy (N=3). Weekly CBCTs (N=25) were acquired and the nodal clinical target volumes and organs at risk were contoured by a physician. The percent nodal volume receiving prescription dose was recorded as amore » ground truth. Using the recorded shifts performed by the radiation therapists at the time of image acquisition, CBCTs were aligned with the planning kVCT. Mutual image information (MI) was calculated between the CBCT and the aligned planning CT within the contour of the nodal PTV. Due to variable CBCT fields-of-view, CBCT images covering less than 90% of the nodal volume were excluded from the analysis, resulting in the removal of eight CBCTs. Results: A correlation coefficient of 0.40 was observed between the MI metric and the percent of the nodal target volume receiving the prescription dose. One patient's CBCTs had clear outliers from the rest of the patients. Upon further investigation, we discovered image artifacts that were present only in that patient's images. When those four images were excluded, the correlation improved to 0.81. Conclusion: This pilot study shows the potential of predicting pelvic nodal dosimetry by computing the mutual image information between planning CTs and patient setup CBCTs. Importantly, this technique does not involve manual or automatic contouring of the CBCT images. Additional patients and more robust exclusion criteria will help validate our findings.« less

  16. Nodal to nodeless superconducting energy-gap structure change concomitant with Fermi-surface reconstruction in the heavy-fermion compound CeCoIn 5

    DOE PAGES

    Kim, Hyunsoo; Tanatar, M. A.; Flint, R.; ...

    2015-01-15

    The London penetration depth, λ(T), was measured in single crystals of Ce 1-xR xCoIn 5, R=La, Nd and Yb down to T min ≈ 50 mK (T c/T min ~50) using a tunnel-diode resonator. In the cleanest samples Δλ(T) is best described by the power law, Δλ(T) ∝ T n, with n ~ 1, consistent with line nodes. Substitutions of Ce with La, Nd and Yb lead to similar monotonic suppressions of T c, however the effects on Δλ(T) differ. While La and Nd dopings lead to increase of the exponent n and saturation at n ~ 2, as expectedmore » for a dirty nodal superconductor, Yb doping leads to n > 3, suggesting a change from nodal to nodeless superconductivity. As a result, this superconducting gap structure change happen in the same doping range where changes of the Fermi surface topology were reported, implying that the nodal structure and Fermi surface topology are closely linked.« less

  17. Hybrid nodal loop metal: Unconventional magnetoresponse and material realization

    NASA Astrophysics Data System (ADS)

    Zhang, Xiaoming; Yu, Zhi-Ming; Lu, Yunhao; Sheng, Xian-Lei; Yang, Hui Ying; Yang, Shengyuan A.

    2018-03-01

    A nodal loop is formed by a band crossing along a one-dimensional closed manifold, with each point on the loop a linear nodal point in the transverse dimensions, and can be classified as type I or type II depending on the band dispersion. Here, we propose a class of nodal loops composed of both type-I and type-II points, which are hence termed as hybrid nodal loops. Based on first-principles calculations, we predict the realization of such loops in the existing electride material Ca2As . For a hybrid loop, the Fermi surface consists of coexisting electron and hole pockets that touch at isolated points for an extended range of Fermi energies, without the need for fine-tuning. This leads to unconventional magnetic responses, including the zero-field magnetic breakdown and the momentum-space Klein tunneling observable in the magnetic quantum oscillations, as well as the peculiar anisotropy in the cyclotron resonance.

  18. Delineation of Internal Mammary Nodal Target Volumes in Breast Cancer Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jethwa, Krishan R.; Kahila, Mohamed M.; Hunt, Katie N.

    Purpose: The optimal clinical target volume for internal mammary (IM) node irradiation is uncertain in an era of increasingly conformal volume-based treatment planning for breast cancer. We mapped the location of gross internal mammary lymph node (IMN) metastases to identify areas at highest risk of harboring occult disease. Methods and Materials: Patients with axial imaging of IMN disease were identified from a breast cancer registry. The IMN location was transferred onto the corresponding anatomic position on representative axial computed tomography images of a patient in the treatment position and compared with consensus group guidelines of IMN target delineation. Results: Themore » IMN location in 67 patients with 130 IMN metastases was mapped. The location was in the first 3 intercostal spaces in 102 of 130 nodal metastases (78%), whereas 18 of 130 IMNs (14%) were located caudal to the third intercostal space and 10 of 130 IMNs (8%) were located cranial to the first intercostal space. Of the 102 nodal metastases within the first 3 intercostal spaces, 54 (53%) were located within the Radiation Therapy Oncology Group consensus volume. Relative to the IM vessels, 19 nodal metastases (19%) were located medially with a mean distance of 2.2 mm (SD, 2.9 mm) whereas 29 (28%) were located laterally with a mean distance of 3.6 mm (SD, 2.5 mm). Ninety percent of lymph nodes within the first 3 intercostal spaces would have been encompassed within a 4-mm medial and lateral expansion on the IM vessels. Conclusions: In women with indications for elective IMN irradiation, a 4-mm medial and lateral expansion on the IM vessels may be appropriate. In women with known IMN involvement, cranial extension to the confluence of the IM vein with the brachiocephalic vein with or without caudal extension to the fourth or fifth interspace may be considered provided that normal tissue constraints are met.« less

  19. Classification of reflection-symmetry-protected topological semimetals and nodal superconductors

    NASA Astrophysics Data System (ADS)

    Chiu, Ching-Kai; Schnyder, Andreas P.

    2014-11-01

    While the topological classification of insulators, semimetals, and superconductors in terms of nonspatial symmetries is well understood, less is known about topological states protected by crystalline symmetries, such as mirror reflections and rotations. In this work, we systematically classify topological semimetals and nodal superconductors that are protected, not only by nonspatial (i.e., global) symmetries, but also by a crystal reflection symmetry. We find that the classification crucially depends on (i) the codimension of the Fermi surface (nodal line or point) of the semimetal (superconductor), (ii) whether the mirror symmetry commutes or anticommutes with the nonspatial symmetries, and (iii) how the Fermi surfaces (nodal lines or points) transform under the mirror reflection and nonspatial symmetries. The classification is derived by examining all possible symmetry-allowed mass terms that can be added to the Bloch or Bogoliubov-de Gennes Hamiltonian in a given symmetry class and by explicitly deriving topological invariants. We discuss several examples of reflection-symmetry-protected topological semimetals and nodal superconductors, including topological crystalline semimetals with mirror Z2 numbers and topological crystalline nodal superconductors with mirror winding numbers.

  20. Brady's Geothermal Field Nodal Seismometer Earthquake Data

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kurt Feigl

    90-second records of data from 238 three-component nodal seismometer deployed at Bradys geothermal field. The time window catches an earthquake arrival. Earthquake data from USGS online catalog: Magnitude: 4.3 ml +/- 0.4 Location: 38.479 deg N 118.366 deg W +/- 0.7 km Depth: 9.9 km +/- 0.7 Date and Time: 2016-03-21 07:37:10.535 UTC

  1. Type-I and type-II topological nodal superconductors with s -wave interaction

    NASA Astrophysics Data System (ADS)

    Huang, Beibing; Yang, Xiaosen; Xu, Ning; Gong, Ming

    2018-01-01

    Topological nodal superconductors with protected gapless points in momentum space are generally realized based on unconventional pairings. In this work we propose a minimal model to realize these topological nodal phases with only s -wave interaction. In our model the linear and quadratic spin-orbit couplings along the two orthogonal directions introduce anisotropic effective unconventional pairings in momentum space. This model may support different nodal superconducting phases characterized by either an integer winding number in BDI class or a Z2 index in D class at the particle-hole invariant axes. In the vicinity of the nodal points the effective Hamiltonian can be described by either type-I or type-II Dirac equations, and the Lifshitz transition from type-I nodal phases to type-II nodal phases can be driven by external in-plane magnetic fields. We show that these nodal phases are robust against weak impurities, which only slightly renormalizes the momentum-independent parameters in the impurity-averaged Hamiltonian, thus these phases are possible to be realized in experiments with real semi-Dirac materials. The smoking-gun evidences to verify these phases based on scanning tunneling spectroscopy method are also briefly discussed.

  2. Persistence of RSV promotes proliferation and epithelial-mesenchymal transition of bronchial epithelial cells through Nodal signaling.

    PubMed

    Xiang, Zhao; Liang, Zhang; Yanfeng, Huang; Leitao, Kang

    2017-10-01

    Nodal may play an important role in the development of cancers. The present study was designed to determine the effects of Nodal induced by respiratory syncytial virus (RSV) infection on the occurrence and development of lung cancer and the underlying mechanisms. After verification of RSV infection by observation of cytopathic effect and indirect immunofluorescence, real-time PCR, Western blot and methylation assays were used to verify the influence of RSV on Nodal expression. Then, a Nodal overexpressed vector was constructed and the effects of Nodal on the proliferation and apoptosis of bronchial epithelial cells (BECs) and epithelial-mesenchymal transition (EMT) were assayed by flow cytometry and Western blot, respectively. Moreover, Lefty and pSmad2/3 were assayed by Western blot and Cyclin D1, CDK4, c-myc and Bcl-2 induced by Nodal overepression or RSV infection were also assayed by real-time PCR. The results showed that Nodal over expression and demethylation of the promoter were observed in BECs after RSV infection. Activation of Nodal promoted proliferation, colony formation and EMT and inhibited apoptosis of BECs. Nodal also promoted malignant change by promoting expression of cyclin D1 and related-dependent kinase and inhibiting apoptosis. Besides, RSV infection inhibited Lefty expression and promoted the activation of pSmad2/3. RSV also promoted Cyclin D1, CDK4, c-myc and Bcl-2 expression through the activation of pSmad2/3. Our data showed that persistence of RSV promoted the proliferation, epithelial-mesenchymal transition and expression of oncogenes through Nodal signaling, which may be associated with the occurrence and development of lung cancers.

  3. Tumor microvessel density–associated mast cells in canine nodal lymphoma

    PubMed Central

    Mann, Elizabeth; Whittington, Lisa

    2014-01-01

    Objective: Mast cells are associated in angiogenesis in various human and animal neoplasms. However, association of mast cells with tumor microvessel density in canine lymphoma was not previously documented. The objective of the study is to determine if mast cells are increased in canine nodal lymphomas and to evaluate their correlation with tumor microvessel density and grading of lymphomas. Methods: Nodal lymphomas from 33 dogs were studied and compared with nonneoplastic lymph nodes from 6 dogs as control. Mast cell count was made on Toluidine blue stained sections. Immunohistochemistry using antibody against Factor VIII was employed to visualize and determine microvessel density. Results: The mast cell count in lymphoma (2.95 ± 2.4) was significantly higher (p < 0.05) than that in the control (0.83 ± 0.3) and was positively correlated with tumor microvessel density (r = 0.44, p = 0.009). Significant difference was not observed in mast cell count and tumor microvessel density among different gradings of lymphomas. Conclusions: Mast cells are associated with tumor microvessel density in canine nodal lymphoma with no significant difference among gradings of lymphomas. Mast cells may play an important role in development of canine nodal lymphomas. Further detailed investigation on the role of mast cells as important part of tumor microenvironment in canine nodal lymphomas is recommended. PMID:26770752

  4. Increased expression of EZH2 in Merkel cell carcinoma is associated with disease progression and poorer prognosis.

    PubMed

    Harms, Kelly L; Chubb, Heather; Zhao, Lili; Fullen, Douglas R; Bichakjian, Christopher K; Johnson, Timothy M; Carskadon, Shannon; Palanisamy, Nallasivam; Harms, Paul W

    2017-09-01

    Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that affects tumorigenesis by epigenetic gene silencing. Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma that has a high risk of disease progression with nodal and distant metastases. Here, we evaluated EZH2 expression by immunohistochemistry in a cohort of 85 MCC tumors (29 primary tumors, 41 lymph node metastases, 13 in-transit metastases, and 2 distant metastases) with clinical follow-up. We show strong/moderate EZH2 expression in 54% of tumors. Importantly, weak expression of EZH2 in the primary tumor, but not nodal metastases, correlated with improved prognosis compared to moderate/strong EZH2 expression (5-year MCC-specific survival of 68% versus 22%, respectively, P=.024). In addition, EZH2 was expressed at higher levels in nodal metastases compared to primary tumors (P=.005). Our data demonstrate that EZH2 has prognostic value and may play an oncogenic role in MCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. RW Per - Nodal motion changes its amplitude by 1.4 mag

    NASA Technical Reports Server (NTRS)

    Schaefer, Bradley E.; Fried, Robert E.

    1991-01-01

    RW Per was found to have large secular changes in its eclipse amplitude. In blue light, for example, the amplitude was 3.2 mag in the early 1900s, 2.2 mag in the late 1960s, and 1.75 mag in 1990. Throughout this time, the brightness at maximum was constant in all colors. It is shown that the only possible explanation is nodal motion, where the inclination varies with a period of roughly 100,000 yr. The nodal motion is caused by a third star, for which the light curve, the colors, and the O - C curve already provide evidence. Thus, RW Per is only the fourth known star with large changes of eclipse amplitude and is only the second example of nodal motion.

  6. Defining the Risk of Involvement for Each Neck Nodal Level in Patients With Early T-Stage Node-Positive Oropharyngeal Carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sanguineti, Giuseppe; Califano, Joseph; Stafford, Edward

    Purpose: To assess the risk of ipsilateral subclinical neck nodal involvement for early T-stage/node-positive oropharyngeal squamous cell carcinoma. Methods and Materials: Patients undergoing multilevel upfront neck dissection (ND) at Johns Hopkins Hospital within the last 10 years for early clinical T-stage (cT1-2) node-positive (cN+) oropharyngeal squamous cell carcinoma were identified. Pathologic involvement of Levels IB-V was determined. For each nodal level, the negative predictive value of imaging results was computed by using sensitivity/specificity data for computed tomography (CT). This was used to calculate 1 - negative predictive value, or the risk that a negative level on CT harbors subclinical disease.more » Results: One hundred three patients met the criteria. Radical ND was performed in 14.6%; modified radical ND, in 70.9%; and selective ND, in 14.6%. Pathologic positivity rates were 9.5%, 91.3%, 40.8%, 18.0%, and 3.3% for Levels IB-V, respectively. Risks of subclinical disease despite negative CT imaging results were calculated as 3.1%, 76.3%, 17.5%, 6.3%, and 1.0% for Levels IB-V, respectively. Conclusions: Levels IB and V are at very low (<5%) risk of involvement, even with ipsilateral to pathologically proven neck disease; this can guide radiation planning. Levels II and III should be included in high-risk volumes regardless of imaging results, and Level IV should be included within the lowest risk volume.« less

  7. Long-term survival of 42 patients with resected N2 non-small-cell lung cancer: the impact of 2-(18)F-fluoro-2-deoxy-D-glucose positron emission tomogram mediastinal staging.

    PubMed

    Barnett, Stephen; Baste, Jean-Marc; Murugappan, Kowsi; Tog, Check; Berlangieri, Salvatore; Scott, Andrew; Seevanayagam, Siven; Knight, Simon

    2011-01-01

    Prognostic information known preoperatively allows stratification of patients to surgery; induction therapy and surgery; or definitive chemoradiotherapy and may prevent a futile thoracotomy. Attention has focussed on the standard uptake value (SUV) of the primary tumour but less has been described regarding the 18F-fluoro-2-deoxy-D-glucose (18F-FDG) avidity of mediastinal nodes. We aimed, in a group of surgically resected cN0-1 but pN2 tumours, to compare the survival of patients with and without 18F-FDG avid mediastinal nodes. Retrospective review of a surgical database identified cN0-1 non-small-cell lung cancer (NSCLC) patients with pN2 disease after resection. Survival of non-FDG avid N2 versus FDG avid N2 groups was compared after stratification according to variables found on univariate analysis to affect survival. From January 1993 to December 2006, 42 patients were identified; 27 (64%) had non-FDG avid N2 disease. Five-year and median survival were better in the non-FDG avid N2 disease group, 25% versus 0% and 30 (16-44) versus 13 (10-16) months, respectively (p=0.02). After 1998, the difference in survival was 41% versus 0% and 35 (14-56) versus 12 (16-18) months, respectively (p=0.02). After resection, patients with non-FDG avid N2 disease have better survival than patients with FDG avid N2 disease. Exploratory thoracotomy alone (after frozen section analysis) cannot be advocated in patients with non-FDG avid N2 disease as survival after resection appears at least equivalent to alternate therapeutic approaches in this group. This assertion may be tempered if right pneumonectomy is required or R0 resection is unachievable. Mediastinal nodal avidity may improve stratification in future studies of long-term survival in NSCLC. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  8. Nodal signalling and asymmetry of the nervous system

    PubMed Central

    Signore, Iskra A.; Palma, Karina

    2016-01-01

    The role of Nodal signalling in nervous system asymmetry is still poorly understood. Here, we review and discuss how asymmetric Nodal signalling controls the ontogeny of nervous system asymmetry using a comparative developmental perspective. A detailed analysis of asymmetry in ascidians and fishes reveals a critical context-dependency of Nodal function and emphasizes that bilaterally paired and midline-unpaired structures/organs behave as different entities. We propose a conceptual framework to dissect the developmental function of Nodal as asymmetry inducer and laterality modulator in the nervous system, which can be used to study other types of body and visceral organ asymmetries. Using insights from developmental biology, we also present novel evolutionary hypotheses on how Nodal led the evolution of directional asymmetry in the brain, with a particular focus on the epithalamus. We intend this paper to provide a synthesis on how Nodal signalling controls left–right asymmetry of the nervous system. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821531

  9. Maternal nodal and zebrafish embryogenesis.

    PubMed

    Bennett, James T; Stickney, Heather L; Choi, Wen-Yee; Ciruna, Brian; Talbot, William S; Schier, Alexander F

    2007-11-08

    In fish and amphibians, the dorsal axis is specified by the asymmetric localization of maternally provided components of the Wnt signalling pathway. Gore et al. suggest that the Nodal signal Squint (Sqt) is required as a maternally provided dorsal determinant in zebrafish. Here we test their proposal and show that the maternal activities of sqt and the related Nodal gene cyclops (cyc) are not required for dorsoventral patterning.

  10. A nodal domain theorem for integrable billiards in two dimensions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Samajdar, Rhine; Jain, Sudhir R., E-mail: srjain@barc.gov.in

    Eigenfunctions of integrable planar billiards are studied — in particular, the number of nodal domains, ν of the eigenfunctions with Dirichlet boundary conditions are considered. The billiards for which the time-independent Schrödinger equation (Helmholtz equation) is separable admit trivial expressions for the number of domains. Here, we discover that for all separable and non-separable integrable billiards, ν satisfies certain difference equations. This has been possible because the eigenfunctions can be classified in families labelled by the same value of mmodkn, given a particular k, for a set of quantum numbers, m,n. Further, we observe that the patterns in a familymore » are similar and the algebraic representation of the geometrical nodal patterns is found. Instances of this representation are explained in detail to understand the beauty of the patterns. This paper therefore presents a mathematical connection between integrable systems and difference equations. - Highlights: • We find that the number of nodal domains of eigenfunctions of integrable, planar billiards satisfy a class of difference equations. • The eigenfunctions labelled by quantum numbers (m,n) can be classified in terms of mmodkn. • A theorem is presented, realising algebraic representations of geometrical patterns exhibited by the domains. • This work presents a connection between integrable systems and difference equations.« less

  11. Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

    PubMed

    Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J

    2017-07-01

    Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Theoretical and Experimental Evidence for a Nodal Energy Gap in MgB2

    DTIC Science & Technology

    2017-02-17

    1   Theoretical and Experimental Evidence for a Nodal Energy Gap in MgB2 Y. Dan Agassia and Daniel E. Oatesb aConsultant, Jerusalem, Israel bMIT...surface impedance and intermodulation distortion in high-quality thin films. We briefly review experimental evidence in support of our hypothesis and...demonstrates, this experimental evidence agrees with the l = 6 hypothesis, while inconsistent with s-wave symmetry. To give the l = 6 hypothesis a

  13. Pelvic Nodal Dosing With Registration to the Prostate: Implications for High-Risk Prostate Cancer Patients Receiving Stereotactic Body Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kishan, Amar U., E-mail: aukishan@mednet.ucla.edu; Lamb, James M.; Jani, Shyam S.

    2015-03-15

    Purpose: To determine whether image guidance with rigid registration (RR) to intraprostatic markers (IPMs) yields acceptable coverage of the pelvic lymph nodes in the context of a stereotactic body radiation therapy (SBRT) regimen. Methods and Materials: Four to seven kilovoltage cone-beam CTs (CBCTs) from 12 patients with high-risk prostate cancer were analyzed, allowing approximation of an SBRT regimen. The nodal clinical target volume (CTV{sub N}) and bladder were contoured on all kilovoltage CBCTs. The V{sub 100} CTV{sub N}, expressed as a ratio to the same parameter on the initial plan, and the magnitude of translational shift between RR to themore » IPMs versus RR to the pelvic bones, were computed. The ability of a multimodality bladder filling protocol to minimize bladder height variation was assessed in a separate cohort of 4 patients. Results: Sixty-five CBCTs were assessed. The average V{sub 100} CTV{sub N} was 92.6%, but for a subset of 3 patients the average was 80.0%, compared with 97.8% for the others (P<.0001). The average overall and superior–inferior axis magnitudes of the bony-to-fiducial translations were significantly larger in the subgroup with suboptimal nodal coverage (8.1 vs 3.9 mm and 5.8 vs 2.4 mm, respectively; P<.0001). Relative bladder height changes were also significantly larger in the subgroup with suboptimal nodal coverage (42.9% vs 18.5%; P<.05). Use of a multimodality bladder-filling protocol minimized bladder height variation (P<.001). Conclusion: A majority of patients had acceptable nodal coverage after RR to IPMs, even when approximating SBRT. However, a subset of patients had suboptimal nodal coverage. These patients had large bony-to-fiducial translations and large variations in bladder height. Nodal coverage should be excellent if the superior–inferior axis bony-to-fiducial translation and the relative bladder height change (both easily measured on CBCT) are kept to a minimum. Implementation of a strict bladder

  14. Nodal signalling determines biradial asymmetry in Hydra.

    PubMed

    Watanabe, Hiroshi; Schmidt, Heiko A; Kuhn, Anne; Höger, Stefanie K; Kocagöz, Yigit; Laumann-Lipp, Nico; Ozbek, Suat; Holstein, Thomas W

    2014-11-06

    In bilaterians, three orthogonal body axes define the animal form, with distinct anterior-posterior, dorsal-ventral and left-right asymmetries. The key signalling factors are Wnt family proteins for the anterior-posterior axis, Bmp family proteins for the dorsal-ventral axis and Nodal for the left-right axis. Cnidarians, the sister group to bilaterians, are characterized by one oral-aboral body axis, which exhibits a distinct biradiality of unknown molecular nature. Here we analysed the biradial growth pattern in the radially symmetrical cnidarian polyp Hydra, and we report evidence of Nodal in a pre-bilaterian clade. We identified a Nodal-related gene (Ndr) in Hydra magnipapillata, and this gene is essential for setting up an axial asymmetry along the main body axis. This asymmetry defines a lateral signalling centre, inducing a new body axis of a budding polyp orthogonal to the mother polyp's axis. Ndr is expressed exclusively in the lateral bud anlage and induces Pitx, which encodes an evolutionarily conserved transcription factor that functions downstream of Nodal. Reminiscent of its function in vertebrates, Nodal acts downstream of β-Catenin signalling. Our data support an evolutionary scenario in which a 'core-signalling cassette' consisting of β-Catenin, Nodal and Pitx pre-dated the cnidarian-bilaterian split. We presume that this cassette was co-opted for various modes of axial patterning: for example, for lateral branching in cnidarians and left-right patterning in bilaterians.

  15. Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lao, Louis; Department of Radiation Oncology, Auckland City Hospital, Auckland; Hope, Andrew J.

    2014-09-01

    Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses atmore » the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.« less

  16. Neural Networks for Nodal Staging of Non–Small Cell Lung Cancer with FDG PET and CT: Importance of Combining Uptake Values and Sizes of Nodes and Primary Tumor

    PubMed Central

    Vesselle, Hubert J.

    2014-01-01

    Purpose To evaluate the effect of adding lymph node size to three previously explored artificial neural network (ANN) input parameters (primary tumor maximum standardized uptake value or tumor uptake, tumor size, and nodal uptake at N1, N2, and N3 stations) in the structure of the ANN. The goal was to allow the resulting ANN structure to relate lymph node uptake for size to primary tumor uptake for size in the determination of the status of nodes as human readers do. Materials and Methods This prospective study was approved by the institutional review board, and informed consent was obtained from all participants. The authors developed a back-propagation ANN with one hidden layer and eight processing units. The data set used to train the network included node and tumor size and uptake from 133 patients with non–small cell lung cancer with surgically proved N status. Statistical analysis was performed with the paired t test. Results The ANN correctly predicted the N stage in 99.2% of cases, compared with 72.4% for the expert reader (P < .001). In categorization of N0 and N1 versus N2 and N3 disease, the ANN performed with 99.2% accuracy versus 92.2% for the expert reader (P < .001). Conclusion The ANN is 99.2% accurate in predicting surgical-pathologic nodal status with use of four fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)–derived parameters. Malignant and benign inflammatory lymph nodes have overlapping appearances at FDG PET/CT but can be differentiated by ANNs when the crucial input of node size is used. © RSNA, 2013 Online supplemental material is available for this article. PMID:24056403

  17. Off-diagonal Jacobian support for Nodal BCs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Peterson, John W.; Andrs, David; Gaston, Derek R.

    In this brief note, we describe the implementation of o-diagonal Jacobian computations for nodal boundary conditions in the Multiphysics Object Oriented Simulation Environment (MOOSE) [1] framework. There are presently a number of applications [2{5] based on the MOOSE framework that solve complicated physical systems of partial dierential equations whose boundary conditions are often highly nonlinear. Accurately computing the on- and o-diagonal Jacobian and preconditioner entries associated to these constraints is crucial for enabling ecient numerical solvers in these applications. Two key ingredients are required for properly specifying the Jacobian contributions of nonlinear nodal boundary conditions in MOOSE and nite elementmore » codes in general: 1. The ability to zero out entire Jacobian matrix rows after \

  18. Three-dimensional conformal radiation therapy for esophageal squamous cell carcinoma: is elective nodal irradiation necessary?

    PubMed

    Zhao, Kuai-le; Ma, Jin-bo; Liu, Guang; Wu, Kai-liang; Shi, Xue-hui; Jiang, Guo-liang

    2010-02-01

    To evaluate the local control, survival, and toxicity associated with three-dimensional conformal radiotherapy (3D-CRT) for squamous cell carcinoma (SCC) of the esophagus, to determine the appropriate target volumes, and to determine whether elective nodal irradiation is necessary in these patients. A prospective study of 3D-CRT was undertaken in patients with esophageal SCC without distant metastases. Patients received 68.4 Gy in 41 fractions over 44 days using late-course accelerated hyperfractionated 3D-CRT. Only the primary tumor and positive lymph nodes were irradiated. Isolated out-of-field regional nodal recurrence was defined as a recurrence in an initially uninvolved regional lymph node. All 53 patients who made up the study population tolerated the irradiation well. No acute or late Grade 4 or 5 toxicity was observed. The median survival time was 30 months (95% confidence interval, 17.7-41.8). The overall survival rate at 1, 2, and 3 years was 77%, 56%, and 41%, respectively. The local control rate at 1, 2, and 3 years was 83%, 74%, and 62%, respectively. Thirty-nine of the 53 patients (74%) showed treatment failure. Seventeen of the 39 (44%) developed an in-field recurrence, 18 (46%) distant metastasis with or without regional failure, and 3 (8%) an isolated out-of-field nodal recurrence only. One patient died of disease in an unknown location. In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. Local failure and distant metastases remained the predominant problems. Copyright 2010 Elsevier Inc. All rights reserved.

  19. [Does nodal irradiation (clavicular and internal mammary chains) increase the toxicity of adjuvant breast radiotherapy?].

    PubMed

    Riou, O; Bourgier, C; Fenoglietto, P; Azria, D

    2015-06-01

    Treatment volume is a major risk factor of radiation-induced toxicity. As nodal irradiation increases treatment volume, radiation toxicity should be greater. Nevertheless, scientific randomised data do not support this fact. However, a radiation-induced toxicity is possible outside tangential fields in the nodal volumes not related to breast-only treatment. Treatment should not be adapted only to the disease but personalized to the individual risk of toxicity for each patient. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  20. Chiral topological insulating phases from three-dimensional nodal loop semimetals

    NASA Astrophysics Data System (ADS)

    Li, Linhu; Yin, Chuanhao; Chen, Shu; Araujo, Miguel

    We begin with a minimal model of three-dimensional nodal loop semimetals, and study the effect of anticommuting gap terms. The resulting topological insulating phases are protected by a chiral symmetry, and can be characterized by a winding number defined along the nodal loop. We illustrate the geometric relation between the nodal loop and the gap terms, which has a correspondence to the nodal loop winding number. We further investigate a lattice model and study its edge states under open boundary condition. The edge states hold Dirac cones with the same number as the summation of the winding numbers of each nodal loop in the first Brillouin zone.

  1. Topological Nodal-Net Semimetal in a Graphene Network Structure

    NASA Astrophysics Data System (ADS)

    Wang, Jian-Tao; Nie, Simin; Weng, Hongming; Kawazoe, Yoshiyuki; Chen, Changfeng

    2018-01-01

    Topological semimetals are characterized by the nodal points in their electronic structure near the Fermi level, either discrete or forming a continuous line or ring, which are responsible for exotic properties related to the topology of bulk bands. Here we identify by ab initio calculations a distinct topological semimetal that exhibits nodal nets comprising multiple interconnected nodal lines in bulk and have two coupled drumheadlike flat bands around the Fermi level on its surface. This nodal net semimetal state is proposed to be realized in a graphene network structure that can be constructed by inserting a benzene ring into each C- C bond in the bct-C4 lattice or by a crystalline modification of the (5,5) carbon nanotube. These results expand the realm of nodal manifolds in topological semimetals, offering a new platform for exploring novel physics in these fascinating materials.

  2. Symmorphic Intersecting Nodal Rings in Semiconducting Layers

    NASA Astrophysics Data System (ADS)

    Gong, Cheng; Xie, Yuee; Chen, Yuanping; Kim, Heung-Sik; Vanderbilt, David

    2018-03-01

    The unique properties of topological semimetals have strongly driven efforts to seek for new topological phases and related materials. Here, we identify a critical condition for the existence of intersecting nodal rings (INRs) in symmorphic crystals, and further classify all possible kinds of INRs which can be obtained in the layered semiconductors with Amm2 and Cmmm space group symmetries. Several honeycomb structures are suggested to be topological INR semimetals, including layered and "hidden" layered structures. Transitions between the three types of INRs, named as α , β , and γ type, can be driven by external strains in these structures. The resulting surface states and Landau-level structures, more complicated than those resulting from a simple nodal loop, are also discussed.

  3. Unilateral dampening of Bmp activity by nodal generates cardiac left-right asymmetry.

    PubMed

    Veerkamp, Justus; Rudolph, Franziska; Cseresnyes, Zoltan; Priller, Florian; Otten, Cécile; Renz, Marc; Schaefer, Liliana; Abdelilah-Seyfried, Salim

    2013-03-25

    Signaling by Nodal and Bmp is essential for cardiac laterality. How activities of these pathways translate into left-right asymmetric organ morphogenesis is largely unknown. We show that, in zebrafish, Nodal locally reduces Bmp activity on the left side of the cardiac field. This effect is mediated by the extracellular matrix enzyme Hyaluronan synthase 2, expression of which is induced by Nodal. Unilateral reduction of Bmp signaling results in lower expression of nonmuscle myosin II and higher cell motility on the left, driving asymmetric displacement of the entire cardiac field. In silico modeling shows that left-right differences in cell motility are sufficient to induce a robust, directional migration of cardiac tissue. Thus, the mechanism underlying the formation of cardiac left-right asymmetry involves Nodal modulating an antimotogenic Bmp activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Quantum criticality and nodal superconductivity in the FeAs-based superconductor KFe2As2.

    PubMed

    Dong, J K; Zhou, S Y; Guan, T Y; Zhang, H; Dai, Y F; Qiu, X; Wang, X F; He, Y; Chen, X H; Li, S Y

    2010-02-26

    The in-plane resistivity rho and thermal conductivity kappa of the FeAs-based superconductor KFe2As2 single crystal were measured down to 50 mK. We observe non-Fermi-liquid behavior rho(T) approximately T{1.5} at H{c{2}}=5 T, and the development of a Fermi liquid state with rho(T) approximately T{2} when further increasing the field. This suggests a field-induced quantum critical point, occurring at the superconducting upper critical field H{c{2}}. In zero field, there is a large residual linear term kappa{0}/T, and the field dependence of kappa_{0}/T mimics that in d-wave cuprate superconductors. This indicates that the superconducting gaps in KFe2As2 have nodes, likely d-wave symmetry. Such a nodal superconductivity is attributed to the antiferromagnetic spin fluctuations near the quantum critical point.

  5. Nodal portraits of quantum billiards: Domains, lines, and statistics

    NASA Astrophysics Data System (ADS)

    Jain, Sudhir Ranjan; Samajdar, Rhine

    2017-10-01

    This is a comprehensive review of the nodal domains and lines of quantum billiards, emphasizing a quantitative comparison of theoretical findings to experiments. The nodal statistics are shown to distinguish not only between regular and chaotic classical dynamics but also between different geometric shapes of the billiard system itself. How a random superposition of plane waves can model chaotic eigenfunctions is discussed and the connections of the complex morphology of the nodal lines thereof to percolation theory and Schramm-Loewner evolution are highlighted. Various approaches to counting the nodal domains—using trace formulas, graph theory, and difference equations—are also illustrated with examples. The nodal patterns addressed pertain to waves on vibrating plates and membranes, acoustic and electromagnetic modes, wave functions of a "particle in a box" as well as to percolating clusters, and domains in ferromagnets, thus underlining the diversity and far-reaching implications of the problem.

  6. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Digital Electronic Message Service Nodal... AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.503 Digital Electronic Message Service Nodal Stations. 10.6 GHz DEMS Nodal Stations may be...

  7. Canine nodal marginal zone lymphoma: Descriptive insight into the biological behaviour.

    PubMed

    Cozzi, M; Marconato, L; Martini, V; Aresu, L; Riondato, F; Rossi, F; Stefanello, D; Comazzi, S

    2018-06-01

    Canine nodal marginal zone lymphoma (nMZL) is classified as an indolent lymphoma. Such lymphomas are typified by low mitotic rate and slow clinical progression. While the clinical behaviour of canine splenic MZL has been described, characterized by an indolent course and a good prognosis following splenectomy, there are no studies specifically describing nMZL. The aim of this study was to describe the clinical features of and outcome for canine nMZL. Dogs with histologically confirmed nMZL undergoing a complete staging work-up (including blood analysis, flow cytometry [FC] on lymph node [LN], peripheral blood and bone marrow, imaging, histology and immunohistochemistry on a surgically removed peripheral LN) were retrospectively enrolled. Treatment consisted of chemotherapy or chemo-immunotherapy. Endpoints were response rate (RR), time to progression (TTP) and lymphoma-specific survival (LSS). A total of 35 cases were enrolled. At diagnosis, all dogs showed generalized lymphadenopathy. One-third was systemically unwell. All dogs had stage V disease; one-third also had extranodal involvement. The LN population was mainly composed of medium-sized CD21+ cells with scant resident normal lymphocytes. Histology revealed diffuse LN involvement, referring to "late-stage" MZL. Median TTP and LSS were 149 and 259 days, respectively. Increased LDH activity and substage b were significantly associated with a shorter LSS. Dogs with nMZL may show generalized lymphadenopathy and an advanced disease stage. Overall, the outcome is poor, despite the "indolent" designation. The best treatment option still needs to be defined. © 2017 John Wiley & Sons Ltd.

  8. Risk of Subclinical Micrometastatic Disease in the Supraclavicular Nodal Bed According to the Anatomic Distribution in Patients With Advanced Breast Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reed, Valerie K.; Cavalcanti, Jose L.; Strom, Eric A.

    Purpose: To determine the anatomic distribution of gross supraclavicular nodes within the supraclavicular fossa using 2-deoxy-2-[F-18] fluoro-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) scans, and to evaluate likely coverage of specific regions of the supraclavicular fossa using standard radiation fields. Methods and Materials: We identified 33 patients with advanced or metastatic breast cancer who had a PET/CT scan demonstrating hypermetabolic supraclavicular lymph nodes in 2005. The locations of the involved lymph nodes were mapped onto a single CT set of images of the supraclavicular fossa. These lymph nodes were also mapped onto the treatment-planning CT dataset of 4 patients treatedmore » in our institution (2 patients with biopsy-proven supraclavicular nodes and 2 patients with clinically negative supraclavicular nodes). Results: We were able to determine the distribution of 52 supraclavicular lymph nodes in 32 patients. Of 32 patients, 28 (87%) had a history of metastatic disease, and 2 patients had isolated nodal recurrences. Five patients had supraclavicular nodes posterior to the vertebral body transverse process, and several lymph nodes were in close proximity to the medial field border, raising the possibility of geographic miss in these areas. Conclusions: In patients with locally advanced disease, increased coverage of the supraclavicular fossa medially and posteriorly may be warranted.« less

  9. Nodal weighting factor method for ex-core fast neutron fluence evaluation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chiang, R. T.

    The nodal weighting factor method is developed for evaluating ex-core fast neutron flux in a nuclear reactor by utilizing adjoint neutron flux, a fictitious unit detector cross section for neutron energy above 1 or 0.1 MeV, the unit fission source, and relative assembly nodal powers. The method determines each nodal weighting factor for ex-core neutron fast flux evaluation by solving the steady-state adjoint neutron transport equation with a fictitious unit detector cross section for neutron energy above 1 or 0.1 MeV as the adjoint source, by integrating the unit fission source with a typical fission spectrum to the solved adjointmore » flux over all energies, all angles and given nodal volume, and by dividing it with the sum of all nodal weighting factors, which is a normalization factor. Then, the fast neutron flux can be obtained by summing the various relative nodal powers times the corresponding nodal weighting factors of the adjacent significantly contributed peripheral assembly nodes and times a proper fast neutron attenuation coefficient over an operating period. A generic set of nodal weighting factors can be used to evaluate neutron fluence at the same location for similar core design and fuel cycles, but the set of nodal weighting factors needs to be re-calibrated for a transition-fuel-cycle. This newly developed nodal weighting factor method should be a useful and simplified tool for evaluating fast neutron fluence at selected locations of interest in ex-core components of contemporary nuclear power reactors. (authors)« less

  10. Nodal network generator for CAVE3

    NASA Technical Reports Server (NTRS)

    Palmieri, J. V.; Rathjen, K. A.

    1982-01-01

    A new extension of CAVE3 code was developed that automates the creation of a finite difference math model in digital form ready for input to the CAVE3 code. The new software, Nodal Network Generator, is broken into two segments. One segment generates the model geometry using a Tektronix Tablet Digitizer and the other generates the actual finite difference model and allows for graphic verification using Tektronix 4014 Graphic Scope. Use of the Nodal Network Generator is described.

  11. Nodal lines and nodal loops in nonsymmorphic odd-parity superconductors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Micklitz, T.; Norman, M. R.

    2017-01-01

    We discuss the nodal structure of odd-parity superconductors in the presence of nonsymmorphic crystal symmetries, both with and without spin-orbit coupling, and with and without time-reversal symmetry. We comment on the relation of our work to previous work in the literature, and also the implications for unconventional superconductors such as UPt3.

  12. Motion deficit in nodal interphalangeal joint osteoarthritis by digital goniometer in housewives.

    PubMed

    Ventura-Ríos, L; Hayes-Salinas, M; Ferrusquia-Toriz, D; Cariño-Escobar, R I; Cruz-Arenas, E; Gutiérrez-Martínez, J; González-Ramírez, L; Hernández-Díaz, C

    2018-06-01

    Range of motion (ROM) measured objectively in nodal hand osteoarthritis (NHOA) is missing. Evaluation of collateral ligaments by ultrasound (US) is unknown in NHOA also. To compare ROM in interphalangeal joints in housewives with nodal OA, with a control group by a digital system using angle to voltage (Multielgon). The second objective was to assess correlation between collateral radial and ulnar ligaments thickness and ROM. For this cross-sectional observational study, we assessed 60 hands with symptomatic NHOA and 30 hands of healthy housewives matched for age. We obtained clinical and demographic characteristics (a complete standardized physical examination of hand joints, DASH questionnaire, pain surveys, gross grasp hand goniometer, and ROM measurements by Multielgon. Presence of synovitis, power Doppler signal, osteophytes, and collateral ligaments thickness was evaluated by US. We used descriptive statistics, Spearman correlation, X 2 test, t test and odds ratio. Significant less gross grasp and ROM in the right hand were observed in NHOA (p = 0.01 for both). Presence of OA, painful joints, disease duration, and score DASH were significant correlated with reduced ROM (OR 4.12, 4.12, 1.04 and 1.09, respectively). Reduced ROM was statistical significant in thumb MCP and IP joints, second and third DIP in dominant hand. There was no association between collateral radial and ulnar ligaments and reduced ROM. Synovitis and osteophytes were more prevalent in OA group. Multielgon demonstrated the pattern of reduced ROM in nodal OA of housewives particularly in MCP and IP thumb joints, second and third distal interphalangeal joints.

  13. Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node–Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Müller, Arndt-Christian, E-mail: arndt-christian.mueller@med.uni-tuebingen.de; Eckert, Franziska; Paulsen, Frank

    2016-02-01

    Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement − n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 × 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 × 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN–pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapymore » sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series.« less

  14. Evaluation of the reliability of clinical staging of T2 N0 esophageal cancer: a review of the Society of Thoracic Surgeons database.

    PubMed

    Crabtree, Traves D; Kosinski, Andrzej S; Puri, Varun; Burfeind, William; Bharat, Ankit; Patterson, G Alexander; Hofstetter, Wayne; Meyers, Bryan F

    2013-08-01

    Clinical staging of esophageal cancer has improved with positron-emission tomography/computed tomography and endoscopic ultrasound imaging. Despite such progress, small single-center studies have questioned the reliability of clinical staging of T2 N0 esophageal cancer. This study broadly examines the adequacy of clinical staging of T2 N0 disease using The Society of Thoracic Surgeons database. We retrospectively studied 810 clinical stage T2 N0 patients from 2002 to 2011, with 58 excluded because of incomplete pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded. Logistic regression analysis was used to identify factors associated with upstaging at the time of surgical intervention. Among 752 clinical stage T2 N0 patients, 270 (35.9%) received induction therapy before the operation. Of 482 patients who went directly to surgical intervention, 132 (27.4%) were confirmed as pathologic T2 N0, 125 (25.9%) were downstaged (ie, T0-1 N0), and 225 (46.7%) were upstaged at the operation (T3-4 N0 or Tany N1-3). Exclusive tumor upstaging (ie, pathologic T3-4 N0) accounted for 41 patients (18.2%), whereas exclusive nodal upstaging (ie, pathological T1-2 N1-3) accounted for 100 (44.5%). Combined tumor and nodal upstaging (ie, pathological T3-4 N1-3) accounted for 84 patients (37.3%). Among patients who received induction therapy, 103 (38.1%) were upstaged vs 225 (46.7%) without induction therapy (p = 0.026). Comparing the induction therapy group and the primary surgical group, postoperative 30-day mortality (3.7% vs 3.7%, p > 0.99) and morbidity (46.3% vs 45%, p = 0.76) were similar. Despite advances in staging techniques, clinical staging of T2 N0 esophageal cancer remains unreliable. Recognizing T2 N0 as a threshold for induction therapy in esophageal cancer, many surgeons have opted to treat T2 N0 disease with induction therapy, even though one-quarter of these patients will be pathologic T1 N0. Although this study

  15. United States Military Cancer Institute Clinical Trials Group (USMCI GI-01) randomized controlled trial comparing targeted nodal assessment and ultrastaging with standard pathological evaluation for colon cancer.

    PubMed

    Nissan, Aviram; Protic, Mladjan; Bilchik, Anton J; Howard, Robin S; Peoples, George E; Stojadinovic, Alexander

    2012-09-01

    Our randomized controlled trial previously demonstrated improved staging accuracy with targeted nodal assessment and ultrastaging (TNA-us) in colon cancer (CC). Our objective was to test the hypothesis that TNA-us improves disease-free survival (DFS) in CC. In this randomized trial, targeted nodal assessment and ultrastaging resulted in enhanced lymph node diagnostic yield associated with improved staging accuracy, which was further associated with improved disease-free survival in early colon cancer. Clinical parameters of the control (n = 94) and TNA-us (n = 98) groups were comparable. Median (interquartile range) lymph node yield was higher in the TNA-us arm: 16 (12-22) versus 13 (10-18); P = 0.002. Median follow-up was 46 (29-70) months. Overall 5-year DFS was 61% in the control arm and 71% in the TNA-us arm (P = 0.11). Clinical parameters of node-negative patients in the control (n = 51) and TNA-us (n = 55) groups were comparable. Lymph node yield was higher in the TNA-us arm: 15 (12-21) versus 13 (8-18); P = 0.03. Five-year DFS differed significantly between groups with node-negative CC (control 71% vs TNA-us 86%; P = 0.04). Survival among stage II CC alone was higher in the TNA-us group, 83% versus 65%; P = 0.03. Adjuvant chemotherapy use was nearly identical between groups. TNA-us stratified CC prognosis; DFS differed significantly between ultrastaged and conventionally staged node-negative patients [control pN0 72% vs TNA-us pN0(i-) 87%; P = 0.03]. Survival varied according to lymph node yield in patients with node-negative CC [5-year DFS: <12 lymph nodes = 57% vs 12+ lymph nodes = 85%; P = 0.011] but not in stage III CC. TNA-us is associated with improved nodal diagnostic yield and enhanced staging accuracy (stage migration), which is further associated with improved DFS in early CC. This study is registered at clinicaltrials.gov under the registration number: NCT01623258.

  16. Prophylactic Level VII Nodal Dissection as a Prognostic Factor in Papillary Thyroid Carcinoma: a Pilot Study of 27 Patients.

    PubMed

    Fayek, Ihab Samy

    2015-01-01

    Prognostic value of prophylactic level VII nodal dissection in papillary thyroid carcinoma has been highlighted. A total of 27 patients with papillary thyroid carcinoma with N0 neck underwent total thyroidectomy with level VI and VII nodal dissection through same collar neck incision. Multicentricity, bilaterality, extrathyroidal extension, level VI and VII lymph nodes were studied as separate and independent prognostic factors for DFS at 24 months. 21 females and 6 males with a mean age of 34.6 years old, tumor size was 5-24 mm. (mean 12.4 mm.), multicentricity in 11 patients 2-4 foci (mean 2.7), bilaterality in 8 patients and extrathyroidal extension in 8 patients. Dissected level VI LNs 2-8 (mean 5 LNs) and level VII LNs 1-4 (mean 1.9). Metastatic level VI LNs 0-3 (mean 1) and level VII LNs 0-2 (mean 0.5). Follow-up from 6-51 months (mean 25.6) with 7 patients showed recurrence (3 local and 4 distant). Cumulative DFS at 24 months was 87.8% and was significantly affected in relation to bilaterality (p-value<0.001), extrathyroidal extension (p-value<0.001), level VI positive ((p-value<0.001) and level VII positive ((p-value<0.001) LNs. No recurrences were detected during the follow-up period in the absence of level VI and level VII nodal involvement. Level VII prophylactic nodal dissection is an important and integral prognostic factor in papillary thyroid carcinoma. A larger multicenter study is crucial to reach a satisfactory conclusion about the necessity and safety of this approach.

  17. Comparative assessment of genetic and epigenetic variation among regenerants of potato (Solanum tuberosum) derived from long-term nodal tissue-culture and cell selection.

    PubMed

    Dann, Alison L; Wilson, Calum R

    2011-04-01

    Three long-term nodal tissued cultured Russet Burbank potato clones and nine thaxtomin A-treated regenerant lines, derived from the nodal lines, were assessed for genetic and epigenetic (in the form of DNA methylation) differences by AFLP and MSAP. The treated regenerant lines were originally selected for superior resistance to common scab disease and acceptable tuber yield in pot and field trials. The long-term, tissue culture clone lines exhibited genetic (8.75-15.63% polymorphisms) and epigenetic (12.56-26.13% polymorphisms) differences between them and may represent a stress response induced by normal plant growth disruption. The thaxtomin A-treated regenerant lines exhibited much higher significant (p < 0.05) genetic (2-29.38%) and epigenetic (45.22-51.76%) polymorphisms than the nodal cultured parent clones. Methylation-sensitive mutations accumulated within the regenerant lines are significantly correlated (p < 0.05) to disease resistance. However, linking phenotypic differences that could be of benefit to potato growers, to single gene sequence polymorphisms in a tetraploid plant such as the potato would be extremely difficult since it is assumed many desirable traits are under polygenic control.

  18. Response of millet and sorghum to a varying water supply around the primary and nodal roots

    PubMed Central

    Rostamza, M.; Richards, R. A.; Watt, M.

    2013-01-01

    Background and Aims Cereals have two root systems. The primary system originates from the embryo when the seed germinates and can support the plant until it produces grain. The nodal system can emerge from stem nodes throughout the plant's life; its value for yield is unclear and depends on the environment. The aim of this study was to test the role of nodal roots of sorghum and millet in plant growth in response to variation in soil moisture. Sorghum and millet were chosen as both are adapted to dry conditions. Methods Sorghum and millet were grown in a split-pot system that allowed the primary and nodal roots to be watered separately. Key Results When primary and nodal roots were watered (12 % soil water content; SWC), millet nodal roots were seven times longer than those of sorghum and six times longer than millet plants in dry treatments, mainly from an 8-fold increase in branch root length. When soil was allowed to dry in both compartments, millet nodal roots responded and grew 20 % longer branch roots than in the well-watered control. Sorghum nodal roots were unchanged. When only primary roots received water, nodal roots of both species emerged and elongated into extremely dry soil (0·6–1·5 % SWC), possibly with phloem-delivered water from the primary roots in the moist inner pot. Nodal roots were thick, short, branchless and vertical, indicating a tropism that was more pronounced in millet. Total nodal root length increased in both species when the dry soil was covered with plastic, suggesting that stubble retention or leaf mulching could facilitate nodal roots reaching deeper moist layers in dry climates. Greater nodal root length in millet than in sorghum was associated with increased shoot biomass, water uptake and water use efficiency (shoot mass per water). Millet had a more plastic response than sorghum to moisture around the nodal roots due to (1) faster growth and progression through ontogeny for earlier nodal root branch length and (2

  19. Response of millet and sorghum to a varying water supply around the primary and nodal roots.

    PubMed

    Rostamza, M; Richards, R A; Watt, M

    2013-07-01

    Cereals have two root systems. The primary system originates from the embryo when the seed germinates and can support the plant until it produces grain. The nodal system can emerge from stem nodes throughout the plant's life; its value for yield is unclear and depends on the environment. The aim of this study was to test the role of nodal roots of sorghum and millet in plant growth in response to variation in soil moisture. Sorghum and millet were chosen as both are adapted to dry conditions. Sorghum and millet were grown in a split-pot system that allowed the primary and nodal roots to be watered separately. When primary and nodal roots were watered (12 % soil water content; SWC), millet nodal roots were seven times longer than those of sorghum and six times longer than millet plants in dry treatments, mainly from an 8-fold increase in branch root length. When soil was allowed to dry in both compartments, millet nodal roots responded and grew 20 % longer branch roots than in the well-watered control. Sorghum nodal roots were unchanged. When only primary roots received water, nodal roots of both species emerged and elongated into extremely dry soil (0.6-1.5 % SWC), possibly with phloem-delivered water from the primary roots in the moist inner pot. Nodal roots were thick, short, branchless and vertical, indicating a tropism that was more pronounced in millet. Total nodal root length increased in both species when the dry soil was covered with plastic, suggesting that stubble retention or leaf mulching could facilitate nodal roots reaching deeper moist layers in dry climates. Greater nodal root length in millet than in sorghum was associated with increased shoot biomass, water uptake and water use efficiency (shoot mass per water). Millet had a more plastic response than sorghum to moisture around the nodal roots due to (1) faster growth and progression through ontogeny for earlier nodal root branch length and (2) partitioning to nodal root length from primary roots

  20. Elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for squamous cell carcinoma of the thoracic esophagus.

    PubMed

    Onozawa, Masakatsu; Nihei, Keiji; Ishikura, Satoshi; Minashi, Keiko; Yano, Tomonori; Muto, Manabu; Ohtsu, Atsushi; Ogino, Takashi

    2009-08-01

    There are some reports indicating that prophylactic three-field lymph node dissection for esophageal cancer can lead to improved survival. But the benefit of ENI in CRT for thoracic esophageal cancer remains controversial. The purpose of the present study is to retrospectively evaluate the efficacy of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal cancer. Patients with squamous cell carcinoma (SCC) of the thoracic esophagus newly diagnosed between February 1999 and April 2001 in our institution was recruited from our database. Definitive chemoradiotherapy consisted of two cycles of cisplatin/5FU repeated every 5 weeks, with concurrent radiation therapy of 60 Gy in 30 fractions. Up to 40 Gy radiation therapy was delivered to the cervical, periesophageal, mediastinal and perigastric lymph nodes as ENI. One hundred two patients were included in this analysis, and their characteristics were as follows: median age, 65 years; male/female, 85/17; T1/T2/T3/T4, 16/11/61/14; N0/N1, 48/54; M0/M1, 84/18. The median follow-up period for the surviving patients was 41 months. Sixty patients achieved complete response (CR). After achieving CR, only one (1.0%; 95% CI, 0-5.3%) patient experienced elective nodal failure without any other site of recurrence. In CRT for esophageal SCC, ENI is effective for preventing regional nodal failure. Further evaluation of whether ENI leads to an improved overall survival is needed.

  1. Model for breast cancer survival: relative prognostic roles of axillary nodal status, TNM stage, estrogen receptor concentration, and tumor necrosis.

    PubMed

    Shek, L L; Godolphin, W

    1988-10-01

    The independent prognostic effects of certain clinical and pathological variables measured at the time of primary diagnosis were assessed with Cox multivariate regression analysis. The 859 patients with primary breast cancer, on which the proportional hazards model was based, had a median follow-up of 60 months. Axillary nodal status (categorized as N0, N1-3 or N4+) was the most significant and independent factor in overall survival, but inclusion of TNM stage, estrogen receptor (ER) concentration and tumor necrosis significantly improved survival predictions. Predictions made with the model showed striking subset survival differences within stage: 5-year survival from 36% (N4+, loge[ER] = 0, marked necrosis) to 96% (N0, loge[ER] = 6, no necrosis) in TNM I, and from 0 to 70% for the same categories in TNM IV. Results of the model were used to classify patients into four distinct risk groups according to a derived hazard index. An 8-fold variation in survival was seen with the highest (greater than 3) to lowest index values (less than 1). Each hazard index level included patients with varied combinations of the above factors, but could be considered to denote the same degree of risk of breast cancer mortality. A model with ER concentration, nodal status, and tumor necrosis was found to best predict survival after disease recurrence in 369 patients, thus confirming the enduring biological significance of these factors.

  2. Tumor histology predicts mediastinal nodal status and may be used to guide limited lymphadenectomy in patients with clinical stage I non-small cell lung cancer.

    PubMed

    Cheng, Xinghua; Zheng, Difan; Li, Yuan; Li, Hang; Sun, Yihua; Xiang, Jiaqing; Chen, Haiquan

    2018-06-01

    Methods to minimize surgical trauma from mediastinal lymphadenectomy in patients with early-stage lung cancer are still immature. This study aimed to identify predictors of negative pathologic N2, which may be used to select patients for limited mediastinal lymphadenectomy. Clinicopathologic features of 1430 patients with resected clinical stage I non-small cell lung cancer and complete mediastinal lymphadenectomy were retrospectively analyzed for variables associated with negative N2 nodal metastasis (2008-2015). Overall and recurrence-free survival in patients after complete or limited mediastinal lymphadenectomy were assessed via Kaplan-Meier survival analysis and log-rank testing. The accuracy of frozen section diagnosis for predicting final pathology was retrospectively assessed in 126 randomly selected patients after the surgery. Multivariable analysis revealed that tumor size ≤2 cm, negative pN1, lymphovascular invasion, and lepidic adenocarcinoma were associated with negative mediastinal nodal metastasis. Notably, none of the patients with histology of adenocarcinoma in situ, minimally invasive adenocarcinoma, or lepidic pattern-predominant adenocarcinoma on final pathology had pN2 disease, and the 5-year overall and recurrence free-survival of these patients (99.3% and 99.3%, respectively) was not different from those after limited mediastinal lymphadenectomy (98.7% and 100%, P = .582 and .511, respectively). If these subtypes were classified together as the low-risk group, the concordance rate between frozen section and final pathology diagnosis was 88.9% in the retrospective test cohort. Tumor histology may predict negative mediastinal metastasis in patients with early-stage lung cancer. Future prospective studies are merited to validate the feasibility of using frozen section to select patients for limited mediastinal lymphadenectomy. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  3. Super-nodal methods for space-time kinetics

    NASA Astrophysics Data System (ADS)

    Mertyurek, Ugur

    The purpose of this research has been to develop an advanced Super-Nodal method to reduce the run time of 3-D core neutronics models, such as in the NESTLE reactor core simulator and FORMOSA nuclear fuel management optimization codes. Computational performance of the neutronics model is increased by reducing the number of spatial nodes used in the core modeling. However, as the number of spatial nodes decreases, the error in the solution increases. The Super-Nodal method reduces the error associated with the use of coarse nodes in the analyses by providing a new set of cross sections and ADFs (Assembly Discontinuity Factors) for the new nodalization. These so called homogenization parameters are obtained by employing consistent collapsing technique. During this research a new type of singularity, namely "fundamental mode singularity", is addressed in the ANM (Analytical Nodal Method) solution. The "Coordinate Shifting" approach is developed as a method to address this singularity. Also, the "Buckling Shifting" approach is developed as an alternative and more accurate method to address the zero buckling singularity, which is a more common and well known singularity problem in the ANM solution. In the course of addressing the treatment of these singularities, an effort was made to provide better and more robust results from the Super-Nodal method by developing several new methods for determining the transverse leakage and collapsed diffusion coefficient, which generally are the two main approximations in the ANM methodology. Unfortunately, the proposed new transverse leakage and diffusion coefficient approximations failed to provide a consistent improvement to the current methodology. However, improvement in the Super-Nodal solution is achieved by updating the homogenization parameters at several time points during a transient. The update is achieved by employing a refinement technique similar to pin-power reconstruction. A simple error analysis based on the relative

  4. Elevated CO2 alters distribution of nodal leaf area and enhances nitrogen uptake contributing to yield increase of soybean cultivars grown in Mollisols.

    PubMed

    Jin, Jian; Li, Yansheng; Liu, Xiaobing; Wang, Guanghua; Tang, Caixian; Yu, Zhenhua; Wang, Xiaojuan; Herbert, Stephen J

    2017-01-01

    Understanding how elevated CO2 affects dynamics of nodal leaf growth and N assimilation is crucial for the construction of high-yielding canopy via breeding and N management to cope with the future climate change. Two soybean cultivars were grown in two Mollisols differing in soil organic carbon (SOC), and exposed to ambient CO2 (380 ppm) or elevated CO2 (580 ppm) throughout the growth stages. Elevated CO2 induced 4-5 more nodes, and nearly doubled the number of branches. Leaf area duration at the upper nodes from R5 to R6 was 4.3-fold greater and that on branches 2.4-fold higher under elevated CO2 than ambient CO2, irrespective of cultivar and soil type. As a result, elevated CO2 markedly increased the number of pods and seeds at these corresponding positions. The yield response to elevated CO2 varied between the cultivars but not soils. The cultivar-specific response was likely attributed to N content per unit leaf area, the capacity of C sink in seeds and N assimilation. Elevated CO2 did not change protein concentration in seeds of either cultivar. These results indicate that elevated CO2 increases leaf area towards the upper nodes and branches which in turn contributes yield increase.

  5. Fluorodeoxyglucose positron emission tomography–computed tomography in evaluation of pelvic and para-aortic nodal involvement in early stage and operable cervical cancer: Comparison with surgicopathological findings

    PubMed Central

    Bansal, Vandana; Damania, Kaizad; Sharma, Anshu Rajnish

    2011-01-01

    Introduction: Nodal metastases in cervical cancer have prognostic implications. Imaging is used as an adjunct to clinical staging for evaluation of nodal metastases. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has an advantage of superior resolution of its CT component and detecting nodal disease based on increased glycolytic activity rather than node size. But there are limited studies describing its limitations in early stage cervical cancers. Objective: We have done meta-analysis with an objective to evaluate the efficacy of FDG PET/CT and its current clinical role in early stage and operable cervical cancer. Materials and Methods: Studies in which FDG PET/CT was performed before surgery in patients with early stage cervical cancers were included for analysis. PET findings were confirmed with histopathological diagnosis rather than clinical follow-up. FDG PET/CT showed lower sensitivity and clinically unacceptable negative predictive value in detecting nodal metastases in early stage cervical cancer and therefore, can not replace surgicopathological staging. False negative results in presence of microscopic disease and sub-centimeter diseased nodes are still the area of concern for metabolic imaging. However, these studies are single institutional and performed in a small group of patients. There is enough available evidence of clinical utility of FDG PET/CT in locally advanced cervical cancer. But these results can not be extrapolated for early stage disease. Conclusion: The current data suggest that FDG PET/CT is suboptimal in nodal staging in early stage cervical cancer. PMID:23559711

  6. Reactivation of Embryonic Nodal Signaling is Associated with Tumor Progression and Promotes the Growth of Prostate Cancer Cells

    PubMed Central

    Lawrence, Mitchell G.; Margaryan, Naira V.; Loessner, Daniela; Collins, Angus; Kerr, Kris M.; Turner, Megan; Seftor, Elisabeth A.; Stephens, Carson R.; Lai, John; BioResource, APC; Postovit, Lynne-Marie; Clements, Judith A.; Hendrix, Mary J.C.

    2011-01-01

    Background Nodal is a member of the Transforming Growth Factor β (TGFβ) superfamily that directs embryonic patterning and promotes the plasticity and tumorigenicity of tumor cells, but its role in the prostate is unknown. The goal of this study was to characterize the expression and function of Nodal in prostate cancer and determine whether, like other TGFβ ligands, it modulates androgen receptor (AR) activity. Methods Nodal expression was investigated using immunohistochemistry of tissue microarrays and Western blots of prostate cell lines. The functional role of Nodal was examined using Matrigel and soft agar growth assays. Cross-talk between Nodal and AR signaling was assessed with luciferase reporter assays and expression of endogenous androgen regulated genes. Results Significantly increased Nodal expression was observed in cancer compared with benign prostate specimens. Nodal was only expressed by DU145 and PC3 cells. All cell lines expressed Nodal’s co-receptor, Cripto-1, but lacked Lefty, a critical negative regulator of Nodal signaling. Recombinant human Nodal triggered downstream Smad2 phosphorylation in DU145 and LNCaP cells, and stable transfection of pre-pro-Nodal enhanced the growth of LNCaP cells in Matrigel and soft agar. Finally, Nodal attenuated AR signaling, reducing the activity of a PSA promoter construct in luciferase assays and down-regulating the endogenous expression of androgen regulated genes. Conclusions An aberrant Nodal signaling pathway is re-expressed and functionally active in prostate cancer cells. PMID:21656830

  7. A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality

    NASA Astrophysics Data System (ADS)

    Noël, Emily S.; Verhoeven, Manon; Lagendijk, Anne Karine; Tessadori, Federico; Smith, Kelly; Choorapoikayil, Suma; den Hertog, Jeroen; Bakkers, Jeroen

    2013-11-01

    Breaking left-right symmetry in bilateria is a major event during embryo development that is required for asymmetric organ position, directional organ looping and lateralized organ function in the adult. Asymmetric expression of Nodal-related genes is hypothesized to be the driving force behind regulation of organ laterality. Here we identify a Nodal-independent mechanism that drives asymmetric heart looping in zebrafish embryos. In a unique mutant defective for the Nodal-related southpaw gene, preferential dextral looping in the heart is maintained, whereas gut and brain asymmetries are randomized. As genetic and pharmacological inhibition of Nodal signalling does not abolish heart asymmetry, a yet undiscovered mechanism controls heart chirality. This mechanism is tissue intrinsic, as explanted hearts maintain ex vivo retain chiral looping behaviour and require actin polymerization and myosin II activity. We find that Nodal signalling regulates actin gene expression, supporting a model in which Nodal signalling amplifies this tissue-intrinsic mechanism of heart looping.

  8. Nodal aberration theory for wild-filed asymmetric optical systems

    NASA Astrophysics Data System (ADS)

    Chen, Yang; Cheng, Xuemin; Hao, Qun

    2016-10-01

    Nodal Aberration Theory (NAT) was used to calculate the zero field position in Full Field Display (FFD) for the given aberration term. Aiming at wide-filed non-rotational symmetric decentered optical systems, we have presented the nodal geography behavior of the family of third-order and fifth-order aberrations. Meanwhile, we have calculated the wavefront aberration expressions when one optical element in the system is tilted, which was not at the entrance pupil. By using a three-piece-cellphone lens example in optical design software CodeV, the nodal geography is testified under several situations; and the wavefront aberrations are calculated when the optical element is tilted. The properties of the nodal aberrations are analyzed by using Fringe Zernike coefficients, which are directly related with the wavefront aberration terms and usually obtained by real ray trace and wavefront surface fitting.

  9. Maternal Gdf3 is an obligatory cofactor in Nodal signaling for embryonic axis formation in zebrafish

    PubMed Central

    Bisgrove, Brent W; Su, Yi-Chu

    2017-01-01

    Zebrafish Gdf3 (Dvr1) is a member of the TGFβ superfamily of cell signaling ligands that includes Xenopus Vg1 and mammalian Gdf1/3. Surprisingly, engineered homozygous mutants in zebrafish have no apparent phenotype. Elimination of Gdf3 in oocytes of maternal-zygotic mutants results in embryonic lethality that can be fully rescued with gdf3 RNA, demonstrating that Gdf3 is required only early in development, beyond which mutants are viable and fertile. Gdf3 mutants are refractory to Nodal ligands and Nodal repressor Lefty1. Signaling driven by TGFβ ligand Activin and constitutively active receptors Alk4 and Alk2 remain intact in gdf3 mutants, indicating that Gdf3 functions at the same pathway step as Nodal. Targeting gdf3 and ndr2 RNA to specific lineages indicates that exogenous gdf3 is able to fully rescue mutants only when co-expressed with endogenous Nodal. Together, these findings demonstrate that Gdf3 is an essential cofactor of Nodal signaling during establishment of the embryonic axis. PMID:29140249

  10. Details of recurrence sites after elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D-CRT) combined with chemotherapy for thoracic esophageal squamous cell carcinoma--a retrospective analysis.

    PubMed

    Yamashita, Hideomi; Okuma, Kae; Wakui, Reiko; Kobayashi-Shibata, Shino; Ohtomo, Kuni; Nakagawa, Keiichi

    2011-02-01

    To describe patterns of recurrence of elective nodal irradiation (ENI) in definitive chemoradiotherapy (CRT) for thoracic esophageal squamous cell carcinoma (SqCC) using 3D-conformal radiotherapy. One hundred and twenty-six consecutive patients with stages I-IVB thoracic esophageal SqCC newly diagnosed between June 2000 and July 2009 and treated with 3D-CRT in our institution were recruited from our database. Definitive CRT consisted of two cycles of nedaplatin/5FU repeated every 4 weeks, with concurrent radiation therapy of 50-50.4 Gy in 25-28 fractions. Until completion, radiotherapy was delivered to the N1 and M1a lymph nodes as ENI in addition to gross tumor volume. All 126 patients were included in this analysis, and their tumors were staged as follows: T1/T2/T3/T4, 28/18/54/26; N0/N1, 50/76; M0/M1a/M1b, 91/5/30. The mean follow-up period for the 63 surviving patients was 28.3 (±22.8) months. Eighty-seven patients (69%) achieved complete response (CR) without any residual tumor at least once after completion of CRT. After achieving CR, each of 40 patients experienced failures (local=20 and distant=20) and no patient experienced elective nodal failure without having any other site of recurrence. The upper thoracic esophageal carcinoma showed significantly more (34%) relapses at the local site than the middle (9%) or lower thoracic (11%) carcinomas. The 2-year and 3-year overall survival was 56% and 43%, respectively. The 1-year, 2-year and 3-year disease-free survival was 46%, 38% and 33%, respectively. In CRT for esophageal SqCC, ENI was effective for preventing regional nodal failure. The upper thoracic esophageal carcinomas had significantly more local recurrences than the middle or lower thoracic sites. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Assessment of Ultrasound Features Predicting Axillary Nodal Metastasis in Breast Cancer: The Impact of Cortical Thickness

    PubMed Central

    Stachs, A.; Thi, A. Tra-Ha; Dieterich, M.; Stubert, J.; Hartmann, S.; Glass, Ä.; Reimer, T.; Gerber, B.

    2015-01-01

    Purpose: To evaluate the accuracy of axillary ultrasound (AUS) in detecting nodal metastasis in patients with early-stage breast cancer and to identify AUS features with high predictive power. Materials and Methods: Prospective single-center preliminary study in 105 patients with a primary diagnosis of breast cancer and clinically negative axilla. AUS was performed using a 12 MHz linear-array transducer before ultrasound-guided needle biopsy. Nodal characteristics (shape, longitudinal-transverse [LT] axis ratio, margins, cortical thickness, hyperechoic hilum) were correlated with histopathological nodal status after SLNB or axillary lymph node dissection (ALND). Results: Nodal metastases were present in 42/105 patients (40.0%). Univariate analyses showed that absence of hyperechoic hilum, round shape, LT axis ratio<2, sharp margins and cortical thickness>3 mm were associated with lymph node metastasis. Multivariate logistic regression analysis revealed cortical thickness > 3 mm as an independent predictive parameter for nodal involvement. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 66.7, 74.6, 63.6, 77.0% and 71.4% respectively when cortical thickness > 3 mm was applied as the criterion for AUS positivity. Axillary tumor volume was low in patients with pT1/2 tumors and negative AUS, since only 3.2% of patients had > 2 metastatic lymph nodes. Conclusion: Cortical thickness>3 mm is a reliable predictor of nodal metastatic involvement. Negative AUS does not exclude lymph node metastases, but extensive axillary tumor volume is rare. PMID:27689144

  12. Orbital nodal surfaces: Topological challenges for density functionals

    NASA Astrophysics Data System (ADS)

    Aschebrock, Thilo; Armiento, Rickard; Kümmel, Stephan

    2017-06-01

    Nodal surfaces of orbitals, in particular of the highest occupied one, play a special role in Kohn-Sham density-functional theory. The exact Kohn-Sham exchange potential, for example, shows a protruding ridge along such nodal surfaces, leading to the counterintuitive feature of a potential that goes to different asymptotic limits in different directions. We show here that nodal surfaces can heavily affect the potential of semilocal density-functional approximations. For the functional derivatives of the Armiento-Kümmel (AK13) [Phys. Rev. Lett. 111, 036402 (2013), 10.1103/PhysRevLett.111.036402] and Becke88 [Phys. Rev. A 38, 3098 (1988), 10.1103/PhysRevA.38.3098] energy functionals, i.e., the corresponding semilocal exchange potentials, as well as the Becke-Johnson [J. Chem. Phys. 124, 221101 (2006), 10.1063/1.2213970] and van Leeuwen-Baerends (LB94) [Phys. Rev. A 49, 2421 (1994), 10.1103/PhysRevA.49.2421] model potentials, we explicitly demonstrate exponential divergences in the vicinity of nodal surfaces. We further point out that many other semilocal potentials have similar features. Such divergences pose a challenge for the convergence of numerical solutions of the Kohn-Sham equations. We prove that for exchange functionals of the generalized gradient approximation (GGA) form, enforcing correct asymptotic behavior of the potential or energy density necessarily leads to irregular behavior on or near orbital nodal surfaces. We formulate constraints on the GGA exchange enhancement factor for avoiding such divergences.

  13. Influence of FDG-PET on primary nodal target volume definition for head and neck carcinomas.

    PubMed

    van Egmond, Sylvia L; Piscaer, Vera; Janssen, Luuk M; Stegeman, Inge; Hobbelink, Monique G; Grolman, Wilko; Terhaard, Chris H

    The role of 2-[ 18 F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in routine diagnostic staging remains controversial. In case of discordance between FDG-PET and CT, a compromise has to be made between the risk of false positive FDG-PET and the risk of delaying appropriate salvage intervention. Second, with intensity modulated radiation therapy (IMRT), smaller radiation fields allow tissue sparing, but could also lead to more marginal failures. We retrospectively studied 283 patients with head and neck carcinoma scheduled for radiotherapy between 2002 and 2010. We analyzed the influence of FDG-PET/CT versus CT alone on defining nodal target volume definition and evaluated its long-term clinical results. Second, the location of nodal recurrences was related to the radiation regional dose distribution. In 92 patients, CT and FDG-PET, performed in mold, showed discordant results. In 33%, nodal staging was altered by FDG-PET. In 24%, FDG-PET also led to an alteration in nodal treatment, including a nodal upstage of 18% and downstage of 6%. In eight of these 92 patients, a regional recurrence occurred. Only two patients had a recurrence in the discordant node on FDG-PET and CT and both received a boost (high dose radiation). These results support the complementary value of FDG-PET/CT compared to CT alone in defining nodal target volume definition for radiotherapy of head and neck cancer.

  14. Topological and trivial magnetic oscillations in nodal loop semimetals

    NASA Astrophysics Data System (ADS)

    Oroszlány, László; Dóra, Balázs; Cserti, József; Cortijo, Alberto

    2018-05-01

    Nodal loop semimetals are close descendants of Weyl semimetals and possess a topologically dressed band structure. We argue by combining the conventional theory of magnetic oscillation with topological arguments that nodal loop semimetals host coexisting topological and trivial magnetic oscillations. These originate from mapping the topological properties of the extremal Fermi surface cross sections onto the physics of two dimensional semi-Dirac systems, stemming from merging two massless Dirac cones. By tuning the chemical potential and the direction of magnetic field, a sharp transition is identified from purely trivial oscillations, arising from the Landau levels of a normal two dimensional (2D) electron gas, to a phase where oscillations of topological and trivial origin coexist, originating from 2D massless Dirac and semi-Dirac points, respectively. These could in principle be directly identified in current experiments.

  15. Rapid enhancement of nodal quasiparticle mass with heavily underdoping in Bi2212

    NASA Astrophysics Data System (ADS)

    Anzai, Hiroaki; Arita, Masashi; Namatame, Hirofumi; Taniguchi, Masaki; Ishikado, Motoyuki; Fujita, Kazuhiro; Ishida, Shigeyuki; Uchida, Shin-ichi; Ino, Akihiro

    2018-05-01

    We report substantial advance of our low-energy angle-resolved photoemission study of nodal quasiparticles in Bi2Sr2CaCu2O8+δ. The new data cover the samples from underdoped down to heavily underdoped levels. We also present the nodal Fermi velocities that determined by using an excitation-photon energy of hν = 7.0 eV over a wide doping range. The consistency between the results with hν = 8.1 and 7.0 eV allows us to rule out the effect of photoemission matrix elements. In comparison with the data previously reported, the nodal effective mass increases by a factor of ∼ 1.5 in going from optimally doped to heavily underdoped levels. We find a rapid enhancement of the nodal quasiparticle mass at low doping levels near the superconductor-to-insulator transition. The effective coupling spectrum, λ (ω) , is extracted directly from the energy derivatives of the quasiparticle dispersion and scattering rate, as a causal function of the mass enhancement factor. A steplike increase in Reλ (ω) around ∼ 65 meV is demonstrated clearly by the Kramers-Kronig transform of Imλ (ω) . To extract the low-energy renormalization effect, we calculated a simple model for the electron-boson interaction. This model reveals that the contribution of the renormalization at | ω | ≤ 15 meV to the quasiparticle mass is larger than that around 65 meV in underdoped samples.

  16. Cerberus-Nodal-Lefty-Pitx signaling cascade controls left-right asymmetry in amphioxus.

    PubMed

    Li, Guang; Liu, Xian; Xing, Chaofan; Zhang, Huayang; Shimeld, Sebastian M; Wang, Yiquan

    2017-04-04

    Many bilaterally symmetrical animals develop genetically programmed left-right asymmetries. In vertebrates, this process is under the control of Nodal signaling, which is restricted to the left side by Nodal antagonists Cerberus and Lefty. Amphioxus, the earliest diverging chordate lineage, has profound left-right asymmetry as a larva. We show that Cerberus , Nodal , Lefty , and their target transcription factor Pitx are sequentially activated in amphioxus embryos. We then address their function by transcription activator-like effector nucleases (TALEN)-based knockout and heat-shock promoter (HSP)-driven overexpression. Knockout of Cerberus leads to ectopic right-sided expression of Nodal , Lefty , and Pitx , whereas overexpression of Cerberus represses their left-sided expression. Overexpression of Nodal in turn represses Cerberus and activates Lefty and Pitx ectopically on the right side. We also show Lefty represses Nodal , whereas Pitx activates Nodal These data combine in a model in which Cerberus determines whether the left-sided gene expression cassette is activated or repressed. These regulatory steps are essential for normal left-right asymmetry to develop, as when they are disrupted embryos may instead form two phenotypic left sides or two phenotypic right sides. Our study shows the regulatory cassette controlling left-right asymmetry was in place in the ancestor of amphioxus and vertebrates. This includes the Nodal inhibitors Cerberus and Lefty, both of which operate in feedback loops with Nodal and combine to establish asymmetric Pitx expression. Cerberus and Lefty are missing from most invertebrate lineages, marking this mechanism as an innovation in the lineage leading to modern chordates.

  17. Modification of atrioventricular nodal electrophysiology by selective radiofrequency delivery on the anterior or posterior approaches.

    PubMed

    Chorro, F J; Sanchis, J; Such, L; Artal, L; Llavador, J J; Llavador, E; Monmeneu, J V; López-Merino, V

    1997-05-01

    An analysis was made in 14 isolated and perfused rabbit hearts of the electrophysiological effects of selective radiofrequency (RF) delivery in the anterior (group I, n = 7) or posterior zone (group II, n = 7) of the Koch triangle, with the aim of modifying atrioventricular nodal (AVN) conduction without suppressing 1:1 transmission. After opening the right atrium, RF was delivered (0.5 W) with a 1-mm diameter unipolar electrode positioned in the selected zone until a prolongation of no less than 15% was obtained in the Wenckebach cycle length (WCL). Before and after (30 min) RF, anterograde and retrograde AVN refractoriness and conduction were evaluated, stimulating from the crista terminalis (CT), the interatrial septum (IAS), and from the RV epicardium. After RF, the following percentage increments were observed in group I: AH(CT) = 36% +/- 9%, AH(IAS) = 38% +/- 11%, WCL(CT) = 28% +/- 8%, WCL(IAS) = 22% +/- 6%, functional refractory period (FRP) of the AVN(CT) = 13% +/- 11%, FRP-AVN(IAS) = 13% +/- 8%, retrograde WCL = 20% +/- 19%, and retrograde FRPVA = 13% +/- 16%. The increments observed in group II and the significances of the differences with respect to group I were: AH(CT) = 11% +/- 14% (P < 0.01), AH(IAS) = 19% +/- 32% (NS), WCL(CT) = 42% +/- 14% (P < 0.05), WCL(IAS) = 42% +/- 16% (P < 0.01), FRP-AVN(CT) = 28% +/- 28% (NS), FRP-AVN(LAS) = 21% +/- 19% (NS), retrograde WCL = 35% +/- 24% (NS), and retrograde FRP = 16% +/- 13% (NS). In both groups, the AH interval variations were not correlated with those of the rest of the parameters analyzed. Truncated nodal function curves suggestive of a dual AV nodal pathway were obtained in three experiments, though in only one of them was this observed under basal conditions. In the other two experiments, with dual AV nodal physiology only after RF (one from each group), AV nodal reentrant tachycardias were triggered with atrial extrastimulus at coupling intervals equal to or shorter than at those that cause a sudden

  18. Lymphovascular Space Invasion is an Independent Risk Factor for Nodal Disease and Poor Outcomes in Endometrioid Endometrial Cancer

    PubMed Central

    Guntupalli, Saketh R.; Zighelboim, Israel; Kizer, Nora T.; Zhang, Qin; Powell, Matthew A.; Thaker, Premal H.; Goodfellow, Paul J.; Mutch, David G.

    2014-01-01

    Objective Adjuvant radiotherapy improves local control but not survival in women with endometrial cancer. This benefit was shown in staged patients with "high intermediate risk" (HIR) disease. Other studies have challenged the need for systematic staging including lymphadenectomy. We sought to determine whether LVSI alone or in combination with other histologic factors predicts lymph node (LN) metastasis in patients with endometrioid endometrial cancer. Methods A retrospective review was conducted of patients with endometrioid endometrial carcinoma who had confirmed presence/absence of LVSI and clinicopathologic data necessary to identify HIR criteria. Kaplan-Meier curves were generated and univariate and multivariate analyses performed as appropriate. Results We identified 757 eligible patients and 628 underwent systematic lymphadenectomy for staging purposes. In the surgically staged group, 242 (38%) patients met uterine HIR criteria and 196 (31%) had LVSI. Both HIR and LVSI were significantly associated with LN metastasis. Among the HIR positive group, 59 had LN metastasis (OR 4.46, 95% CI 2.72–7.32, P<0.0001). Sixty-six LVSI positive patients had nodal metastasis (OR 11.04, 95% CI 6.39–19.07, P<0.0001). The NPV of LVSI and HIR negative specimens was 95.6% and 93.4% respectively. In multivariate analysis, PFS and OS were significantly reduced in both LVSI positive (P<0.0001) and HIR patients (P<0.0001) when compared to patients who were LVSI and HIR negative Conclusions HIR status and LVSI are highly associated with LN metastasis. These features are useful in assessing risk of metastatic disease and may serve as a surrogate for prediction of extrauterine disease. PMID:22030404

  19. Nodal Topological Phases in s-wave Superfluid of Ultracold Fermionic Gases

    NASA Astrophysics Data System (ADS)

    Huang, Bei-Bing; Yang, Xiao-Sen

    2018-02-01

    The gapless Weyl superfluid has been widely studied in the three-dimensional ultracold fermionic superfluid. In contrast to Weyl superfluid, there exists another kind of gapless superfluid with topologically protected nodal lines, which can be regarded as the superfluid counterpart of nodal line semimetal in the condensed matter physics, just as Weyl superfluid with Weyl semimetal. In this paper we study the ground states of the cold fermionic gases in cubic optical lattices with one-dimensional spin-orbit coupling and transverse Zeeman field and map out the topological phase diagram of the system. We demonstrate that in addition to a fully gapped topologically trivial phase, some different nodal line superfluid phases appear when the Zeeman field is adjusted. The presence of topologically stable nodal lines implies the dispersionless zero-energy flat band in a finite region of the surface Brillouin zone. Experimentally these nodal line superfluid states can be detected via the momentum-resolved radio-frequency spectroscopy. The nodal line topological superfluid provide fertile grounds for exploring exotic quantum matters in the context of ultracold atoms. Supported by National Natural Science Foundation of China under Grant Nos. 11547047 and 11504143

  20. Tumour thickness as a predictor of nodal metastases in oral cancer: comparison between tongue and floor of mouth subsites.

    PubMed

    Balasubramanian, Deepak; Ebrahimi, Ardalan; Gupta, Ruta; Gao, Kan; Elliott, Michael; Palme, Carsten E; Clark, Jonathan R

    2014-12-01

    To identify whether tumour thickness as a predictor of nodal metastases in oral squamous cell carcinoma differs between tongue and floor of mouth (FOM) subsites. Retrospective review of 343 patients treated between 1987 and 2012. The neck was considered positive in the presence of pathologically proven nodal metastases on neck dissection or during follow-up. There were 222 oral tongue and 121 FOM tumours. In patients with FOM tumours 2.1-4mm thick, the rate of nodal metastases was 41.7%. In contrast, for tongue cancers of a similar thickness the rate was only 11.2%. This increased to 38.5% in patients with tongue cancers that were 4.1-6mm thick. Comparing these two subsites, FOM cancers cross the critical 20% threshold of probability for nodal metastases between 1 and 2mm whereas tongue cancers cross the 20% threshold just under 4mm thickness. On logistic regression adjusting for relevant covariates, there was a significant difference in the propensity for nodal metastases based on tumour thickness according to subsite (p=0.028). Thin FOM tumours (2.1-4mm) have a high rate of nodal metastases. Elective neck dissection is appropriate in FOM tumours ⩾2mm thick and in tongue tumours ⩾4mm thick. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Topological Phase Transitions in Line-nodal Superconductors

    NASA Astrophysics Data System (ADS)

    Cho, Gil Young; Han, Sangeun; Moon, Eun-Gook

    Fathoming interplay between symmetry and topology of many-electron wave-functions deepens our understanding in quantum nature of many particle systems. Topology often protects zero-energy excitation, and in a certain class, symmetry is intrinsically tied to the topological protection. Namely, unless symmetry is broken, topological nature is intact. We study one specific case of such class, symmetry-protected line-nodal superconductors in three spatial dimensions (3d). Mismatch between phase spaces of order parameter fluctuation and line-nodal fermion excitation induces an exotic universality class in a drastic contrast to one of the conventional ϕ4 theory in 3d. Hyper-scaling violation and relativistic dynamic scaling with unusually large quantum critical region are main characteristics, and their implication in experiments is discussed. For example, continuous phase transition out of line-nodal superconductors has a linear phase boundary in a temperature-tuning parameter phase-diagram. This work was supported by the Brain Korea 21 PLUS Project of Korea Government and KAIST start-up funding.

  2. Targeting nodal in conjunction with dacarbazine induces synergistic anticancer effects in metastatic melanoma.

    PubMed

    Hardy, Katharine M; Strizzi, Luigi; Margaryan, Naira V; Gupta, Kanika; Murphy, George F; Scolyer, Richard A; Hendrix, Mary J C

    2015-04-01

    Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. Despite a complete response in fewer than 5% of patients, the chemotherapeutic agent dacarbazine (DTIC) remains the reference drug after almost 40 years. More recently, FDA-approved drugs have shown promise but patient outcome remains modest, predominantly due to drug resistance. As such, combinatorial targeting has received increased attention, and will advance with the identification of new molecular targets. One attractive target for improving melanoma therapy is the growth factor Nodal, whose normal expression is largely restricted to embryonic development, but is reactivated in metastatic melanoma. In this study, we sought to determine how Nodal-positive human melanoma cells respond to DTIC treatment and to ascertain whether targeting Nodal in combination with DTIC would be more effective than monotherapy. A single treatment with DTIC inhibited cell growth but did not induce apoptosis. Rather than reducing Nodal expression, DTIC increased the size of the Nodal-positive subpopulation, an observation coincident with increased cellular invasion. Importantly, clinical tissue specimens from patients with melanomas refractory to DTIC therapy stained positive for Nodal expression, both in pre- and post-DTIC tumors, underscoring the value of targeting Nodal. In vitro, anti-Nodal antibodies alone had some adverse effects on proliferation and apoptosis, but combining DTIC treatment with anti-Nodal antibodies decreased cell growth and increased apoptosis synergistically, at concentrations incapable of producing meaningful effects as monotherapy. Targeting Nodal in combination with DTIC therapy holds promise for the treatment of metastatic melanoma. ©2015 American Association for Cancer Research.

  3. On the Viability of Using Autonomous Three-Component Nodal Geophones to Calculate Teleseismic Ps Receiver Functions with an Application to the Old Faithful Hydrothermal System and the Cascadia Subduction Zone

    NASA Astrophysics Data System (ADS)

    Ward, K. M.; Lin, F. C.

    2017-12-01

    Recent advances in seismic data-acquisition technology paired with an increasing interest from the academic passive source seismological community have opened up new scientific targets and imaging possibilities, often referred to as Large-N experiments (large number of instruments). The success of these and other deployments has motivated individual researchers, as well as the larger seismological community, to invest in the next generation of nodal geophones. Although the new instruments have battery life and bandwidth limitations compared to broadband instruments, the relatively low deployment and procurement cost of these new nodal geophones provides an additional novel tool for researchers. Here, we explore the viability of using autonomous three-component nodal geophones to calculate teleseismic Ps receiver functions by comparison of co-located broadband stations and highlight some potential advantages with a dense nodal array deployed around the Upper Geyser basin in Yellowstone National Park. Two key findings from this example include (1) very dense nodal arrays can be used to image small-scale features in the shallow crust that typical broadband station spacing would alias, and (2) nodal arrays with a larger footprint could be used to image deeper features with greater or equal detail as typical broadband deployments but at a reduced deployment cost. The success of the previous example has motivated a larger 2-D line across the Cascadia subduction zone. In the summer of 2017, we deployed 174 nodal geophones with an average site spacing of 750 m. Synthetic tests with dense station spacing ( 1 km) reveal subtler features of the system that is consistent with our preliminary receiver function results from our Cascadia deployment. With the increasing availability of nodal geophones to individual researchers and the successful demonstration that nodal geophones are a viable instrument for receiver function studies, numerous scientific targets can be investigated

  4. The nodal count {0,1,2,3,…} implies the graph is a tree

    PubMed Central

    Band, Ram

    2014-01-01

    Sturm's oscillation theorem states that the nth eigenfunction of a Sturm–Liouville operator on the interval has n−1 zeros (nodes) (Sturm 1836 J. Math. Pures Appl. 1, 106–186; 373–444). This result was generalized for all metric tree graphs (Pokornyĭ et al. 1996 Mat. Zametki 60, 468–470 (doi:10.1007/BF02320380); Schapotschnikow 2006 Waves Random Complex Media 16, 167–178 (doi:10.1080/1745530600702535)) and an analogous theorem was proved for discrete tree graphs (Berkolaiko 2007 Commun. Math. Phys. 278, 803–819 (doi:10.1007/S00220-007-0391-3); Dhar & Ramaswamy 1985 Phys. Rev. Lett. 54, 1346–1349 (doi:10.1103/PhysRevLett.54.1346); Fiedler 1975 Czechoslovak Math. J. 25, 607–618). We prove the converse theorems for both discrete and metric graphs. Namely if for all n, the nth eigenfunction of the graph has n−1 zeros, then the graph is a tree. Our proofs use a recently obtained connection between the graph's nodal count and the magnetic stability of its eigenvalues (Berkolaiko 2013 Anal. PDE 6, 1213–1233 (doi:10.2140/apde.2013.6.1213); Berkolaiko & Weyand 2014 Phil. Trans. R. Soc. A 372, 20120522 (doi:10.1098/rsta.2012.0522); Colin de Verdière 2013 Anal. PDE 6, 1235–1242 (doi:10.2140/apde.2013.6.1235)). In the course of the proof, we show that it is not possible for all (or even almost all, in the metric case) the eigenvalues to exhibit a diamagnetic behaviour. In addition, we develop a notion of ‘discretized’ versions of a metric graph and prove that their nodal counts are related to those of the metric graph. PMID:24344337

  5. The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development.

    PubMed

    Reissmann, E; Jörnvall, H; Blokzijl, A; Andersson, O; Chang, C; Minchiotti, G; Persico, M G; Ibáñez, C F; Brivanlou, A H

    2001-08-01

    Nodal proteins have crucial roles in mesendoderm formation and left-right patterning during vertebrate development. The molecular mechanisms of signal transduction by Nodal and related ligands, however, are not fully understood. In this paper, we present biochemical and functional evidence that the orphan type I serine/threonine kinase receptor ALK7 acts as a receptor for mouse Nodal and Xenopus Nodal-related 1 (Xnr1). Receptor reconstitution experiments indicate that ALK7 collaborates with ActRIIB to confer responsiveness to Xnr1 and Nodal. Both receptors can independently bind Xnr1. In addition, Cripto, an extracellular protein genetically implicated in Nodal signaling, can independently interact with both Xnr1 and ALK7, and its expression greatly enhances the ability of ALK7 and ActRIIB to respond to Nodal ligands. The Activin receptor ALK4 is also able to mediate Nodal signaling but only in the presence of Cripto, with which it can also interact directly. A constitutively activated form of ALK7 mimics the mesendoderm-inducing activity of Xnr1 in Xenopus embryos, whereas a dominant-negative ALK7 specifically blocks the activities of Nodal and Xnr1 but has little effect on other related ligands. In contrast, a dominant-negative ALK4 blocks all mesoderm-inducing ligands tested, including Nodal, Xnr1, Xnr2, Xnr4, and Activin. In agreement with a role in Nodal signaling, ALK7 mRNA is localized to the ectodermal and organizer regions of Xenopus gastrula embryos and is expressed during early stages of mouse embryonic development. Therefore, our results indicate that both ALK4 and ALK7 can mediate signal transduction by Nodal proteins, although ALK7 appears to be a receptor more specifically dedicated to Nodal signaling.

  6. The orphan receptor ALK7 and the Activin receptor ALK4 mediate signaling by Nodal proteins during vertebrate development

    PubMed Central

    Reissmann, Eva; Jörnvall, Henrik; Blokzijl, Andries; Andersson, Olov; Chang, Chenbei; Minchiotti, Gabriella; Persico, M. Graziella; Ibáñez, Carlos F.; Brivanlou, Ali H.

    2001-01-01

    Nodal proteins have crucial roles in mesendoderm formation and left–right patterning during vertebrate development. The molecular mechanisms of signal transduction by Nodal and related ligands, however, are not fully understood. In this paper, we present biochemical and functional evidence that the orphan type I serine/threonine kinase receptor ALK7 acts as a receptor for mouse Nodal and Xenopus Nodal-related 1 (Xnr1). Receptor reconstitution experiments indicate that ALK7 collaborates with ActRIIB to confer responsiveness to Xnr1 and Nodal. Both receptors can independently bind Xnr1. In addition, Cripto, an extracellular protein genetically implicated in Nodal signaling, can independently interact with both Xnr1 and ALK7, and its expression greatly enhances the ability of ALK7 and ActRIIB to respond to Nodal ligands. The Activin receptor ALK4 is also able to mediate Nodal signaling but only in the presence of Cripto, with which it can also interact directly. A constitutively activated form of ALK7 mimics the mesendoderm-inducing activity of Xnr1 in Xenopus embryos, whereas a dominant-negative ALK7 specifically blocks the activities of Nodal and Xnr1 but has little effect on other related ligands. In contrast, a dominant-negative ALK4 blocks all mesoderm-inducing ligands tested, including Nodal, Xnr1, Xnr2, Xnr4, and Activin. In agreement with a role in Nodal signaling, ALK7 mRNA is localized to the ectodermal and organizer regions of Xenopus gastrula embryos and is expressed during early stages of mouse embryonic development. Therefore, our results indicate that both ALK4 and ALK7 can mediate signal transduction by Nodal proteins, although ALK7 appears to be a receptor more specifically dedicated to Nodal signaling. PMID:11485994

  7. Comparison of a sentinel lymph node mapping algorithm and comprehensive lymphadenectomy in the detection of stage IIIC endometrial carcinoma at higher risk for nodal disease.

    PubMed

    Ducie, Jennifer A; Eriksson, Ane Gerda Zahl; Ali, Narisha; McGree, Michaela E; Weaver, Amy L; Bogani, Giorgio; Cliby, William A; Dowdy, Sean C; Bakkum-Gamez, Jamie N; Soslow, Robert A; Keeney, Gary L; Abu-Rustum, Nadeem R; Mariani, Andrea; Leitao, Mario M

    2017-12-01

    To determine if a sentinel lymph node (SLN) mapping algorithm will detect metastatic nodal disease in patients with intermediate-/high-risk endometrial carcinoma. Patients were identified and surgically staged at two collaborating institutions. The historical cohort (2004-2008) at one institution included patients undergoing complete pelvic and paraaortic lymphadenectomy to the renal veins (LND cohort). At the second institution an SLN mapping algorithm, including pathologic ultra-staging, was performed (2006-2013) (SLN cohort). Intermediate-risk was defined as endometrioid histology (any grade), ≥50% myometrial invasion; high-risk as serous or clear cell histology (any myometrial invasion). Patients with gross peritoneal disease were excluded. Isolated tumor cells, micro-metastases, and macro-metastases were considered node-positive. We identified 210 patients in the LND cohort, 202 in the SLN cohort. Nodal assessment was performed for most patients. In the intermediate-risk group, stage IIIC disease was diagnosed in 30/107 (28.0%) (LND), 29/82 (35.4%) (SLN) (P=0.28). In the high-risk group, stage IIIC disease was diagnosed in 20/103 (19.4%) (LND), 26 (21.7%) (SLN) (P=0.68). Paraaortic lymph node (LN) assessment was performed significantly more often in intermediate-/high-risk groups in the LND cohort (P<0.001). In the intermediate-risk group, paraaortic LN metastases were detected in 20/96 (20.8%) (LND) vs. 3/28 (10.7%) (SLN) (P=0.23). In the high-risk group, paraaortic LN metastases were detected in 13/82 (15.9%) (LND) and 10/56 (17.9%) (SLN) (%, P=0.76). SLN mapping algorithm provides similar detection rates of stage IIIC endometrial cancer. The SLN algorithm does not compromise overall detection compared to standard LND. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Evaluation of the use of nodal methods for MTR neutronic analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reitsma, F.; Mueller, E.Z.

    1997-08-01

    Although modern nodal methods are used extensively in the nuclear power industry, their use for research reactor analysis has been very limited. The suitability of nodal methods for material testing reactor analysis is investigated with the emphasis on the modelling of the core region (fuel assemblies). The nodal approach`s performance is compared with that of the traditional finite-difference fine mesh approach. The advantages of using nodal methods coupled with integrated cross section generation systems are highlighted, especially with respect to data preparation, simplicity of use and the possibility of performing a great variety of reactor calculations subject to strict timemore » limitations such as are required for the RERTR program.« less

  9. Optical conductivity of three and two dimensional topological nodal-line semimetals

    NASA Astrophysics Data System (ADS)

    Barati, Shahin; Abedinpour, Saeed H.

    2017-10-01

    The peculiar shape of the Fermi surface of topological nodal-line semimetals at low carrier concentrations results in their unusual optical and transport properties. We analytically investigate the linear optical responses of three- and two-dimensional nodal-line semimetals using the Kubo formula. The optical conductivity of a three-dimensional nodal-line semimetal is anisotropic. Along the axial direction (i.e., the direction perpendicular to the nodal-ring plane), the Drude weight has a linear dependence on the chemical potential at both low and high carrier dopings. For the radial direction (i.e., the direction parallel to the nodal-ring plane), this dependence changes from linear into quadratic in the transition from low into high carrier concentration. The interband contribution into optical conductivity is also anisotropic. In particular, at large frequencies, it saturates to a constant value for the axial direction and linearly increases with frequency along the radial direction. In two-dimensional nodal-line semimetals, no interband optical transition could be induced and the only contribution to the optical conductivity arises from the intraband excitations. The corresponding Drude weight is independent of the carrier density at low carrier concentrations and linearly increases with chemical potential at high carrier doping.

  10. Incidence, Risk Factors, and Analysis of Survival of Unexpected N2 Disease in Stage I Non-Small Cell Lung Cancer.

    PubMed

    Fiorelli, Alfonso; Sagan, Dariusz; Mackiewicz, Lukasz; Cagini, Lucio; Scarnecchia, Elisa; Chiodini, Paolo; Caronia, Francesco Paolo; Puma, Francesco; Santini, Mario; Ragusa, Mark

    2015-10-01

    To evaluate the incidence, predictors, and survival of unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer. This is a retrospective observational multicenter study on all consecutive patients operated for clinical stage I non-small cell lung cancer from January 2006 to December 2012. Medical records were reviewed to investigate the incidence and risk factors for unexpected pN2 disease. Then, the survival of patients with unexpected pN2 disease was statistically compared with that of patients with clinical N2 disease operated after induction therapy in the same period. Our study population counted 901 patients. An incidence of 12% (108/901) unexpected pN2 disease was found. Among 3,389 lymph nodes sampled, 124 distinct metastases were found. Of the 108 patients, 92 (85%) had metastases in single N2 station and 16 (15%) patients had disease in multiple N2 stations; 47 (44%) had pN2 disease without pN1 involvement (skip metastases) and 61/108 (56%) had also pN1 metastases. Factors associated with unexpected pN2 disease were central tumor location (p < 0.003), cT2a (p < 0.0001) and pT2a stage (p < 0.0001), pN1 disease (p = 0.004), and a standard uptake value > 4.0 (0.007). Patients with pN2 disease compared with patients with cN2 disease presented a better median overall survival (56 versus 20 months; p = 0.001) and disease-free survival (46 versus 11 months; p < 0.0001). The preoperative effort to discover unexpected pN2 disease in patients with clinical stage I non-small cell lung cancer is not justified, considering their good survival. Thus, preoperative invasive mediastinal procedures in such cases are not indicated. Georg Thieme Verlag KG Stuttgart · New York.

  11. Winding numbers of nodal points in Fe-based superconductors

    NASA Astrophysics Data System (ADS)

    Chichinadze, Dmitry V.; Chubukov, Andrey V.

    2018-03-01

    We analyze the nodal points in multiorbital Fe-based superconductors from a topological perspective. We consider the s+- gap structure with accidental nodes, and the d -wave gap with nodes along the symmetry directions. In both cases, the nodal points can be moved by varying an external parameter, e.g., a degree of interpocket pairing. Eventually, the nodes merge and annihilate via a Lifshitz-type transition. We discuss the Lifshitz transition in Fe-based superconductors from a topological point of view. We show, both analytically and numerically, that the merging nodal points have winding numbers of opposite sign. This is consistent with the general reasoning that the total winding number is a conserved quantity in the Lifshitz transition.

  12. Local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer.

    PubMed

    Kimoto, Takuya; Yamazaki, Hideya; Suzuki, Gen; Aibe, Norihiro; Masui, Koji; Tatekawa, Kotoha; Sasaki, Naomi; Fujiwara, Hitoshi; Shiozaki, Atsushi; Konishi, Hirotaka; Nakamura, Satoaki; Yamada, Kei

    2017-09-01

    Radiotherapy is an effective treatment for the postoperative loco-regional recurrence of esophageal cancer; however, the optimal treatment field remains controversial. This study aims to evaluate the outcome of local field radiotherapy without elective nodal irradiation for postoperative loco-regional recurrence of esophageal cancer. We retrospectively investigated 35 patients treated for a postoperative loco-regional recurrence of esophageal cancer with local field radiotherapy between December 2008 and March 2016. The median irradiation dose was 60 Gy (range: 50-67.5 Gy). Thirty-one (88.6%) patients received concurrent chemotherapy. The median follow-up period was 18 months (range: 5-94 months). The 2-year overall survival was 55.7%, with a median survival time of 29.9 months. In the univariate analysis, the maximal diameter ≤20 mm (P = 0.0383), solitary lesion (P = 0.0352), and the complete remission after treatment (P = 0.00411) had a significantly better prognosis. A total of 27 of 35 patients (77.1%) had progressive disease (loco-regional failure [n = 9], distant metastasis [n = 7], and both loco-regional failure and distant metastasis [n = 11]). No patients had Grade 3 or greater mucositis. Local field radiotherapy is a considerable treatment option for postoperative loco-regional recurrence of esophageal cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  13. Pathology of nodal marginal zone lymphomas.

    PubMed

    Pileri, Stefano; Ponzoni, Maurilio

    Nodal marginal zone B cell lymphomas (NMZLs) are a rare group of lymphoid disorders part of the spectrum of marginal zone B-cell lymphomas, which encompass splenic marginal one B-cell lymphoma (SMZL) and extra nodal marginal zone of B-cell lymphoma (EMZL), often of MALT-type. Two clinicopathological forms of NMZL are recognized: adult-type and pediatric-type, respectively. NMZLs show overlapping features with other types of MZ, but distinctive features as well. In this review, we will focus on the salient distinguishing features of NMZL mostly under morphological/immunophenotypical/molecular perspectives in views of the recent acquisitions and forthcoming updated 2016 WHO classification of lymphoid malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder.

    PubMed

    Lefèvre, Guillaume; Copin, Marie-Christine; Roumier, Christophe; Aubert, Hélène; Avenel-Audran, Martine; Grardel, Nathalie; Poulain, Stéphanie; Staumont-Sallé, Delphine; Seneschal, Julien; Salles, Gilles; Ghomari, Kamel; Terriou, Louis; Leclech, Christian; Morati-Hafsaoui, Chafika; Morschhauser, Franck; Lambotte, Olivier; Ackerman, Félix; Trauet, Jacques; Geffroy, Sandrine; Dumezy, Florent; Capron, Monique; Roche-Lestienne, Catherine; Taieb, Alain; Hatron, Pierre-Yves; Dubucquoi, Sylvain; Hachulla, Eric; Prin, Lionel; Labalette, Myriam; Launay, David; Preudhomme, Claude; Kahn, Jean-Emmanuel

    2015-08-01

    The CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome is characterized by hypereosinophilia and clonal circulating CD3(-)CD4(+) T cells. Peripheral T-cell lymphoma has been described during this disease course, and we observed in our cohort of 23 patients 2 cases of angio-immunoblastic T-cell lymphoma. We focus here on histopathological (n=12 patients) and immunophenotypic (n=15) characteristics of CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome. Atypical CD4(+) T cells lymphoid infiltrates were found in 10 of 12 CD3(-)CD4(+) L-HES patients, in lymph nodes (n=4 of 4 patients), in skin (n=9 of 9) and other extra-nodal tissues (gut, lacrymal gland, synovium). Lymph nodes displayed infiltrates limited to the interfollicular areas or even an effacement of nodal architecture, associated with proliferation of arborizing high endothelial venules and increased follicular dendritic cell meshwork. Analysis of 2 fresh skin samples confirmed the presence of CD3(-)CD4(+) T cells. Clonal T cells were detected in at least one tissue in 8 patients, including lymph nodes (n=4 of 4): the same clonal T cells were detected in blood and in at least one biopsy, with a maximum delay of 23 years between samples. In the majority of cases, circulating CD3(-)CD4(+) T cells were CD2(hi) (n=9 of 14), CD5(hi) (n=12 of 14), and CD7(-)(n=4 of 14) or CD7(low) (n=10 of 14). Angio-immunoblastic T-cell lymphoma can also present with CD3(-)CD4(+) T cells; despite other common histopathological and immunophenotypic features, CD10 expression and follicular helper T-cell markers were not detected in lymphoid variant of hypereosinophilic syndrome patients, except in both patients who developed angio-immunoblastic T-cell lymphoma, and only at T-cell lymphoma diagnosis. Taken together, persistence of tissular clonal T cells and histopathological features define CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome as a peripheral indolent clonal T-cell lymphoproliferative

  15. Evaluating Mesorectal Lymph Nodes in Rectal Cancer Before and After Neoadjuvant Chemoradiation Using Thin-Section T2-Weighted Magnetic Resonance Imaging

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koh, Dow-Mu; Chau, Ian; Tait, Diana

    2008-06-01

    Purpose: To apply thin-section T2-weighted magnetic resoance imaging (MRI) to evaluate the number, size, distribution, and morphology of benign and malignant mesorectal lymph nodes before and after chemoradiation treatment compared with histopathologic findings. Methods and Materials: Twenty-five patients with poor-risk adenocarcinoma of the rectum treated with neoadjuvant chemoradiation were evaluated prospectively. Thin-section T2-weighted MR images obtained before and after chemoradiation treatment were independently reviewed in consensus by 2 expert radiologists to determine the tumor stage, nodal size, nodal distribution, and nodal stage. Total mesorectal excision surgery after chemoradiation allowed MR nodal stage to be compared with histopathology using {kappa} statistics.more » Nodal downstaging was compared using the Chi-square test. Results: Before chemoradiation, 152 mesorectal nodes were visible (mean, 6.2 mm; 100 benign, 52 malignant) and 4 of 52 malignant nodes were in contact with the mesorectal fascia. The nodal staging was 7/25 N0, 10/25 N1, and 7/25 N2. After chemoradiation, only 29 nodes (mean, 4.1 mm; 24 benign, 5 malignant) were visible, and none were in contact with the mesorectal fascia. Nodal downstaging was observed: 20/25 N0 and 5/25 N1 (p < 0.01, Chi-square test). There was good agreement between MRI and pathologic T-staging ({kappa} = 0.64) and N-staging ({kappa} = 0.65) after chemoradiation. Conclusions: Neoadjuvant chemoradiation treatment resulted in a decrease in size and number of malignant- and benign-appearing mesorectal nodes on MRI. Nodal downstaging and nodal regression from the mesorectal fascia were observed after treatment. MRI is a useful tool for assessing nodal response to neoadjuvant treatment.« less

  16. A quantitative description of normal AV nodal conduction curve in man.

    PubMed

    Teague, S; Collins, S; Wu, D; Denes, P; Rosen, K; Arzbaecher, R

    1976-01-01

    The AV nodal conduction curve generated by the atrial extrastimulus technique has been described only qualitatively in man, making clinical comparison of known normal curves with those of suspected AV nodal dysfunction difficult. Also, the effects of physiological and pharmacological interventions have not been quantifiable. In 50 patients with normal AV conduction as defined by normal AH (less than 130 ms), normal AV nodal effective and functional refractory periods (less than 380 and less than 500 ms), and absence of demonstrable dual AV nodal pathways, we found that conduction curves (at sinus rhythm or longest paced cycle length) can be described by an exponential equation of the form delta = Ae-Bx. In this equation, delta is the increase in AV nodal conduction time of an extrastimulus compared to that of a regular beat and x is extrastimulus interval. The natural logarithm of this equation is linear in the semilogarithmic plane, thus permitting the constants A and B to be easily determined by a least-squares regression analysis with a hand calculator.

  17. Amyloid precursor protein at node of Ranvier modulates nodal formation

    PubMed Central

    Xu, De-En; Zhang, Wen-Min; Yang, Zara Zhuyun; Zhu, Hong-Mei; Yan, Ke; Li, Shao; Bagnard, Dominique; Dawe, Gavin S; Ma, Quan-Hong; Xiao, Zhi-Cheng

    2014-01-01

    Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR. In APP-knockout (KO) mice, nodal length is significantly increased, while sodium channels are still clustered at NORs. Moreover, APP KO and APP-overexpressing transgenic (APP TG) mice exhibited a decreased and an increased thickness of myelin in spinal cords, respectively, although the changes are limited in comparison to their littermate WT mice. The thickness of myelin in APP KO sciatic nerve also increased in comparison to that in WT mice. Our observations indicate that APP acts as a novel component at CNS NORs, modulating nodal formation and has minor effects in promoting myelination. PMID:25482638

  18. Regional Nodal Irradiation After Breast Conserving Surgery for Early HER2-Positive Breast Cancer: Results of a Subanalysis From the ALTTO Trial.

    PubMed

    Gingras, Isabelle; Holmes, Eileen; De Azambuja, Evandro; Nguyen, David H A; Izquierdo, Miguel; Anne Zujewski, Jo; Inbar, Moshe; Naume, Bjorn; Tomasello, Gianluca; Gralow, Julie R; Wolff, Antonio C; Harris, Lyndsay; Gnant, Michael; Moreno-Aspitia, Alvaro; Piccart, Martine J; Azim, Hatem A

    2017-08-01

    Two randomized trials recently demonstrated that regional nodal irradiation (RNI) could reduce the risk of recurrence in early breast cancer; however, these trials were conducted in the pretrastuzumab era. Whether these results are applicable to human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients treated with anti-HER2-targeted therapy is unknown. This retrospective analysis was performed on patients with node-positive breast cancer who were enrolled in the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization phase III adjuvant trial and subjected to BCS. The primary objective of the present study was to examine the effect of RNI on disease-free survival (DFS). A multivariable cox regression analysis adjusted for number of positive lymph nodes, tumor size, grade, age, hormone receptors status, presence of macrometastatis, treatment arm, and chemotherapy timing was carried out to investigate the relationship between RNI and DFS. One thousand six hundred sixty-four HER2-positive breast cancer patients were included, of whom 878 (52.8%) had received RNI to the axillary, supraclavicular, and/or internal mammary lymph nodes. Patients in the RNI group had higher nodal burden and more frequently had tumors larger than 2 cm. At a median follow-up of 4.5 years, DFS was 84.3% in the RNI group and 88.3% in the non-RNI group. No differences in regional recurrence (0.9 % vs 0.6 %) or in overall survival (93.6% vs 95.3%) were observed between the two groups. After adjustment in multivariable analysis, there was no statistically significant association between RNI and DFS (hazard ratio = 0.96, 95% confidence interval = 0.71 to 1.29). Our analysis did not demonstrate a DFS benefit of RNI in HER2-positive, node-positive patients treated with adjuvant HER2-targeted therapy. The benefit of RNI in HER2-positive breast cancer needs further testing within randomized clinical trials. © The Author 2017. Published by Oxford University Press. All

  19. Targeting Nodal in Conjunction with Dacarbazine Induces Synergistic Anti-cancer Effects in Metastatic Melanoma

    PubMed Central

    Hardy, Katharine M.; Strizzi, Luigi; Margaryan, Naira V.; Gupta, Kanika; Murphy, George F.; Scolyer, Richard A.; Hendrix, Mary J.C.

    2015-01-01

    Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. Despite a complete response in fewer than 5% of patients, the chemotherapeutic agent Dacarbazine (DTIC) remains the reference drug after almost 40 years. More recently FDA approved drugs have shown promise but patient outcome remains modest, predominantly due to drug resistance. As such, combinatorial targeting has received increased attention, and will advance with the identification of new molecular targets. One attractive target for improving melanoma therapy is the growth factor Nodal, whose normal expression is largely restricted to embryonic development, but is reactivated in metastatic melanoma. In this study, we sought to determine how Nodal-positive human melanoma cells respond to DTIC treatment and to ascertain if targeting Nodal in combination with DTIC would be more effective than monotherapy. A single treatment with DTIC inhibited cell growth but did not induce apoptosis. Rather than reducing Nodal expression, DTIC increased the size of the Nodal-positive subpopulation, an observation coincident with increased cellular invasion. Importantly, clinical tissue specimens from patients with melanomas refractory to DTIC therapy stained positive for Nodal expression, both in pre- and post-DTIC tumors, underscoring the value of targeting Nodal. In vitro, anti-Nodal antibodies alone had some adverse effects on proliferation and apoptosis, but combining DTIC treatment with anti-Nodal antibodies decreased cell growth and increased apoptosis synergistically, at concentrations incapable of producing meaningful effects as monotherapy. Implications Targeting Nodal in combination with DTIC therapy holds promise for the treatment of metastatic melanoma. PMID:25767211

  20. Cilia are required for asymmetric nodal induction in the sea urchin embryo.

    PubMed

    Tisler, Matthias; Wetzel, Franziska; Mantino, Sabrina; Kremnyov, Stanislav; Thumberger, Thomas; Schweickert, Axel; Blum, Martin; Vick, Philipp

    2016-08-23

    Left-right (LR) organ asymmetries are a common feature of metazoan animals. In many cases, laterality is established by a conserved asymmetric Nodal signaling cascade during embryogenesis. In most vertebrates, asymmetric nodal induction results from a cilia-driven leftward fluid flow at the left-right organizer (LRO), a ciliated epithelium present during gastrula/neurula stages. Conservation of LRO and flow beyond the vertebrates has not been reported yet. Here we study sea urchin embryos, which use nodal to establish larval LR asymmetry as well. Cilia were found in the archenteron of embryos undergoing gastrulation. Expression of foxj1 and dnah9 suggested that archenteron cilia were motile. Cilia were polarized to the posterior pole of cells, a prerequisite of directed flow. High-speed videography revealed rotating cilia in the archenteron slightly before asymmetric nodal induction. Removal of cilia through brief high salt treatments resulted in aberrant patterns of nodal expression. Our data demonstrate that cilia - like in vertebrates - are required for asymmetric nodal induction in sea urchin embryos. Based on these results we argue that the anterior archenteron represents a bona fide LRO and propose that cilia-based symmetry breakage is a synapomorphy of the deuterostomes.

  1. Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling

    PubMed Central

    Norris, Megan L; Pauli, Andrea; Gagnon, James A; Lord, Nathan D; Rogers, Katherine W; Mosimann, Christian; Zon, Leonard I

    2017-01-01

    Toddler/Apela/Elabela is a conserved secreted peptide that regulates mesendoderm development during zebrafish gastrulation. Two non-exclusive models have been proposed to explain Toddler function. The ‘specification model’ postulates that Toddler signaling enhances Nodal signaling to properly specify endoderm, whereas the ‘migration model’ posits that Toddler signaling regulates mesendodermal cell migration downstream of Nodal signaling. Here, we test key predictions of both models. We find that in toddler mutants Nodal signaling is initially normal and increasing endoderm specification does not rescue mesendodermal cell migration. Mesodermal cell migration defects in toddler mutants result from a decrease in animal pole-directed migration and are independent of endoderm. Conversely, endodermal cell migration defects are dependent on a Cxcr4a-regulated tether of the endoderm to mesoderm. These results suggest that Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling and indirectly affects endodermal cell migration via Cxcr4a-signaling. PMID:29117894

  2. Nodal patterning without Lefty inhibitory feedback is functional but fragile

    PubMed Central

    Gagnon, James A; Pauli, Andrea; Zimmerman, Steven; Aksel, Deniz C; Reyon, Deepak; Tsai, Shengdar Q; Joung, J Keith

    2017-01-01

    Developmental signaling pathways often activate their own inhibitors. Such inhibitory feedback has been suggested to restrict the spatial and temporal extent of signaling or mitigate signaling fluctuations, but these models are difficult to rigorously test. Here, we determine whether the ability of the mesendoderm inducer Nodal to activate its inhibitor Lefty is required for development. We find that zebrafish lefty mutants exhibit excess Nodal signaling and increased specification of mesendoderm, resulting in embryonic lethality. Strikingly, development can be fully restored without feedback: Lethal patterning defects in lefty mutants can be rescued by ectopic expression of lefty far from its normal expression domain or by spatially and temporally uniform exposure to a Nodal inhibitor drug. While drug-treated mutants are less tolerant of mild perturbations to Nodal signaling levels than wild type embryos, they can develop into healthy adults. These results indicate that patterning without inhibitory feedback is functional but fragile. PMID:29215332

  3. Majorana surface modes of nodal topological pairings in spin-3/2 semimetals

    NASA Astrophysics Data System (ADS)

    Yang, Wang; Xiang, Tao; Wu, Congjun

    2017-10-01

    When solid state systems possess active orbital-band structures subject to spin-orbit coupling, their multicomponent electronic structures are often described in terms of effective large-spin fermion models. Their topological structures of superconductivity are beyond the framework of spin singlet and triplet Cooper pairings for spin-1/2 systems. Examples include the half-Heusler compound series of RPtBi, where R stands for a rare-earth element. Their spin-orbit coupled electronic structures are described by the Luttinger-Kohn model with effective spin-3/2 fermions and are characterized by band inversion. Recent experiments provide evidence to unconventional superconductivity in the YPtBi material with nodal spin-septet pairing. We systematically study topological pairing structures in spin-3/2 systems with the cubic group symmetries and calculate the surface Majorana spectra, which exhibit zero energy flat bands, or, cubic dispersion depending on the specific symmetry of the superconducting gap functions. The signatures of these surface states in the quasiparticle interference patterns of tunneling spectroscopy are studied, which can be tested in future experiments.

  4. Encapsulation of nodal cuttings and shoot tips for storage and exchange of cassava germplasm.

    PubMed

    Danso, K E; Ford-Lloyd, B V

    2003-04-01

    We report the encapsulation of in vitro-derived nodal cuttings or shoot tips of cassava in 3% calcium alginate for storage and germplasm exchange purposes. Shoot regrowth was not significantly affected by the concentration of sucrose in the alginate matrix while root formation was. In contrast, increasing the sucrose concentration in the calcium chloride polymerisation medium significantly reduced regrowth from encapsulated nodal cuttings of accession TME 60444. Supplementing the alginate matrix with increased concentrations of 6-benzylaminopurine and alpha-naphthaleneacetic acid enhanced complete plant regrowth within 2 weeks. Furthermore, plant regrowth by encapsulated nodal cuttings and shoot tips was significantly affected by the duration of the storage period as shoot recovery decreased from almost 100% to 73.3% for encapsulated nodal cuttings and 94.4% to 60% for shoot tips after 28 days of storage. The high frequency of plant regrowth from alginate-coated micropropagules coupled with high viability percentage after 28 days of storage is highly encouraging for the exchange of cassava genetic resources. Such encapsulated micropropagules could be used as an alternative to synthetic seeds derived from somatic embryos.

  5. Room-temperature magnetic topological Weyl fermion and nodal line semimetal states in half-metallic Heusler Co 2TiX (X=Si, Ge, or Sn)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang, Guoqing; Xu, Su -Yang; Zheng, Hao

    Topological semimetals (TSMs) including Weyl semimetals and nodal-line semimetals are expected to open the next frontier of condensed matter and materials science. Although the first inversion breaking Weyl semimetal was recently discovered in TaAs, its magnetic counterparts, i.e., the time-reversal breaking Weyl and nodal line semimetals, remain elusive. They are predicted to exhibit exotic properties distinct from the inversion breaking TSMs including TaAs. In this paper, we identify the magnetic topological semimetal states in the ferromagnetic half-metal compounds Co 2TiX (X = Si, Ge, or Sn) with Curie temperatures higher than 350 K. Our first-principles band structure calculations show that,more » in the absence of spin-orbit coupling, Co 2TiX features three topological nodal lines. The inclusion of spin-orbit coupling gives rise to Weyl nodes, whose momentum space locations can be controlled as a function of the magnetization direction. Lastly, our results not only open the door for the experimental realization of topological semimetal states in magnetic materials at room temperature, but also suggest potential applications such as unusual anomalous Hall effect in engineered monolayers of the Co 2TiX compounds at high temperature.« less

  6. Room-temperature magnetic topological Weyl fermion and nodal line semimetal states in half-metallic Heusler Co 2TiX (X=Si, Ge, or Sn)

    DOE PAGES

    Chang, Guoqing; Xu, Su -Yang; Zheng, Hao; ...

    2016-12-15

    Topological semimetals (TSMs) including Weyl semimetals and nodal-line semimetals are expected to open the next frontier of condensed matter and materials science. Although the first inversion breaking Weyl semimetal was recently discovered in TaAs, its magnetic counterparts, i.e., the time-reversal breaking Weyl and nodal line semimetals, remain elusive. They are predicted to exhibit exotic properties distinct from the inversion breaking TSMs including TaAs. In this paper, we identify the magnetic topological semimetal states in the ferromagnetic half-metal compounds Co 2TiX (X = Si, Ge, or Sn) with Curie temperatures higher than 350 K. Our first-principles band structure calculations show that,more » in the absence of spin-orbit coupling, Co 2TiX features three topological nodal lines. The inclusion of spin-orbit coupling gives rise to Weyl nodes, whose momentum space locations can be controlled as a function of the magnetization direction. Lastly, our results not only open the door for the experimental realization of topological semimetal states in magnetic materials at room temperature, but also suggest potential applications such as unusual anomalous Hall effect in engineered monolayers of the Co 2TiX compounds at high temperature.« less

  7. CD3−CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder

    PubMed Central

    Lefèvre, Guillaume; Copin, Marie-Christine; Roumier, Christophe; Aubert, Hélène; Avenel-Audran, Martine; Grardel, Nathalie; Poulain, Stéphanie; Staumont-Sallé, Delphine; Seneschal, Julien; Salles, Gilles; Ghomari, Kamel; Terriou, Louis; Leclech, Christian; Morati-Hafsaoui, Chafika; Morschhauser, Franck; Lambotte, Olivier; Ackerman, Félix; Trauet, Jacques; Geffroy, Sandrine; Dumezy, Florent; Capron, Monique; Roche-Lestienne, Catherine; Taieb, Alain; Hatron, Pierre-Yves; Dubucquoi, Sylvain; Hachulla, Eric; Prin, Lionel; Labalette, Myriam; Launay, David; Preudhomme, Claude; Kahn, Jean-Emmanuel

    2015-01-01

    The CD3−CD4+ lymphoid variant of hypereosinophilic syndrome is characterized by hypereosinophilia and clonal circulating CD3−CD4+ T cells. Peripheral T-cell lymphoma has been described during this disease course, and we observed in our cohort of 23 patients 2 cases of angio-immunoblastic T-cell lymphoma. We focus here on histopathological (n=12 patients) and immunophenotypic (n=15) characteristics of CD3−CD4+ lymphoid variant of hypereosinophilic syndrome. Atypical CD4+ T cells lymphoid infiltrates were found in 10 of 12 CD3−CD4+ L-HES patients, in lymph nodes (n=4 of 4 patients), in skin (n=9 of 9) and other extra-nodal tissues (gut, lacrymal gland, synovium). Lymph nodes displayed infiltrates limited to the interfollicular areas or even an effacement of nodal architecture, associated with proliferation of arborizing high endothelial venules and increased follicular dendritic cell meshwork. Analysis of 2 fresh skin samples confirmed the presence of CD3−CD4+ T cells. Clonal T cells were detected in at least one tissue in 8 patients, including lymph nodes (n=4 of 4): the same clonal T cells were detected in blood and in at least one biopsy, with a maximum delay of 23 years between samples. In the majority of cases, circulating CD3−CD4+ T cells were CD2hi (n=9 of 14), CD5hi (n=12 of 14), and CD7−(n=4 of 14) or CD7low (n=10 of 14). Angio-immunoblastic T-cell lymphoma can also present with CD3−CD4+ T cells; despite other common histopathological and immunophenotypic features, CD10 expression and follicular helper T-cell markers were not detected in lymphoid variant of hypereosinophilic syndrome patients, except in both patients who developed angio-immunoblastic T-cell lymphoma, and only at T-cell lymphoma diagnosis. Taken together, persistence of tissular clonal T cells and histopathological features define CD3−CD4+ lymphoid variant of hypereosinophilic syndrome as a peripheral indolent clonal T-cell lymphoproliferative disorder, which should not be

  8. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... DEMS Nodal Station licenses should specify the maximum number of 10.6 GHz DEMS User Stations to be served by that nodal station. Any increase in that number must be applied for pursuant to § 1.913 of this... Stations. 101.503 Section 101.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY...

  9. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... DEMS Nodal Station licenses should specify the maximum number of 10.6 GHz DEMS User Stations to be served by that nodal station. Any increase in that number must be applied for pursuant to § 1.913 of this... Stations. 101.503 Section 101.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY...

  10. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... DEMS Nodal Station licenses should specify the maximum number of 10.6 GHz DEMS User Stations to be served by that nodal station. Any increase in that number must be applied for pursuant to § 1.913 of this... Stations. 101.503 Section 101.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY...

  11. 47 CFR 101.503 - Digital Electronic Message Service Nodal Stations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... DEMS Nodal Station licenses should specify the maximum number of 10.6 GHz DEMS User Stations to be served by that nodal station. Any increase in that number must be applied for pursuant to § 1.913 of this... Stations. 101.503 Section 101.503 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY...

  12. Epstein-Barr virus-positive nodal T/NK-cell lymphoma: an analysis of 15 cases with distinct clinicopathological features.

    PubMed

    Jeon, Yoon Kyung; Kim, Jo-Heon; Sung, Ji-Youn; Han, Jae Ho; Ko, Young-Hyeh

    2015-07-01

    Nodal peripheral T-cell lymphoma, not otherwise specified, is a heterogeneous entity with variable biologic behavior. We analyze the clinicopathological features of 15 patients with Epstein-Barr virus-positive (EBV+) nodal T/NK-cell lymphoma, including 9 males and 6 females, with a median age of 64 years. All patients presented with multiple lymphadenopathy with common B symptoms (80%, 12/15) at an advanced Ann Arbor stage (III, IV) (87%, 13/15). The International Prognostic Index was high or high/intermediate in 87% (13/15) of patients, and the prognostic index for peripheral T-cell lymphoma was group 3 or 4 in 73% (11/15). Spleen and liver involvement was observed in 73% (11/15) and 60% (9/15) of patients, respectively. In contrast, extranodal involvement was infrequent, with no more than 1 site in 71% (10/15) of patients. Moreover, none had nasal lesions, and only 1 had mucocutaneous involvement. The cell lineage of EBV+ tumor cells was determined to be T cell in all except 1 patient, who was NK-cell lineage. Cytotoxic molecules were expressed in all cases, and 64% (9/14) of patients expressed the αβT-cell receptor. Moreover, most patients (67%, 10/15) showed CD8 positivity, with 2 of them being CD4CD8 double positive; the others were CD4 positive (n = 2) or CD4CD8 double negative (n = 3). The clinical course was very aggressive, with a median survival time of 3.5 months, and 10 patients died within 6 months of diagnosis. Taken together, our data demonstrate that EBV+ nodal T/NK-cell lymphoma is a distinct clinicopathological entity characterized by cytotoxic molecule expression, a frequent CD8-positive αβT-cell lineage, and a very aggressive clinical behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Elsevier Trophoblast Research Award lecture: The multifaceted role of Nodal signaling during mammalian reproduction.

    PubMed

    Park, C B; Dufort, D

    2011-03-01

    Nodal, a secreted signaling protein in the transforming growth factor-beta (TGF-β) superfamily, has established roles in vertebrate development. However, components of the Nodal signaling pathway are also expressed at the maternal-fetal interface and have been implicated in many processes of mammalian reproduction. Emerging evidence indicates that Nodal and its extracellular inhibitor Lefty are expressed in the uterus and complex interactions between the two proteins mediate menstruation, decidualization and embryo implantation. Furthermore, several studies have shown that Nodal from both fetal and maternal sources may regulate trophoblast cell fate and facilitate placentation as both embryonic and uterine-specific Nodal knockout mouse strains exhibit disrupted placenta morphology. Here we review the established and prospective roles of Nodal signaling in facilitating successful pregnancy, including recent evidence supporting a potential link to parturition and preterm birth. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. A comparison of an A1 adenosine receptor agonist (CVT-510) with diltiazem for slowing of AV nodal conduction in guinea-pig

    PubMed Central

    Snowdy, Stephen; Liang, Hui Xiu; Blackburn, Brent; Lum, Robert; Nelson, Marek; Wang, Lisa; Pfister, Jürg; Sharma, Bhavender P; Wolff, Andrew; Belardinelli, Luiz

    1999-01-01

    The purpose of this study was to compare the pharmacological properties (i.e. the AV nodal depressant, vasodilator, and inotropic effects) of two AV nodal blocking agents belonging to different drug classes; a novel A1 adenosine receptor (A1 receptor) agonist, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside (CVT-510), and the prototypical calcium channel blocker diltiazem.In the atrial-paced isolated heart, CVT-510 was approximately 5 fold more potent to prolong the stimulus-to-His bundle (S–H interval), a measure of slowing AV nodal conduction (EC50=41 nM) than to increase coronary conductance (EC50=200 nM). At concentrations of CVT-510 (40 nM) and diltiazem (1 μM) that caused equal prolongation of S–H interval (∼10 ms), diltiazem, but not CVT-510, significantly reduced left ventricular developed pressure (LVP) and markedly increased coronary conductance. CVT-510 shortened atrial (EC50=73 nM) but not the ventricular monophasic action potentials (MAP).In atrial-paced anaesthetized guinea-pigs, intravenous infusions of CVT-510 and diltiazem caused nearly equal prolongations of P–R interval. However, diltiazem, but not CVT-510, significantly reduced mean arterial blood pressure.Both CVT-510 and diltiazem prolonged S–H interval, i.e., slowed AV nodal conduction. However, the A1 receptor-selective agonist CVT-510 did so without causing the negative inotropic, vasodilator, and hypotensive effects associated with diltiazem. Because CVT-510 did not affect the ventricular action potential, it is unlikely that this agonist will have a proarrythmic action in ventricular myocardium. PMID:10051130

  15. Surgical management of sentinel lymph node biopsy outside major nodal basin in patients with cutaneous melanoma.

    PubMed

    Caracò, Corrado; Marone, Ugo; Di Monta, Gianluca; Aloj, Luigi; Caracò, Corradina; Anniciello, Annamaria; Lastoria, Secondo; Botti, Gerardo; Mozzillo, Nicola

    2014-01-01

    To assess the incidence of nonmajor lymphatic basin sentinel nodes in patients with cutaneous melanoma in order to propose a correct nomenclature and inform appropriate surgical management. This was a retrospective review of 1,045 consecutive patients with cutaneous melanoma who underwent sentinel lymph node biopsy and dynamic lymphoscintigraphy to identify sentinel node site. Nonmajor drainage sites were classified as uncommon (located in a minor lymphatic basin along the lymphatic drainage to a major classical nodal basin) or interval (located anywhere along the lymphatics between the primary tumor site and the nearest lymphatic basin) sentinel nodes. Nonclassical sentinel nodes were identified in 32 patients (3.0 %). Uncommon sentinel nodes were identified in 3.2 % (n = 17) of trunk melanoma primary disease and in 1.5 % (n = 7) of upper and lower extremity sites. Interval sentinel nodes were identified in 1.3 % (n = 7) of trunk primary lesions, with none from upper and lower extremities melanomas. The incidence of tumor-positive sentinel nodes was 24.1 % (245 of 1,013) in classical sites and 12.5 % (4 of 32) in uncommon/interval sites. The definition of uncommon and interval sentinel nodes allows the identification of different lymphatic pathways and inform appropriate surgical treatment. Wider experience with uncommon/interval sentinel nodes will better clarify the clinical implications and surgical management to be adopted in the management of uncommon and interval sentinel node sites.

  16. Lymph node density vs. the American Joint Committee on Cancer TNM nodal staging system in node-positive bladder cancer in patients undergoing extended or super-extended pelvic lymphadenectomy.

    PubMed

    Lee, Donghyun; Yoo, Sangjun; You, Dalsan; Hong, Bumsik; Cho, Yong Mee; Hong, Jun Hyuk; Kim, Choung-Soo; Ahn, Hanjonh; Ro, Jae Y; Jeong, In Gab

    2017-04-01

    We compared the prognostic value of the American Joint Committee on Cancer (AJCC) TNM nodal staging system with that of lymph node (LN) density in patients with LN-positive bladder cancer who received extended or super-extended pelvic lymphadenectomy. Of the 1,018 patients, who underwent radical cystectomy and pelvic lymphadenectomy between February 2005 and August 2014, 110 patients with LN metastases with extended (n = 68) or super-extended (n = 42) pelvic lymphadenectomy were included. All patients were staged using the 2002 (sixth edition) and 2010 (seventh edition) AJCC TNM staging systems. The association of several variables with recurrence-free survival (RFS) and overall survival (OS) was evaluated. The median number of total LNs removed was 29 (6-118) and the median LN density was 12.5% (1.6%-100%). RFS and OS were not significantly different between the 2002 (pN1-pM1) and 2010 (pN1-N3) AJCC TNM nodal staging systems (sixth edition: P = 0.512 and P = 0.519; seventh edition: P = 0.676 and P = 0.671, respectively). The 2-year RFS and OS rates according to the LN density quartiles were 58.5% and 76.9% in Q1, 39.1% and 70.8% in Q2, 28.8% and 50.1% in Q3, and 12.7% and 20.8% in Q4 (P = 0.001 and P = 0.001, respectively). Multivariate analysis adjusted for the 2010 AJCC TNM staging system showed that LN density was associated with a decreased OS (HR = 1.024; 95% CI: 1.010-1.039; P = 0.001). The nodal staging system (2002 or 2010) was not associated with the RFS and OS. LN density shows a better prognostic value than the AJCC TNM nodal staging system in patients with LN-positive bladder cancer receiving extended or super-extended pelvic lymphadenectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. The Likely Sites of Nodal Metastasis Differs According to the Tumor Extent in Distal Bile Duct Cancer.

    PubMed

    Kato, Yuichiro; Takahashi, Shinichiro; Gotohda, Naoto; Konishi, Masaru

    2016-09-01

    In the revised Japanese and Worldwide TNM classification of distal bile duct cancer, the lymph node status is defined as N0 or N1 without reference to the tumor location or extent, according to the presence/absence of metastasis to the regional lymph nodes. Data of 94 patients with distal bile duct cancer who had undergone pancreaticoduodenectomy were reviewed retrospectively. In formalin-fixed specimens, we measured the longitudinal lengths from the papilla to the lower and upper margins of the tumor, in order to investigate the correlation of the tumor extent with the likely sites of nodal metastasis. The frequencies of metastasis to the posterior pancreaticoduodenal nodes (7.1 %) and superior mesenteric artery nodes (0.0 %) were significantly lower in the cases in which the length from the papilla to the lower margin of the tumor was ≥30 mm. The frequencies of nodal metastasis to the common hepatic artery nodes (0.0 %) and hepatoduodenal ligament nodes (6.7 %) were significantly lower in the cases in which the length from the papilla to the upper margin was <40 mm. The likely sites of nodal metastasis differ according to the extent of the tumor in cases of bile duct cancer.

  18. Comparison of Modal to Nodal Approaches for Wavefront Correction,

    DTIC Science & Technology

    1986-02-01

    the influence function of the wavefront corrector. (Implicit here is the assumption that the influence function is the same for every node, which is...To implement a nodal correction, the wavefront to be corrected is -. .. decomposed using a basis which is determined by the nodal (actuator) influence ... function of the wavefront corrector. This decomposition results in a set of coefficients which correspond to the drive signal required at the

  19. Prognostic implications of occult nodal tumour cells in stage I and II colon cancer: The correlation between micrometastasis and disease recurrence.

    PubMed

    Sloothaak, D A M; van der Linden, R L A; van de Velde, C J H; Bemelman, W A; Lips, D J; van der Linden, J C; Doornewaard, H; Tanis, P J; Bosscha, K; van der Zaag, E S; Buskens, C J

    2017-08-01

    Occult nodal tumour cells should be categorised as micrometastasis (MMs) and isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, but not ITCs, are prognostic for disease recurrence in patients with stage I/II colon cancer. The objective of this retrospective multicenter study was to correlate MMs and ITCs to characteristics of the primary tumour, and to determine their prognostic value in patients with stage I/II colon cancer. One hundred ninety two patients were included in the study with a median follow up of 46 month (IQR 33-81 months). MMs were found in eight patients (4.2%), ITCs in 37 (19.3%) and occult tumour cells were absent in 147 patients (76.6%). Between these groups, tumour differentiation and venous or lymphatic invasion was equally distributed. Advanced stage (pT3/pT4) was found in 66.0% of patients without occult tumour cells (97/147), 72.9% of patients with ITCs (27/37), and 100% in patients with MMs (8/8), although this was a non-significant trend. Patients with MMs showed a significantly reduced 3 year-disease free survival compared to patients with ITCs or patients without occult tumour cells (75.0% versus 88.0% and 94.8%, respectively, p = 0.005). When adjusted for T-stage, MMs independently predicted recurrence of cancer (OR 7.6 95% CI 1.5-37.4, p = 0.012). In this study, the incidence of MMs and ITCs in patients with stage I/II colon cancer was 4.2% and 19.3%, respectively. MMs were associated with an reduced 3 year disease free survival rate, but ITCs were not. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  20. Integration of nodal and BMP signals in the heart requires FoxH1 to create left-right differences in cell migration rates that direct cardiac asymmetry.

    PubMed

    Lenhart, Kari F; Holtzman, Nathalia G; Williams, Jessica R; Burdine, Rebecca D

    2013-01-01

    Failure to properly establish the left-right (L/R) axis is a major cause of congenital heart defects in humans, but how L/R patterning of the embryo leads to asymmetric cardiac morphogenesis is still unclear. We find that asymmetric Nodal signaling on the left and Bmp signaling act in parallel to establish zebrafish cardiac laterality by modulating cell migration velocities across the L/R axis. Moreover, we demonstrate that Nodal plays the crucial role in generating asymmetry in the heart and that Bmp signaling via Bmp4 is dispensable in the presence of asymmetric Nodal signaling. In addition, we identify a previously unappreciated role for the Nodal-transcription factor FoxH1 in mediating cell responsiveness to Bmp, further linking the control of these two pathways in the heart. The interplay between these TGFβ pathways is complex, with Nodal signaling potentially acting to limit the response to Bmp pathway activation and the dosage of Bmp signals being critical to limit migration rates. These findings have implications for understanding the complex genetic interactions that lead to congenital heart disease in humans.

  1. Barrier tunneling of the loop-nodal semimetal in the hyperhoneycomb lattice

    NASA Astrophysics Data System (ADS)

    Guan, Ji-Huan; Zhang, Yan-Yang; Lu, Wei-Er; Xia, Yang; Li, Shu-Shen

    2018-05-01

    We theoretically investigate the barrier tunneling in the 3D model of the hyperhoneycomb lattice, which is a nodal-line semimetal with a Dirac loop at zero energy. In the presence of a rectangular potential, the scattering amplitudes for different injecting states around the nodal loop are calculated, by using analytical treatments of the effective model, as well as numerical simulations of the tight binding model. In the low energy regime, states with remarkable transmissions are only concentrated in a small range around the loop plane. When the momentum of the injecting electron is coplanar with the nodal loop, nearly perfect transmissions can occur for a large range of injecting azimuthal angles if the potential is not high. For higher potential energies, the transmission shows a resonant oscillation with the potential, but still with peaks being perfect transmissions that do not decay with the potential width. These strikingly robust transports of the loop-nodal semimetal can be approximately explained by a momentum dependent Dirac Hamiltonian.

  2. Electrodynamics of the nodal metal state in weakly doped high- Tc cuprates

    NASA Astrophysics Data System (ADS)

    Lee, Y. S.; Segawa, Kouji; Li, Z. Q.; Padilla, W. J.; Dumm, M.; Dordevic, S. V.; Homes, C. C.; Ando, Yoichi; Basov, D. N.

    2005-08-01

    We report on the detailed analysis of the infrared (IR) conductivity of two prototypical high- Tc systems YBa2Cu3Oy and La2-xSrxCuO4 throughout the complex phase diagram of these compounds. Our focus in this work is to thoroughly document the electromagnetic response of the nodal metal state which is initiated with only a few holes doped in parent antiferromagnetic systems and extends up to the pseudogap boundary in the phase diagram. The key signature of the nodal metal is the two-component conductivity: the Drude mode at low energies followed by a resonance in mid-IR. The Drude component can be attributed to the response of coherent quasiparticles residing on the Fermi arcs detected in photoemission experiments. The microscopic origin of the mid-IR band is yet to be understood. A combination of transport and IR data uncovers fingerprints of the Fermi liquid behavior in the response of the nodal metal. The comprehensive nature of the data sets presented in this work allows us to critically re-evaluate common approaches to the interpretation of the optical data. Specifically we re-examine the role of magnetic excitations in generating electronic self-energy effects through the analysis of the IR data in a high magnetic field.

  3. Enhancement of neuronal differentiation by using small molecules modulating Nodal/Smad, Wnt/β-catenin, and FGF signaling.

    PubMed

    Song, Yonghee; Lee, Somyung; Jho, Eek-Hoon

    2018-06-08

    Pluripotent embryonic stem cells are one of the best modalities for the disease treatment due to their potential for self-renewal and differentiation into various cell types. Induction of stem cell differentiation into specific cell lineages has been investigated for decades, especially in vitro neuronal differentiation of embryonic stem cells. However, in vitro differentiation methods do not yield sufficient amounts of neurons for use in the therapeutic treatment of neurological disorders. Here, we provide an improved neuronal differentiation method based on a combination of small regulatory molecules for specific signaling pathways (FGF4 for FGF signaling, SB431542 for Nodal/Smad signaling, and XAV939 and BIO for Wnt signaling) in N2B27 media. We found that FGF4 was required for neural induction, SB431542 accelerated neural precursor differentiation, and treatment with XAV939 and BIO at different periods enhanced neuronal differentiation. These optimized neuronal differentiation conditions may allow a greater neuron cell yield within a shorter time than current methods and be the basis for treatment of neurological dysfunction using stem cells. Copyright © 2018. Published by Elsevier Inc.

  4. Quantum anomalies in nodal line semimetals

    NASA Astrophysics Data System (ADS)

    Burkov, A. A.

    2018-04-01

    Topological semimetals are a new class of condensed matter systems with nontrivial electronic structure topology. Their unusual observable properties may often be understood in terms of quantum anomalies. In particular, Weyl and Dirac semimetals, which have point band-touching nodes, are characterized by the chiral anomaly, which leads to the Fermi arc surface states, anomalous Hall effect, negative longitudinal magnetoresistance, and planar Hall effect. In this paper, we explore analogous phenomena in nodal line semimetals. We demonstrate that such semimetals realize a three-dimensional analog of the parity anomaly, which is a known property of two-dimensional Dirac semimetals arising, for example, on the surface of a three-dimensional topological insulator. We relate one of the characteristic properties of nodal line semimetals, namely, the drumhead surface states, to this anomaly, and derive the field theory, which encodes the corresponding anomalous response.

  5. Three-dimensional graphdiyne as a topological nodal-line semimetal

    NASA Astrophysics Data System (ADS)

    Nomura, Takafumi; Habe, Tetsuro; Sakamoto, Ryota; Koshino, Mikito

    2018-05-01

    We study the electronic band structure of three-dimensional ABC-stacked (rhombohedral) graphdiyne, which is a new planar carbon allotrope recently fabricated. Using first-principles calculation, we show that the system is a nodal-line semimetal, in which the conduction band and valence band cross at a closed ring in the momentum space. We derive the minimum tight-binding model and the low-energy effective Hamiltonian in a 4 ×4 matrix form. The nodal line is protected by a nontrivial winding number, and it ensures the existence of the topological surface state in a finite-thickness slab. The Fermi surface of the doped system exhibits a peculiar, self-intersecting hourglass structure, which is quite different from the torus or pipe shape in the previously proposed nodal semimetals. Despite its simple configuration, three-dimensional graphdiyne offers unique electronic properties distinct from any other carbon allotropes.

  6. Primary nodal hemangiosarcoma in four dogs.

    PubMed

    Chan, Catherine M; Zwahlen, Courtney H; de Lorimier, Louis-Philippe; Yeomans, Stephen M; Hoffmann, Karon L; Moore, Antony S

    2016-11-01

    CASE DESCRIPTION 4 dogs with a slow-growing mass in the cervical region were evaluated. CLINICAL FINDINGS All dogs had no clinical signs at the time of the evaluation. There was no apparent evidence of visceral metastases or other primary tumor based on available CT or MRI data for any dog. TREATMENT AND OUTCOME For each dog, surgery to remove the mass was performed. Histologic examination of the excised tissue revealed a completely excised grade 1 or 2 lymph node hemangiosarcoma. All dogs received adjuvant chemotherapy; 2 dogs underwent curative intent chemotherapy, 1 dog underwent metronomic treatment with cyclophosphamide, and 1 dog underwent metronomic treatment with chlorambucil. The survival time was 259 days in 1 dog; 3 dogs were still alive 615, 399, and 365 days after surgery. CLINICAL RELEVANCE Primary nodal hemangiosarcoma in dogs is a rare and, to the authors' knowledge, previously undescribed disease that appears to develop in the cervical lymph nodes as a slow-growing mass or masses. Surgical excision and adjunct treatment resulted in long survival times for 3 of the 4 dogs of the present report. Given the aggressive biologic behavior of hemangiosarcomas in other body locations, adjunct chemotherapy should be considered for affected dogs, although its role in the cases described in this report was unclear. Additional clinical information is required to further characterize the biologic behavior of this tumor type and determine the expected survival times and associated risk factors in dogs.

  7. Long period nodal motion of sun synchronous orbits

    NASA Technical Reports Server (NTRS)

    Duck, K. I.

    1975-01-01

    An approximative model is formulated for assessing these perturbations that significantly affect long term modal motion of sun synchronous orbits. Computer simulations with several independent computer programs consider zonal and tesseral gravitational harmonics, third body gravitational disturbances induced by the sun and the moon, and atmospheric drag. A pendulum model consisting of evenzonal harmonics through order 4 and solar gravity dominated nodal motion approximation. This pendulum motion results from solar gravity inducing an inclination oscillation which couples into the nodal precession induced by the earth's oblateness. The pendulum model correlated well with simulations observed flight data.

  8. Topological nodal superconducting phases and topological phase transition in the hyperhoneycomb lattice

    NASA Astrophysics Data System (ADS)

    Bouhon, Adrien; Schmidt, Johann; Black-Schaffer, Annica M.

    2018-03-01

    We establish the topology of the spin-singlet superconducting states in the bare hyperhoneycomb lattice, and we derive analytically the full phase diagram using only symmetry and topology in combination with simple energy arguments. The phase diagram is dominated by two states preserving time-reversal symmetry. We find a line-nodal state dominating at low doping levels that is topologically nontrivial and exhibits surface Majorana flatbands, which we show perfectly match the bulk-boundary correspondence using the Berry phase approach. At higher doping levels, we find a fully gapped state with trivial topology. By analytically calculating the topological invariant of the nodal lines, we derive the critical point between the line-nodal and fully gapped states as a function of both pairing parameters and doping. We find that the line-nodal state is favored not only at lower doping levels but also if symmetry-allowed deformations of the lattice are present. Adding simple energy arguments, we establish that a fully gapped state with broken time-reversal symmetry likely appears covering the actual phase transition. We find this fully gapped state to be topologically trivial, while we find an additional point-nodal state at very low doing levels that also break time-reversal symmetry and has nontrivial topology with associated Fermi surface arcs. We eventually address the robustness of the phase diagram to generalized models also including adiabatic spin-orbit coupling, and we show how all but the point-nodal state are reasonably stable.

  9. Postoperative chemoradiotherapy in patients with head and neck cancer aged 70 or older with positive margins or extranodal extension and the influence of nodal classification.

    PubMed

    Yoshida, Emi J; Luu, Michael; David, John M; Kim, Sungjin; Mita, Alain; Scher, Kevin; Shiao, Stephen L; Tighiouart, Mourad; Ho, Allen S; Zumsteg, Zachary S

    2018-06-01

    Postoperative concomitant chemoradiotherapy (CRT) improves outcomes for younger adults with head and neck squamous cell carcinoma (HNSCC) and positive margins or extranodal extension (ENE), but its benefit for older adults is not well established. Patients from the National Cancer Data Base (NCDB) with HNSCC undergoing curative-intent resection, neck dissection, and postoperative radiation with positive margins or ENE were identified. This analysis included 1199 patients aged ≥ 70 years with median follow-up of 42.6 months. Postoperative concurrent CRT was associated with improved overall survival (OS; hazard ratio [HR] 0.752; 95% confidence interval [CI] 0.638-0.886) compared to radiation alone in multivariable analysis. Three-year OS was 52.4% with CRT versus 43.4% with radiation (P = .012) in propensity-score matched cohorts. The survival impact of CRT varied by N classification (P = .002 for interaction), with benefit seen only in those with N2 to N3 disease. Postoperative concurrent CRT may benefit older patients with HNSCC with positive margins or ENE, particularly those with higher nodal burden. © 2018 Wiley Periodicals, Inc.

  10. Hypofractionated Nodal Radiation Therapy for Breast Cancer Was Not Associated With Increased Patient-Reported Arm or Brachial Plexopathy Symptoms.

    PubMed

    Leong, Nelson; Truong, Pauline T; Tankel, Keith; Kwan, Winkle; Weir, Lorna; Olivotto, Ivo A

    2017-12-01

    To determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25 to 2.5 Gy per fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx. Two cancer registries were used to identify subjects who received computed tomography-planned nodal RT for pT1-3, pN0-2, M0 breast cancer, from 2007 to 2010 at 2 cancer institutions. After ethics approval, patients were mailed an explanatory letter and the Self-reported Arm Symptom Scale, a validated instrument with 8 questions about arm symptoms and 5 related to activities of daily living. Clinicopathologic characteristics and Self-reported Arm Symptom Scale scores were compared between HF/CF cohorts using nonparametric analysis, χ 2 analysis, and multivariate ordinal regression. Of 1759 patients, 800 (45.5%) returned a completed survey. A total of 708 eligible cases formed the study cohort. Of these, 406 (57%) received HFRT (40 Gy/16 fx, 45 Gy/20 fx), and 302 (43%) received CFRT (45-50 Gy/25 fx, 50.4 Gy/28 fx). Median time interval after RT was 5.7 years. Forty-three percent and 75% of patients received breast-conserving surgery and chemotherapy, respectively. Twenty-two percent received breast boost RT, independent of fractionation. Median age at diagnosis was 59 years (HF) and 53 years (CF) (P<.001). The mean numbers of excised (n=12) and involved (n=3) nodes were similar between fractionation cohorts (P=.44), as were the mean sums of responses in arm symptoms (P=.17) and activities of daily living (P=.85). Patients receiving HF reported lower rates of shoulder stiffness (P=.04), trouble moving the arm (P=.02), and difficulty reaching overhead (P<.01) compared with the CF cohort. There was no difference in self-reported arm swelling or symptoms related to brachial plexopathy. Nodal RT with hypofractionation was not associated with increased patient-reported arm symptoms or functional deficits

  11. Differential role of Sloan–Kettering Institute (Ski) protein in Nodal and transforming growth factor-beta (TGF-β)-induced Smad signaling in prostate cancer cells

    PubMed Central

    Khan, Shafiq A.

    2012-01-01

    Transforming growth factor-beta (TGF-β) signaling pathways contain both tumor suppressor and tumor promoting activities. We have demonstrated that Nodal, another member of the TGF-β superfamily, and its receptors are expressed in prostate cancer cells. Nodal and TGF-β exerted similar biological effects on prostate cells; both inhibited proliferation in WPE, RWPE1 and DU145 cells, whereas neither had any effect on the proliferation of LNCaP or PC3 cells. Interestingly, Nodal and TGF-β induced migration in PC3 cells, but not in DU145 cells. TGF-β induced predominantly phosphorylation of Smad3, whereas Nodal induced phosphorylation of only Smad2. We also determined the expression and differential role of Ski, a corepressor of Smad2/3, in Nodal and TGF-β signaling in prostate cancer cells. Similar levels of Ski mRNA were found in several established prostate cell lines; however, high levels of Ski protein were only detected in prostate cancer cells and prostate cancer tissue samples. Exogenous Nodal and TGF-β had no effects on Ski mRNA levels. On the other hand, TGF-β induced a rapid degradation of Ski protein mediated by the proteasomal pathway, whereas Nodal had no effect on Ski protein. Reduced Ski levels correlated with increased basal and TGF-β-induced Smad2/3 phosphorylation. Knockdown of endogenous Ski reduced proliferation in DU145 cells and enhanced migration of PC3 cells. We conclude that high levels of Ski expression in prostate cancer cells may be responsible for repression of TGF-β and Smad3 signaling, but Ski protein levels do not influence Nodal and Smad2 signaling. PMID:22843506

  12. Prevalence, location and concurrent diseases of ultrasonographic cyst-like lesions of abdominal lymph nodes in dogs.

    PubMed

    Liotta, A; Billen, F; Heimann, M; Hamaide, A; Rizza, M; Etienne, A L; Bolen, G

    2017-04-01

    Lymph nodal cyst-like lesions are occasionally identified during abdominal ultrasound in dogs. However, a study evaluating their prevalence and clinical significance is lacking. The aim of this observational cross-sectional study was to evaluate prevalence, most common location and concurrent diseases of cyst-like lymph nodes detected during abdominal ultrasound. Affected lymph nodes, patient signalment and concurrent diseases of dogs with cyst-like lymph nodal lesions having undergone abdominal ultrasound over a one-year period were recorded. Twenty-three affected lymph nodes were observed in 17/553 dogs (prevalence=3 per cent). The most commonly affected was the lumbar lymphocenter (7/23), followed by the coeliac (6/23), the cranial mesenteric (5/23) and the iliosacral (5/23). Twenty-three concurrent diseases were diagnosed in 17 dogs, among which 16/23 were non-neoplastic (70 per cent). The most common concurrent disease was renal insufficiency (8/23), followed by neoplasia (7/23), gastroenteropathy (3/23), benign prostatic disease (2/23), pancreatitis (1/23), peritonitis (1/23) and neurological disease (1/23). No statistical correlation existed between cyst-like lymph nodal lesion and a specific neoplastic or non-neoplastic disease. In conclusion, in the present study, cyst-like lymph nodal lesions have a low prevalence, involve different lymphocenters and were found in dogs affected by different diseases, including both non-neoplastic and neoplastic aetiologies. British Veterinary Association.

  13. Cervical nodal metastases in squamous cell carcinoma of the head and neck: what to expect.

    PubMed

    Mukherji, S K; Armao, D; Joshi, V M

    2001-11-01

    The treatment and management of malignancies of the head and neck is directly altered by the presence of metastatic cervical adenopathy. The treatment of nodal metastases in squamous cell carcinoma of the head and neck (HNSCCA) is determined by the lymphatic drainage of the upper aerodigestive tract. The lymphatic drainage is site-specific and occurs in a predictable manner. The purpose of this text is to provide an overview of the normal routes of lymphatic drainage in the head and neck and correlate this with the current nodal classification system. The specific aims of this manuscript are to 1) illustrate the expected lymphatic drainage patterns of HNSCCA arising in the different subsites (nasopharynx, oropharynx, oral cavity, larynx, and hypopharynx) and 2) review the expected frequency of metastases within nodal groups for HNSCCA that arise in these locations. An understanding of the topographical distribution and incidence of cervical lymph node metastases plays an integral role in the physical examination and radiological evaluation of patients with HNSCCA. For the neuroradiologist, this information may increases the ability to identify those nodal groups at risk for metastatic involvement. Copyright 2001 John Wiley & Sons, Inc. Head Neck 23: 995-1005, 2001.

  14. Brady's Geothermal Field Nodal Seismometers Metadata

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lesley Parker

    Metadata for the nodal seismometer array deployed at the POROTOMO's Natural Laboratory in Brady Hot Spring, Nevada during the March 2016 testing. Metadata includes location and timing for each instrument as well as file lists of data to be uploaded in a separate submission.

  15. Reduced radiation dose for elective nodal irradiation in node-negative anal cancer: back to the roots?

    PubMed

    Henkenberens, Christoph; Meinecke, Daniela; Michael, Stoll; Bremer, Michael; Christiansen, Hans

    2015-11-01

    Chemoradiation (CRT) is the standard of care in patients with node-positive (cN+) and node-negative (cN0) anal cancer. Depending on the tumor size (T-stage), total doses of 50-60 Gray (Gy) in daily fractions of 1.8-2.0 Gy are usually applied to the tumor site. Inguinal and iliac lymph nodes usually receive a dose of ≥ 45 Gy. Since 2010, our policy has been to apply a reduced total dose of 39.6 Gy to uninvolved nodal regions. This paper provides preliminary results of the efficacy and safety of this protocol. Overall, 30 patients with histologically confirmed and node-negative anal cancer were treated in our department from 2009-2014 with definitive CRT. Histology all cases showed squamous cell carcinoma. A total dose of 39.6 Gy [single dose (SD) 1.8 Gy] was delivered to the iliac/inguinal lymph nodes. The area of the primary tumor received 50-59.4 Gy, depending on the T-stage. In parallel with the irradiation, 5-fluorouracil (5-FU) at a dose of 1000 mg/m(2) was administered by continuous intravenous infusion over 24 h on days 1-4 and 29-32, and mitomycin C (MMC) at a dose of 10 mg/m(2) (maximum absolute dose 14 mg) was administered on days 1 and 29. The distribution of the tumor stages was as follows: T1, n = 8; T2, n = 17; T3 n = 3. Overall survival (OS), local control (LC) of the lymph nodes, colostomy-free survival (CFS), and acute and chronic toxicities were assessed. The median follow-up was 27.3 months (range 2.7-57.4 months). Three patients (10.0 %) died, 2 of cardiopulmonary diseases and one of liver failure, yielding a 3-year OS of 90.0 %. Two patients (6.7 %) relapsed early and received salvage colostomies, yielding a 3-year CFS of 93.3 %. No lymph node relapses were observed, giving a lymph node LC of 100 %. According to the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE V. 4.0), there were no grade IV gastrointestinal or genitourinary acute toxicities. Seven patients showed acute grade

  16. The Effect of Anatomical Location of Lymph Node Metastases on Cancer Specific Survival in Patients with Clear Cell Renal Cell Carcinoma.

    PubMed

    Nini, Alessandro; Larcher, Alessandro; Cianflone, Francesco; Trevisani, Francesco; Terrone, Carlo; Volpe, Alessandro; Regis, Federica; Briganti, Alberto; Salonia, Andrea; Montorsi, Francesco; Bertini, Roberto; Capitanio, Umberto

    2018-01-01

    Positive nodal status (pN1) is an independent predictor of survival in renal cell carcinoma (RCC) patients. However, no study to date has tested whether the location of lymph node (LN) metastases does affect oncologic outcomes in a population submitted to radical nephrectomy (RN) and extended lymph node dissection (eLND). To describe nodal disease dissemination in clear cell RCC (ccRCC) patients and to assess the effect of the anatomical sites and the number of nodal areas affected on cancer specific mortality (CSM). The study included 415 patients who underwent RN and eLND, defined as the removal of hilar, side-specific (pre/paraaortic or pre/paracaval) and interaortocaval LNs for ccRCC, at two institutions. Descriptive statistics were used to depict nodal dissemination in pN1 patients, stratified according to nodal site and number of involved areas. Multivariable Cox regression analyses and Kaplan-Meier curves were used to explore the relationship between pN1 disease features and survival outcomes. Median number of removed LN was 14 (IQR 9-19); 23% of patients were pN1. Among patients with one involved nodal site, 54 and 26% of patients were positive only in side-specific and interaortocaval station, respectively. The most frequent nodal site was the interaortocaval and side-specific one, for right and left ccRCC, respectively. Interaortocaval nodal positivity (HR 2.3, CI 95%: 1.3-3.9, p < 0.01) represented an independent predictor of CSM. When ccRCC patient harbour nodal disease, its spreading can occur at any nodal station without involving the others. The presence of interoartocaval positive nodes does affect oncologic outcomes. Lymph node invasion in patients with clear cell renal cell carcinoma is not following a fixed anatomical pattern. An extended lymph node dissection, during treatment for primary kidney tumour, would aid patient risk stratification and multimodality upfront treatment.

  17. Left-right asymmetry in the level of active Nodal protein produced in the node is translated into left-right asymmetry in the lateral plate of mouse embryos.

    PubMed

    Kawasumi, Aiko; Nakamura, Tetsuya; Iwai, Naomi; Yashiro, Kenta; Saijoh, Yukio; Belo, Jose Antonio; Shiratori, Hidetaka; Hamada, Hiroshi

    2011-05-15

    Left-right (L-R) asymmetry in the mouse embryo is generated in the node and is dependent on cilia-driven fluid flow, but how the initial asymmetry is transmitted from the node to the lateral plate has remained unknown. We have now identified a transcriptional enhancer (ANE) in the human LEFTY1 gene that exhibits marked L>R asymmetric activity in perinodal cells of the mouse embryo. Dissection of ANE revealed that it is activated in the perinodal cells on the left side by Nodal signaling, suggesting that Nodal activity in the node is asymmetric at a time when Nodal expression is symmetric. Phosphorylated Smad2/3 (pSmad2) indeed manifested an L-R asymmetric distribution at the node, being detected in perinodal cells preferentially on the left side. This asymmetry in pSmad2 distribution was found to be generated not by unidirectional transport of Nodal but rather as a result of LNodal antagonist Cerl2. For various mutant embryos examined, the asymmetry in pSmad2 distribution among the perinodal cells closely matched that in lateral plate mesoderm (LPM). However, autocrine-paracrine Nodal signaling in perinodal cells is dispensable for L-R patterning of LPM, given that its inhibition by expression of dominant negative forms of Smad3 or ALK4 was still associated with normal (left-sided) Nodal expression in LPM. Our results suggest that LPM is the direct target of Nodal secreted by the perinodal cells, and that an L>R distribution of active Nodal in the node is translated into the asymmetry in LPM. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Amplification and protein overexpression of cyclin D1: Predictor of occult nodal metastasis in early oral cancer.

    PubMed

    Noorlag, Rob; Boeve, Koos; Witjes, Max J H; Koole, Ronald; Peeters, Ton L M; Schuuring, Ed; Willems, Stefan M; van Es, Robert J J

    2017-02-01

    Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain (FADD), and CTTN, is often amplified in oral cancer with nodal metastases. However, evidence in predicting occult nodal metastases is limited. In 158 patients with early tongue and floor of mouth (FOM) squamous cell carcinomas, both CCND1 amplification and cyclin D1, FADD, and cortactin protein expression were correlated with occult nodal metastases. CCND1 amplification and cyclin D1 expression correlated with occult nodal metastases. Cyclin D1 expression was validated in an independent multicenter cohort, confirming the correlation with occult nodal metastases in early FOM cancers. Cyclin D1 is a predictive biomarker for occult nodal metastases in early FOM cancers. Prospective research on biopsy material should confirm these results before implementing its use in routine clinical practice. © 2016 Wiley Periodicals, Inc. Head Neck 39: 326-333, 2017. © 2016 Wiley Periodicals, Inc.

  19. Brady's Geothermal Field - Map of DAS, Nodal, Vibroseis and Reftek Station Deployment

    DOE Data Explorer

    Kurt Feigl

    2016-10-15

    Map of DAS, nodal, vibroseis and Reftek stations during March 2016 deployment. The plot on the left has nodal stations labeled; the plot on the right has vibroseis observations labeled. Stations are shown in map-view using Brady's rotated X-Y coordinates with side plots denoting elevation with respect to the WGS84 ellipsoid. Blue circles denote vibroseis data, x symbols denote DAS (cyan for horizontal and magenta for vertical), black asterisks denote Reftek data, and red plus signs denote nodal data. This map can be found on UW-Madison's askja server at /PoroTomo/DATA/MAPS/Deployment_Stations.pdf

  20. Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

    PubMed Central

    van den Brand, Michiel; van Krieken, J. Han J.M.

    2013-01-01

    The diagnosis of nodal marginal zone lymphoma is one of the remaining problem areas in hematopathology. Because no established positive markers exist for this lymphoma, it is frequently a diagnosis of exclusion, making distinction from other low-grade B-cell lymphomas difficult or even impossible. This systematic review summarizes and discusses the current knowledge on nodal marginal zone lymphoma, including clinical features, epidemiology and etiology, histology, and cytogenetic and molecular features. In particular, recent advances in diagnostics and pathogenesis are discussed. New immunohistochemical markers have become available that could be used as positive markers for nodal marginal zone lymphoma. These markers could be used to ensure more homogeneous study groups in future research. Also, recent gene expression studies and studies describing specific gene mutations have provided clues to the pathogenesis of nodal marginal zone lymphoma, suggesting deregulation of the nuclear factor kappa B pathway. Nevertheless, nodal marginal zone lymphoma remains an enigmatic entity, requiring further study to define its pathogenesis to allow an accurate diagnosis and tailored treatment. However, recent data indicate that it is not related to splenic or extranodal lymphoma, and that it is also not related to lymphoplasmacytic lymphoma. Thus, even though the diagnosis is not always easy, it is clearly a separate entity. PMID:23813646

  1. Fusion positron emission/computed tomography underestimates the presence of hilar nodal metastases in patients with resected non-small cell lung cancer.

    PubMed

    Carrillo, Sergio A; Daniel, Vincent C; Hall, Nathan; Hitchcock, Charles L; Ross, Patrick; Kassis, Edmund S

    2012-05-01

    The 5-year survival for patients with resected stage II (N1) non-small cell lung cancer ranges from 40% to 55%. No data exist addressing the benefit of neoadjuvant therapy for patients with stage II disease. This is largely in part due to the lack of a reliable, minimally invasive method to assess hilar nodes. This study is aimed at determining the ability of fusion positron emission/computed tomography (PET/CT) to identify hilar metastases in patients with resected non-small cell lung cancer. A retrospective review of surgically resected patients with fusion PET/CT within 30 days of resection was performed. The sensitivity, specificity, positive predictive value, and negative predictive value for PET/CT in detecting hilar nodal metastases was calculated for a range of maximum standardized uptake values (SUVmax). Hilar nodes from patients with falsely positive PET/CT scans were analyzed for the presence of histoplasmosis. Additionally, the impact of hilar node size greater than 1 centimeter on the calculated values was assessed. There were 119 patients evaluated. The number of lymph nodes resected ranged from 1 to 12 (X=2.98). There was decreased sensitivity and increased specificity with higher SUVmax cutoff values. At the standard SUVmax value of 2.5, the sensitivity and specificity were only 48.5% and 80.2%. The addition of size of hilar node by CT led to a modest improvement in sensitivity at all SUVmax cutoff values. Fusion PET/CT lacks sensitivity and specificity in identifying hilar nodal metastasis in patients with resected non-small cell lung cancer. Further prospective studies assessing the utility of PET/CT versus alternative sampling techniques are warranted. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Para-aortic nodal metastases in cervical cancer: a blind spot in the International Federation of Gynecology and Obstetrics staging system: current diagnosis and management.

    PubMed

    Hwang, Lindsay; Bailey, April; Lea, Jayanthi; Albuquerque, Kevin

    2015-01-01

    In cervical cancer, para-aortic nodal (PALN) metastases at presentation is a strong indicator of poor prognosis. Despite this, International Federation of Gynecology and Obstetrics staging system does not require evaluation of lymph node involvement and does not incorporate clinically detected PALN into the staging system. In the USA, despite screening, a significant number of women still present at an advanced stage often with nodal metastases. While the presence of PALN metastases often indicates occult systemic disease, it is possible with modern therapies to provide long-term control of disease in a percentage of patients. We review the epidemiology, diagnosis and treatment of PALN metastases in cervical cancer outlining advances in modern imaging and combined modality therapies (surgery, chemotherapy and radiation therapy).

  3. Neuroendocrine Merkel cell nodal carcinoma of unknown primary site: management and outcomes of a rare entity.

    PubMed

    Kotteas, E A; Pavlidis, N

    2015-04-01

    Merkel cell nodal carcinoma of unknown primary (MCCUP) is a rare neuroendocrine tumour with distinct clinical and biological behaviour. We conducted a review of retrospective data extracted from 90 patients focusing on the management and outcome of this disease. We also compared life expectancy of these patients with the outcome of patients with known Merkel primaries and with neuroendocrine cancers of unidentifiable primary. There is a limited body of data for this type of malignancy, however, patients with Merkel cell nodal carcinoma of unknown primary site, seem to have better survival when treated aggressively than patients with cutaneous Merkel tumours of the same stage and equal survival with patients with low-grade neuroendocrine tumour of unknown origin. The lack of prospective trials, and the inadequate data, hamper the management of these tumours. Establishment of treatment guidelines is urgently needed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Concurrent chemoradiotherapy with S-1 in patients with stage III-IV oral squamous cell carcinoma: A retrospective analysis of nodal classification based on the neck node level.

    PubMed

    Murakami, Ryuji; Semba, Akiko; Kawahara, Kenta; Matsuyama, Keiya; Hiraki, Akimitsu; Nagata, Masashi; Toya, Ryo; Yamashita, Yasuyuki; Oya, Natsuo; Nakayama, Hideki

    2017-07-01

    The aim of the present study was to retrospectively evaluate the treatment outcomes of concurrent chemoradiotherapy (CCRT) with S-1, an oral fluoropyrimidine anticancer agent, for advanced oral squamous cell carcinoma (SCC). The study population consisted of 47 patients with clinical stage III or IV oral SCC, who underwent CCRT with S-1. Pretreatment variables, including patient age, clinical stage, T classification, midline involvement of the primary tumor and nodal status, were analyzed as predictors of survival. In addition to the N classification (node-positive, multiple and contralateral), the prognostic impact of the level of nodal involvement was assessed. Nodal involvement was mainly observed at levels Ib and II; involvement at levels Ia and III-V was considered to be anterior and inferior extension, respectively, and was recorded as extensive nodal involvement (ENI). The 3-year overall survival (OS) and progression-free survival (PFS) rates were 37 and 27%, respectively. A finding of ENI was a significant factor for OS [hazard ratio (HR)=2.16; 95% confidence interval (CI): 1.03-4.55; P=0.038] and PFS (HR=2.65; 95% CI: 1.32-5.33; P=0.005); the 3-year OS and PFS rates in patients with vs. those without ENI were 23 vs. 50% and 9 vs. 43%, respectively. The other variables were not significant. Therefore, CCRT with S-1 may be an alternative treatment for advanced oral SCC; favorable outcomes are expected in patients without ENI.

  5. Retrospective Analysis of Outcome Differences in Preoperative Concurrent Chemoradiation With or Without Elective Nodal Irradiation for Esophageal Squamous Cell Carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hsu, Feng-Ming; Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan

    2011-11-15

    Purpose: To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. Methods and Materials: We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-freemore » survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. Results: The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. Conclusions: ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for

  6. Retrospective analysis of outcome differences in preoperative concurrent chemoradiation with or without elective nodal irradiation for esophageal squamous cell carcinoma.

    PubMed

    Hsu, Feng-Ming; Lee, Jang-Ming; Huang, Pei-Ming; Lin, Chia-Chi; Hsu, Chih-Hung; Tsai, Yu-Chieh; Lee, Yung-Chie; Chia-Hsien Cheng, Jason

    2011-11-15

    To evaluate the efficacy and patterns of failure of elective nodal irradiation (ENI) in patients with esophageal squamous cell carcinoma (SCC) undergoing preoperative concurrent chemoradiation (CCRT) followed by radical surgery. We retrospectively studied 118 patients with AJCC Stage II to III esophageal SCC undergoing preoperative CCRT (median, 36 Gy), followed by radical esophagectomy. Of them, 73 patients (62%) had ENI and 45 patients (38%) had no ENI. Patients with ENI received radiotherapy to either supraclavicular (n = 54) or celiac (n = 19) lymphatics. Fifty-six patients (57%) received chemotherapy with paclitaxel plus cisplatin. The 3-year progression-free survival, overall survival, and patterns of failure were analyzed. Distant nodal recurrence was classified into M1a and M1b regions. A separate analysis using matched cases was conducted. The median follow-up was 38 months. There were no differences in pathological complete response rate (p = 0.12), perioperative mortality rate (p = 0.48), or delayed Grade 3 or greater cardiopulmonary toxicities (p = 0.44), between the groups. More patients in the non-ENI group had M1a failure than in the ENI group, with 3-year rates of 11% and 3%, respectively (p = 0.05). However, the 3-year isolated distant nodal (M1a + M1b) failure rates were not different (ENI, 10%; non-ENI, 14%; p = 0.29). In multivariate analysis, pathological nodal status was the only independent prognostic factor associated with overall survival (hazard ratio = 1.78, p = 0.045). The 3-year overall survival and progression-free survival were 45% and 45%, respectively, in the ENI group, and 52% and 43%, respectively, in the non-ENI group (p = 0.31 and 0.89, respectively). Matched cases analysis did not show a statistical difference in outcomes between the groups. ENI reduced the M1a failure rate but was not associated with improved outcomes in patients undergoing preoperative CCRT for esophageal SCC. Pathological nodal metastasis predicted poor

  7. Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Predictor of Outcome in Head-and-Neck Squamous Cell Carcinoma Patients With Nodal Metastases

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shukla-Dave, Amita, E-mail: davea@mskcc.org; Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY; Lee, Nancy Y.

    2012-04-01

    Purpose: Dynamic contrast-enhanced MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of this study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery. Methods and Materials: Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using the Tofts model. DCE-MRI parameters weremore » related to treatment outcome (progression-free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD), or dead of other causes (DOC). Prognostic significance was assessed using the log-rank test for single variables and Cox proportional hazards regression for combinations of variables. Results: At last clinical follow-up, for Stage III, all 12 patients were NED. For Stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. K{sup trans} is volume transfer constant. In a stepwise Cox regression, skewness of K{sup trans} (volume transfer constant) was the strongest predictor for Stage IV patients (PFS and OS: p <0.001). Conclusion: Our study shows that skewness of K{sup trans} was the strongest predictor of PFS and OS in Stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter K{sup trans} as a predictor of outcome in these patients.« less

  8. Implications of improved diagnostic imaging of small nodal metastases in head and neck cancer: Radiotherapy target volume transformation and dose de-escalation.

    PubMed

    van den Bosch, Sven; Vogel, Wouter V; Raaijmakers, Cornelis P; Dijkema, Tim; Terhaard, Chris H J; Al-Mamgani, Abrahim; Kaanders, Johannes H A M

    2018-05-03

    Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and "gross" tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10-15 mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity-modulated radiotherapy: a Phase 2 study.

    PubMed

    Li, Mei; Huang, Xiao-Guang; Yang, Zhi-Ning; Lu, Jia-Yang; Zhan, Yi-Zhou; Xie, Wen-Jia; Zhou, Dong-Jie; Wang, Li; Zhu, Di-Xia; Lin, Zhi-Xiong

    2016-09-01

    To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT). We conducted a Phase 2 prospective study in 123 newly diagnosed IB-negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node ≥2 cm/with extracapsular spread; (2) ≥2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated. Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high-dose irradiation with a mean dose (Dmean) ≥50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy. ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted. Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT.

  10. Emergent loop-nodal s(±)-wave superconductivity in CeCu(2)Si(2): similarities to the iron-based superconductors.

    PubMed

    Ikeda, Hiroaki; Suzuki, Michi-To; Arita, Ryotaro

    2015-04-10

    Heavy-fermion superconductors are prime candidates for novel electron-pairing states due to the spin-orbital coupled degrees of freedom and electron correlations. Superconductivity in CeCu_{2}Si_{2} discovered in 1979, which is a prototype of unconventional (non-BCS) superconductors in strongly correlated electron systems, still remains unsolved. Here we provide the first report of superconductivity based on the advanced first-principles theoretical approach. We find that the promising candidate is an s_{±}-wave state with loop-shaped nodes on the Fermi surface, different from the widely expected line-nodal d-wave state. The dominant pairing glue is magnetic but high-rank octupole fluctuations. This system shares the importance of multiorbital degrees of freedom with the iron-based superconductors. Our findings reveal not only the long-standing puzzle in this material, but also urge us to reconsider the pairing states and mechanisms in all heavy-fermion superconductors.

  11. Transport and optics at the node in a nodal loop semimetal

    NASA Astrophysics Data System (ADS)

    Mukherjee, S. P.; Carbotte, J. P.

    2017-06-01

    We use a Kubo formalism to calculate both AC conductivity and DC transport properties of a dirty nodal loop semimetal. The optical conductivity as a function of photon energy Ω exhibits an extended flat background σBG as in graphene provided the scattering rate Γ is small as compared to the radius of the nodal ring b (in energy units). Modifications to the constant background arise for Ω ≤Γ and the minimum DC conductivity σDC, which is approached as Ω22 as Ω →0 , is found to be proportional to √{Γ/2+b2 }vF with vF the Fermi velocity. For b =0 we recover the known three-dimensional point node Dirac result σDC˜Γ/vF while for b >Γ , σDC becomes independent of Γ (universal) and the ratio σ/DCσBG=8/π2 where all reference to material parameters has dropped out. As b is reduced and becomes of the order Γ , the flat background is lost as the optical response evolves towards that of a three-dimensional point node Dirac semimetal which is linear in Ω for the clean limit. For finite Γ there are modifications from linearity in the photon region Ω ≤Γ . When the chemical potential μ (temperature T ) is nonzero the DC conductivity increases as μ22 (T22 ) for μ/Γ (T/Γ )≤1 . Such laws apply as well for thermal conductivity and thermopower with coefficients of the quadratic law only slightly modified from their value in the three-dimensional point node Dirac case. However in the μ =T =0 limit both have the same proportionality factor of √{Γ2+b2 } as does σDC. Consequently the Lorentz number is largely unmodified. For larger values of μ >Γ away from the nodal region the conductivity shows a Drude-like contribution about Ω ≊0 which is followed by a dip in the Pauli blocked region Ω ≤2 μ after which it increases to merge with the flat background (two-dimensional graphene like) for μ b .

  12. NODAL in the Uterus Is Necessary for Proper Placental Development and Maintenance of Pregnancy1

    PubMed Central

    Park, Craig B.; DeMayo, Francesco J.; Lydon, John P.; Dufort, Daniel

    2012-01-01

    Preterm birth is the single leading cause of perinatal mortality in developed countries, affecting approximately 12% of pregnancies and accounting for 75% of neonatal loss in the United States. Despite the prevalence and severity of premature delivery, the causes and mechanisms that underlie spontaneous and idiopathic preterm birth remain unknown. Our inability to elucidate these fundamental causes has been attributed to a poor understanding of the signaling pathways associated with the premature induction of parturition and a lack of suitable animal models available for preterm birth research. In this study, we describe the generation and analysis of a novel conditional knockout of the transforming growth factor beta (TGFB) superfamily member, Nodal, from the maternal reproductive tract of mice. Strikingly, uterine Nodal knockout females exhibited a severe malformation of the maternal decidua basalis during placentation, leading to significant intrauterine growth restriction, and ultimately preterm birth and fetal loss on Day 17.5 of gestation. Using several approaches, we characterized aberrant placental development and demonstrated that reduced proliferation combined with increased apoptosis resulted in a diminished decidua basalis and compromised maternal-fetal interface. Last, we evaluated various components of the established parturition cascade and determined that preterm birth derived from the maternal Nodal knockout occurs prior to PTGS2 (COX-2) upregulation at the placental interface. Taken together, the results presented in this study highlight an in vivo role for maternal NODAL during placentation, present an interesting link between disrupted decidua basalis formation and premature parturition, and describe a potentially valuable model toward elucidating the complex processes that underlie preterm birth. PMID:22378764

  13. A standardized technique of systematic mediastinal lymph node dissection by video-assisted thoracoscopic surgery (VATS) leads to a high rate of nodal upstaging in early-stage non-small cell lung cancer.

    PubMed

    Reichert, Martin; Steiner, Dagmar; Kerber, Stefanie; Bender, Julia; Pösentrup, Bernd; Hecker, Andreas; Bodner, Johannes

    2016-03-01

    A substantial part of the oncologic surgical procedure in non-small cell lung cancer (NSCLC) is systematic lymph node dissection (sLND). However, controversies still exist regarding the quality of minimally invasive (video-assisted thoracoscopic surgery, VATS) sLND in oncologic resections. The rate of stage migration from clinical to pathological N-status has been discussed as one parameter for the quality of sLND. Between March 2011 and May 2014, seventy-seven patients (62 male, 15 female) were scheduled for anatomical lung resection and sLND by VATS for clinical stage I (UICC 7th edition) NSCLC. Preoperative staging was performed by [18F]-fluorodesoxyglucose positron emission tomography with computed tomography (FDG-PET/CT). Patient data were retrospectively analyzed with regard to divergence in clinical and pathological N-factor. FDG-PET/CTs of patients with lymph node (LN) upstaging after VATS resections were blindly re-evaluated by an experienced radiologist. In FDG-PET/CT, preoperative tumor stage was cT1N0M0 in 41 (53.2%) and cT2aN0M0 in 28 (36.4%) patients. In six (7.8%) patients the primary tumor was not suspicious for malignancy, and in two (2.6%) patients the tumor was not evaluable due to prior wedge resection before FDG-PET/CT. Thirty-one (40.3%) left-sided and 46 (59.7%) right-sided pulmonary resections with sLND were performed; 19.57 ± 0.99 LNs were dissected. In 13 (16.9%) patients a nodal stage migration from preoperative clinical to postoperative pathological N-stage was observed [cN0 to pN1 in 9 (11.7%) and cN0 to pN2 in 4 (5.2%) cases]. In correlation to the clinical T-factor, the rate of N-factor upstaging for cT1 was 12.2% and for cT2a was 28.6%, respectively. In 50% of the patients with postoperative nodal staging shift, no changes were observed on re-evaluation of the preoperative FDG-PET/CT. In this series of clinical stage I NSCLC patients, the rate of nodal stage migration after sLND by VATS is higher than previously reported

  14. Predictors of Nodal Upstaging in Clinical Node Negative Patients With Penile Carcinoma: A National Cancer Database Analysis.

    PubMed

    Winters, Brian R; Mossanen, Matthew; Holt, Sarah K; Lin, Daniel W; Wright, Jonathan L

    2016-10-01

    To examine the risk factors associated with upstaging at inguinal lymph node dissection (ILND) in men with penile cancer and clinically negative lymph nodes (cN0) using a large US cancer database. The National Cancer Data Base was queried from 1998 to 2012 to identify men with penile cancer who underwent ILND and had complete clinical or pathologic node status available. Lymphovascular invasion (LVI) was available after 2010. Multivariate logistic regression evaluated factors (cT stage, grade, LVI) associated with pathologic nodal upstaging in those with cN0 disease. Correlations between clinical and pathologic node status were also calculated with weighted kappa statistics. Complete clinical and pathologic LN status was available for 875 patients. Of these, 461 (53%) were cN0. Upstaging occurred in 111 (24%). When stratified by low, intermediate, and high-risk groups, the proportion with pathologically positive LNs was 16%, 20%, and 27%, respectively (P = .12). On multivariate analysis, limited to men with LVI data available (N = 206), LVI (odds ratio 3.10, 95% confidence interval 1.39-6.92), but not increasing stage (univariate only) or grade (univariate only), was significantly associated with upstaging at ILND. In this analysis, of 461 patients with node-negative penile cancer undergoing ILND, upstaging was observed in 24%. LVI was the strongest independent predictor of occult lymph node disease. These findings corroborate the presence of LVI as the significant risk factor for occult micrometastases and suggest a possible improvement in existing risk stratification groupings, with the presence of LVI, regardless of stage or grade, to be considered high-risk disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A nodal signaling pathway regulates the laterality of neuroanatomical asymmetries in the zebrafish forebrain.

    PubMed

    Concha, M L; Burdine, R D; Russell, C; Schier, A F; Wilson, S W

    2000-11-01

    Animals show behavioral asymmetries that are mediated by differences between the left and right sides of the brain. We report that the laterality of asymmetric development of the diencephalic habenular nuclei and the photoreceptive pineal complex is regulated by the Nodal signaling pathway and by midline tissue. Analysis of zebrafish embryos with compromised Nodal signaling reveals an early role for this pathway in the repression of asymmetrically expressed genes in the diencephalon. Later signaling mediated by the EGF-CFC protein One-eyed pinhead and the forkhead transcription factor Schmalspur is required to overcome this repression. When expression of Nodal pathway genes is either absent or symmetrical, neuroanatomical asymmetries are still established but are randomized. This indicates that Nodal signaling is not required for asymmetric development per se but is essential to determine the laterality of the asymmetry.

  16. Nodal signalling in Xenopus: the role of Xnr5 in left/right asymmetry and heart development.

    PubMed

    Tadjuidje, Emmanuel; Kofron, Matthew; Mir, Adnan; Wylie, Christopher; Heasman, Janet; Cha, Sang-Wook

    2016-08-01

    Nodal class TGF-β signalling molecules play essential roles in establishing the vertebrate body plan. In all vertebrates, nodal family members have specific waves of expression required for tissue specification and axis formation. In Xenopus laevis, six nodal genes are expressed before gastrulation, raising the question of whether they have specific roles or act redundantly with each other. Here, we examine the role of Xnr5. We find it acts at the late blastula stage as a mesoderm inducer and repressor of ectodermal gene expression, a role it shares with Vg1. However, unlike Vg1, Xnr5 depletion reduces the expression of the nodal family member xnr1 at the gastrula stage. It is also required for left/right laterality by controlling the expression of the laterality genes xnr1, antivin (lefty) and pitx2 at the tailbud stage. In Xnr5-depleted embryos, the heart field is established normally, but symmetrical reduction in Xnr5 levels causes a severely stunted midline heart, first evidenced by a reduction in cardiac troponin mRNA levels, while left-sided reduction leads to randomization of the left/right axis. This work identifies Xnr5 as the earliest step in the signalling pathway establishing normal heart laterality in Xenopus. © 2016 The Authors.

  17. The Effect of Anatomical Location of Lymph Node Metastases on Cancer Specific Survival in Patients with Clear Cell Renal Cell Carcinoma

    PubMed Central

    Nini, Alessandro; Larcher, Alessandro; Cianflone, Francesco; Trevisani, Francesco; Terrone, Carlo; Volpe, Alessandro; Regis, Federica; Briganti, Alberto; Salonia, Andrea; Montorsi, Francesco; Bertini, Roberto; Capitanio, Umberto

    2018-01-01

    Background Positive nodal status (pN1) is an independent predictor of survival in renal cell carcinoma (RCC) patients. However, no study to date has tested whether the location of lymph node (LN) metastases does affect oncologic outcomes in a population submitted to radical nephrectomy (RN) and extended lymph node dissection (eLND). Objective To describe nodal disease dissemination in clear cell RCC (ccRCC) patients and to assess the effect of the anatomical sites and the number of nodal areas affected on cancer specific mortality (CSM). Design, setting and partecipants The study included 415 patients who underwent RN and eLND, defined as the removal of hilar, side-specific (pre/paraaortic or pre/paracaval) and interaortocaval LNs for ccRCC, at two institutions. Outcome measurement and statistical analysis Descriptive statistics were used to depict nodal dissemination in pN1 patients, stratified according to nodal site and number of involved areas. Multivariable Cox regression analyses and Kaplan-Meier curves were used to explore the relationship between pN1 disease features and survival outcomes. Results and limitations Median number of removed LN was 14 (IQR 9–19); 23% of patients were pN1. Among patients with one involved nodal site, 54 and 26% of patients were positive only in side-specific and interaortocaval station, respectively. The most frequent nodal site was the interaortocaval and side-specific one, for right and left ccRCC, respectively. Interaortocaval nodal positivity (HR 2.3, CI 95%: 1.3–3.9, p < 0.01) represented an independent predictor of CSM. Conclusions When ccRCC patient harbour nodal disease, its spreading can occur at any nodal station without involving the others. The presence of interoartocaval positive nodes does affect oncologic outcomes. Patient summary Lymph node invasion in patients with clear cell renal cell carcinoma is not following a fixed anatomical pattern. An extended lymph node dissection, during treatment for primary

  18. The Maternal Maverick/GDF15-like TGF-β Ligand Panda Directs Dorsal-Ventral Axis Formation by Restricting Nodal Expression in the Sea Urchin Embryo.

    PubMed

    Haillot, Emmanuel; Molina, Maria Dolores; Lapraz, François; Lepage, Thierry

    2015-01-01

    Specification of the dorsal-ventral axis in the highly regulative sea urchin embryo critically relies on the zygotic expression of nodal, but whether maternal factors provide the initial spatial cue to orient this axis is not known. Although redox gradients have been proposed to entrain the dorsal-ventral axis by acting upstream of nodal, manipulating the activity of redox gradients only has modest consequences, suggesting that other factors are responsible for orienting nodal expression and defining the dorsal-ventral axis. Here we uncover the function of Panda, a maternally provided transforming growth factor beta (TGF-β) ligand that requires the activin receptor-like kinases (Alk) Alk3/6 and Alk1/2 receptors to break the radial symmetry of the embryo and orient the dorsal-ventral axis by restricting nodal expression. We found that the double inhibition of the bone morphogenetic protein (BMP) type I receptors Alk3/6 and Alk1/2 causes a phenotype dramatically more severe than the BMP2/4 loss-of-function phenotype, leading to extreme ventralization of the embryo through massive ectopic expression of nodal, suggesting that an unidentified signal acting through BMP type I receptors cooperates with BMP2/4 to restrict nodal expression. We identified this ligand as the product of maternal Panda mRNA. Double inactivation of panda and bmp2/4 led to extreme ventralization, mimicking the phenotype caused by inactivation of the two BMP receptors. Inhibition of maternal panda mRNA translation disrupted the early spatial restriction of nodal, leading to persistent massive ectopic expression of nodal on the dorsal side despite the presence of Lefty. Phylogenetic analysis indicates that Panda is not a prototypical BMP ligand but a member of a subfamily of TGF-β distantly related to Inhibins, Lefty, and TGF-β that includes Maverick from Drosophila and GDF15 from vertebrates. Indeed, overexpression of Panda does not appear to directly or strongly activate phosphoSmad1

  19. The Maternal Maverick/GDF15-like TGF-β Ligand Panda Directs Dorsal-Ventral Axis Formation by Restricting Nodal Expression in the Sea Urchin Embryo

    PubMed Central

    Haillot, Emmanuel; Molina, Maria Dolores; Lapraz, François; Lepage, Thierry

    2015-01-01

    Specification of the dorsal-ventral axis in the highly regulative sea urchin embryo critically relies on the zygotic expression of nodal, but whether maternal factors provide the initial spatial cue to orient this axis is not known. Although redox gradients have been proposed to entrain the dorsal-ventral axis by acting upstream of nodal, manipulating the activity of redox gradients only has modest consequences, suggesting that other factors are responsible for orienting nodal expression and defining the dorsal-ventral axis. Here we uncover the function of Panda, a maternally provided transforming growth factor beta (TGF-β) ligand that requires the activin receptor-like kinases (Alk) Alk3/6 and Alk1/2 receptors to break the radial symmetry of the embryo and orient the dorsal-ventral axis by restricting nodal expression. We found that the double inhibition of the bone morphogenetic protein (BMP) type I receptors Alk3/6 and Alk1/2 causes a phenotype dramatically more severe than the BMP2/4 loss-of-function phenotype, leading to extreme ventralization of the embryo through massive ectopic expression of nodal, suggesting that an unidentified signal acting through BMP type I receptors cooperates with BMP2/4 to restrict nodal expression. We identified this ligand as the product of maternal Panda mRNA. Double inactivation of panda and bmp2/4 led to extreme ventralization, mimicking the phenotype caused by inactivation of the two BMP receptors. Inhibition of maternal panda mRNA translation disrupted the early spatial restriction of nodal, leading to persistent massive ectopic expression of nodal on the dorsal side despite the presence of Lefty. Phylogenetic analysis indicates that Panda is not a prototypical BMP ligand but a member of a subfamily of TGF-β distantly related to Inhibins, Lefty, and TGF-β that includes Maverick from Drosophila and GDF15 from vertebrates. Indeed, overexpression of Panda does not appear to directly or strongly activate phosphoSmad1

  20. An approach to model reactor core nodalization for deterministic safety analysis

    NASA Astrophysics Data System (ADS)

    Salim, Mohd Faiz; Samsudin, Mohd Rafie; Mamat @ Ibrahim, Mohd Rizal; Roslan, Ridha; Sadri, Abd Aziz; Farid, Mohd Fairus Abd

    2016-01-01

    Adopting good nodalization strategy is essential to produce an accurate and high quality input model for Deterministic Safety Analysis (DSA) using System Thermal-Hydraulic (SYS-TH) computer code. The purpose of such analysis is to demonstrate the compliance against regulatory requirements and to verify the behavior of the reactor during normal and accident conditions as it was originally designed. Numerous studies in the past have been devoted to the development of the nodalization strategy for small research reactor (e.g. 250kW) up to the bigger research reactor (e.g. 30MW). As such, this paper aims to discuss the state-of-arts thermal hydraulics channel to be employed in the nodalization for RTP-TRIGA Research Reactor specifically for the reactor core. At present, the required thermal-hydraulic parameters for reactor core, such as core geometrical data (length, coolant flow area, hydraulic diameters, and axial power profile) and material properties (including the UZrH1.6, stainless steel clad, graphite reflector) have been collected, analyzed and consolidated in the Reference Database of RTP using standardized methodology, mainly derived from the available technical documentations. Based on the available information in the database, assumptions made on the nodalization approach and calculations performed will be discussed and presented. The development and identification of the thermal hydraulics channel for the reactor core will be implemented during the SYS-TH calculation using RELAP5-3D® computer code. This activity presented in this paper is part of the development of overall nodalization description for RTP-TRIGA Research Reactor under the IAEA Norwegian Extra-Budgetary Programme (NOKEBP) mentoring project on Expertise Development through the Analysis of Reactor Thermal-Hydraulics for Malaysia, denoted as EARTH-M.

  1. An approach to model reactor core nodalization for deterministic safety analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Salim, Mohd Faiz, E-mail: mohdfaizs@tnb.com.my; Samsudin, Mohd Rafie, E-mail: rafies@tnb.com.my; Mamat Ibrahim, Mohd Rizal, E-mail: m-rizal@nuclearmalaysia.gov.my

    Adopting good nodalization strategy is essential to produce an accurate and high quality input model for Deterministic Safety Analysis (DSA) using System Thermal-Hydraulic (SYS-TH) computer code. The purpose of such analysis is to demonstrate the compliance against regulatory requirements and to verify the behavior of the reactor during normal and accident conditions as it was originally designed. Numerous studies in the past have been devoted to the development of the nodalization strategy for small research reactor (e.g. 250kW) up to the bigger research reactor (e.g. 30MW). As such, this paper aims to discuss the state-of-arts thermal hydraulics channel to bemore » employed in the nodalization for RTP-TRIGA Research Reactor specifically for the reactor core. At present, the required thermal-hydraulic parameters for reactor core, such as core geometrical data (length, coolant flow area, hydraulic diameters, and axial power profile) and material properties (including the UZrH{sub 1.6}, stainless steel clad, graphite reflector) have been collected, analyzed and consolidated in the Reference Database of RTP using standardized methodology, mainly derived from the available technical documentations. Based on the available information in the database, assumptions made on the nodalization approach and calculations performed will be discussed and presented. The development and identification of the thermal hydraulics channel for the reactor core will be implemented during the SYS-TH calculation using RELAP5-3D{sup ®} computer code. This activity presented in this paper is part of the development of overall nodalization description for RTP-TRIGA Research Reactor under the IAEA Norwegian Extra-Budgetary Programme (NOKEBP) mentoring project on Expertise Development through the Analysis of Reactor Thermal-Hydraulics for Malaysia, denoted as EARTH-M.« less

  2. Is the non-sentinel lymph node compartment the next site for melanoma progression from the sentinel lymph node compartment in the regional nodal basin?

    PubMed Central

    Rios-Cantu, Andrei; Lu, Ying; Melendez-Elizondo, Victor; Chen, Michael; Gutierrez-Range, Alejandra; Fadaki, Niloofar; Thummala, Suresh; West-Coffee, Carla; Cleaver, James; Kashani–Sabet, Mohammed

    2018-01-01

    Melanoma patients with additional positive lymph nodes in the completion lymph node dissection (CLND) following a positive sentinel lymph node (SLN) biopsy would have a poorer prognosis than patients with no additional positive lymph nodes. We hypothesize that the progression of disease from the SLN to the non-SLN compartment is orderly and is associated with the worsening of the disease status. Thus, the SLN and non-SLN compartments are biologically different in that cancer cells, in general, arrive in the SLN compartment before spreading to the non-SLN compartment. To validate this concept, we used a large cohort of melanoma patients from our prospective SLN database in an academic tertiary medical center. Adult cutaneous melanoma patients (n = 291) undergoing CLND after a positive SLN biopsy from 1994 to 2009 were analyzed. Comparison of 5-year disease-free survival and 5-year overall survival between positive (n = 66) and negative (n = 225) CLND groups was made. The 5-year disease-free survival rates were 55% (95% CI 49–62%) for patients with no additional LN on CLND versus 14% (95% CI 8–26%) in patients with positive LN on CLND (p < 0.0001, log-rank test). The median disease-free survival time was 7.4 years with negative CLND (95% CI 4.4–15+ years) and 1.2 years with positive CLND (95% CI 1.0–1.8 years). The 5-year overall survival rates were 67% (95% CI 61–74%) for negative CLND versus 38% (95% CI 28–52%) for positive CLND (p < 0.0001, log-rank test). The median overall survival time was 12.1 years for negative CLND (95% CI 9.3–15+ years) and 2.5 years for positive CLND (95% CI 2.2–5.7 years). This study shows that CLND status is a significant prognostic factor for patients with positive SLNs undergoing CLND. Also, it suggests an orderly progression of metastasis from the SLN to the non-SLN compartment. Thus, the SLN in the regional nodal basin draining the primary melanoma may serve as an important gateway for metastasis to the non

  3. Structural insights into the interaction of a monoclonal antibody and Nodal peptides by STD-NMR spectroscopy.

    PubMed

    Calvanese, Luisa; Focà, Annalia; Sandomenico, Annamaria; Focà, Giuseppina; Caporale, Andrea; Doti, Nunzianna; Iaccarino, Emanuela; Leonardi, Antonio; D'Auria, Gabriella; Ruvo, Menotti; Falcigno, Lucia

    2017-12-15

    Nodal is a growth factor expressed during early embryonic development, but reactivated in several advanced-stage cancers. Targeting of Nodal signaling, which occurs via the binding to Cripto-1 co-receptor, results in inhibition of cell aggressiveness and reduced tumor growth. The Nodal binding region to Cripto-1 was identified and targeted with a high affinity monoclonal antibody (3D1). By STD-NMR technique, we investigated the interaction of Nodal fragments with 3D1 with the aim to elucidate at atomic level the interaction surface. Data indicate with high accuracy the antibody-antigen contact atoms and confirm the information previously obtained by immune-enzymatic methods. Main residues contacted by 3D1 are P46, V47, E49 and E50, which belong to the Nodal loop involved in the interaction with the co-receptor. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. An efficient in vitro regeneration protocol for a natural dye yielding plant, Strobilanthes flaccidifolious Nees., from nodal explants.

    PubMed

    Deb, Chitta Ranjan; Arenmongla, T

    2012-11-01

    Adventitious shoot buds formation from axillary buds of nodal segments of S. flaccidifolious was achieved on MS medium containing sucrose (3%, w/v), and a-naphthalene acetic acid (NAA; 3 microM) and benzyl adenine (3 microM) in combination. The nodal segments were primed on 'Growtak Sieve' for 48 h on MS medium containing sucrose (2%), polyvinyl pyrollidone (200 mgL(-1)) as antioxidant. About 80% of primed nodal segments responded positively and formed approximately 12 adventitious shoot buds per explants from explants collected during October-November months of every year. The shoot buds converted into plantlets on MS medium containing sucrose (3%) and kinetin (3 microM) where approximately 7 micro shoots developed per subculture after 8 weeks of culture. The regenerated micro shoots induced average 14 roots/plant on medium containing NAA (3 microM). The regenerates were hardened for 6-7 weeks on medium with 1/2MS salt solution and sucrose (2%) under normal laboratory condition before transferring to potting mix. About 70% transplants survived after two months of transfer.

  5. Analysis of nodal aberration properties in off-axis freeform system design.

    PubMed

    Shi, Haodong; Jiang, Huilin; Zhang, Xin; Wang, Chao; Liu, Tao

    2016-08-20

    Freeform surfaces have the advantage of balancing off-axis aberration. In this paper, based on the framework of nodal aberration theory (NAT) applied to the coaxial system, the third-order astigmatism and coma wave aberration expressions of an off-axis system with Zernike polynomial surfaces are derived. The relationship between the off-axis and surface shape acting on the nodal distributions is revealed. The nodal aberration properties of the off-axis freeform system are analyzed and validated by using full-field displays (FFDs). It has been demonstrated that adding Zernike terms, up to nine, to the off-axis system modifies the nodal locations, but the field dependence of the third-order aberration does not change. On this basis, an off-axis two-mirror freeform system with 500 mm effective focal length (EFL) and 300 mm entrance pupil diameter (EPD) working in long-wave infrared is designed. The field constant aberrations induced by surface tilting are corrected by selecting specific Zernike terms. The design results show that the nodes of third-order astigmatism and coma move back into the field of view (FOV). The modulation transfer function (MTF) curves are above 0.4 at 20 line pairs per millimeter (lp/mm) which meets the infrared reconnaissance requirement. This work provides essential insight and guidance for aberration correction in off-axis freeform system design.

  6. The Impact of the Size of Nodal Metastases on Recurrence Risk in Breast Cancer Patients With 1-3 Positive Axillary Nodes After Mastectomy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Harris, Eleanor E.R., E-mail: Eleanor.harris@moffitt.org; Freilich, Jessica; Lin, Hui-Yi

    Purpose: Use of postmastectomy radiation therapy (PMRT) in breast cancer patients with 1-3 positive nodes is controversial. The objective of this study was to determine whether the size of nodal metastases in this subset could predict who would benefit from PMRT. Methods and Materials: We analyzed 250 breast cancer patients with 1-3 positive nodes after mastectomy treated with contemporary surgery and systemic therapy at our institution. Of these patients, 204 did not receive PMRT and 46 did receive PMRT. Local and regional recurrence risks were stratified by the size of the largest nodal metastasis measured as less than or equalmore » to 5 mm or greater than 5 mm. Results: The median follow-up was 65.6 months. In the whole group, regional recurrences occurred in 2% of patients in whom the largest nodal metastasis measured 5 mm or less vs 6% for those with metastases measuring greater than 5 mm. For non-irradiated patients only, regional recurrence rates were 2% and 9%, respectively. Those with a maximal nodal size greater than 5 mm had a significantly higher cumulative incidence of regional recurrence (P=.013). The 5-year cumulative incidence of a regional recurrence in the non-irradiated group was 2.7% (95% confidence interval [CI], 0.7%-7.2%) for maximal metastasis size of 5 mm or less, 6.9% (95% CI, 1.7%-17.3%) for metastasis size greater than 5 mm, and 16% (95% CI, 3.4%-36.8%) for metastasis size greater than 10 mm. The impact of the maximal nodal size on regional recurrences became insignificant in the multivariable model. Conclusions: In patients with 1-3 positive lymph nodes undergoing mastectomy without radiation, nodal metastasis greater than 5 mm was associated with regional recurrence after mastectomy, but its effect was modified by other factors (such as tumor stage). The size of the largest nodal metastasis may be useful to identify high-risk patients who may benefit from radiation therapy after mastectomy.« less

  7. Electrophysiologic effects of a novel selective adenosine A1 agonist (CVT-510) on atrioventricular nodal conduction in humans.

    PubMed

    Lerman, B B; Ellenbogen, K A; Kadish, A; Platia, E; Stein, K M; Markowitz, S M; Mittal, S; Slotwiner, D J; Scheiner, M; Iwai, S; Belardinelli, L; Jerling, M; Shreeniwas, R; Wolff, A A

    2001-07-01

    CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside, is a selective A(1)-adenosine receptor agonist with potential potent antiarrhythmic effects in tachycardias involving the atrioventricular (AV) node. This study, the first in humans, was designed to determine the effects of CVT-510 on AV nodal conduction and hemodynamics. Patients in sinus rhythm with normal AV nodal function at electrophysiologic study (n = 32) received a single intravenous bolus of CVT-510. AH and HV intervals were measured during sinus rhythm and during atrial pacing at 1, 5, 10, 15, 20, 30, 45, and 60 minutes after the bolus. Increasing doses of CVT-510 (0.3 to 10 microg/kg) caused a dose-dependent increase in the AH interval. At 1 minute, a dose of 10 microg/kg increased the AH interval during sinus rhythm from 93 +/- 23 msec to 114 +/- 37 msec, p = 0.01 and from 114 +/- 31 msec to 146 +/- 44 msec during atrial pacing at 600 msec, p = 0.003). The AH interval returned to baseline by 20 minutes. CVT-510 at doses of 0.3 to 10 microg/kg had no effect on sinus rate, HV interval, or systemic blood pressure, and was not associated with serious adverse effects. At doses of 15 and 30 microg/kg, CVT-510 produced transient second/third degree AV heart block in all four patients treated. One of these patients also had a prolonged sedative effect that was reversed with aminophylline. CVT-510 promptly prolongs AV nodal conduction and does not affect sinus rate or blood pressure. Selective stimulation of the A(1)-adenosine receptor by CVT-510 may be useful for immediate control of heart rate in atrial fibrillation/flutter and to convert paroxysmal supraventricular tachycardia to sinus rhythm, while avoiding vasodilatation mediated by the A(2)-adenosine receptor, as well as the vasodepressor and negative inotropic effects associated with beta-adrenergic receptor blockade and/or calcium channel blockers.

  8. Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation between primary and metastatic nodal lesion in colorectal cancer.

    PubMed

    Jang, Tae Jung

    2016-02-01

    O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the side chain hydroxyl of a serine or threonine residue. The E-cadherin/β-catenin system, an integral component of epithelial to mesenchymal transition (EMT)/mesenchymal to epithelial transition (MET), is affected through O-GlcNAcylation. The current study examined the status of EMT/MET in both the tumor center and invasive front of the primary colorectal carcinoma (CRC) and metastatic nodal lesions, which were compared to O-GlcNAcylation expression levels in those areas. In addition, the cliniopathological significance of O-GlcNAcylation was studied Immunohistochemical staining for E-cadherin, β-catenin, Snail, O-GlcNAc and Ki67 was performed in 40 primary CRC tissues, 40 nonneoplastic colons, and 17 nodal metastatic lesions. Western blot was also conducted in primary CRC tissue Membranous E-cadherin expression was lowest in the invasive front, but showed greater increases in metastatic nodal lesions. Moreover, its expression level was negatively correlated with that of nuclear β-catenin and Snail. The Ki67 labeling index (LI) was lowest in the invasive front, and increased in metastatic nodal lesions. Primary CRC showed higher expression of O-GlcNAcylation and O-GlcNAc-transferase (OGT) than nonneoplastic colons. O-GlcNAcylation expression decreased in metastatic nodal lesions compared to the invasive front and tumor center, and was inversely correlated with Ki67 LI. However, O-GlcNAcylation expression was only slightly changed between tumor center and invasive front. In addition, there was no correlation between its expression and the level of nuclear β-catenin, membranous E-cadherin and Snail. No significant relationship was observed between O-GlcNAcylation level and cliniopathological parameters. Differential membranous E-cadherin expression, cell proliferation and O-GlcNAcylation in metastatic nodal lesion compared to primary CRC may play role in establishing its lesions

  9. Segregated nodal domains of two-dimensional multispecies Bose-Einstein condensates

    NASA Astrophysics Data System (ADS)

    Chang, Shu-Ming; Lin, Chang-Shou; Lin, Tai-Chia; Lin, Wen-Wei

    2004-09-01

    In this paper, we study the distribution of m segregated nodal domains of the m-mixture of Bose-Einstein condensates under positive and large repulsive scattering lengths. It is shown that components of positive bound states may repel each other and form segregated nodal domains as the repulsive scattering lengths go to infinity. Efficient numerical schemes are created to confirm our theoretical results and discover a new phenomenon called verticillate multiplying, i.e., the generation of multiple verticillate structures. In addition, our proposed Gauss-Seidel-type iteration method is very effective in that it converges linearly in 10-20 steps.

  10. Index theorem for the flat Andreev bound states at a dirty surface of a nodal superconductor

    NASA Astrophysics Data System (ADS)

    Ikegaya, Satoshi; Asano, Yasuhiro

    2018-03-01

    We discuss the stability of at-band Andreev bound states appearing at a surface of a nodal unconventional superconductor. In the clean limit, the existence of the surface bound states is topologically characterized by a momentum-dependent topological invariant: one-dimensional winding number de ned in the restricted Brillouin zone. Thus, such topological invariant is ill-defined in the presence of potential disorder which is inevitable in experiments. By paying attention to chiral symmetry of the Hamiltonian, we provide an alternative topological index N ZES that predicts the number of Andreev bound states at a dirty surface of an unconventional superconductor. Moreover, we demonstrate that the zero-bias differential conductance in a normal metal/unconventional superconductor junction is quantized at (4e 2 /h)|N ZES | in the limit of strong impurity scattering in the normal metal.

  11. The distance between breast cancer and the skin is associated with axillary nodal metastasis.

    PubMed

    Eom, Yong Hwa; Kim, Eun Jin; Chae, Byung Joo; Song, Byung Joo; Jung, Sang Seol

    2015-06-01

    More superficially located tumors may be more likely than deeper tumors to metastasize to the axillary nodes via the lymphatics. The aim of this study was to determine whether breast cancer distance from the skin affects axillary node metastasis, ipsilateral breast cancer recurrence, or recurrence-free survival. A total of 1,005 consecutive patients with breast cancer who underwent surgery between January 2003 and December 2009 were selected. The distance of the tumor from the skin was measured from the skin to the most anterior hypoechoic leading edge of the lesion. In total, 603 (68%) patients had no axillary nodal metastasis, and 288 (32%) had axillary nodal metastasis. A breast cancer distance from the skin <3 mm induced more axillary nodal metastasis (P = 0.039). However, no significant correlation was observed between breast cancer distance from the skin <3 mm and ipsilateral breast cancer recurrence (P = 0.788) or recurrence-free survival (P = 0.353). Breast cancers located closer to the skin had a higher incidence of axillary nodal metastasis. Therefore, tumor distance from the skin should be considered when evaluating a patient with breast cancer and considering the risk of nodal metastasis. © 2015 Wiley Periodicals, Inc.

  12. Adaptive Nodal Transport Methods for Reactor Transient Analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Thomas Downar; E. Lewis

    2005-08-31

    Develop methods for adaptively treating the angular, spatial, and time dependence of the neutron flux in reactor transient analysis. These methods were demonstrated in the DOE transport nodal code VARIANT and the US NRC spatial kinetics code, PARCS.

  13. Involved-field radiotherapy (IFRT) versus elective nodal irradiation (ENI) in combination with concurrent chemotherapy for 239 esophageal cancers: a single institutional retrospective study.

    PubMed

    Yamashita, Hideomi; Takenaka, Ryousuke; Omori, Mami; Imae, Toshikazu; Okuma, Kae; Ohtomo, Kuni; Nakagawa, Keiichi

    2015-08-14

    This retrospective study on early and locally advanced esophageal cancer was conducted to evaluate locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy. We assessed all patients with esophageal cancer of stages I-IV treated with definitive radiotherapy from June 2000 to March 2014. Between 2000 and 2011, ENI was used for all cases excluding high age cases. After Feb 2011, a prospective study about IFRT was started, and therefore IFRT was used since then for all cases. Concurrent chemotherapy regimen was nedaplatin (80 mg/m(2) at D1 and D29) and 5-fluorouracil (800 mg/m(2) at D1-4 and D29-32). Of the 239 consecutive patients assessed (120 ENI vs. 119 IFRT), 59 patients (24.7%) had stage IV disease and all patients received at least one cycle of chemotherapy. The median follow-up time for survivors was 34.0 months. There were differences in 3-year local control (44.8% vs. 55.5%, p = 0.039), distant control (53.8% vs. 69.9%, p = 0.021) and overall survival (34.8% vs. 51.6%, p = 0.087) rates between ENI vs. IFRT, respectively. Patients treated with IFRT (8 %) demonstrated a significantly lower risk (p = 0.047) of high grade late toxicities than with ENI (16%). IFRT did not increase the risk of initially uninvolved or isolated nodal failures (27.5% in ENI and 13.4% in IFRT). Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients. Both tendencies of improved loco-regional progression-free survival and a significant increased overall survival rate favored the IFRT arm over the ENI arm in this study.

  14. Incremental cancer detection of locoregional restaging with diagnostic mammography combined with whole breast and regional nodal ultrasound in women with newly-diagnosed breast cancer

    PubMed Central

    Candelaria, Rosalind P.; Huang, Monica L.; Adrada, Beatriz E.; Bassett, Roland; Hunt, Kelly K.; Kuerer, Henry M.; Smith, Benjamin D.; Chavez-MacGregor, Mariana; Yang, Wei Tse

    2016-01-01

    RATIONALE AND OBJECTIVES To determine if locoregional restaging with diagnostic mammography and ultrasound of the whole breast and regional nodes performed for quality assurance in women with newly-diagnosed breast cancer referred to a tertiary care center yields incremental cancer detection. MATERIALS AND METHODS An institutional review board-approved retrospective, single institution database review was performed on the first 1000 women referred to our center in 2010 with a provisional breast cancer diagnosis. Locoregional restaging consisted of diagnostic full-field digital mammography combined with ultrasound of the whole breast and regional nodal basins. Bilateral whole breast ultrasound was performed in women with contralateral mammographic abnormality or had heterogeneously or extremely dense parenchyma. Demographic, clinical and pathologic factors were analyzed. RESULTS Final analyses included 401 women. 34% (138/401) of women did not have their outside images available for review upon referral. Median age was 54 years, range 21–92; median tumor size was 2.9 cm, range 0.6–18, for women whose disease was upstaged and 2.2 cm, range 0.4–15, for women whose disease was not upstaged. Incremental cancer detection rates were 15.5% (62/401) in the ipsilateral breast and 3.9% (6/154) in the contralateral breast (p<0.0001). Total upstage rate was 25% (100/401). Surgical management changed from segmentectomy to mastectomy in 12% (50/401). Re-excision rate after segmentectomy was 19% (35/189). CONCLUSION Locoregional restaging with diagnostic mammography combined with whole breast and regional nodal ultrasound that is performed for standardization of the imaging workup for newly-diagnosed breast cancer patients can reduce underestimation of disease burden and impact therapeutic planning. PMID:27955877

  15. Unilateral Radiotherapy for the Treatment of Tonsil Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chronowski, Gregory M., E-mail: gchronowski@mdanderson.org; Garden, Adam S.; Morrison, William H.

    2012-05-01

    Purpose: To assess, through a retrospective review, clinical outcomes of patients with squamous cell carcinoma of the tonsil treated at the M. D. Anderson Cancer Center with unilateral radiotherapy techniques that irradiate the involved tonsil region and ipsilateral neck only. Methods and Materials: Of 901 patients with newly diagnosed squamous cell carcinoma of the tonsil treated with radiotherapy at our institution, we identified 102 that were treated using unilateral radiotherapy techniques. All patients had their primary site of disease restricted to the tonsillar fossa or anterior pillar, with <1 cm involvement of the soft palate. Patients had TX (n =more » 17 patients), T1 (n = 52), or T2 (n = 33) disease, with Nx (n = 3), N0 (n = 33), N1 (n = 23), N2a (n = 21), or N2b (n = 22) neck disease. Results: Sixty-one patients (60%) underwent diagnostic tonsillectomy before radiotherapy. Twenty-seven patients (26%) underwent excision of a cervical lymph node or neck dissection before radiotherapy. Median follow-up for surviving patients was 38 months. Locoregional control at the primary site and ipsilateral neck was 100%. Two patients experienced contralateral nodal recurrence (2%). The 5-year overall survival and disease-free survival rates were 95% and 96%, respectively. The 5-year freedom from contralateral nodal recurrence rate was 96%. Nine patients required feeding tubes during therapy. Of the 2 patients with contralateral recurrence, 1 experienced an isolated neck recurrence and was salvaged with contralateral neck dissection only and remains alive and free of disease. The other patient presented with a contralateral base of tongue tumor and involved cervical lymph node, which may have represented a second primary tumor, and died of disease. Conclusions: Unilateral radiotherapy for patients with TX-T2, N0-N2b primary tonsil carcinoma results in high rates of disease control, with low rates of contralateral nodal failure and a low incidence of acute toxicity

  16. Interplay between short-range correlated disorder and Coulomb interaction in nodal-line semimetals

    NASA Astrophysics Data System (ADS)

    Wang, Yuxuan; Nandkishore, Rahul M.

    2017-09-01

    In nodal-line semimetals, Coulomb interactions and short-range correlated disorder are both marginal perturbations to the clean noninteracting Hamiltonian. We analyze their interplay using a weak-coupling renormalization group approach. In the clean case, the Coulomb interaction has been found to be marginally irrelevant, leading to Fermi liquid behavior. We extend the analysis to incorporate the effects of disorder. The nodal line structure gives rise to kinematical constraints similar to that for a two-dimensional Fermi surface, which plays a crucial role in the one-loop renormalization of the disorder couplings. For a twofold degenerate nodal loop (Weyl loop), we show that disorder flows to strong coupling along a unique fixed trajectory in the space of symmetry inequivalent disorder couplings. Along this fixed trajectory, all symmetry inequivalent disorder strengths become equal. For a fourfold degenerate nodal loop (Dirac loop), disorder also flows to strong coupling, however, the strengths of symmetry inequivalent disorder couplings remain different. We show that feedback from disorder reverses the sign of the beta function for the Coulomb interaction, causing the Coulomb interaction to flow to strong coupling as well. However, the Coulomb interaction flows to strong coupling asymptotically more slowly than disorder. Extrapolating our results to strong coupling, we conjecture that at low energies nodal line semimetals should be described by a noninteracting nonlinear sigma model. We discuss the relation of our results with possible many-body localization at zero temperatures in such materials.

  17. Triply degenerate nodal points and topological phase transitions in NaCu3Te2

    NASA Astrophysics Data System (ADS)

    Xia, Yunyouyou; Li, Gang

    2017-12-01

    Quasiparticle excitations of free electrons in condensed-matter physics, characterized by the dimensionality of the band crossing, can find their elementary-particle analogs in high-energy physics, such as Majorana, Weyl, and Dirac fermions, while crystalline symmetry allows more quasiparticle excitations and exotic fermions to emerge. Using symmetry analysis and ab initio calculations, we propose that the three-dimensional honeycomb crystal NaCu3Te2 hosts triply degenerate nodal points (TDNPs) residing at the Fermi level. Furthermore, in this system we find a tunable phase transition between a trivial insulator, a TDNP phase, and a weak topological insulator (TI), triggered by a symmetry-allowed perturbation and the spin-orbital coupling (SOC). Such a topological nontrivial ternary compound not only serves as a perfect candidate for studying three-component fermions, but also provides an excellent playground for understanding the topological phase transitions between TDNPs, TIs, and trivial insulators, which distinguishes this system from other TDNP candidates.

  18. Constructing a polynomial whose nodal set is the three-twist knot 52

    NASA Astrophysics Data System (ADS)

    Dennis, Mark R.; Bode, Benjamin

    2017-06-01

    We describe a procedure that creates an explicit complex-valued polynomial function of three-dimensional space, whose nodal lines are the three-twist knot 52. The construction generalizes a similar approach for lemniscate knots: a braid representation is engineered from finite Fourier series and then considered as the nodal set of a certain complex polynomial which depends on an additional parameter. For sufficiently small values of this parameter, the nodal lines form the three-twist knot. Further mathematical properties of this map are explored, including the relationship of the phase critical points with the Morse-Novikov number, which is nonzero as this knot is not fibred. We also find analogous functions for other simple knots and links. The particular function we find, and the general procedure, should be useful for designing knotted fields of particular knot types in various physical systems.

  19. Scanning Tunneling Microscopy Study on Dirac Nodal-line Semimetal ZrSiS

    NASA Astrophysics Data System (ADS)

    Su, Chih-Chuan; Guan, Syu-You; Wang, Tzu-Cheng; Sankar, Raman; Guo, Guang-Yu; Chou, Fangcheng; Chang, Chia-Seng; Chuang, Tien-Ming

    The discovery of 3D Dirac nodal-line protected by non-symmophic symmetry in ZrSiS family has been reported by angle resolved photoemission spectroscopy (ARPES) and quantum oscillation measurements. ZrSiS also exhibits a butterfly shaped titanic angular magnetoresistance and strong Zeeman splitting in quantum oscillation. These observations with its layered crystal structure make the ZrSiS family an interesting candidate to understand the novel properties of the nodal-line semimetals. Here, we study the electronic structures of the single crystal ZrSiS by using spectroscopic-imaging scanning tunneling microscope at T= 4.2K. Our quasiparticle scattering interference imaging reveals the characteristic wave vectors with linear dispersion from Dirac line nodes in the bulk and its surface states. Our results are in excellent agreement with the first principle calculation, and also in consistent with ARPES and quantum oscillation measurements.

  20. Development of a phenotyping platform for high throughput screening of nodal root angle in sorghum.

    PubMed

    Joshi, Dinesh C; Singh, Vijaya; Hunt, Colleen; Mace, Emma; van Oosterom, Erik; Sulman, Richard; Jordan, David; Hammer, Graeme

    2017-01-01

    In sorghum, the growth angle of nodal roots is a major component of root system architecture. It strongly influences the spatial distribution of roots of mature plants in the soil profile, which can impact drought adaptation. However, selection for nodal root angle in sorghum breeding programs has been restricted by the absence of a suitable high throughput phenotyping platform. The aim of this study was to develop a phenotyping platform for the rapid, non-destructive and digital measurement of nodal root angle of sorghum at the seedling stage. The phenotyping platform comprises of 500 soil filled root chambers (50 × 45 × 0.3 cm in size), made of transparent perspex sheets that were placed in metal tubs and covered with polycarbonate sheets. Around 3 weeks after sowing, once the first flush of nodal roots was visible, roots were imaged in situ using an imaging box that included two digital cameras that were remotely controlled by two android tablets. Free software ( openGelPhoto.tcl ) allowed precise measurement of nodal root angle from the digital images. The reliability and efficiency of the platform was evaluated by screening a large nested association mapping population of sorghum and a set of hybrids in six independent experimental runs that included up to 500 plants each. The platform revealed extensive genetic variation and high heritability (repeatability) for nodal root angle. High genetic correlations and consistent ranking of genotypes across experimental runs confirmed the reproducibility of the platform. This low cost, high throughput root phenotyping platform requires no sophisticated equipment, is adaptable to most glasshouse environments and is well suited to dissect the genetic control of nodal root angle of sorghum. The platform is suitable for use in sorghum breeding programs aiming to improve drought adaptation through root system architecture manipulation.

  1. Effectiveness of Implemented Interventions on Pathologic Nodal Staging of Non-Small Cell Lung Cancer.

    PubMed

    Ray, Meredith A; Faris, Nicholas R; Smeltzer, Matthew P; Fehnel, Carrie; Houston-Harris, Cheryl; Levy, Paul; Wiggins, Lynn; Sachdev, Vishal; Robbins, Todd; Spencer, David; Osarogiagbon, Raymond U

    2018-03-10

    Accurate pathologic nodal staging improves early-stage non-small-cell lung cancer survival. In an ongoing implementation study, we measured the impact of a surgical lymph node specimen collection kit and a more thorough pathologic gross dissection method, on attainment of guideline-recommended pathologic nodal staging quality. We prospectively collected data on curative-intent non-small cell lung cancer resections from 2009-2016 from 11 hospitals in 4 contiguous Dartmouth Hospital Referral Regions. We categorized patients into 4 groups based on exposure to the two interventions in our staggered implementation study design. We used Chi-squared tests to examine the differences in demographic and disease characteristics and surgical quality criteria across implementation groups. Of 2,469 patients, 1,615 (65%) received neither intervention; 167 (7%) received only the pathology intervention; 264 (11%) received only the surgery intervention; 423 (17%) had both. Rates of non-examination of lymph nodes reduced sequentially in the order of no intervention, novel dissection, kit, and combined interventions, including non-examination of: any lymph nodes, hilar/intrapulmonary and mediastinal nodes (p<0.001 for all comparisons). The rates of attainment of National Comprehensive Cancer Network, Commission on Cancer, American Joint Committee on Cancer, and American College of Surgeons Oncology Group guidelines increased significantly in the same sequential order (p<0.001 for all comparisons). The combined effect of two interventions to improve pathologic lymph node examination has a greater effect on attainment of a range of surgical quality criteria than either intervention alone. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Encouraging experience in the treatment of nasal type extra-nodal NK/T-cell lymphoma in a non-Asian population.

    PubMed

    Qi, Shunan; Yahalom, Joachim; Hsu, Meier; Chelius, Monica; Lunning, Matthew; Moskowitz, Alison; Horwitz, Steven

    2016-11-01

    Extra-nodal NK/T-cell lymphoma, nasal type (EN-NK/TCL-NT), is rare in the Western world. We launched the current single-institutional retrospective study with Institutional Review Board approval to better understand the disease. 43 EN-NK/TCL-NT patients treated from 1996 to 2014 were analyzed, including 10 (23%) Asians and 33 (76%) non-Asians. 19/26 (73%) early-stage patients received short-course chemotherapy followed by radiotherapy. 14/17 (82%) advanced-stage patients received primary chemotherapy. Complete response rate was significantly higher in the modified-SMILE group than the accelerated-CHOP group (80% vs. 30%, p = 0.015). The 2-year overall survival (OS) and progression-free survival (PFS) were 60% and 40%, respectively. Early-stage disease had significantly higher 2-year OS (87% vs. 21%) and PFS (56% vs.18%) than advanced-stage (p < 0.001). Ethnicity had no prognostic difference. EN-NK/TCL-NT in non-Asians shared similar disease characteristics and treatment outcomes with Asians. Most early-stage patients have achieved durable remissions. Management of advanced-stage disease remains challenging, with frequent progression and high mortality.

  3. Anomalous contagion and renormalization in networks with nodal mobility

    NASA Astrophysics Data System (ADS)

    Manrique, Pedro D.; Qi, Hong; Zheng, Minzhang; Xu, Chen; Hui, Pak Ming; Johnson, Neil F.

    2016-07-01

    A common occurrence in everyday human activity is where people join, leave and possibly rejoin clusters of other individuals —whether this be online (e.g. social media communities) or in real space (e.g. popular meeting places such as cafes). In the steady state, the resulting interaction network would appear static over time if the identities of the nodes are ignored. Here we show that even in this static steady-state limit, a non-zero nodal mobility leads to a diverse set of outbreak profiles that is dramatically different from known forms, and yet matches well with recent real-world social outbreaks. We show how this complication of nodal mobility can be renormalized away for a particular class of networks.

  4. Histopathological Parameters predicting Occult Nodal Metastases in Tongue Carcinoma Cases: An Indian Perspective.

    PubMed

    Jacob, Tina Elizabeth; Malathi, N; Rajan, Sharada T; Augustine, Dominic; Manish, N; Patil, Shankargouda

    2016-01-01

    It is a well-established fact that in squamous cell carcinoma cases, the presence of lymph node metastases decreased the 5-year survival rate by 50% and also caused the recurrence of the primary tumor with development of distant metastases. Till date, the predictive factors for occult cervical lymph nodes metastases in cases of tongue squamous cell carcinoma remain inconclusive. Therefore, it is imperative to identify patients who are at the greatest risk for occult cervical metastases. This study was thus performed with the aim to identify various histopathologic parameters of the primary tumor that predict occult nodal metastases. The clinicopathologic features of 56 cases of lateral tongue squamous cell carcinoma with cT1NoMo/cT2NoMo as the stage and without prior radiotherapy or chemotherapy were considered. The surgical excision of primary tumor was followed by elective neck dissection. The glossectomy specimen along with the neck nodes were fixed in formalin and 5 urn thick sections were obtained. The hematoxylin & eosin stained sections were then subjected to microscopic examination. The primary tumor characteristics that were analyzed include tumor grade, invading front, depth of tumor, lymphovascular invasion, perineural invasion and inflammatory response. The nodes were examined for possible metastases using hematoxylin & eosin followed by cytokeratin immunohistochemistry. A total of 12 cases were found with positive occult nodal metastases. On performing univariate analysis, the histopathologic parameters that were found to be statistically significant were lymphovascular invasion (p = 0.004) and perineural invasion (p = 0.003) along with a cut-off depth of infiltration more than 5 mm (p = 0.01). Histopathologic assessment of the primary tumor specimen therefore continues to provide information that is central to guide clinical management, particularly in cases of occult nodal metastases. Clinical significance The study highlights the importance of

  5. An institutional approach to support the conduct and use of health policy and systems research: The Nodal Institute in the Eastern Mediterranean Region.

    PubMed

    El-Jardali, Fadi; Saleh, Shadi; Khodor, Rawya; Abu Al Rub, Raeda; Arfa, Chokri; Ben Romdhane, Habiba; Hamadeh, Randah R

    2015-10-01

    The use of health policy and systems research (HPSR) to support decision making in health systems is limited in the Eastern Mediterranean Region (EMR). This is partly due to the lack of effective initiatives to strengthen regional HPSR capacities and promote its use in decision making. This paper offers a structured reflection on the establishment and core functioning of a HPSR Nodal Institute for the EMR with specific focus on the approach used to support the conduct and use of HPSR. It seeks to gain better understanding of the activities conducted by the Nodal Institute, the methods by which the Nodal Institute implemented these activities, and the outcomes of these activities. A multi-faceted approach was implemented by the Nodal Institute in collaboration with regional academic/research institutions, Sub-Nodes. The overall approach was a phased one that included the selection of Sub-Nodes, mapping of academic/research institutions in the EMR, stakeholders' meetings, and HPSR capacity building workshops, and culminated with a regional meeting. The mapping of academic/research institutions in the EMR resulted in the identification of 50 institutions, of which only 32 were engaged in HPSR. These institutions have the highest HPSR involvement in information/evidence (84%) and the lowest in human resources for health (34%). Their main HPSR focus areas included quality of healthcare services, patient safety, management of non-communicable diseases, and human resources for health. Regional HPSR challenges among these institutions were identified. The validation and ranking questionnaires resulted in the identification of country-specific HPSR priorities according to stakeholders in three countries. From these results, cross-cutting HPSR priorities among the countries related to primary healthcare, non-communicable diseases, human resources for health, as well as cross-cutting HPSR priorities among stakeholders and according to stakeholders of the countries, were

  6. Ratio between maximum standardized uptake value of N1 lymph nodes and tumor predicts N2 disease in patients with non-small cell lung cancer in 18F-FDG PET-CT scan.

    PubMed

    Honguero Martínez, A F; García Jiménez, M D; García Vicente, A; López-Torres Hidalgo, J; Colon, M J; van Gómez López, O; Soriano Castrejón, Á M; León Atance, P

    2016-01-01

    F-18 fluorodeoxyglucose integrated PET-CT scan is commonly used in the work-up of lung cancer to improve preoperative disease stage. The aim of the study was to analyze the ratio between SUVmax of N1 lymph nodes and primary lung cancer to establish prediction of mediastinal disease (N2) in patients operated on non-small cell lung cancer. This is a retrospective study of a prospective database. Patients operated on non-small cell lung cancer (NSCLC) with N1 disease by PET-CT scan were included. None of them had previous induction treatment, but they underwent standard surgical resection plus systematic lymphadenectomy. There were 51 patients with FDG-PET-CT scan N1 disease. 44 (86.3%) patients were male with a mean age of 64.1±10.8 years. Type of resection: pneumonectomy=4 (7.9%), lobectomy/bilobectomy=44 (86.2%), segmentectomy=3 (5.9%). adenocarcinoma=26 (51.0%), squamous=23 (45.1%), adenosquamous=2 (3.9%). Lymph nodes after surgical resection: N0=21 (41.2%), N1=12 (23.5%), N2=18 (35.3%). Mean ratio of the SUVmax of N1 lymph node to the SUVmax of the primary lung tumor (SUVmax N1/T ratio) was 0.60 (range 0.08-2.80). ROC curve analysis to obtain the optimal cut-off value of SUVmax N1/T ratio to predict N2 disease was performed. At multivariate analysis, we found that a ratio of 0.46 or greater was an independent predictor factor of N2 mediastinal lymph node metastases with a sensitivity and specificity of 77.8% and 69.7%, respectively. SUVmax N1/T ratio in NSCLC patients correlates with mediastinal lymph node metastasis (N2 disease) after surgical resection. When SUVmax N1/T ratio on integrated PET-CT scan is equal or superior to 0.46, special attention should be paid on higher probability of N2 disease. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  7. Nodal failure index approach to groundwater remediation design

    USGS Publications Warehouse

    Lee, J.; Reeves, H.W.; Dowding, C.H.

    2008-01-01

    Computer simulations often are used to design and to optimize groundwater remediation systems. We present a new computationally efficient approach that calculates the reliability of remedial design at every location in a model domain with a single simulation. The estimated reliability and other model information are used to select a best remedial option for given site conditions, conceptual model, and available data. To evaluate design performance, we introduce the nodal failure index (NFI) to determine the number of nodal locations at which the probability of success is below the design requirement. The strength of the NFI approach is that selected areas of interest can be specified for analysis and the best remedial design determined for this target region. An example application of the NFI approach using a hypothetical model shows how the spatial distribution of reliability can be used for a decision support system in groundwater remediation design. ?? 2008 ASCE.

  8. Concordance Between FISH Analysis of Her-2/Neu Gene in Breast Duct Carcinoma and Corresponding Axillary Nodal Metastases: Egyptian National Cancer Institute Experience.

    PubMed

    Badawy, Omnia M; Hassan, Hannan; ELBakey, Heba A; Mosaad, Maha

    2018-05-10

    Breast cancer is a major health problem in Egypt. Her-2/Neu gene is routinely assessed for all breast cancer patients primarily by immunohistochemistry. At National Cancer Institute (NCI), Cairo University, Flourescence In Situ hybridization (FISH) analysis of Her-2/Neu gene is carried out for Her-2/Neu score 2 and for some cases of score 3 (particularly those assessed outside NCI). The test is performed essentially on the primary tumor. However, some situations require testing on corresponding lymph node metastases. There is a debate about the concordance between Her-2/Neu status in the primary tumor and synchronous lymph node metastases in various studies. The aim of this study was to test for the concordance between Her-2/Neu status in the primary breast tumor and corresponding axillary nodal metastases. This is a retrospective study in which FISH analysis of Her-2/Neu was carried out simultaneously on archived material of 50 cases previously diagnosed as invasive duct carcinoma and the corresponding nodal metastases from the Pathology Department, NCI. There was complete concordance between Her-2 status in the primary tumor and the corresponding axillary lymph node metastatic deposits in which Her-2 was amplified in 44% of the studied cohort of Egyptian patients. Her-2/Neu gene assessed by FISH analysis on synchronous lymph node metastases is strongly correlated with the primary tumor. Hence, it is justified to carry out the Her-2/Neu test on synchronous lymph nodes to decide on whether to carry out anti-Her-2/Neu target therapy. Further studies on other metastatic sites is recommended.

  9. Dual time point 2-deoxy-2-[18F]fluoro-D-glucose PET/CT: nodal staging in locally advanced breast cancer.

    PubMed

    García Vicente, A M; Soriano Castrejón, A; Cruz Mora, M Á; Ortega Ruiperez, C; Espinosa Aunión, R; León Martín, A; González Ageitos, A; Van Gómez López, O

    2014-01-01

    To assess dual time point 2-deoxy-2-[(18)F]fluoro-D-glucose (18)(F)FDG PET-CT accuracy in nodal staging and in detection of extra-axillary involvement. Dual time point [(18)F] FDG PET/CT scan was performed in 75 patients. Visual and semiquantitative assessment of lymph nodes was performed. Semiquantitative measurement of SUV and ROC-analysis were carried out to calculate SUV(max) cut-off value with the best diagnostic performance. Axillary and extra-axillary lymph node chains were evaluated. Sensitivity and specificity of visual assessment was 87.3% and 75%, respectively. SUV(max) values with the best sensitivity were 0.90 and 0.95 for early and delayed PET, respectively. SUV(max) values with the best specificity were 1.95 and 2.75, respectively. Extra-axillary lymph node involvement was detected in 26.7%. FDG PET/CT detected extra-axillary lymph node involvement in one-fourth of the patients. Semiquantitative lymph node analysis did not show any advantage over the visual evaluation. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  10. Observation of nodal line in non-symmorphic topological semimetal InBi

    DOE PAGES

    Ekahana, Sandy Adhitia; Wu, Shu-Chun; Jiang, Juan; ...

    2017-05-30

    Topological nodal semimetal (TNS), characterized by its touching conduction and valence bands, is a newly discovered state of quantum matter which exhibits various exotic physical phenomena. Recently, a new type of TNS called topological nodal line semimetal (TNLS) is predicted where its conduction and valence band form a degenerate one-dimension line which is further protected by its crystal symmetry. In this work, we systematically investigated the bulk and surface electronic structure of the non-symmorphic, TNLS in InBi (which is also a type II Dirac semimetal) with strong spin–orbit coupling by using angle resolved photoemission spectroscopy. By tracking the crossing points of the bulk bands at the Brillouin zone boundary, we discovered the nodal-line feature along themore » $${{k}}_{{z}}$$ direction, in agreement with the ab initio calculations and confirmed it to be a new compound in the TNLS family. Our discovery provides a new material platform for the study of these exotic topological quantum phases and paves the way for possible future applications.« less

  11. Efficacy of an inactivated bivalent vaccine against the prevalent strains of Newcastle disease and H9N2 avian influenza.

    PubMed

    Zhao, Jing; Yang, Huiming; Xu, Hongjun; Ma, Zengbin; Zhang, Guozhong

    2017-03-16

    Newcastle disease (ND) and avian influenza subtype H9N2 (H9N2 AI) are two of the most important diseases of poultry, causing severe economic losses in the global poultry industry. Vaccination is an effective way to prevent and control the spread of ND virus (NDV) and H9N2 AI virus (AIV), but the antigenic differences between the current circulating strains and the vaccine strains might account for recent ND and H9N2 AI outbreaks in vaccinated poultry flocks. We developed an inactivated bivalent H9N2 and NDV vaccine based on the current prevalent strains of H9N2 AIV and NDV in China and evaluated its efficacy in chickens in this study. The results indicated that the inactivated bivalent vaccine could induce a fast antibody response in vaccinated chickens. The hemagglutination inhibition (HI) titer in the sera increased rapidly, and the highest HI titer was observed at 4 weeks post-vaccination (wpv) with a mean titre of 8.6 log 2 for NDV and 9.5 log 2 for H9N2. Up until 15 wpv, HI titers were still detectable at a high level of over 6 log 2 . The immunized chickens showed no signs of disease after challenge at 3 wpv with the prevalent strains of NDV and H9N2 AIV isolated in 2012-2014. Moreover, viral shedding was completely inhibited in vaccinated chickens after challenge with H9N2 AIV and inhibited by at least 90% with NDV compared to the controls at 5dpc. Our findings suggest that the inactivated NDV and H9N2 vaccine induces a fast and strong antibody response in vaccinated chickens and is efficacious in poultry against NDVs and H9N2 AIVs.

  12. p53 predictive value for pT1-2 N0 disease at radical cystectomy.

    PubMed

    Shariat, Shahrokh F; Lotan, Yair; Karakiewicz, Pierre I; Ashfaq, Raheela; Isbarn, Hendrik; Fradet, Yves; Bastian, Patrick J; Nielsen, Matthew E; Capitanio, Umberto; Jeldres, Claudio; Montorsi, Francesco; Müller, Stefan C; Karam, Jose A; Heukamp, Lukas C; Netto, George; Lerner, Seth P; Sagalowsky, Arthur I; Cote, Richard J

    2009-09-01

    Approximately 15% to 30% of patients with pT1-2N0M0 urothelial carcinoma of the bladder experience disease progression despite radical cystectomy with curative intent. We determined whether p53 expression would improve the prediction of disease progression after radical cystectomy for pT1-2N0M0 UCB. In a multi-institutional retrospective cohort we identified 324 patients with pT1-2N0M0 urothelial carcinoma of the bladder who underwent radical cystectomy. Analysis focused on a testing cohort of 272 patients and an external validation of 52. Competing risks regression models were used to test the association of variables with cancer specific mortality after accounting for nonbladder cancer caused mortality. In the testing cohort 91 patients (33.5%) had altered p53 expression (p53alt). On multivariate competing risks regression analysis altered p53 achieved independent status for predicting disease recurrence and cancer specific mortality (each p <0.001). Adding p53 increased the accuracy of multivariate competing risks regression models predicting recurrence and cancer specific mortality by 5.7% (62.0% vs 67.7%) and 5.4% (61.6% vs 67.0%), respectively. Alterations in p53 represent a highly promising marker of disease recurrence and cancer specific mortality after radical cystectomy for urothelial carcinoma of the bladder. Analysis confirmed previous findings and showed that considering p53 can result in substantial accuracy gains relative to the use of standard predictors. The value and the level of the current evidence clearly exceed previous proof of the independent predictor status of p53 for predicting recurrence and cancer specific mortality.

  13. Incremental Cancer Detection of Locoregional Restaging with Diagnostic Mammography Combined with Whole-Breast and Regional Nodal Ultrasound in Women with Newly Diagnosed Breast Cancer.

    PubMed

    Candelaria, Rosalind P; Huang, Monica L; Adrada, Beatriz E; Bassett, Roland; Hunt, Kelly K; Kuerer, Henry M; Smith, Benjamin D; Chavez-MacGregor, Mariana; Yang, Wei Tse

    2017-02-01

    This study aims to determine if locoregional restaging with diagnostic mammography and ultrasound (US) of the whole breast and regional nodes performed for quality assurance in women with newly diagnosed breast cancer who were referred to a tertiary care center yields incremental cancer detection. An institutional review board-approved retrospective, single-institution database review was performed on the first 1000 women referred to our center in 2010 with a provisional breast cancer diagnosis. Locoregional restaging consisted of diagnostic full-field digital mammography combined with US of the whole breast and regional nodal basins. Bilateral whole-breast US was performed in women with contralateral mammographic abnormality or had heterogeneously or extremely dense parenchyma. Demographic, clinical, and pathologic factors were analyzed. Final analyses included 401 women. Of the 401 women, 138 (34%) did not have their outside images available for review upon referral. The median age was 54 years (range 21-92); the median tumor size was 2.9 cm (range 0.6-18.0) for women whose disease was upstaged and 2.2 cm (range 0.4-15.0) for women whose disease was not upstaged. Incremental cancer detection rates were 15.5% (62 of 401) in the ipsilateral breast and 3.9% (6 of 154) in the contralateral breast (P < 0.0001). The total upstage rate was 25% (100 of 401). Surgical management changed from segmentectomy to mastectomy in 12% (50 of 401). The re-excision rate after segmentectomy was 19% (35 of 189). Locoregional restaging with diagnostic mammography combined with whole-breast and regional nodal US that is performed for standardization of the imaging workup for newly diagnosed breast cancer patients can reduce underestimation of disease burden and impact therapeutic planning. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  14. Treatment of cutaneous and/or soft tissue manifestations of corticosteroids refractory chronic graft versus host disease (cGVHD) by a total nodal irradiation (TNI).

    PubMed

    Peyraga, Guillaume; Lizee, Thibaut; Gustin, Pierre; Clement-Colmou, Karen; Di Bartolo, Christelle; Supiot, Stephane; Mahe, Marc-Andre; François, Sylvie; Mege, Martine

    2017-04-01

    The management of corticosteroids refractory chronic graft versus host disease (cGVHD) remains controversial. Retrospective analysis of patients treated at the Integrated Center of Oncology by total nodal irradiation (TNI) was performed to evaluate its therapy potency. TNI delivers a dose of 1 Gy in a single session. The delimitation of the fields is clinical (upper limit: external auditory meatus; lower limit: mid-femur). No pre-therapeutic dosimetry scanner was necessary. Evaluation of the efficacy was by clinical measures at 6 months after the treatment. Twelve patients were treated by TNI between January 2010 and December 2013. TNI was used in second-line treatment or beyond. The median time between allograft and TNI was 31.2 months, and the median time between the first manifestations of cGVHD and TNI was about 24.2 months. Of the 12 patients, nine had a clinical response at 6 months (75%), including five complete clinical responses (41.6%). Five patients could benefit from a reduction of corticosteroid doses. Three patients had hematologic toxicity. TNI could be considered as an option for the treatment of a cutaneous and/or soft tissues corticosteroids refractory cGVHD. However, prospective randomized and double-blind trials remain essential to answer the questions about TNI safety and effectiveness. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Nodal liquids in extended t-J models and dynamical supersymmetry

    NASA Astrophysics Data System (ADS)

    Mavromatos, Nick E.; Sarkar, Sarben

    2000-08-01

    In the context of extended t-J models, with intersite Coulomb interactions of the form -V∑ninj, with ni denoting the electron number operator at site i, nodal liquids are discussed. We use the spin-charge separation ansatz as applied to the nodes of a d-wave superconducting gap. Such a situation may be of relevance to the physics of high-temperature superconductivity. We point out the possibility of existence of certain points in the parameter space of the model characterized by dynamical supersymmetries between the spinon and holon degrees of freedom, which are quite different from the symmetries in conventional supersymmetric t-J models. Such symmetries pertain to the continuum effective-field theory of the nodal liquid, and one's hope is that the ancestor lattice model may differ from the continuum theory only by renormalization-group irrelevant operators in the infrared. We give plausible arguments that nodal liquids at such supersymmetric points are characterized by superconductivity of Kosterlitz-Thouless type. The fact that quantum fluctuations around such points can be studied in a controlled way, probably makes such systems of special importance for an eventual nonperturbative understanding of the complex phase diagram of the associated high-temperature superconducting materials.

  16. Long-term outcome of ultrasound-guided percutaneous ethanol ablation of selected "recurrent" neck nodal metastases in 25 patients with TNM stages III or IVA papillary thyroid carcinoma previously treated by surgery and 131I therapy.

    PubMed

    Hay, Ian D; Lee, Robert A; Davidge-Pitts, Caroline; Reading, Carl C; Charboneau, J William

    2013-12-01

    Ultrasound-guided percutaneous ethanol ablation (UPEA) of neck nodal metastases (NNM) has rarely been reported in papillary thyroid carcinoma (PTC) patients with advanced localized disease. We ablated 25 PTC patients with stage III or IVA disease (mean age 58 years) who had "recurrent" NNM after surgery and 131I therapy. Diagnosis of 37 selected NNM was proven by ultrasound-guided biopsy. UPEA was usually performed in 2 outpatient sessions. After UPEA, 35 of 37 NNM (95%) decreased in size. None had significant Doppler flow. Seventeen (46%) disappeared on rescanning. Serum thyroglobulin fell in 19 of 22 (86%) without thyroglobulin autoantibodies. None of the UPEA-treated NNM, followed on average for 5.4 years, required further intervention. Six patients (24%) subsequently developed 18 "new" recurrences. Of the 18, 15 (83%) were managed successfully by UPEA rather than operation. None of the 25 patients developed permanent hoarseness or have died from PTC. At our institution, where patients undergoing nodal dissections are charged $35-45,000, each outpatient UPEA procedure saves health providers approximately $38,400. Our 25 ablated patients, by avoiding 40 further neck reexplorations, on average, saved $61,440 in charges. UPEA for NNM in advanced localized PTC has proved safe and effective. It is also considerably less expensive than the conventional operative alternative of nodal dissection. Copyright © 2013 Mosby, Inc. All rights reserved.

  17. Involved field radiotherapy (IFRT) versus elective nodal irradiation (ENI) for locally advanced non-small cell lung cancer: a meta-analysis of incidence of elective nodal failure (ENF).

    PubMed

    Li, Ruijian; Yu, Liang; Lin, Sixiang; Wang, Lina; Dong, Xin; Yu, Lingxia; Li, Weiyi; Li, Baosheng

    2016-09-21

    The use of involved field radiotherapy (IFRT) has generated concern about the increasing incidence of elective nodal failure (ENF) in contrast to elective nodal irradiation (ENI). This meta-analysis aimed to provide more reliable and up-to-date evidence on the incidence of ENF between IFRT and ENI. We searched three databases for eligible studies where locally advanced non-small cell lung cancer (NSCLC) patients received IFRT or ENI. Outcome of interest was the incidence of ENF. The fixed-effects model was used to pool outcomes across the studies. There were 3 RCTs and 3 cohort studies included with low risk of bias. There was no significant difference in incidence of ENF between IFRT and ENI either among RCTs (RR = 1.38, 95 % CI: 0.59-3.25, p = 0.46) or among cohort studies (RR = 0.99, 95 % CI: 0.46-2.10, p = 0.97). There was also no significant difference in incidence of ENF between IFRT and ENI when RCTs and cohort studies were combined (RR = 1.15, 95 % CI: 0.65-2.01, p = 0.64). I 2 of test for heterogeneity was 0 %. This meta-analysis provides more reliable and stable evidence that there is no significant difference in incidence of ENF between IFRT and ENI.

  18. Impaired Long Distance Functional Connectivity and Weighted Network Architecture in Alzheimer's Disease

    PubMed Central

    Liu, Yong; Yu, Chunshui; Zhang, Xinqing; Liu, Jieqiong; Duan, Yunyun; Alexander-Bloch, Aaron F.; Liu, Bing; Jiang, Tianzi; Bullmore, Ed

    2014-01-01

    Alzheimer's disease (AD) is increasingly recognized as a disconnection syndrome, which leads to cognitive impairment due to the disruption of functional activity across large networks or systems of interconnected brain regions. We explored abnormal functional magnetic resonance imaging (fMRI) resting-state dynamics, functional connectivity, and weighted functional networks, in a sample of patients with severe AD (N = 18) and age-matched healthy volunteers (N = 21). We found that patients had reduced amplitude and regional homogeneity of low-frequency fMRI oscillations, and reduced the strength of functional connectivity, in several regions previously described as components of the default mode network, for example, medial posterior parietal cortex and dorsal medial prefrontal cortex. In patients with severe AD, functional connectivity was particularly attenuated between regions that were separated by a greater physical distance; and loss of long distance connectivity was associated with less efficient global and nodal network topology. This profile of functional abnormality in severe AD was consistent with the results of a comparable analysis of data on 2 additional groups of patients with mild AD (N = 17) and amnestic mild cognitive impairment (MCI; N = 18). A greater degree of cognitive impairment, measured by the mini-mental state examination across all patient groups, was correlated with greater attenuation of functional connectivity, particularly over long connection distances, for example, between anterior and posterior components of the default mode network, and greater reduction of global and nodal network efficiency. These results indicate that neurodegenerative disruption of fMRI oscillations and connectivity in AD affects long-distance connections to hub nodes, with the consequent loss of network efficiency. This profile was evident also to a lesser degree in the patients with less severe cognitive impairment, indicating that the potential of resting

  19. Long-term outcome of concurrent chemoradiotherapy with elective nodal irradiation for inoperable esophageal cancer.

    PubMed

    Jing, Zhao; Chen, Tian; Zhang, Xuebang; Wu, Shixiu

    2017-09-01

    Elective nodal irradiation (ENI) might improve overall survival in patients with inoperable esophageal cancer. We conducted a retrospective analysis to assess the long-term survival and toxicity of esophageal cancer patients treated with ENI versus conventional-field irradiation (CFI). All data in the present study were based on our institutional experience from 2000 to 2005 of patients with inoperable esophageal cancer treated with ENI or CFI plus two concurrent cycles of paclitaxel/cisplatin. Based on the inclusion and exclusion criteria, 89 patients were included in the analysis. Of these patients, 51 were treated with ENI, whereas 38 were treated with CFI. For the per-protocol population, the patients in the ENI group significantly improved in terms of their 10-year disease-specific overall survival (43.1% vs 10.5%, P = 0.019), 10-year disease-free survival (36.7% vs 10.2%, P = 0.040) and 10-year local recurrence-free survival (47.2% vs 17.2%, P = 0.018) compared with the CFI group. Aside from radiation esophagitis, the incidence of grade 3 or greater acute toxicities did not differ between the two groups. Multivariate analysis showed that radiation field, tumor length and clinical stage were independent prognostic factors associated with OS. Concurrent chemoradiotherapy with ENI improves both disease-specific overall survival and loco-regional control in patients with inoperable esophageal cancer receiving per-protocol treatment. The regimen has a manageable tolerability profile. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  20. Molecular pathogenesis of splenic and nodal marginal zone lymphoma.

    PubMed

    Spina, Valeria; Rossi, Davide

    Genomic studies have improved our understanding of the biological basis of splenic (SMZL) and nodal (NMZL) marginal zone lymphoma by providing a comprehensive and unbiased view of the genes/pathways that are deregulated in these diseases. Consistent with the physiological involvement of NOTCH, NF-κB, B-cell receptor and toll-like receptor signaling in mature B-cells differentiation into the marginal zone B-cells, many oncogenic mutations of genes involved in these pathways have been identified in SMZL and NMZL. Beside genetic lesions, also epigenetic and post-transcriptional modifications contribute to the deregulation of marginal zone B-cell differentiation pathways in SMZL and NMZL. This review describes the progress in understanding the molecular mechanism underlying SMZL and NMZL, including molecular and post-transcriptional modifications, and discusses how information gained from these efforts has provided new insights on potential targets of diagnostic, prognostic and therapeutic relevance in SMZL and NMZL. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Childhood nodal marginal zone lymphoma with unusual clinicopathologic and cytogenetic features for the pediatric variant: a case report.

    PubMed

    Aqil, Barina; Merritt, Brian Y; Elghetany, M Tarek; Kamdar, Kala Y; Lu, Xinyan Y; Curry, Choladda V

    2015-01-01

    Nodal marginal zone lymphoma (NMZL) is a B-cell lymphoma that shares morphologic and immunophenotypic features with extranodal and splenic marginal zone lymphomas but lacks extranodal or splenic involvement at presentation. NMZL occurs mostly in adults with no sex predilection, at advanced stage (III or IV), with frequent relapses and a high incidence of tumoral genetic abnormalities including trisomies 3 and 18 and gain of 7q. Pediatric NMZL, however, is a rare but distinct variant of NMZL with characteristic features including male predominance, asymptomatic and localized (stage I) disease, low relapse rates with excellent outcomes, and a lower incidence of essentially similar genetic aberrations compared to adult NMZL. Here we describe a unique case of childhood NMZL with unusual clinicopathologic features for the pediatric variant including generalized lymphadenopathy, high-stage disease with persistence after therapy, unusual immunophenotype (CD5, CD23, and BCL6 positive), and unique chromosomal abnormalities including monosomy 20 and add(10)(p11.2).

  2. Isospectral discrete and quantum graphs with the same flip counts and nodal counts

    NASA Astrophysics Data System (ADS)

    Juul, Jonas S.; Joyner, Christopher H.

    2018-06-01

    The existence of non-isomorphic graphs which share the same Laplace spectrum (to be referred to as isospectral graphs) leads naturally to the following question: what additional information is required in order to resolve isospectral graphs? It was suggested by Band, Shapira and Smilansky that this might be achieved by either counting the number of nodal domains or the number of times the eigenfunctions change sign (the so-called flip count) (Band et al 2006 J. Phys. A: Math. Gen. 39 13999–4014 Band and Smilansky 2007 Eur. Phys. J. Spec. Top. 145 171–9). Recent examples of (discrete) isospectral graphs with the same flip count and nodal count have been constructed by Ammann by utilising Godsil–McKay switching (Ammann private communication). Here, we provide a simple alternative mechanism that produces systematic examples of both discrete and quantum isospectral graphs with the same flip and nodal counts.

  3. Surface and 3D Quantum Hall Effects from Engineering of Exceptional Points in Nodal-Line Semimetals

    NASA Astrophysics Data System (ADS)

    Molina, Rafael A.; González, José

    2018-04-01

    We show that, under a strong magnetic field, a 3D nodal-line semimetal is driven into a topological insulating phase in which the electronic transport takes place at the surface of the material. When the magnetic field is perpendicular to the nodal ring, the surface states of the semimetal are transmuted into Landau states which correspond to exceptional points, i.e., branch points in the spectrum of a non-Hermitian Hamiltonian which arise upon the extension to complex values of the momentum. The complex structure of the spectrum then allows us to express the number of zero-energy flat bands in terms of a new topological invariant counting the number of exceptional points. When the magnetic field is parallel to the nodal ring, we find that the bulk states are built from the pairing of surfacelike evanescent waves, giving rise to a 3D quantum Hall effect with a flat level of Landau states residing in parallel 2D slices of the 3D material. The Hall conductance is quantized in either case in units of e2/h , leading in the 3D Hall effect to a number of channels growing linearly with the section of the surface and opening the possibility to observe a macroscopic chiral current at the surface of the material.

  4. Advanced nodal neutron diffusion method with space-dependent cross sections: ILLICO-VX

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rajic, H.L.; Ougouag, A.M.

    1987-01-01

    Advanced transverse integrated nodal methods for neutron diffusion developed since the 1970s require that node- or assembly-homogenized cross sections be known. The underlying structural heterogeneity can be accurately accounted for in homogenization procedures by the use of heterogeneity or discontinuity factors. Other (milder) types of heterogeneity, burnup-induced or due to thermal-hydraulic feedback, can be resolved by explicitly accounting for the spatial variations of material properties. This can be done during the nodal computations via nonlinear iterations. The new method has been implemented in the code ILLICO-VX (ILLICO variable cross-section method). Numerous numerical tests were performed. As expected, the convergence ratemore » of ILLICO-VX is lower than that of ILLICO, requiring approx. 30% more outer iterations per k/sub eff/ computation. The methodology has also been implemented as the NOMAD-VX option of the NOMAD, multicycle, multigroup, two- and three-dimensional nodal diffusion depletion code. The burnup-induced heterogeneities (space dependence of cross sections) are calculated during the burnup steps.« less

  5. The prognostic value of node status in different breast cancer subtypes

    PubMed Central

    Hou, Xin-Wei; Chi, Jiang-Rui; Ge, Jie; Wang, Xin; Cao, Xu-Chen

    2017-01-01

    Nodal metastases and breast cancer subtypes (BCS) are both well-recognized prognostic indicators. However, the association between nodal metastases and BCS, and the prognostic value of nodal metastases in different BCS are still remains unclear. Our aim was to investigate the association between nodal metastases and BCS, and the prognostic value of nodal metastases in the different BCS. We found that the breast cancer subtype was closely associated with the pN stage. pN stage and breast cancer subtype were significantly associated with disease-free survival. The subgroup analysis showed that the patients in higher pN stage had a poor outcome than patients in lower pN stage in each breast cancer subtype. Furthermore, when the analysis was stratified by breast cancer subtype, we found that even in the same pN stage (pN0-pN2), there was significant survival difference among patients in different BCS, and Luminal A breast cancer patients had the best survival outcome. However, there were no significant survival difference between Luminal A patients and other breast cancer subtype when patients in pN3 stage. Thus, our study suggested that both lymph node status and molecular subtype played important roles in the outcome of breast cancer patients and they cannot replace each other. PMID:27999188

  6. Could machine learning improve the prediction of pelvic nodal status of prostate cancer patients? Preliminary results of a pilot study.

    PubMed

    De Bari, B; Vallati, M; Gatta, R; Simeone, C; Girelli, G; Ricardi, U; Meattini, I; Gabriele, P; Bellavita, R; Krengli, M; Cafaro, I; Cagna, E; Bunkheila, F; Borghesi, S; Signor, M; Di Marco, A; Bertoni, F; Stefanacci, M; Pasinetti, N; Buglione, M; Magrini, S M

    2015-07-01

    We tested and compared performances of Roach formula, Partin tables and of three Machine Learning (ML) based algorithms based on decision trees in identifying N+ prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also verified on an independent population of 204 operated cN0 patients, with a known pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on the surgical population, with accuracy, specificity, and sensitivity ranging between 48-86%, 35-91%, and 17-79%, respectively. ML potentially allows better prediction of the nodal status of PC, potentially allowing a better tailoring of pelvic irradiation.

  7. Characterization of Lifshitz transitions in topological nodal line semimetals

    NASA Astrophysics Data System (ADS)

    Jiang, Hui; Li, Linhu; Gong, Jiangbin; Chen, Shu

    2018-04-01

    We introduce a two-band model of three-dimensional nodal line semimetals (NLSMs), the Fermi surface of which at half-filling may form various one-dimensional configurations of different topology. We study the symmetries and "drumhead" surface states of the model, and find that the transitions between different configurations, namely, the Lifshitz transitions, can be identified solely by the number of gap-closing points on some high-symmetry planes in the Brillouin zone. A global phase diagram of this model is also obtained accordingly. We then investigate the effect of some extra terms analogous to a two-dimensional Rashba-type spin-orbit coupling. The introduced extra terms open a gap for the NLSMs and can be useful in engineering different topological insulating phases. We demonstrate that the behavior of surface Dirac cones in the resulting insulating system has a clear correspondence with the different configurations of the original nodal lines in the absence of the gap terms.

  8. Nodal Green’s Function Method Singular Source Term and Burnable Poison Treatment in Hexagonal Geometry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    A.A. Bingham; R.M. Ferrer; A.M. ougouag

    2009-09-01

    An accurate and computationally efficient two or three-dimensional neutron diffusion model will be necessary for the development, safety parameters computation, and fuel cycle analysis of a prismatic Very High Temperature Reactor (VHTR) design under Next Generation Nuclear Plant Project (NGNP). For this purpose, an analytical nodal Green’s function solution for the transverse integrated neutron diffusion equation is developed in two and three-dimensional hexagonal geometry. This scheme is incorporated into HEXPEDITE, a code first developed by Fitzpatrick and Ougouag. HEXPEDITE neglects non-physical discontinuity terms that arise in the transverse leakage due to the transverse integration procedure application to hexagonal geometry andmore » cannot account for the effects of burnable poisons across nodal boundaries. The test code being developed for this document accounts for these terms by maintaining an inventory of neutrons by using the nodal balance equation as a constraint of the neutron flux equation. The method developed in this report is intended to restore neutron conservation and increase the accuracy of the code by adding these terms to the transverse integrated flux solution and applying the nodal Green’s function solution to the resulting equation to derive a semi-analytical solution.« less

  9. Theory of nodal s ±-wave pairing symmetry in the Pu-based 115 superconductor family

    DOE PAGES

    Das, Tanmoy; Zhu, Jian -Xin; Graf, Matthias J.

    2015-02-27

    The spin-fluctuation mechanism of superconductivity usually results in the presence of gapless or nodal quasiparticle states in the excitation spectrum. Nodal quasiparticle states are well established in copper-oxide, and heavy-fermion superconductors, but not in iron-based superconductors. Here, we study the pairing symmetry and mechanism of a new class of plutonium-based high-T c superconductors and predict the presence of a nodal s⁺⁻ wave pairing symmetry in this family. Starting from a density-functional theory (DFT) based electronic structure calculation we predict several three-dimensional (3D) Fermi surfaces in this 115 superconductor family. We identify the dominant Fermi surface “hot-spots” in the inter-band scatteringmore » channel, which are aligned along the wavevector Q = (π, π, π), where degeneracy could induce sign-reversal of the pairing symmetry. Our calculation demonstrates that the s⁺⁻ wave pairing strength is stronger than the previously thought d-wave pairing; and more importantly, this pairing state allows for the existence of nodal quasiparticles. Finally, we predict the shape of the momentum- and energy-dependent magnetic resonance spectrum for the identification of this pairing symmetry.« less

  10. Quantum oscillation signatures of spin-orbit interactions controlling the residual nodal bilayer-splitting in underdoped high-Tc cuprates

    NASA Astrophysics Data System (ADS)

    Harrison, Neil; Shekhter, Arkady

    2015-03-01

    We investigate the origin of the small residual nodal bilayer-splitting in the underdoped high-Tc superconductor YBa2Cu3O6+x using the results of recently published angle-resolved quantum oscillation data [Sebastian et al., Nature 511, 61 (2014)]. A crucial clue to the origin of the residual bilayer-splitting is found to be provided by the anomalously small Zeeman-splitting of some of the observed cyclotron orbits. We show that such an anomalously Zeeman-splitting (or small effective g-factor) for a subset of orbits can be explained by spin-orbit interactions, which become significant in the nodal regions as a result of the vanishing bilayer coupling. The primary effect of spin-orbit interactions is to cause quasiparticles traversing the nodal region of the Brillouin zone to undergo a spin flip. We suggest that the Rashba-like spin-orbit interactions, naturally present in bilayer systems, have the right symmetry and magnitude to give rise to a network of coupled orbits consistent with experimental observations in underdoped YBa2Cu3O6+x. This work is supported by the DOEm BES proposal LANLF100, while the magnet lab is supported by the NSF and Florida State.

  11. Intensity-Modulated Radiation Therapy for the Treatment of Squamous Cell Anal Cancer With Para-aortic Nodal Involvement

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hodges, Joseph C.; Das, Prajnan, E-mail: PrajDas@mdanderson.or; Eng, Cathy

    2009-11-01

    Purpose: To determine the rates of toxicity, locoregional control, distant control, and survival in anal cancer patients with para-aortic nodal involvement, treated with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy at a single institution. Methods and Materials: Between 2001 and 2007, 6 patients with squamous cell anal cancer and para-aortic nodal involvement were treated with IMRT and concurrent infusional 5-fluorouracil and cisplatin. The primary tumor was treated with a median dose of 57.5 Gy (range, 54-60 Gy), involved para-aortic, pelvic, and inguinal lymph nodes were treated with a median dose of 55 Gy (range, 50.5-55 Gy), and noninvolved nodal regions weremore » treated with a median dose of 45 Gy (range, 43.5-45 Gy). Results: After a median follow-up of 25 months, none of the patients had a recurrence at the primary tumor, pelvic/inguinal nodes, or para-aortic nodes, whereas 2 patients developed distant metastases to the liver. Four of the 6 patients are alive. The 3-year actuarial locoregional control, distant control, and overall survival rates were 100%, 56%, and 63%, respectively. Four of the 6 patients developed Grade 3 acute gastrointestinal toxicity during chemoradiation. Conclusions: Intensity-modulated radiotherapy and concurrent chemotherapy could potentially serve as definitive therapy in anal cancer patients with para-aortic nodal involvement. Adjuvant chemotherapy may be indicated in these patients, as demonstrated by the distant failure rates. These patients need to be followed carefully because of the potential for treatment-related toxicities.« less

  12. Atlas-Based Segmentation Improves Consistency and Decreases Time Required for Contouring Postoperative Endometrial Cancer Nodal Volumes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Young, Amy V.; Department of Radiation Oncology, St. Luke's-Roosevelt Hospital, New York, NY; Wortham, Angela

    2011-03-01

    Purpose: Accurate target delineation of the nodal volumes is essential for three-dimensional conformal and intensity-modulated radiotherapy planning for endometrial cancer adjuvant therapy. We hypothesized that atlas-based segmentation ('autocontouring') would lead to time savings and more consistent contours among physicians. Methods and Materials: A reference anatomy atlas was constructed using the data from 15 postoperative endometrial cancer patients by contouring the pelvic nodal clinical target volume on the simulation computed tomography scan according to the Radiation Therapy Oncology Group 0418 trial using commercially available software. On the simulation computed tomography scans from 10 additional endometrial cancer patients, the nodal clinical targetmore » volume autocontours were generated. Three radiation oncologists corrected the autocontours and delineated the manual nodal contours under timed conditions while unaware of the other contours. The time difference was determined, and the overlap of the contours was calculated using Dice's coefficient. Results: For all physicians, manual contouring of the pelvic nodal target volumes and editing the autocontours required a mean {+-} standard deviation of 32 {+-} 9 vs. 23 {+-} 7 minutes, respectively (p = .000001), a 26% time savings. For each physician, the time required to delineate the manual contours vs. correcting the autocontours was 30 {+-} 3 vs. 21 {+-} 5 min (p = .003), 39 {+-} 12 vs. 30 {+-} 5 min (p = .055), and 29 {+-} 5 vs. 20 {+-} 5 min (p = .0002). The mean overlap increased from manual contouring (0.77) to correcting the autocontours (0.79; p = .038). Conclusion: The results of our study have shown that autocontouring leads to increased consistency and time savings when contouring the nodal target volumes for adjuvant treatment of endometrial cancer, although the autocontours still required careful editing to ensure that the lymph nodes at risk of recurrence are properly included in the

  13. Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

    PubMed

    Barton, M; Boyages, J; Crennan, E; Davis, S; Fisher, R J; Hook, C; Johnson, N; Joseph, D; Khoo, V; Liew, K H; Morgan, G; O'Brien, P; Pendlebury, S; Pratt, G; Quong, G; Roos, D E; Thornton, D; Trotter, G; Walker, Q; Wallington, M

    1996-04-01

    To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and

  14. Pediatric nodal marginal zone lymphoma may develop in the adult population.

    PubMed

    Gitelson, Elena; Al-Saleem, Tahseen; Robu, Valentin; Millenson, Michael M; Smith, Mitchell R

    2010-01-01

    Pediatric nodal marginal zone lymphoma (NMZL) is described as a separate variant of NMZL in the most recent WHO classification of tumors of hematologic and lymphoid tissues. It has distinctive morphology and clinical presentation and stands out as an indolent disease with remarkably better overall prognosis compared to classic NMZL. Here we report two adult patients with NMZL with clinical and morphologic features consistent with pediatric NMZL (pNMZL) and review available literature describing the clinical and histologic presentation of pNMZL. Two men, ages 44 and 18 years, each presented with localized cervical lymphadenopathy, both demonstrated florid proliferation of the marginal zone and disruption of reactive germinal centers, progressive transformation of germinal centers-like morphologic features typical for pNMZL and clonal disease with immunophenotype consistent with NMZL. This is the first report of pNMZL in a middle-aged person. Distinct histologic features and characteristic benign clinical course will help to distinguish this rare variant from other NMZL in the adults. Clinically, recognition is important to understand the true incidence of this rare form in the adult population and to avoid unnecessary overtreatment of this indolent form.

  15. Universal heat conduction in Ce 1-xYb xCoIn 5: Evidence for robust nodal d-wave superconducting gap

    DOE PAGES

    Xu, Y.; Petrovic, C.; Dong, J. K.; ...

    2016-02-01

    In the heavy-fermion superconductor Ce 1-xYb xCoIn 5, Yb doping was reported to cause a possible change from nodal d-wave superconductivity to a fully gapped d-wave molecular superfluid of composite pairs near x ≈ 0.07 (nominal value x nom = 0.2). Here we present systematic thermal conductivity measurements on Ce 1-xYb xCoIn 5 (x = 0.013, 0.084, and 0.163) single crystals. The observed finite residual linear term κ 0/T is insensitive to Yb doping, verifying the universal heat conduction of the nodal d-wave superconducting gap in Ce 1-xYb xCoIn 5. Similar universal heat conduction is also observed in the CeCo(Inmore » 1–yCd y) 5 system. Furthermore, these results reveal a robust nodal d-wave gap in CeCoIn 5 upon Yb or Cd doping.« less

  16. The N2 paradox: similar outcomes of pre- and postoperatively identified single-zone N2a positive non-small-cell lung cancer.

    PubMed

    Tsitsias, Thomas; Boulemden, Anas; Ang, Keng; Nakas, Apostolos; Waller, David A

    2014-05-01

    Resection of N2a non-small-cell lung cancer (NSCLC) diagnosed preoperatively is controversial but there is support for resection of unexpected N2 disease discovered at surgery. Since the seventh TNM edition, we have intentionally resected clinical N2a disease. To validate this policy, we determined prognostic factors associated with all resected N2 disease. From a prospective database of 1131 consecutive patients undergoing elective resection for primary lung cancer over a period of 8 years, we identified 68 patients (35 females (51.4%), mean age 66 years, standard deviation (SD) 9 years) who had pathological N2 disease. All patients had positron emission computed tomography (CT-PET) staging and selective mediastinoscopy. A Cox-regression analysis was performed to identify prognostic factors. At a median follow-up of 38.7 months (standard error 10, 95% confidence interval (CI) 19.0-58.4), the overall median survival was 22.2 months (95% CI 14.6-29.8) with 1-, 2- and 5-year survival rates of 63.3, 46.6 and 13.2%, respectively. Survival after resection of pN2 disease is adversely affected by the need for pneumonectomy, multizone pN2b involvement and by non-compliance with adjuvant chemotherapy. Pathological involvement of the subcarinal zone but no other zone appears to be associated with an adverse prognosis (hazard ratio (HR) 1.87, P = 0.063). Importantly, long-term survival is not different between those patients who have a negative preoperative PET-CT scan and yet are found to have pN2 after resection, and those who are single-zone cN2a positive before resection on PET-CT scan (HR 1.37, P = 0.335). Our results support a policy of intentionally resecting single-zone N2a NSCLC identified preoperatively as part of a multimodality therapy.

  17. Disappearance of nodal gap across the insulator-superconductor transition in a copper-oxide superconductor.

    PubMed

    Peng, Yingying; Meng, Jianqiao; Mou, Daixiang; He, Junfeng; Zhao, Lin; Wu, Yue; Liu, Guodong; Dong, Xiaoli; He, Shaolong; Zhang, Jun; Wang, Xiaoyang; Peng, Qinjun; Wang, Zhimin; Zhang, Shenjin; Yang, Feng; Chen, Chuangtian; Xu, Zuyan; Lee, T K; Zhou, X J

    2013-01-01

    The parent compound of the copper-oxide high-temperature superconductors is a Mott insulator. Superconductivity is realized by doping an appropriate amount of charge carriers. How a Mott insulator transforms into a superconductor is crucial in understanding the unusual physical properties of high-temperature superconductors and the superconductivity mechanism. Here we report high-resolution angle-resolved photoemission measurement on heavily underdoped Bi₂Sr₂-xLaxCuO(₆+δ) system. The electronic structure of the lightly doped samples exhibit a number of characteristics: existence of an energy gap along the nodal direction, d-wave-like anisotropic energy gap along the underlying Fermi surface, and coexistence of a coherence peak and a broad hump in the photoemission spectra. Our results reveal a clear insulator-superconductor transition at a critical doping level of ~0.10 where the nodal energy gap approaches zero, the three-dimensional antiferromagnetic order disappears, and superconductivity starts to emerge. These observations clearly signal a close connection between the nodal gap, antiferromagnetism and superconductivity.

  18. Assessing the risk of pelvic and para-aortic nodal involvement in apparent early-stage ovarian cancer: A predictors- and nomogram-based analyses.

    PubMed

    Bogani, Giorgio; Tagliabue, Elena; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Casarin, Jvan; Chiappa, Valentina; Dondi, Giulia; Leone Roberti Maggiore, Umberto; Scaffa, Cono; Borghi, Chiara; Montanelli, Luca; Lorusso, Domenica; Raspagliesi, Francesco

    2017-10-01

    To estimate the prevalence of lymph node involvement in early-stage epithelial ovarian cancer in order to assess the prognostic value of lymph node dissection. Data of consecutive patients undergoing staging for early-stage epithelial ovarian cancer were retrospectively evaluated. Logistic regression and a nomogram-based analysis were used to assess the risk of lymph node involvement. Overall, 290 patients were included. All patients had lymph node dissection including pelvic and para-aortic lymphadenectomy. Forty-two (14.5%) patients were upstaged due to lymph node metastatic disease. Pelvic and para-aortic nodal metastases were observed in 22 (7.6%) and 42 (14.5%) patients. Lymph node involvement was observed in 18/95 (18.9%), 1/37 (2.7%), 4/29 (13.8%), 11/63 (17.4%), 3/41 (7.3%) and 5/24 (20.8%) patients with high-grade serous, low-grade-serous, endometrioid G1, endometrioid G2&3, clear cell and undifferentiated, histology, respectively (p=0.12, Chi-square test). We observed that high-grade serous histology was associated with an increased risk of pelvic node involvement; while, histology rather than low-grade serous and bilateral tumors were independently associated with para-aortic lymph node involvement (p<0.05). Nomograms displaying the risk of nodal involvement in the pelvic and para-aortic areas were built. High-grade serous histology and bilateral tumors are the main characteristics suggesting lymph node positivity. Our data suggested that high-grade serous and bilateral early-stage epithelial ovarian cancer are at high risk of having disease harboring in the lymphatic tissues of both pelvic and para-aortic area. After receiving external validation, our data will help to identify patients deserving comprehensive retroperitoneal staging. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Pelvic lymphadenectomy during robot-assisted radical prostatectomy: Assessing nodal yield, perioperative outcomes, and complications.

    PubMed

    Zorn, Kevin C; Katz, Mark H; Bernstein, Andrew; Shikanov, Sergey A; Brendler, Charles B; Zagaja, Gregory P; Shalhav, Arieh L

    2009-08-01

    To describe our pelvic lymphadenectomy (PLND) technique during robot-assisted radical prostatectomy and to evaluate the nodal yield and perioperative outcomes. PLND is commonly performed with radical prostatectomy for localized prostate cancer. Because of the limitations of the robotic arm pitch in accessing the pelvic sidewall and undersurface of the iliac bifurcation, uro-oncologists have questioned the adequacy of robotic PLND. PLND was routinely performed on men with higher risk preoperative prostate cancer parameters (ie, prostrate-specific antigen >10 ng/mL, primary Gleason score > or =4, or clinical Stage T2b or greater). The outcomes of robot-assisted radical prostatectomy with bilateral, standard template PLND (group 1; n = 296 [26%]) were compared with those of a cohort of 859 robot-assisted radical prostatectomy patients (74%) without PLND (group 2). We also compared these data with those from a single-surgeon experience of open, standard-template PLND for retropubic radical prostatectomy. The mean number of lymph nodes removed was 12.5 (interquartile range 7-16). The mean operative time (224 vs 216 minutes; P = .09), estimated blood loss (206 vs 229 mL; P = .14), and hospital stay (1.32 vs 1.24 days; P = .46) were comparable between the 2 groups. The rate of intraoperative complications (1% vs 1.5%; P = .2), overall postoperative complications (9% vs 7%; P = .8), and lymphocele formation (2% vs 0%; P = .9) were not significantly different. The review of our open series and the historically published open standard-template PLND series revealed a mean yield of 15 and a range of 6.7-15 lymph nodes removed, respectively. Our data support the feasibility and low complication rate of robotic standard-template PLND with lymph node yields comparable to those with open PLND. Considering the low morbidity of PLND in experienced hands, coupled with the potential of preoperative undergrading and understaging and the therapeutic benefit to patients with

  20. Breast cancer metastases to the thyroid gland - an uncommon sentinel for diffuse metastatic disease: a case report and review of the literature.

    PubMed

    Plonczak, Agata M; DiMarco, Aimee N; Dina, Roberto; Gujral, Dorothy M; Palazzo, Fausto F

    2017-09-22

    Metastases to the thyroid are rare. The most common primary cancer to metastasize to the thyroid is renal cell carcinoma, followed by malignancies of the gastrointestinal tract, lungs, and skin, with breast cancer metastases to the thyroid being rare. Overall, the outcomes in malignancies that have metastasized to the thyroid are poor. There are no prospective studies addressing the role of surgery in metastatic disease of the thyroid. Isolated thyroidectomy has been proposed as a local disease control option to palliate and prevent the potential morbidity of tumor extension related to the airway. Here, we present a case of a patient with breast cancer metastases to the thyroid gland and discuss the role of thyroidectomy in the context of the current literature. A 62-year-old Afro-Caribbean woman was diagnosed as having bilateral breast carcinoma in 2004, for which she underwent bilateral mastectomy. The pathology revealed multifocal disease on the right, T2N0(0/20)M0 grade 1 and 2 invasive ductal carcinoma, and on the left side, T3N1(2/18)M0 grade 1 invasive ductal carcinoma. Surgery was followed by adjuvant chemotherapy and regional radiotherapy. The disease was under control on hormonal therapy until 2016, when she developed cervical lymphadenopathy. The fine-needle aspiration cytology of the thyroid was reported as papillary thyroid cancer; and the fine-needle biopsy of the left lateral nodal disease was more suggestive of breast malignancy. She underwent a total thyroidectomy and a clearance of the central compartment lymph nodes and a biopsy of the lateral nodal disease. The histopathological analysis was consistent with metastatic breast cancer in the thyroid and lymph nodes with no evidence of a primary thyroid malignancy. A past history of a malignancy elsewhere should raise the index of suspicion of metastatic disease in patients presenting with thyroid lumps with or without cervical lymphadenopathy. Detection of metastases to the thyroid generally

  1. Recovering tubewise power from three-dimensional nodal kinetics calculation during material relocation in an HWR

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kalimullah; Morris, E.E.; Yang, W.S.

    1994-12-31

    To analyze severe accidents in some special-purpose heavy-water reactors made of assemblies consisting of a number of coaxial tubes of aluminum-clad U-Al fuel and aluminum-clad neutron-capturing material, a mechanistic model, MARTINS, for tube beatup, melting, and molten material relocation has been developed and integrated with the DIF3D nodal hexagonal-z reactor kinetics and other phenomenological modules. The DIF3D kinetics homogenizes all materials located and computes the total power produced in an axial segment of a fuel assembly. This paper presents an approximate method, used in MARTINS, to calculate the distribution of this total nodal power into the intact fuel and capturingmore » material tubes and the meat-cladding mixtures relocating during tube disruption. The method accounts for the change in intraassembly radial power profile due to assembly geometry change with the progress of segment-by-segment disruption of different tubes. Earlier methods to recover pinwise power from nodal calculation for liquid-metal-cooled reactors and light water reactors (X-Y and hexagonal unit cells) are not practical for a disrupting assembly having material relocation. Figure 1 shows the assembly`s end view, divided into rings for modeling and analysis. A ring is a coolant subchannel plus the outer surrounding tube. The present method for distributing the nodal power consists of two parts: (a) calculation of the relative values of ring-by-ring power per unit uranium mass and power per unit mass of neutron-capturing material in a given assembly segment, and (b) normalization of these relative values such that the total power of all rings (intact tubes and U-Al-Cp meat-cladding mixtures, where Cp implies the neutron-capturing material) equals the DIF3D-calculated nodal power for the assembly axial segment.« less

  2. Utility of Adjuvant Chemotherapy After Neoadjuvant Chemoradiation and Esophagectomy for Esophageal Cancer.

    PubMed

    Burt, Bryan M; Groth, Shawn S; Sada, Yvonne H; Farjah, Farhood; Cornwell, Lorraine; Sugarbaker, David J; Massarweh, Nader N

    2017-08-01

    To determine whether adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and esophagectomy is associated with improved overall survival for patients with locally advanced esophageal cancer, and to evaluate how pathologic disease response to neoadjuvant treatment impacts this effect. Neoadjuvant chemoradiation is currently the preferred management approach for locoregional esophageal cancer. Although there is interest in the use of AC, the benefit of systemic therapy after neoadjuvant chemoradiation and esophagectomy is unclear. Retrospective cohort study of patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy in the National Cancer Data Base (2006-2012). Among 3592 patients with esophageal cancer (84.7% adenocarcinoma, 15.2% squamous cell carcinoma), 335 (9.3%) were treated with AC. AC was not associated with a significantly lower risk of death among patients with no residual disease (ypT0N0) or residual non-nodal disease (ypT+N0). Among patients with residual nodal disease (ypTanyN+), AC was associated with a 30% lower risk of death in the overall cohort [hazard ratio (HR) 0.70, (0.57-0.85)] and among those with adenocarcinoma [HR 0.69 (0.57-0.85)]. Using a 90-day postoperative landmark, findings were similar. Among patients with postoperative length of stay ≤10 days and no unplanned readmission, AC was associated with approximately 40% lower risk of death among patients with residual nodal disease [overall cohort, HR 0.63 (0.48-0.84); adenocarcinoma, HR 0.66 (0.49-0.88)]. AC after neoadjuvant chemoradiation and esophagectomy is associated with improved survival in patients with residual nodal disease. Our findings suggest AC may provide additional benefit for esophageal cancer patients, and merits further investigation.

  3. Biological evaluation of N-2-hydroxypropyl trimethyl ammonium chloride chitosan as a carrier for the delivery of live Newcastle disease vaccine.

    PubMed

    Zhao, Kai; Sun, Yanwei; Chen, Gang; Rong, Guangyu; Kang, Hong; Jin, Zheng; Wang, Xiaohua

    2016-09-20

    Mucosal immune system plays a very important role in antiviral immune response. We prepared Newcastle disease viruses (NDV) encapsulated in N-2-hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC) nanoparticles (NDV/La Sota-N-2-HACC-NPs) by an ionic cross linking method, and assessed the potential of N-2-HACC-NPs as a mucosal immune delivery carrier. The properties of the nanoparticles were determined by transmission electron microscopy, Zeta potential and particle size analysis, encapsulation efficiency and loading capacity. NDV/La Sota-N-2-HACC-NPs have regular spherical morphologies and high stability; with 303.88±49.8nm mean diameter, 45.77±0.75mV Zeta potential, 94.26±0.42% encapsulation efficiency and 54.06±0.21% loading capacity. In vitro release assay indicated that the release of NDV from NDV/La Sota-N-2-HACC-NPs is slow. The NDV/La Sota-N-2-HACC-NPs have good biological characteristics, very low toxicity and high level of safety. Additionally, specific pathogen-free chickens immunized with NDV/La Sota-N-2-HACC-NPs showed much stronger cellular, humoral and mucosal immune responses than commercial attenuated live Newcastle disease vaccine, and NDV/La Sota-N-2-HACC-NPs reached the sustainable release effect. Our study here provides a foundation for the further development of mucosal vaccines and drugs, and the N-2-HACC-NPs should be a potential drug delivery carrier with immense potential in medical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Identification and expression of Smads associated with TGF-beta/activin/nodal signaling pathways in the rainbow trout (Oncorhynuchus mykiss)

    USDA-ARS?s Scientific Manuscript database

    The Smad proteins are essential components of the TGF-beta/activin/nodal family signaling pathway. We report the identification and characterization of transcripts representing 3 receptor Smads (Smad2a, Smad2b, Smad3), 2 common Smads (Smad4a, Smad4b) and one inhibitory Smad (Smad7). Phylogenetic an...

  5. Left Septal Slow Pathway Ablation for Atrioventricular Nodal Reentrant Tachycardia.

    PubMed

    Katritsis, Demosthenes G; John, Roy M; Latchamsetty, Rakesh; Muthalaly, Rahul G; Zografos, Theodoros; Katritsis, George D; Stevenson, William G; Efimov, Igor R; Morady, Fred

    2018-03-01

    Immunohistochemistry studies suggest that the anatomic substrate of the slow pathway in atrioventricular nodal reentrant tachycardia (AVNRT) is the left inferior nodal extension. We hypothesized that slow pathway ablation from the left septum is an effective alternative to right-sided ablation. We analyzed our databases of AVNRT in search of cases that had used slow pathway ablation from the left septum because of failure of right septal ablation, and then prospectively subjected consenting patients to a left septal-only procedure. Of 1342 patients subjected to right septal slow pathway ablation for AVNRT, 15 patients, 11 with typical and 4 with atypical AVNRT, had a left septal approach after unsuccessful right-sided ablation (R+L group). Eleven patients were subjected to a left septal-only approach for slow pathway ablation without a previous right septal attempt (L group). Fluoroscopy times in the R+L and L groups were 30.5 (21.0-44.0) and 20.0 (17.0-25.0) minutes, respectively ( P =0.061), and radiofrequency current delivery times were 11.3 (5.0-19.1) and 10.0 (7.0-12.0) minutes, respectively ( P =0.897). There was no need for additional ablation lesions at other anatomic sites in either group, and no cases of atrioventricular block were encountered. Recurrence rates of the arrhythmia for the R+L and L groups were 6.7% and 0%, respectively, in the 3 months after ablation ( P =1.000). Left septal ablation at the anatomic site of the left inferior nodal extension is an alternative for ablation of both typical and atypical AVNRT when ablation at the right posterior septum is ineffective. © 2018 American Heart Association, Inc.

  6. GDF3 is a BMP inhibitor that can activate Nodal signaling only at very high doses

    PubMed Central

    Levine, Ariel J.; Levine, Zachary J.; Brivanlou, Ali H.

    2013-01-01

    Within the TGF-β superfamily, there are approximately forty ligands divided into two major branches: the TGF-β/Activin/Nodal ligands and the BMP/GDF ligands. We studied the ligand GDF3 and found that it inhibits signaling by its co-family members, the BMPs; however, GDF3 has been described by others to have Nodal-like activity. Here, we show that GDF3 can activate Nodal signaling, but only at very high doses and only upon mRNA over-expression. In contrast, GDF3 inhibits BMP signaling upon over-expression of GDF3 mRNA, as recombinant protein, and regardless of its dose. We therefore further characterized the mechanism through which GDF3 protein acts as a specific BMP inhibitor and found that the BMP inhibitory activity of GDF3 resides redundantly in the unprocessed, predominant form and in the mature form of the protein. These results confirm and extend the activity that we described for GDF3 and illuminate the experimental basis for the different observations of others. We suggest that GDF3 is either a bi-functional TGF-β ligand, or, more likely, that it is a BMP inhibitor that can artificially activate Nodal signaling under non-physiological conditions. PMID:18823971

  7. The role of nodal and internodal responses in gravitropism and autotropism in Galium aparine L

    NASA Technical Reports Server (NTRS)

    Heathcote, D. G.; Brown, A. H. (Principal Investigator)

    1987-01-01

    This time course and location of gravitropically induced curvatures in stems of goosegrass (Gallium aparine L.), a member of the Rubiaceae, have been investigated. In the early stages of the response (0-5 h), curvature develops throughout the growing region, and is followed by an autotropic straightening which affects the internodes only, leading to the production of essentially straight internodes some 15 h after the onset of gravistimulation. Curvatures developing in the nodal regions, however, continue to increase over this period, and are not subject to reversal by autotropism. The nodal curvatures are not entirely dependent on the presence of any other part of the plant, since marked curvatures can be induced in isolated nodal segments. This pattern of response leads ultimately to correction of the growth direction of the plant by means of curvature responses confined exclusively to the nodes, despite the initial participation of both nodes and internodes in the gravitropic reaction.

  8. Ca(2+)/calmodulin-activated phosphodiesterase 1A is highly expressed in rabbit cardiac sinoatrial nodal cells and regulates pacemaker function.

    PubMed

    Lukyanenko, Yevgeniya O; Younes, Antoine; Lyashkov, Alexey E; Tarasov, Kirill V; Riordon, Daniel R; Lee, Joonho; Sirenko, Syevda G; Kobrinsky, Evgeny; Ziman, Bruce; Tarasova, Yelena S; Juhaszova, Magdalena; Sollott, Steven J; Graham, David R; Lakatta, Edward G

    2016-09-01

    Constitutive Ca(2+)/calmodulin (CaM)-activation of adenylyl cyclases (ACs) types 1 and 8 in sinoatrial nodal cells (SANC) generates cAMP within lipid-raft-rich microdomains to initiate cAMP-protein kinase A (PKA) signaling, that regulates basal state rhythmic action potential firing of these cells. Mounting evidence in other cell types points to a balance between Ca(2+)-activated counteracting enzymes, ACs and phosphodiesterases (PDEs) within these cells. We hypothesized that the expression and activity of Ca(2+)/CaM-activated PDE Type 1A is higher in SANC than in other cardiac cell types. We found that PDE1A protein expression was 5-fold higher in sinoatrial nodal tissue than in left ventricle, and its mRNA expression was 12-fold greater in the corresponding isolated cells. PDE1 activity (nimodipine-sensitive) accounted for 39% of the total PDE activity in SANC lysates, compared to only 4% in left ventricular cardiomyocytes (LVC). Additionally, total PDE activity in SANC lysates was lowest (10%) in lipid-raft-rich and highest (76%) in lipid-raft-poor fractions (equilibrium sedimentation on a sucrose density gradient). In intact cells PDE1A immunolabeling was not localized to the cell surface membrane (structured illumination microscopy imaging), but located approximately within about 150nm inside of immunolabeling of hyperpolarization-activated cyclic nucleotide-gated potassium channels (HCN4), which reside within lipid-raft-rich microenvironments. In permeabilized SANC, in which surface membrane ion channels are not functional, nimodipine increased spontaneous SR Ca(2+) cycling. PDE1A mRNA silencing in HL-1 cells increased the spontaneous beating rate, reduced the cAMP, and increased cGMP levels in response to IBMX, a broad spectrum PDE inhibitor (detected via fluorescence resonance energy transfer microscopy). We conclude that signaling via cAMP generated by Ca(2+)/CaM-activated AC in SANC lipid raft domains is limited by cAMP degradation by Ca(2+)/Ca

  9. Robotic salvage lymph node dissection for nodal-only recurrences after radical prostatectomy: Perioperative and early oncological outcomes.

    PubMed

    Linxweiler, Johannes; Saar, Matthias; Al-Kailani, Zaid; Janssen, Martin; Ezziddin, Samer; Stöckle, Michael; Siemer, Stefan; Ohlmann, Carsten-Henning

    2018-06-01

    Salvage lymph node dissection (sLND) - performed open or minimally-invasive - is a treatment modality that can be offered to patients with nodal recurrence after radical prostatectomy (RP), especially in times where modern imaging methods like choline- or PSMA-PET/CT are available. Yet, there are only very limited data on the safety and oncological effectiveness of robotic sLND. We retrospectively identified patients who underwent robotic sLND at our institution between 2013 and 2017 for nodal recurrence after RP, which had been diagnosed either by 18 F-choline- or 68 Ga-PSMA-PET/CT. We analyzed perioperative data and early oncological outcomes with a focus on the comparison of patients with preoperative choline- vs. those with preoperative PSMA-PET/CT. We identified 36 patients who underwent robotic sLND at a median time of 45.3 months [range 3.1;228.6] after RP, with nodal recurrences detected in 25 patients by PSMA- and in 11 by choline-PET/CT. Median preoperative PSA, operation time and blood loss were 1.98 ng/ml [range 0.09;35.15], 129.5 min [range 65;202] and 50 ml [range 0;400], respectively. No high-grade complications occurred. A median number of 6.5 [range 1;25] lymph nodes were removed with a median of 1 [range 0;9] tumor-occupied node. None of the patients received any adjuvant treatment. Median postoperative PSA-change was -57% [range -100; +58] in the PSMA- and +10% [range -91; +95] in the choline-group (p = 0.015). 44% of patients in the PSMA- and 18% of patients in the choline-group experienced complete biochemical response (cBCR; PSA <0.2 ng/ml). Median time from sLND to the initiation of further therapy was 12 months [range 2;21.5] in the PSMA-group and 4.7 months [range 2.2;18.9] in the choline-group (p = 0.001). This is the hitherto largest series on robotic sLND for nodal recurrence after RP. Robotic sLND is a feasible therapeutic option with low morbidity, which can at least delay the initiation of further therapy - in some

  10. Indications for Pelvic Nodal Treatment in Prostate Cancer Should Change. Validation of the Roach Formula in a Large Extended Nodal Dissection Series

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abdollah, Firas; Cozzarini, Cesare; Suardi, Nazareno

    2012-06-01

    Purpose: Previous studies have criticized the predicting ability of the Roach formula in assessing the risk of lymph node invasion (LNI) in contemporary patients with prostate cancer (PCa) due to a significant overestimation of LNI rates. However, all those studies included patients treated with limited pelvic lymph node dissection (PLND), which is associated with high rates of false negative findings. We hypothesized that the Roach formula is still an accurate tool for LNI predictions if an extended PLND (ePLND) is performed. Methods and Materials: We included 3,115 consecutive patients treated with radical prostatectomy and ePLND between 2000 and 2010 atmore » a single tertiary referral center. Extended PLND consisted of removal of obturator, external iliac, and hypogastric lymph nodes. We externally validated the Roach formula by using the area under the receiver operating characteristics curve and calibration plot method. Moreover, we tested the performance characteristics of different formula-generated cutoff values ranging from 1% to 20%. Results: The accuracy of the Roach formula was 80.3%. The calibration showed only a minor underestimation of the LNI risk in high-risk patients (6.7%). According to the Roach formula, the use of 15% cut off would have allowed 74.2% (2,311/3,115) of patients to avoid nodal irradiation, while up to 32.7% (111/336) of all patients with LNI would have been missed. When the cut off was lowered to 6%, nodal treatment would have been spared in 1,541 (49.5%) patients while missing 41 LNI patients. The sensitivity, specificity, and negative predictive values associated with the 6% cut off were 87.9%, 54%, and 97.3%, respectively. Conclusions: The Roach formula is still accurate and does not overestimate the rate of LNI in contemporary prostate cancer patients if they are treated with ePLND. However, the recommended cut off of 15% would miss approximately one-third of patients with LNI. Based on our results, the cut off should be

  11. The natural history of thin melanoma and the utility of sentinel lymph node biopsy.

    PubMed

    Durham, Alison B; Schwartz, Jennifer L; Lowe, Lori; Zhao, Lili; Johnson, Andrew G; Harms, Kelly L; Bichakjian, Christopher K; Orsini, Amy P; McLean, Scott A; Bradford, Carol R; Cohen, Mark S; Johnson, Timothy M; Sabel, Michael S; Wong, Sandra L

    2017-12-01

    Current literature may overestimate the risk of nodal metastasis from thin melanoma due to reporting of data only from lesions treated with SLNB. Our objective was to define the natural history of thin melanoma, assessing the likelihood of nodal disease, in order to guide selection for SLNB. Retrospective review. The primary outcome was the rate of nodal disease. Clinicopathologic factors were evaluated to find associations with nodal disease. Five hundred and twelve lesions, follow up available for 488 (median: 48 months). Lesions treated with WLE/SLNB compared to WLE alone were more likely to have high-risk features. The rate of nodal disease was higher in the WLE/SLNB group (24 positive SLNB, five false-negative SLNB with nodal recurrence: 10.2%) compared to WLE alone (four nodal recurrences: 2.0%). Univariate analysis showed age ≤45, Breslow depth ≥0.85 mm, mitotic rate >1 mm 2 , and ulceration were associated with nodal disease. Multivariate analysis confirmed the association of age ≤45 and ulceration. SLNB for melanoma 0.75-0.99 mm should be considered in patients age ≤45, Breslow depth ≥0.85 mm, mitotic rate >1 mm 2 , and/or with ulceration. Thin melanoma <0.85 mm without high-risk features may be treated with WLE alone. © 2017 Wiley Periodicals, Inc.

  12. The value of nodal information in predicting lung cancer relapse using 4DPET/4DCT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Heyse, E-mail: heyse.li@mail.utoronto.ca; Becker, Nathan; Raman, Srinivas

    2015-08-15

    Purpose: There is evidence that computed tomography (CT) and positron emission tomography (PET) imaging metrics are prognostic and predictive in nonsmall cell lung cancer (NSCLC) treatment outcomes. However, few studies have explored the use of standardized uptake value (SUV)-based image features of nodal regions as predictive features. The authors investigated and compared the use of tumor and node image features extracted from the radiotherapy target volumes to predict relapse in a cohort of NSCLC patients undergoing chemoradiation treatment. Methods: A prospective cohort of 25 patients with locally advanced NSCLC underwent 4DPET/4DCT imaging for radiation planning. Thirty-seven image features were derivedmore » from the CT-defined volumes and SUVs of the PET image from both the tumor and nodal target regions. The machine learning methods of logistic regression and repeated stratified five-fold cross-validation (CV) were used to predict local and overall relapses in 2 yr. The authors used well-known feature selection methods (Spearman’s rank correlation, recursive feature elimination) within each fold of CV. Classifiers were ranked on their Matthew’s correlation coefficient (MCC) after CV. Area under the curve, sensitivity, and specificity values are also presented. Results: For predicting local relapse, the best classifier found had a mean MCC of 0.07 and was composed of eight tumor features. For predicting overall relapse, the best classifier found had a mean MCC of 0.29 and was composed of a single feature: the volume greater than 0.5 times the maximum SUV (N). Conclusions: The best classifier for predicting local relapse had only tumor features. In contrast, the best classifier for predicting overall relapse included a node feature. Overall, the methods showed that nodes add value in predicting overall relapse but not local relapse.« less

  13. The Parkinson's disease VPS35[D620N] mutation enhances LRRK2-mediated Rab protein phosphorylation in mouse and human

    PubMed Central

    Mir, Rafeeq; Tonelli, Francesca; Lis, Pawel; Macartney, Thomas; Polinski, Nicole K.; Martinez, Terina N.; Chou, Meng-Yun; Howden, Andrew J.M.; König, Theresa; Hotzy, Christoph; Milenkovic, Ivan; Brücke, Thomas; Zimprich, Alexander; Sammler, Esther; Alessi, Dario R.

    2018-01-01

    Missense mutations in the LRRK2 (Leucine-rich repeat protein kinase-2) and VPS35 genes result in autosomal dominant Parkinson's disease. The VPS35 gene encodes for the cargo-binding component of the retromer complex, while LRRK2 modulates vesicular trafficking by phosphorylating a subgroup of Rab proteins. Pathogenic mutations in LRRK2 increase its kinase activity. It is not known how the only thus far described pathogenic VPS35 mutation, [p.D620N] exerts its effects. We reveal that the VPS35[D620N] knock-in mutation strikingly elevates LRRK2-mediated phosphorylation of Rab8A, Rab10, and Rab12 in mouse embryonic fibroblasts. The VPS35[D620N] mutation also increases Rab10 phosphorylation in mouse tissues (the lung, kidney, spleen, and brain). Furthermore, LRRK2-mediated Rab10 phosphorylation is increased in neutrophils as well as monocytes isolated from three Parkinson's patients with a heterozygous VPS35[D620N] mutation compared with healthy donors and idiopathic Parkinson's patients. LRRK2-mediated Rab10 phosphorylation is significantly suppressed by knock-out or knock-down of VPS35 in wild-type, LRRK2[R1441C], or VPS35[D620N] cells. Finally, VPS35[D620N] mutation promotes Rab10 phosphorylation more potently than LRRK2 pathogenic mutations. Available data suggest that Parkinson's patients with VPS35[D620N] develop the disease at a younger age than those with LRRK2 mutations. Our observations indicate that VPS35 controls LRRK2 activity and that the VPS35[D620N] mutation results in a gain of function, potentially causing PD through hyperactivation of the LRRK2 kinase. Our findings suggest that it may be possible to elaborate compounds that target the retromer complex to suppress LRRK2 activity. Moreover, patients with VPS35[D620N] associated Parkinson's might benefit from LRRK2 inhibitor treatment that have entered clinical trials in humans. PMID:29743203

  14. Atlas of the thoracic lymph nodal delineation and recommendations for lymph nodal CTV of esophageal squamous cell cancer in radiation therapy from China.

    PubMed

    Huang, Wei; Huang, Yong; Sun, Jujie; Liu, Xibin; Zhang, Jian; Zhou, Tao; Zhang, Baijiang; Li, Baosheng

    2015-07-01

    To construct an anatomical atlas of thoracic lymph node regions of esophageal cancer (EC) based on definitions from The Japan Esophageal Society (JES) and generate a consensus to delineate the nodal clinical target volume (CTVn) for elective nodal radiation (ENI) of esophageal squamous cell carcinoma (ESCC). An interdisciplinary group including two dedicated radiation oncologists, an experienced radiologist, a pathologist and two thoracic surgeons were gathered to generate a three-dimensional radiological description for the mediastinal lymph node regions of EC on axial CT scans. Then the radiological boundaries of lymph node regions were validated by a relatively large number of physicians in multiple institutions. An atlas of detailed anatomic boundaries of lymph node station No. 105-114 was defined on axial CT, along with illustrations. From the previous work, the study provided a guide of CTVn contouring for ENI of thoracic ESCC from a single center. It is feasible to use such an atlas of thoracic lymph node stations for radiotherapy planning. A phase III study based on the atlas is ongoing in China to measure quantitatively the ENI received by patients with ESCC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Activin- and Nodal-related factors control antero-posterior patterning of the zebrafish embryo.

    PubMed

    Thisse, B; Wright, C V; Thisse, C

    2000-01-27

    Definition of cell fates along the dorso-ventral axis depends on an antagonistic relationship between ventralizing transforming growth factor-beta superfamily members, the bone morphogenetic proteins and factors secreted from the dorsal organizer, such as Noggin and Chordin. The extracellular binding of the last group to the bone morphogenetic proteins prevents them from activating their receptors, and the relative ventralizer:antagonist ratio is thought to specify different dorso-ventral cell fates. Here, by taking advantage of a non-genetic interference method using a specific competitive inhibitor, the Lefty-related gene product Antivin, we provide evidence that cell fate along the antero-posterior axis of the zebrafish embryo is controlled by the morphogenetic activity of another transforming growth factor-beta superfamily subgroup--the Activin and Nodal-related factors. Increasing antivin doses progressively deleted posterior fates within the ectoderm, eventually resulting in the removal of all fates except forebrain and eyes. In contrast, overexpression of activin or nodal-related factors converted ectoderm that was fated to be forebrain into more posterior ectodermal or mesendodermal fates. We propose that modulation of intercellular signalling by Antivin/Activin and Nodal-related factors provides a mechanism for the graded establishment of cell fates along the antero-posterior axis of the zebrafish embryo.

  16. New core-reflector boundary conditions for transient nodal reactor calculations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, E.K.; Kim, C.H.; Joo, H.K.

    1995-09-01

    New core-reflector boundary conditions designed for the exclusion of the reflector region in transient nodal reactor calculations are formulated. Spatially flat frequency approximations for the temporal neutron behavior and two types of transverse leakage approximations in the reflector region are introduced to solve the transverse-integrated time-dependent one-dimensional diffusion equation and then to obtain relationships between net current and flux at the core-reflector interfaces. To examine the effectiveness of new core-reflector boundary conditions in transient nodal reactor computations, nodal expansion method (NEM) computations with and without explicit representation of the reflector are performed for Laboratorium fuer Reaktorregelung und Anlagen (LRA) boilingmore » water reactor (BWR) and Nuclear Energy Agency Committee on Reactor Physics (NEACRP) pressurized water reactor (PWR) rod ejection kinetics benchmark problems. Good agreement between two NEM computations is demonstrated in all the important transient parameters of two benchmark problems. A significant amount of CPU time saving is also demonstrated with the boundary condition model with transverse leakage (BCMTL) approximations in the reflector region. In the three-dimensional LRA BWR, the BCMTL and the explicit reflector model computations differ by {approximately}4% in transient peak power density while the BCMTL results in >40% of CPU time saving by excluding both the axial and the radial reflector regions from explicit computational nodes. In the NEACRP PWR problem, which includes six different transient cases, the largest difference is 24.4% in the transient maximum power in the one-node-per-assembly B1 transient results. This difference in the transient maximum power of the B1 case is shown to reduce to 11.7% in the four-node-per-assembly computations. As for the computing time, BCMTL is shown to reduce the CPU time >20% in all six transient cases of the NEACRP PWR.« less

  17. Topological surface states in nodal superconductors.

    PubMed

    Schnyder, Andreas P; Brydon, Philip M R

    2015-06-24

    Topological superconductors have become a subject of intense research due to their potential use for technical applications in device fabrication and quantum information. Besides fully gapped superconductors, unconventional superconductors with point or line nodes in their order parameter can also exhibit nontrivial topological characteristics. This article reviews recent progress in the theoretical understanding of nodal topological superconductors, with a focus on Weyl and noncentrosymmetric superconductors and their protected surface states. Using selected examples, we review the bulk topological properties of these systems, study different types of topological surface states, and examine their unusual properties. Furthermore, we survey some candidate materials for topological superconductivity and discuss different experimental signatures of topological surface states.

  18. Nodal endoplasmic reticulum, a specialized form of endoplasmic reticulum found in gravity-sensing root tip columella cells

    NASA Technical Reports Server (NTRS)

    Zheng, H. Q.; Staehelin, L. A.

    2001-01-01

    The endoplasmic reticulum (ER) of columella root cap cells has been postulated to play a role in gravity sensing. We have re-examined the ultrastructure of columella cells in tobacco (Nicotiana tabacum) root tips preserved by high-pressure freezing/freeze-substitution techniques to gain more precise information about the organization of the ER in such cells. The most notable findings are: the identification of a specialized form of ER, termed "nodal ER," which is found exclusively in columella cells; the demonstration that the bulk of the ER is organized in the form of a tubular network that is confined to a peripheral layer under the plasma membrane; and the discovery that this ER-rich peripheral region excludes Golgi stacks, vacuoles, and amyloplasts but not mitochondria. Nodal ER domains consist of an approximately 100-nm-diameter central rod composed of oblong subunits to which usually seven sheets of rough ER are attached along their margins. These domains form patches at the interface between the peripheral ER network and the ER-free central region of the cells, and they occupy defined positions within central and flanking columella cells. Over one-half of the nodal ER domains are located along the outer tangential walls of the flanking cells. Cytochalasin D and latrunculin A cause an increase in size and a decrease in numbers of nodal ER domains. We postulate that the nodal ER membranes locally modulate the gravisensing signals produced by the sedimenting amyloplasts, and that the confinement of all ER membranes to the cell periphery serves to enhance the sedimentability of the amyloplasts in the central region of columella cells.

  19. Immunocompromised patients with metastatic cutaneous nodal squamous cell carcinoma of the head and neck: Poor outcome unrelated to the index lesion.

    PubMed

    Lam, Johnson K S; Sundaresan, Puma; Gebski, Val; Veness, Michael J

    2018-05-01

    Immunocompromised patients with metastatic cutaneous nodal head and neck squamous cell carcinoma (HNSCC) have worse outcomes compared to the immunocompetent. The purpose of this study was to investigate the characteristics of the primary cutaneous squamous cell carcinoma (SCC), nodal pathology, and outcome between these 2 groups. Analysis of a prospective database was performed. A 2:1 pooled analysis selected 46 immunocompetent patients matched with 23 immunocompromised patients. Overall survival (OS) and relapse-free survival (RFS) were calculated using the Kaplan-Meier method. No significant difference was found in the primary tumor characteristics between the 2 groups. In the immunocompromised group, RFS (hazard ratio [HR] 2.70; P = .01) and OS (HR 2.32; P = .04) were significantly worse. Extracapsular spread was present in 100% of the immunocompromised patients. No significant difference was identified in the primary cutaneous SCC between the immunocompetent and immunocompromised patients. Immunosuppression predicted worse outcome. © 2018 Wiley Periodicals, Inc.

  20. Observation of topological nodal fermion semimetal phase in ZrSiS

    DOE PAGES

    Neupane, Madhab; Belopolski, Ilya; Hosen, M. Mofazzel; ...

    2016-05-11

    We present that unveiling new topological phases of matter is one of the current objectives in condensed matter physics. Recent experimental discoveries of Dirac and Weyl semimetals prompt the search for other exotic phases of matter. Here we present a systematic angle-resolved photoemission spectroscopy study of ZrSiS, a prime topological nodal semimetal candidate. Our wider Brillouin zone (BZ) mapping shows multiple Fermi surface pockets such as the diamond-shaped Fermi surface, elliptical-shaped Fermi surface, and a small electron pocket encircling at the zone center (Γ) point, the M point, and the X point of the BZ, respectively. We experimentally establish themore » spinless nodal fermion semimetal phase in ZrSiS, which is supported by our first-principles calculations. Our findings evidence that the ZrSiS-type of material family is a new platform on which to explore exotic states of quantum matter; these materials are expected to provide an avenue for engineering two-dimensional topological insulator systems.« less

  1. Fourier-Accelerated Nodal Solvers (FANS) for homogenization problems

    NASA Astrophysics Data System (ADS)

    Leuschner, Matthias; Fritzen, Felix

    2017-11-01

    Fourier-based homogenization schemes are useful to analyze heterogeneous microstructures represented by 2D or 3D image data. These iterative schemes involve discrete periodic convolutions with global ansatz functions (mostly fundamental solutions). The convolutions are efficiently computed using the fast Fourier transform. FANS operates on nodal variables on regular grids and converges to finite element solutions. Compared to established Fourier-based methods, the number of convolutions is reduced by FANS. Additionally, fast iterations are possible by assembling the stiffness matrix. Due to the related memory requirement, the method is best suited for medium-sized problems. A comparative study involving established Fourier-based homogenization schemes is conducted for a thermal benchmark problem with a closed-form solution. Detailed technical and algorithmic descriptions are given for all methods considered in the comparison. Furthermore, many numerical examples focusing on convergence properties for both thermal and mechanical problems, including also plasticity, are presented.

  2. Salinity Variations of the Intermediate Oyashio Waters and Their Relation with the Lunar Nodal Cycle

    NASA Astrophysics Data System (ADS)

    Rogachev, K. A.; Shlyk, N. V.

    2018-01-01

    New oceanographic observations in the period 1990-2015 revealed significant salinity variations in the Oyashio Current. In the last 26 years, the salinity of the upper layer decreased by 0.2 PSU. The most rapid changes in salinity and temperature have been observed in the last five years. The time series of salinity measurements is characterized by the high-amplitude fluctuations synchronized with the lunar nodal cycle (18.6 years); i.e., high salinity is observed in the period of strong tidal currents. Modulation of diurnal tidal currents with the K1 and O1 periods in the lunar nodal cycle is significant [8, 9]. The amplitude was maximal in 1988 and 2006 and minimal in 1997 and 2015. The characteristics of tidal currents in the Oyashio Current and Sea of Okhotsk are considered based on available data of drifting buoys over the Kruzenshtern and Kashevarov banks. The amplitude of salinity variations synchronized with the lunar cycle is approximately 0.1 PSU; therefore, it has made a significant contribution to the salinity decrease in recent years.

  3. Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients

    PubMed Central

    2010-01-01

    recurrence group was 59.53 years. Most common oral sites included the lateral border of tongue and floor of mouth. Recurrence was associated with clinical N-stage disease. The surgical margins in this group was evaluated and found that 17 had non-cohesive invasion, 30 had dysplasia at margin, 21 had vascular invasion, 9 had nerve invasion and 3 had bony invasion. Severe dysplasia was present in 37 patients. Tumour clearance was achieved in only 8 patients. The mean depth of tumour invasion in the recurrence group was 7.6 mm. An interesting finding was that 5/11 patients who died of distant metastasis had their primary disease in the tongue. Nodal disease comparison showed that 8/10 patients who died of locoregional metastasis and 8/11 patients who died from distant metastasis had clinical nodal involvement. Comparing this to pathological nodal disease (pTNM) showed that 10/10 patients and 10/11 patients who died from locoregional and distant metastasis, respectively, had nodal disease. All patients who died from locoregional and distant metastasis were shown to have recurrence after the primary tumour resection. Squamous cell carcinoma of the oral cavity has a poor overall prognosis with a high tendency to recur at the primary site and extend to involve the cervical lymph nodes. Several clinicopathological parameters can be employed to assess outcome, recurrence and overall survival. PMID:20406474

  4. Prognostic effect of isolated paraaortic nodal spread in endometrial cancer.

    PubMed

    Türkmen, Osman; Başaran, Derman; Karalok, Alper; Cömert Kimyon, Günsu; Taşçı, Tolga; Üreyen, Işın; Tulunay, Gökhan; Turan, Taner

    2018-03-28

    To evaluate the prognostic effect of isolated paraaortic lymph node metastasis in endometrial cancer (EC). This retrospective study included patients with FIGO 2009 stage IIIC2 disease due to isolated paraaortic lymph node metastasis (LNM). Patients with sarcomatous histology, synchronous gynecologic cancers and patients with concurrent pelvic lymph node metastases or patients that have intraabdominal tumor spread were excluded. Kaplan-Meier method was used for calculation of progression free survival (PFS) and overall survival. 1614 patients were operated for EC during study period.961 patients underwent lymph node dissection and 25 (2.6%) were found to have isolated LNM in paraaortic region and these constituted the study cohort.20 (80%) patients had endometrioid EC. Median number of retrieved lymph nodes from pelvic region and paraaortic region was 21.5 (range; 5-41) and 34.5 (range; 1-65), respectively. Median number of metastatic paraaortic nodes was 1 (range; 1-32).The median follow-up time was 15 months (range 5-94). 7 (28%) patients recurred after a median of 20 months (range, 3-99) from initial surgery. 3 patients recurred only in pelvis, one patient had upper abdominal spread and 3 had isolated extraabdominal recurrence.İnvolvement of uterine serosa, positive peritoneal cytology and presence of adnexal metastasis were significantly associated with diminished PFS (p<0.05). The presence of serosal involvement or adnexal involvement is as important as gross peritoneal spread and is related with poor survival in patients with isolated paraaortic nodal spread in EC. Chemotherapy should be the mainstay of treatment in this patient cohort which may eradicate systemic tumor spread.

  5. Pelvic Nodal Radiotherapy in Patients With Unfavorable Intermediate and High-Risk Prostate Cancer: Evidence, Rationale, and Future Directions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Morikawa, Lisa K.; Memorial Sloan-Kettering Cancer Center; Roach, Mack, E-mail: mroach@radonc.ucsf.ed

    2011-05-01

    Over the past 15 years, there have been three major advances in the use of external beam radiotherapy in the management of men with clinically localized prostate made. They include: (1) image guided (IG) three-dimensional conformal/intensity modulated radiotherapy; (2) radiation dose escalation; and (3) androgen deprivation therapy. To date only the last of these three advances have been shown to improve overall survival. The presence of occult pelvic nodal involvement could explain the failure of increased conformality and dose escalation to prolong survival, because the men who appear to be at the greatest risk of death from clinically localized prostatemore » cancer are those who are likely to have lymph node metastases. This review discusses the evidence for prophylactic pelvic nodal radiotherapy, including the key trials and controversies surrounding this issue.« less

  6. Nodal-line pairing with 1D-3D coupled Fermi surfaces: A model motivated by Cr-based superconductors

    NASA Astrophysics Data System (ADS)

    Wachtel, Gideon; Kim, Yong Baek

    2016-09-01

    Motivated by the recent discovery of a new family of chromium-based superconductors, we consider a two-band model, where a band of electrons dispersing only in one direction interacts with a band of electrons dispersing in all three directions. Strong 2 kf density fluctuations in the one-dimensional band induces attractive interactions between the three-dimensional electrons, which, in turn, makes the system superconducting. Solving the associated Eliashberg equations, we obtain a gap function which is peaked at the "poles" of the three-dimensional Fermi sphere, and decreases towards the "equator." When strong enough local repulsion is included, the gap actually changes sign around the equator and nodal rings are formed. These nodal rings manifest themselves in several experimentally observable quantities, some of which resemble unconventional observations in the newly discovered superconductors which motivated this work.

  7. Nodal Diffusion Burnable Poison Treatment for Prismatic Reactor Cores

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    A. M. Ougouag; R. M. Ferrer

    2010-10-01

    The prismatic block version of the High Temperature Reactor (HTR) considered as a candidate Very High Temperature Reactor (VHTR)design may use burnable poison pins in locations at some corners of the fuel blocks (i.e., assembly equivalent structures). The presence of any highly absorbing materials, such as these burnable poisons, within fuel blocks for hexagonal geometry, graphite-moderated High Temperature Reactors (HTRs) causes a local inter-block flux depression that most nodal diffusion-based method have failed to properly model or otherwise represent. The location of these burnable poisons near vertices results in an asymmetry in the morphology of the assemblies (or blocks). Hencemore » the resulting inadequacy of traditional homogenization methods, as these “spread” the actually local effect of the burnable poisons throughout the assembly. Furthermore, the actual effect of the burnable poison is primarily local with influence in its immediate vicinity, which happens to include a small region within the same assembly as well as similar regions in the adjacent assemblies. Traditional homogenization methods miss this artifact entirely. This paper presents a novel method for treating the local effect of the burnable poison explicitly in the context of a modern nodal method.« less

  8. Heterozygous Deletion of FOXA2 Segregates with Disease in a Family with Heterotaxy, Panhypopituitarism, and Biliary Atresia

    PubMed Central

    Tsai, Ellen A.; Grochowski, Christopher M.; Falsey, Alexandra M.; Rajagopalan, Ramakrishnan; Wendel, Danielle; Devoto, Marcella; Krantz, Ian D.; Loomes, Kathleen M.; Spinner, Nancy B.

    2015-01-01

    Biliary atresia (BA) is a pediatric cholangiopathy with unknown etiology occurring in isolated and syndromic forms. Laterality defects affecting the cardiovascular and gastrointestinal systems are the most common features present in syndromic BA. Most cases are sporadic, although reports of familial cases have led to the hypothesis of genetic susceptibility in some patients. We identified a child with BA, malrotation, and interrupted inferior vena cava whose father presented with situs inversus, polysplenia, panhypopituitarism, and mildly dysmorphic facial features. Chromosomal microarray analysis demonstrated a 277kb heterozygous deletion on chromosome 20 which included a single gene, FOXA2, in the proband and her father. This deletion was confirmed to be de novo in the father. The proband and her father share a common diagnosis of heterotaxy, but they also each presented with a variety of other issues. Further genetic screening revealed that the proband carried an additional protein-altering polymorphism (rs1904589; p.His165Arg) in the NODAL gene that is not present in the father, and this variant has been shown to decrease expression of the gene. As FOXA2 can be a regulator of NODAL expression, we propose that haploinsufficiency for FOXA2 combined with a decreased expression of NODAL is the likely cause for syndromic BA in this proband. PMID:25765999

  9. In Papillary Thyroid Cancer, Preoperative Central Neck Ultrasound Detects Only Macroscopic Surgical Disease, But Negative Findings Predict Excellent Long-Term Regional Control and Survival

    PubMed Central

    Moreno, Mauricio A.; Edeiken-Monroe, Beth S.; Siegel, Eric R.; Sherman, Steven I.

    2012-01-01

    Background Ultrasound (US) of the central neck compartment (CNC) is considered of limited sensitivity for nodal spread in papillary thyroid cancer (PTC); elective neck dissection is commonly advocated even in the absence of sonographic abnormalities. We hypothesized that US is an accurate predictor for long-term disease-free survival, regardless of the use of elective central neck dissection in patients with PTC. Methods A retrospective chart review of 331 consecutive PTC patients treated with total thyroidectomy at M.D. Anderson Cancer Center between 1996 and 2003 was performed. Information retrieved included preoperative sonographic status of the CNC, surgical treatment of the neck, demographics, cancer staging, histopathological variables and use of adjuvant treatment. The endpoints for the study were nodal recurrence and survival. Results There were 112 males and 219 females with a median age of 44 years (range 11–87). The median follow-up time for the series was 71.5 months (range 12.7–148.7). There were 151 (45.6%) patients with a T1, 58 (17.5%) with a T2, 70 (21.1%) with a T3, and 52 (15.7%) with a T4. Preoperative sonographic abnormalities were present in the CNC in 79 (23.9%) patients. During the surveillance period, 11 (3.2%) patients recurred in the central neck, with an average time for recurrence of 22.8 months. Advanced T stage (T3/T4) and abnormal US were independent prognostic factors for recurrence in the central neck (p=0.013 and p=0.005 respectively). There were 119 (35%) patients with a sonographically negative central compartment who underwent elective central neck dissection; 85 of them (71.4%) were found to be histopathologically N(+) while 34 (28.6%) were pN0. There were no differences in overall survival (p=0.32), disease specific survival (DSS; p=0.49), and recurrence-free survival (p=0.32) between these two groups. Preoperative US of the CNC was an age-independent predictor for overall survival (p<0.001), DSS (p=0.0097), and disease

  10. [Clinical application of positron-emission tomography for the identification of cervical nodal metastases of head and neck cancer compared with CT or MRI and clinical palpation].

    PubMed

    Chen, Zhong-Wei; Zhu, Li-Jun; Hou, Qing-Yi; Wang, Qi-Peng; Jiang, Sui; Feng, Hang

    2008-12-01

    To evaluate the value of positron-emission tomography (PET) for the identification of cervical nodal metastases of head and neck cancer compared with CT/MRI and clinical palpation. Forty patients of head and neck cancer underwent PET and CT/MRI examination 2 weeks before surgery. PET, CT/MRI and clinical palpation were interpreted separately to assess regional lymph node status. Histopathologic analysis was used as the gold standard for assessment of the lymph node involvement. Differences in sensitivity, specificity and accuracy among the imaging modalities and clinical palpation were analyzed. The sensitivity of PET for the identification of nodal metastases was 14.3% higher than that of CT/MRI (P = 0.648) and 14.3% higher than that of clinical palpation (P = 0.648), whereas the specificity of PET was 15.4% higher than that of CT/MRI (P = 0.188) and 7.7% higher than that of clinical palpation (P = 0.482). The accuracy of 18F-FDG PET, CT/MRI, and clinical palpation for the identification of cervical nodal metastases was 85.0%, 70.0% and 75.0% respectively. The sensitivity, specificity and accuracy of PET for the detection of cervical nodal metastases was higher than that of CT/MRI and clinical palpation. Although the results did not show a statistically significant difference, PET can still serve as a supplementary method for the identification of nodal metastases of head and neck cancer.

  11. Brady's Geothermal Field Nodal Seismometer Active Source Data Sample

    DOE Data Explorer

    Kurt Feigl

    2016-03-25

    This data is in sac format and includes recordings of two active source events from 238 three-component nodal seismometers deployed at Bradys Hot Springs geothermal field as part of the PoroTomo project. The source was a viberoseis truck operating in P-wave vibrational mode and generating a swept-frequency signal. The files are 33 seconds long starting 4 seconds before each sweep was initiated. There is some overlap in the file times.

  12. In vitro clonal propagation of Achyranthes aspera L. and Achyranthes bidentata Blume using nodal explants.

    PubMed

    Gnanaraj, Wesely Edward; Antonisamy, Johnson Marimuthu; R B, Mohanamathi; Subramanian, Kavitha Marappampalyam

    2012-01-01

    To develop the reproducible in vitro propagation protocols for the medicinally important plants viz., Achyranthes aspera (A. aspera) L. and Achyranthes bidentata (A. bidentata) Blume using nodal segments as explants. Young shoots of A. aspera and A. bidentata were harvested and washed with running tap water and treated with 0.1% bavistin and rinsed twice with distilled water. Then the explants were surface sterilized with 0.1% (w/v) HgCl2 solutions for 1 min. After rinsing with sterile distilled water for 3-4 times, nodal segments were cut into smaller segments (1 cm) and used as the explants. The explants were placed horizontally as well as vertically on solid basal Murashige and Skoog (MS) medium supplemented with 3% sucrose, 0.6% (w/v) agar (Hi-Media, Mumbai) and different concentration and combination of 6-benzyl amino purine (BAP), kinetin (Kin), naphthalene acetic acid (NAA) and indole acetic acid (IAA) for direct regeneration. Adventitious proliferation was obtained from A. aspera and A. bidentata nodal segments inoculated on MS basal medium with 3% sucrose and augmented with BAP and Kin with varied frequency. MS medium augmented with 3.0 mg/L of BAP showed the highest percentage (93.60±0.71) of shootlets formation for A. aspera and (94.70±0.53) percentages for A. bidentata. Maximum number of shoots/explants (10.60±0.36) for A. aspera and (9.50±0.56) for A. bidentata was observed in MS medium fortified with 5.0 mg/L of BAP. For A. aspera, maximum mean length (5.50±0.34) of shootlets was obtained in MS medium augmented with 3.0 mg/L of Kin and for A. bidentata (5.40±0.61) was observed in the very same concentration. The highest percentage, maximum number of rootlets/shootlet and mean length of rootlets were observed in 1/2 MS medium supplemented with 1.0 mg/L of IBA. Seventy percentages of plants were successfully established in polycups. Sixty eight percentages of plants were well established in the green house condition. Sixty five percentages of

  13. The effect of viscosity on steady transonic flow with a nodal solution topology

    NASA Technical Reports Server (NTRS)

    Owocki, Stanley P.; Zank, Gary P.

    1991-01-01

    The effect of viscosity on a steady, transonic flow for which the inviscid limit has a nodal solution topology near the critical point is investigated. For the accelerating case, viscous solutions tend to repel each other, so that a very delicate choice of initial conditions is required to prevent them from diverging. Only the two critical solutions extend to arbitrarily large distances into both the subsonic and supersonic flows. For the decelerating case, the solutions tend to attract, and so an entire two-parameter family of solutions now extends over large distances. The general effect of viscosity on the solution degeneracy of a nodal topology is thus to reduce or limit it for the accelerating case and to enhance it for the decelerating case. The astrophysical implications of these findings are addressed.

  14. Impact of pathologic diagnosis of internal mammary lymph node metastasis in clinical N2b and N3b breast cancer patients.

    PubMed

    Joo, Ji Hyeon; Kim, Su Ssan; Ahn, Seung-Do; Choi, Eun Kyung; Jung, Jin Hong; Jeong, Yuri; Ahn, Sei Hyun; Son, Byung Ho; Lee, Jong Won; Kim, Hee Jung; Go, Beom Seok; Kim, Hak Hee; Cha, Joo Hee; Shin, Hee Jung; Chae, Eun Young

    2017-11-01

    To analyze the prognostic role of pathologic confirmation of internal mammary lymph nodes (IMNs) for breast cancer patients who received neoadjuvant chemotherapy. Of the patients who were treated with neoadjuvant chemotherapy, surgery, and radiation therapy between 2009 and 2013, 114 women had suspicious IMNs and FNAB was attempted. Clinical IMN metastasis was diagnosed by 18F-FDG PET/CT positivity or pathologic confirmation (N = 70). Patients were divided into the FNAB(+) or FNAB(-) IMN group. The pathologic confirmation rate was 57% (40 of 70 patients). Rates were 74% in US-positive, 70% in MRI-positive, and 55% in PET-positive patients. Nodal stage was cN2b (6%) or cN3b (94%). Five-year progression-free survival (PFS) was significantly worse in patients with FNAB(+) IMN metastasis than FNAB(-) IMN metastasis (61% vs. 87%, P = 0.03). FNAB(+) IMN patients showed worse distant metastasis and regional recurrence-free survival without statistical significance (69% vs. 86%, P = 0.06, and 81% vs. 96%, P = 0.06). With median follow-up of 50.5 months (13.0-97.0 months), overall survival at 5 years was 77%, and PFS was 72%. Patients with FNAB-proven IMN metastasis had worse treatment outcomes compared to patients with clinically diagnosed IMN metastasis in cN2b/N3b breast cancer.

  15. Airway surface mycosis in chronic TH2-associated airway disease.

    PubMed

    Porter, Paul C; Lim, Dae Jun; Maskatia, Zahida Khan; Mak, Garbo; Tsai, Chu-Lin; Citardi, Martin J; Fakhri, Samer; Shaw, Joanne L; Fothergil, Annette; Kheradmand, Farrah; Corry, David B; Luong, Amber

    2014-08-01

    Environmental fungi have been linked to TH2 cell-related airway inflammation and the TH2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. To determine the frequency of fungus isolation and fungus-specific immunity in patients with TH2-associated and non-TH2-associated airway disease. Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. Filamentous fungi were significantly more commonly cultured in patients with TH2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-TH2-associated disease (n = 31): 74% vs 16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell spot (n = 48) and specific IgE (n = 70) data correlated with TH2-associated diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively). The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with TH2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  16. Superconductivity and fluctuations in Ba 1–pK pFe 2As 2 and Ba(Fe 1–nCo n) 2As 2

    DOE PAGES

    Böhm, T.; Hosseinian Ahangharnejhad, R.; Jost, D.; ...

    2016-08-11

    In this paper, we study the interplay of fluctuations and superconductivity in BaFe 2As 2 (Ba-122) compounds with Ba and Fe substituted by K (p doping) and Co (n doping), respectively. To this end, we measured electronic Raman spectra as a function of polarization and temperature. We observe gap excitations and fluctuations for all doping levels studied. The response from fluctuations is much stronger for Co substitution and, according to the selection rules and the temperature dependence, originates from the exchange of two critical spin fluctuations with characteristic wave vectors (±π,0) and (0,±π). At 22% K doping (p = 0.22),more » we find the same selection rules and spectral shape for the fluctuations but the intensity is smaller by a factor of 5. Since there exists no nematic region above the orthorhombic spin-density-wave (SDW) phase, the identification of the fluctuations via the temperature dependence is not possible. The gap excitations in the superconducting state indicate strongly anisotropic near-nodal gaps for Co substitution which make the observation of collective modes difficult. The variation with doping of the spectral weights of the A 1g and B 1g gap features does not support the influence of fluctuations on Cooper pairing. Thus, the observation of Bardasis–Schrieffer modes inside the nearly clean gaps on the K-doped side remains the only experimental evidence for the relevance of fluctuations for pairing.« less

  17. Truncated midkine as a marker of diagnosis and detection of nodal metastases in gastrointestinal carcinomas.

    PubMed Central

    Aridome, K.; Takao, S.; Kaname, T.; Kadomatsu, K.; Natsugoe, S.; Kijima, F.; Aikou, T.; Muramatsu, T.

    1998-01-01

    Midkine (MK) is a growth factor identified as a product of a retinoic acid-responsive gene. A truncated form of MK mRNA, which lacks a sequence encoding the N-terminally located domain, was recently found in cancer cells. We investigated the expression of the truncated MK mRNA in specimens of 47 surgically removed human gastrointestinal organs using polymerase chain reaction. Truncated MK was not detected in all of the 46 corresponding non-cancerous regions. On the other hand, this short MK mRNA was expressed in the primary tumours in 12 of 16 gastric cancers, 8 of 13 colorectal carcinomas, five of nine hepatocellular carcinomas, two of two oesophageal carcinomas and one ampullary duodenal cancer. In addition, truncated MK was detectable in all of the 14 lymph node metastases but in none of three metastatic sites in the liver, suggesting that truncated MK mRNA could become a good marker of nodal metastases in gastrointestinal tract. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9716029

  18. Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.

    PubMed

    Fedele, Laura; Newcombe, Joseph; Topf, Maya; Gibb, Alasdair; Harvey, Robert J; Smart, Trevor G

    2018-03-06

    Genetic and bioinformatic analyses have identified missense mutations in GRIN2B encoding the NMDA receptor GluN2B subunit in autism, intellectual disability, Lennox Gastaut and West Syndromes. Here, we investigated several such mutations using a near-complete, hybrid 3D model of the human NMDAR and studied their consequences with kinetic modelling and electrophysiology. The mutants revealed reductions in glutamate potency; increased receptor desensitisation; and ablation of voltage-dependent Mg 2+ block. In addition, we provide new views on Mg 2+ and NMDA channel blocker binding sites. We demonstrate that these mutants have significant impact on excitatory transmission in developing neurons, revealing profound changes that could underlie their associated neurological disorders. Of note, the NMDAR channel mutant GluN2B V618G unusually allowed Mg 2+ permeation, whereas nearby N615I reduced Ca 2+ permeability. By identifying the binding site for an NMDAR antagonist that is used in the clinic to rescue gain-of-function phenotypes, we show that drug binding may be modified by some GluN2B disease-causing mutations.

  19. An amphioxus nodal gene (AmphiNodal) with early symmetrical expression in the organizer and mesoderm and later asymmetrical expression associated with left-right axis formation

    NASA Technical Reports Server (NTRS)

    Yu, Jr-Kai; Holland, Linda Z.; Holland, Nicholas D.

    2002-01-01

    The full-length sequence and zygotic expression of an amphioxus nodal gene are described. Expression is first detected in the early gastrula just within the dorsal lip of the blastopore in a region of hypoblast that is probably comparable with the vertebrate Spemann's organizer. In the late gastrula and early neurula, expression remains bilaterally symmetrical, limited to paraxial mesoderm and immediately overlying regions of the neural plate. Later in the neurula stage, all neural expression disappears, and mesodermal expression disappears from the right side. All along the left side of the neurula, mesodermal expression spreads into the left side of the gut endoderm. Soon thereafter, all expression is down-regulated except near the anterior and posterior ends of the animal, where transcripts are still found in the mesoderm and endoderm on the left side. At this time, expression also begins in the ectoderm on the left side of the head, in the region where the mouth later forms. These results suggest that amphioxus and vertebrate nodal genes play evolutionarily conserved roles in establishing Spemann's organizer, patterning the mesoderm rostrocaudally and setting up the asymmetrical left-right axis of the body.

  20. Method and apparatus for routing data in an inter-nodal communications lattice of a massively parallel computer system by dynamic global mapping of contended links

    DOEpatents

    Archer, Charles Jens [Rochester, MN; Musselman, Roy Glenn [Rochester, MN; Peters, Amanda [Rochester, MN; Pinnow, Kurt Walter [Rochester, MN; Swartz, Brent Allen [Chippewa Falls, WI; Wallenfelt, Brian Paul [Eden Prairie, MN

    2011-10-04

    A massively parallel nodal computer system periodically collects and broadcasts usage data for an internal communications network. A node sending data over the network makes a global routing determination using the network usage data. Preferably, network usage data comprises an N-bit usage value for each output buffer associated with a network link. An optimum routing is determined by summing the N-bit values associated with each link through which a data packet must pass, and comparing the sums associated with different possible routes.

  1. Predictive model of outcome of targeted nodal assessment in colorectal cancer.

    PubMed

    Nissan, Aviram; Protic, Mladjan; Bilchik, Anton; Eberhardt, John; Peoples, George E; Stojadinovic, Alexander

    2010-02-01

    Improvement in staging accuracy is the principal aim of targeted nodal assessment in colorectal carcinoma. Technical factors independently predictive of false negative (FN) sentinel lymph node (SLN) mapping should be identified to facilitate operative decision making. To define independent predictors of FN SLN mapping and to develop a predictive model that could support surgical decisions. Data was analyzed from 2 completed prospective clinical trials involving 278 patients with colorectal carcinoma undergoing SLN mapping. Clinical outcome of interest was FN SLN(s), defined as one(s) with no apparent tumor cells in the presence of non-SLN metastases. To assess the independent predictive effect of a covariate for a nominal response (FN SLN), a logistic regression model was constructed and parameters estimated using maximum likelihood. A probabilistic Bayesian model was also trained and cross validated using 10-fold train-and-test sets to predict FN SLN mapping. Area under the curve (AUC) from receiver operating characteristics curves of these predictions was calculated to determine the predictive value of the model. Number of SLNs (<3; P = 0.03) and tumor-replaced nodes (P < 0.01) independently predicted FN SLN. Cross validation of the model created with Bayesian Network Analysis effectively predicted FN SLN (area under the curve = 0.84-0.86). The positive and negative predictive values of the model are 83% and 97%, respectively. This study supports a minimum threshold of 3 nodes for targeted nodal assessment in colorectal cancer, and establishes sufficient basis to conclude that SLN mapping and biopsy cannot be justified in the presence of clinically apparent tumor-replaced nodes.

  2. Laminated Composite Shell Element Using Absolute Nodal Coordinate Formulation and Its Application to ANCF Tire Model

    DTIC Science & Technology

    2015-04-24

    Paramsothy Jayakumar US Army TARDEC 6501 E. 11 Mile Road Warren, MI 48397-5000 Hiroyuki Sugiyama Department of Mechanical and Industrial...Part 2: Development of a Physical Tyre Model", Vehicle System Dynamics, vol. 50, pp. 339-356. [4] Sugiyama, H., Yamashita, H. and Jayakumar , P., 2014... Jayakumar , P. and Sugiyama, H., "Continuum Mechanics Based Bi-Linear Shear Deformable Shell Element using Absolute Nodal Coordinate Formulation", ASME

  3. Coexistence of tunable Weyl points and topological nodal lines in ternary transition-metal telluride TaIrT e4

    NASA Astrophysics Data System (ADS)

    Zhou, Xiaoqing; Liu, Qihang; Wu, QuanSheng; Nummy, Tom; Li, Haoxiang; Griffith, Justin; Parham, Stephen; Waugh, Justin; Emmanouilidou, Eve; Shen, Bing; Yazyev, Oleg V.; Ni, Ni; Dessau, Daniel

    2018-06-01

    We report a combined theoretical and experimental study on TaIrT e4 , a potential candidate for a minimal model of type-II Weyl semimetals. Unexpectedly, an intriguing node structure with 12 Weyl points and a pair of nodal lines protected by mirror symmetry was found by first-principles calculations. Some signatures of the complex electronic structure, such as topologically nontrivial band crossings and topologically trivial Fermi arcs, are cross-validated by angle-resolved photoemission spectroscopy. Through external strain, the number of Weyl points can be reduced to a theoretical minimum of four, and the appearance of the nodal lines can be switched between different mirror planes in momentum space. The coexistence of switchable Weyl points and nodal lines establishes transition-metal chalcogenides as a unique test ground for topological state characterization and engineering.

  4. From nodal-ring topological superfluids to spiral Majorana modes in cold atomic systems

    NASA Astrophysics Data System (ADS)

    He, Wen-Yu; Xu, Dong-Hui; Zhou, Benjamin T.; Zhou, Qi; Law, K. T.

    2018-04-01

    In this work, we consider a three-dimensional (3D) cubic optical lattice composed of coupled 1D wires with 1D spin-orbit coupling. When the s -wave pairing is induced through Feshbach resonance, the system becomes a topological superfluid with ring nodes, which are the ring nodal degeneracies in the bulk, and supports a large number of surface Majorana zero-energy modes. The large number of surface Majorana modes remain at zero energy even in the presence of disorder due to the protection from a chiral symmetry. When the chiral symmetry is broken, the system becomes a Weyl topological superfluid with Majorana arcs. With 3D spin-orbit coupling, the Weyl superfluid becomes a gapless phase with spiral Majorana modes on the surface. A spatial-resolved radio-frequency spectroscopy is suggested to detect this nodal-ring topological superfluid phase.

  5. CHOEP-21 chemotherapy for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs) in Maharaj Nakorn Chiang Mai Hospital.

    PubMed

    Rattarittamrong, Ekarat; Norasetthada, Lalita; Tantiworawit, Adisak; Chai-Adisaksopha, Chatree; Nawarawong, Weerasak

    2013-11-01

    To determine the effectiveness and tolerability of the combination of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with the addition of etoposide (CHOEP-21) for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs). Between January 2009 and October 2011, patients aged 18 to 60 years with newly diagnosed nodal PTCLs at the Maharaj Nakorn Chiang Mai Hospital were enrolled to receive CHOEP-21 every three weeks for eight cycles. G-CSF prophylaxis was given to all patients. Twenty-four patients were enrolled. Twenty of them were male with a median age of 49 years. The majority of patients (66.7%) had PTCL, not otherwise specified (PTCL, NOS), and 95.8% of the patients were in stage III or IV. The overall response rate was 58% with 42% having complete response. The response rates were better among patients with ALK-negative anaplastic large cell lymphoma (ALCL; 100%) and angioimmunoblastic T-cell lymphoma (AITL; 85%) than those with PTCL, NOS (44%). With a median follow-up of 21 months, the patients had an estimated 2-year event-free survival, and an overall survival rate of 37.6% and 54.4%, respectively. The most common adverse effects were infection and hematologic toxicities that was manageable. Although CHOEP-21 induced favorable responses in patients with ALK-negative ALCL and AITL, the responses were not durable and further therapy is mandated in management of patients with nodal PTCL.

  6. Heterozygous deletion of FOXA2 segregates with disease in a family with heterotaxy, panhypopituitarism, and biliary atresia.

    PubMed

    Tsai, Ellen A; Grochowski, Christopher M; Falsey, Alexandra M; Rajagopalan, Ramakrishnan; Wendel, Danielle; Devoto, Marcella; Krantz, Ian D; Loomes, Kathleen M; Spinner, Nancy B

    2015-06-01

    Biliary atresia (BA) is a pediatric cholangiopathy with unknown etiology occurring in isolated and syndromic forms. Laterality defects affecting the cardiovascular and gastrointestinal systems are the most common features present in syndromic BA. Most cases are sporadic, although reports of familial cases have led to the hypothesis of genetic susceptibility in some patients. We identified a child with BA, malrotation, and interrupted inferior vena cava whose father presented with situs inversus, polysplenia, panhypopituitarism, and mildly dysmorphic facial features. Chromosomal microarray analysis demonstrated a 277 kb heterozygous deletion on chromosome 20, which included a single gene, FOXA2, in the proband and her father. This deletion was confirmed to be de novo in the father. The proband and her father share a common diagnosis of heterotaxy, but they also each presented with a variety of other issues. Further genetic screening revealed that the proband carried an additional protein-altering polymorphism (rs1904589; p.His165Arg) in the NODAL gene that is not present in the father, and this variant has been shown to decrease expression of the gene. As FOXA2 can be a regulator of NODAL expression, we propose that haploinsufficiency for FOXA2 combined with a decreased expression of NODAL is the likely cause for syndromic BA in this proband. © 2015 WILEY PERIODICALS, INC.

  7. Identification of nodal tissue in the living heart using rapid scanning fiber-optics confocal microscopy and extracellular fluorophores.

    PubMed

    Huang, Chao; Kaza, Aditya K; Hitchcock, Robert W; Sachse, Frank B

    2013-09-01

    Risks associated with pediatric reconstructive heart surgery include injury of the sinoatrial node (SAN) and atrioventricular node (AVN), requiring cardiac rhythm management using implantable pacemakers. These injuries are the result of difficulties in identifying nodal tissues intraoperatively. Here we describe an approach based on confocal microscopy and extracellular fluorophores to quantify tissue microstructure and identify nodal tissue. Using conventional 3-dimensional confocal microscopy we investigated the microstructural arrangement of SAN, AVN, and atrial working myocardium (AWM) in fixed rat heart. AWM exhibited a regular striated arrangement of the extracellular space. In contrast, SAN and AVN had an irregular, reticulated arrangement. AWM, SAN, and AVN tissues were beneath a thin surface layer of tissue that did not obstruct confocal microscopic imaging. Subsequently, we imaged tissues in living rat hearts with real-time fiber-optics confocal microscopy. Fiber-optics confocal microscopy images resembled images acquired with conventional confocal microscopy. We investigated spatial regularity of tissue microstructure from Fourier analysis and second-order image moments. Fourier analysis of fiber-optics confocal microscopy images showed that the spatial regularity of AWM was greater than that of nodal tissues (37.5 ± 5.0% versus 24.3 ± 3.9% for SAN and 23.8 ± 3.7% for AVN; P<0.05). Similar differences of spatial regularities were revealed from second-order image moments (50.0 ± 7.3% for AWM versus 29.3 ± 6.7% for SAN and 27.3 ± 5.5% for AVN; P<0.05). The study demonstrates feasibility of identifying nodal tissue in living heart using extracellular fluorophores and fiber-optics confocal microscopy. Application of the approach in pediatric reconstructive heart surgery may reduce risks of injuring nodal tissues.

  8. Laboratory tests of three Z‐Land Fairfield Nodal 5‐Hz, three‐component sensors

    USGS Publications Warehouse

    Ringler, Adam; Anthony, Robert E.; Karplus, M.S; Holland, Austin; Wilson, David

    2018-01-01

    We conduct a number of laboratory tests at the Albuquerque Seismological Laboratory to verify the self‐noise and fidelity in which 3 three‐component Fairfield Nodal Z‐Land, Generation 2, 5‐Hz sensors are able to record seismic signals. In addition to the incoherent self‐noise of the sensors, we estimate the sensitivity of the units in digital volts/m/s, the damping, and the free period. These three parameters allow us to completely characterize the response of the instruments. We find that the responses of all components match a mean‐derived response to within 5% of amplitude and 0.03 radians in phase. This close agreement suggests that for most applications a nominal response is suitable. We also checked the timing of the units as compared to a Quanterra Q330HR and found good agreement up to 200samples/s . Finally, we compared the results of our noise tests on these sensors to a couple of nodal sensors recently deployed at the Community Wavefield Demonstration Experiment in north‐central Oklahoma and found that local site noise and not the sensor self‐noise is a fundamental limiter in the resolution of these deployed sensors at frequencies above ∼0.1Hz .

  9. Radiofrequency ablation versus cryoablation for atrioventricular nodal re-entrant tachycardia in children: a value comparison.

    PubMed

    Oster, Matthew E; Yang, Zhou; Stewart-Huey, Kay; Glanville, Michelle; Porter, Arlene; Campbell, Robert; Webb, Brad; Strieper, Margaret

    2017-03-01

    It is unclear whether cryoablation or radiofrequency ablation offers better value for treating atrioventricular nodal re-entrant tachycardia in children. We aimed to compare the value of these procedures for treating atrioventricular nodal re-entrant tachycardia in children, with value being outcomes relative to costs. We performed a retrospective cohort study of all atrioventricular nodal re-entrant tachycardia ablations for children (age⩽18 years) from July, 2009 to June, 2011 at our institution. Costs included fixed costs, miscellaneous hospital costs, and labour costs, and key outcomes were acute and long-term success (6 months) of the ablations. We conducted T-tests and regression analyses to investigate the associations between the ablation procedure type and the cost and success of the ablations. Of 96 unique cases performed by three paediatric electrophysiologists, 48 were cryoablation only, 42 radiofrequency ablation only, and six were a combination. Acute success was 100% for the cryoablation only and radiofrequency ablation only cases and 83% for the combination cases. There were no notable adverse events. The average total cost was $9636 for cryoablation cases, $9708 for radiofrequency ablation cases, and $10,967 for combination cases (p=0.51 for cryoablation only versus radiofrequency ablation only). The long-term success rate was 79.1% for cryoablation only, 92.8% for radiofrequency ablation only, and 66.7% for the combination (p=0.01 for cryoablation only versus radiofrequency ablation only), but long-term success varied notably by provider. Cryoablation and radiofrequency ablation offer similar value in the short term for the treatment of atrioventricular nodal re-entrant tachycardia in children. Differences in long-term success may vary substantially by physician, and thus may lead to differences in long-term value.

  10. Identification of PSEN2 mutation p.N141I in Argentine pedigrees with early-onset familial Alzheimer's disease.

    PubMed

    Muchnik, Carolina; Olivar, Natividad; Dalmasso, María Carolina; Azurmendi, Pablo Javier; Liberczuk, Cynthia; Morelli, Laura; Brusco, Luis Ignacio

    2015-10-01

    Presenilin 2 gene (PSEN2) mutations account for <5% of all early-onset familial Alzheimer's disease (EOFAD) cases and only 13 have strong evidence for pathogenicity. We aimed to investigate the presence of PSEN2 mutation p.N141I and characterize the clinical phenotypes in 2 Argentine pedigrees (AR2 and AR3) with clinical symptoms of EOFAD. Detailed clinical assessments and genetic screening for PSEN2 and APOE genes were carried out in 19 individuals of AR2 and AR3 families. The p.N141I mutation was identified in all affected subjects and was associated with prominent early onset, rapidly progressive dementia, neurologic, and behavioral symptoms. AR2 and AR3 families share the same Volga German ancestry as all the families reported presenting this mutation. To our knowledge, this is the first report of PSEN2 mutation p.N141I in Argentina and even more, in South America. Our contribution increases the total number of described families carrying this mutation and help to improve the characterization of clinical phenotype in EOFAD associated to PSEN2 mutations. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Nodal aberration theory applied to freeform surfaces

    NASA Astrophysics Data System (ADS)

    Fuerschbach, Kyle; Rolland, Jannick P.; Thompson, Kevin P.

    2014-12-01

    When new three-dimensional packages are developed for imaging optical systems, the rotational symmetry of the optical system is often broken, changing its imaging behavior and making the optical performance worse. A method to restore the performance is to use freeform optical surfaces that compensate directly the aberrations introduced from tilting and decentering the optical surfaces. In order to effectively optimize the shape of a freeform surface to restore optical functionality, it is helpful to understand the aberration effect the surface may induce. Using nodal aberration theory the aberration fields induced by a freeform surface in an optical system are explored. These theoretical predications are experimentally validated with the design and implementation of an aberration generating telescope.

  12. A human-like H1N2 influenza virus detected during an outbreak of acute respiratory disease in swine in Brazil.

    PubMed

    Schaefer, Rejane; Rech, Raquel Rubia; Gava, Danielle; Cantão, Mauricio Egídio; da Silva, Marcia Cristina; Silveira, Simone; Zanella, Janice Reis Ciacci

    2015-01-01

    Passive monitoring for detection of influenza A viruses (IAVs) in pigs has been carried out in Brazil since 2009, detecting mostly the A(H1N1)pdm09 influenza virus. Since then, outbreaks of acute respiratory disease suggestive of influenza A virus infection have been observed frequently in Brazilian pig herds. During a 2010-2011 influenza monitoring, a novel H1N2 influenza virus was detected in nursery pigs showing respiratory signs. The pathologic changes were cranioventral acute necrotizing bronchiolitis to subacute proliferative and purulent bronchointerstitial pneumonia. Lung tissue samples were positive for both influenza A virus and A(H1N1)pdm09 influenza virus based on RT-qPCR of the matrix gene. Two IAVs were isolated in SPF chicken eggs. HI analysis of both swine H1N2 influenza viruses showed reactivity to the H1δ cluster. DNA sequencing was performed for all eight viral gene segments of two virus isolates. According to the phylogenetic analysis, the HA and NA genes clustered with influenza viruses of the human lineage (H1-δ cluster, N2), whereas the six internal gene segments clustered with the A(H1N1)pdm09 group. This is the first report of a reassortant human-like H1N2 influenza virus derived from pandemic H1N1 virus causing an outbreak of respiratory disease in pigs in Brazil. The emergence of a reassortant IAV demands the close monitoring of pigs through the full-genome sequencing of virus isolates in order to enhance genetic information about IAVs circulating in pigs.

  13. Proposed Lymph Node Staging System Using the International Consensus Guidelines for Lymph Node Levels Is Predictive for Nasopharyngeal Carcinoma Patients From Endemic Areas Treated With Intensity Modulated Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Wen-Fei; Sun, Ying; Mao, Yan-Ping

    2013-06-01

    Purpose: To propose a lymph node (N) staging system for nasopharyngeal carcinoma (NPC) based on the International Consensus Guidelines for lymph node (LN) levels and MRI-determined nodal variables. Methods and Materials: The MRI scans and medical records of 749 NPC patients receiving intensity modulated radiation therapy with or without chemotherapy were retrospectively reviewed. The prognostic significance of nodal level, laterality, maximal axial diameter, extracapsular spread, necrosis, and Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) size criteria were analyzed. Results: Nodal level and laterality were the only independent prognostic factors for distant failure and disease failure in multivariatemore » analysis. Compared with unilateral levels Ib, II, III, and/or Va involvement (hazard ratio [HR] 1), retropharyngeal lymph node involvement alone had a similar prognostic value (HR 0.71; 95% confidence interval [CI] 0.43-1.17; P=.17), whereas bilateral levels Ib, II, III, and/or Va involvement (HR 1.65; 95% CI 1.06-2.58; P=.03) and levels IV, Vb, and/or supraclavicular fossa involvement (HR 3.47; 95% CI 1.92-6.29; P<.01) both significantly increased the HR for distant failure. Thus we propose that the N category criteria could be revised as follows: N0, no regional LN metastasis; N1, retropharyngeal lymph node involvement, and/or unilateral levels Ib, II, III, and/or Va involvement; N2, bilateral levels Ib, II, III, and/or Va involvement; N3, levels IV, Vb, and/or supraclavicular fossa involvement. Compared with the 7th edition of the UICC/AJCC criteria, the proposed N staging system provides a more satisfactory distinction between the HRs for regional failure, distant failure, and disease failure in each N category. Conclusions: The proposed N staging system defined by the International Consensus Guidelines and laterality is predictive and practical. However, because of no measurements of the maximal nodal diameter on

  14. Identification of lesion and nodal resistance in pea (Pisum sativum L.) to Sclerotinia sclerotiorum using genome-wide association studies and RNA-Seq

    USDA-ARS?s Scientific Manuscript database

    Nodal resistance in plants is a phenomenon where a fungal infection is prevented from passing through a node and the infection is limited to an internode region. Nodal resistance has been observed in some pathosystems such as the pea (Pisum sativum L.)-white mold (WM) (Sclerotinia sclerotiorum (Lib....

  15. Relativity mission with two counter-orbiting polar satellites. [nodal dragging effect on earth orbiting satellites

    NASA Technical Reports Server (NTRS)

    Van Patten, R. A.; Everitt, C. W. F.

    1975-01-01

    In 1918, J. Lense and H. Thirring calculated that a moon in orbit around a massive rotating planet would experience a nodal dragging effect due to general relativity. We describe an experiment to measure this effect with two counter-orbiting drag-free satellites in polar earth orbit. For a 2 1/2 year experiment, the measurement accuracy should approach 1%. In addition to precision tracking data from existing ground stations, satellite-to-satellite Doppler ranging data are taken at points of passing near the poles. New geophysical information on both earth harmonics and tidal effects is inherent in the polar ranging data.

  16. Usability study of the EduMod eLearning Program for contouring nodal stations of the head and neck.

    PubMed

    Deraniyagala, Rohan; Amdur, Robert J; Boyer, Arthur L; Kaylor, Scott

    2015-01-01

    A major strategy for improving radiation oncology education and competence evaluation is to develop eLearning programs that reproduce the real work environment. A valuable measure of the quality of an eLearning program is "usability," which is a multidimensional endpoint defined from the end user's perspective. The gold standard for measuring usability is the Software Usability Measurement Inventory (SUMI). The purpose of this study is to use the SUMI to measure usability of an eLearning course that uses innovative software to teach and test contouring of nodal stations of the head and neck. This is a prospective institutional review board-approved study in which all participants gave written informed consent. The study population was radiation oncology residents from 8 different programs across the United States. The subjects had to pass all sections of the same 2 eLearning modules and then complete the SUMI usability evaluation instrument. We reached the accrual goal of 25 participants. Usability results for the EduMod eLearning course, "Nodal Stations of the Head and Neck," were compared with a large database of scores of other major software programs. Results were evaluated in 5 domains: Affect, Helpfulness, Control, Learnability, and Global Usability. In all 5 domains, usability scores for the study modules were higher than the database mean and statistically superior in 4 domains. This is the first study to evaluate usability of an eLearning program related to radiation oncology. Usability of 2 representative modules related to contouring nodal stations of the head and neck was highly favorable, with scores that were superior to the industry standard in multiple domains. These results support the continued development of this type of eLearning program for teaching and testing radiation oncology technical skills. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  17. Infrared spectra and anharmonic coupling of proton-bound nitrogen dimers N2-H+-N2, N2-D+-N2, and 15N2-H+-15N2 in solid para-hydrogen.

    PubMed

    Liao, Hsin-Yi; Tsuge, Masashi; Tan, Jake A; Kuo, Jer-Lai; Lee, Yuan-Pern

    2017-08-09

    The proton-bound nitrogen dimer, N 2 -H + -N 2 , and its isotopologues were investigated by means of vibrational spectroscopy. These species were produced upon electron bombardment of mixtures of N 2 (or 15 N 2 ) and para-hydrogen (p-H 2 ) or normal-D 2 (n-D 2 ) during deposition at 3.2 K. Reduced-dimension anharmonic vibrational Schrödinger equations were constructed to account for the strong anharmonic effects in these protonated species. The fundamental lines of proton motions in N 2 -H + -N 2 were observed at 715.0 (NH + N antisymmetric stretch, ν 4 ), 1129.6 (NH + N bend, ν 6 ), and 2352.7 (antisymmetric NN/NN stretch, ν 3 ) cm -1 , in agreement with values of 763, 1144, and 2423 cm -1 predicted with anharmonic calculations using the discrete-variable representation (DVR) method at the CCSD/aug-cc-pVDZ level. The lines at 1030.2 and 1395.5 cm -1 were assigned to combination bands involving nν 2 + ν 4 (n = 1 and 2) according to theoretical calculations; ν 2 is the N 2 N 2 stretching mode. For 15 N 2 -H + - 15 N 2 in solid p-H 2 , the corresponding major lines were observed at 710.0 (ν 4 ), 1016.7 (ν 2 + ν 4 ), 1124.3 (ν 6 ), 1384.8 (2ν 2 + ν 4 ), and 2274.9 (ν 3 ) cm -1 . For N 2 -D + -N 2 in solid n-D 2 , the corresponding major lines were observed at 494.0 (ν 4 ), 840.7 (ν 2 + ν 4 ), 825.5 (ν 6 ), and 2356.2 (ν 3 ) cm -1 . In addition, two lines at 762.0 (weak) and 808.3 cm -1 were tentatively assigned to be some modes of N 2 -H + -N 2 perturbed or activated by a third N 2 near the proton.

  18. Prophylactic dissection of level V in primary mucosal SCC in the clinically N positive neck: A systematic review.

    PubMed

    McLean, Timothy; Kerr, Stephen J; Giddings, Charles E B

    2017-09-01

    To review the evidence for level V dissection in the management of previously untreated mucosal squamous cell carcinoma (SCC) of the head and neck presenting with nodal metastasis when level V is clinically uninvolved. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) were used to conduct a systematic review of the current literature, including all English language articles published after 1990. A literature search was performed on November 29, 2015, of Medline, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Cochrane Library. The search yielded a total of 270 papers. Strict inclusion and exclusion criteria were applied, leaving 20 eligible papers. Overall prevalence was calculated using random effect meta-analysis. The overall prevalence of level V occult disease in the node (N)-positive neck, irrespective of subsite, was 2.56% (95% confidence interval 1.29-3.84) (2,368 patients and 2,533 necks). The prevalence of occult level V metastasis was up to 7.7% for oral cavity and 8.3% for oropharyngeal tumors. Five studies reported regional recurrence rates over variable time periods. There is exceedingly limited data on outcomes, such as spinal accessory nerve function, quality of life, and perioperative complications. Mucosal head and neck SCC presenting with nodal metastasis but with level V clinically uninvolved has a low prevalence of occult level V disease. Routine dissection of level V does not appear to be warranted; however, a definitive conclusion is unable to be drawn due to limited data on morbidity and oncological outcomes. Laryngoscope, 127:2074-2080, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  19. Analysis of incidental radiation dose to uninvolved mediastinal/supraclavicular lymph nodes in patients with limited-stage small cell lung cancer treated without elective nodal irradiation.

    PubMed

    Ahmed, Irfan; DeMarco, Marylou; Stevens, Craig W; Fulp, William J; Dilling, Thomas J

    2011-01-01

    Classic teaching states that treatment of limited-stage small cell lung cancer (L-SCLC) requires large treatment fields covering the entire mediastinum. However, a trend in modern thoracic radiotherapy is toward more conformal fields, employing positron emission tomography/computed tomography (PET/CT) scans to determine the gross tumor volume (GTV). This analysis evaluates the dosimetric results when using selective nodal irradiation (SNI) to treat a patient with L-SCLC, quantitatively comparing the results to standard Intergroup treatment fields. Sixteen consecutive patients with L-SCLC and central mediastinal disease who also underwent pretherapy PET/CT scans were studied in this analysis. For each patient, we created SNI treatment volumes, based on the PET/CT-based criteria for malignancy. We also created 2 ENI plans, the first without heterogeneity corrections, as per the Intergroup 0096 study (ENI(off)) and the second with heterogeneity corrections while maintaining constant the number of MUs delivered between these latter 2 plans (ENI(on)). Nodal stations were contoured using published guidelines, then placed into 4 "bins" (treated nodes, 1 echelon away, >1 echelon away within the mediastinum, contralateral hilar/supraclavicular). These were aggregated across the patients in the study. Dose to these nodal bins and to tumor/normal structures were compared among these plans using pairwise t-tests. The ENI(on) plans demonstrated a statistically significant degradation in dose coverage compared with the ENI(off) plans. ENI and SNI both created a dose gradient to the lymph nodes across the mediastinum. Overall, the gradient was larger for the SNI plans, although the maximum dose to the "1 echelon away" nodes was not statistically different. Coverage of the GTV and planning target volume (PTV) were improved with SNI, while simultaneously reducing esophageal and spinal cord dose though at the expense of modestly reduced dose to anatomically distant lymph nodes

  20. Nodal-line dynamics via exact polynomial solutions for coherent waves traversing aberrated imaging systems.

    PubMed

    Paganin, David M; Beltran, Mario A; Petersen, Timothy C

    2018-03-01

    We obtain exact polynomial solutions for two-dimensional coherent complex scalar fields propagating through arbitrary aberrated shift-invariant linear imaging systems. These solutions are used to model nodal-line dynamics of coherent fields output by such systems.

  1. Proton therapy may allow for comprehensive elective nodal coverage for patients receiving neoadjuvant radiotherapy for localized pancreatic head cancers.

    PubMed

    Lee, Richard Y; Nichols, Romaine C; Huh, Soon N; Ho, Meng W; Li, Zuofeng; Zaiden, Robert; Awad, Ziad T; Ahmed, Bestoun; Hoppe, Bradfors S

    2013-12-01

    Neoadjuvant radiotherapy has the potential to improve local disease control for patients with localized pancreatic cancers. Concern about an increased risk of surgical complications due to small bowel and gastric exposure, however, has limited enthusiasm for this approach. Dosimetric studies have demonstrated the potential for proton therapy to reduce intestinal exposure compared with X-ray-based therapy. We sought to determine if neoadjuvant proton therapy allowed for field expansions to cover high-risk nodal stations in addition to the primary tumor. Twelve consecutive patients with nonmetastatic cancers of the pancreatic head underwent proton-based planning for neoadjuvant radiotherapy. Gross tumor volume was contoured using diagnostic computed tomography (CT) scans with oral and intravenous contrast. Four-dimensional planning scans were utilized to define an internal clinical target volume (ICTV). Five-mm planning target volume (PTV) expansions on the ICTV were generated to establish an initial PTV (PTV1). A second PTV was created using the initial PTV but was expanded to include the high-risk nodal targets as defined by the RTOG contouring atlas (PTV2). Optimized proton plans were generated for both PTVs for each patient. All PTVs received a dose of 50.4 cobalt gray equivalent (CGE). Normal-tissue exposures to the small bowel space, stomach, right kidney, left kidney and liver were recorded. Point spinal cord dose was limited to 45 CGE. Median PTV1 volume was 308.75 cm(3) (range, 133.33-495.61 cm(3)). Median PTV2 volume was 541.75 cm(3) (range, 399.44-691.14 cm(3)). In spite of the substantial enlargement of the PTV when high-risk lymph nodes were included in the treatment volume, normal-tissue exposures (stomach, bowel space, liver, and kidneys) were only minimally increased relative to the exposures seen when only the gross tumor target was treated. Proton therapy appears to allow for field expansions to cover high-risk lymph nodes without significantly

  2. Exotic Phenomena in Quantum limit in nodal-line semimetal ZrSiS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hu, Jin; Liu, Jinyu; Mao, Zhiqiang

    2017-03-01

    In quantum limit, all carriers condense to the lowest Landau level, leading to possible exotic quantum phenomena such as Lifshitz transition and density waves. Usually, quantum limit is not easily achieved due to relatively large Fermi surface in metals. Fortunately, the nodal-line semimetal ZrSiS possesses a very small Fermi pocket with a characteristic quantum oscillation frequency of 8.4T, which represents the 2D Dirac states protected by non-symmorphic symmetry. The quantum limit of such Dirac bands can be reached in moderate magnetic field ~25T, indicating that ZrSiS could be a nice platform to explore the novel quantum phenomena of Dirac fermionsmore » in quantum limit.« less

  3. Constitutional rho-kinase regulates atrioventricular nodal conduction and ventricular repolarization of the canine heart.

    PubMed

    Sugiyama, Atsushi; Takahara, Akira; Yatomi, Yutaka; Satoh, Yoshioki; Nakamura, Yuji; Hashimoto, Keitaro

    2003-06-01

    Given the limited information, physiological roles of Rho-kinase in the cardiac conduction system and ventricular repolarization process were assessed in comparison with those in the coronary vascular tone. A specific Rho-kinase inhibitor Y-27632 was administered to the nutrient coronary artery of the canine isolated, blood-perfused atrioventricular node preparation under the monitoring of the ventricular monophasic action potentials. Administration of Y-27632 moderately suppressed the atrioventricular nodal conduction, slightly but significantly accelerated the repolarization process, and potently increased the coronary blood flow, whereas it hardly affected the intraventricular conduction. The estimated concentrations of Y-27632 causing the currently observed effects were enough to inhibit Rho-kinase. These results suggest that constitutional Rho-kinase functions to moderately facilitate the atrioventricular nodal conduction, slightly delay ventricular repolarization process, and significantly increase the coronary vascular tone.

  4. Concomitant Wolff-Parkinson-White and Atrioventricular Nodal Reentrant Tachycardia: Which Pathway to Ablate?

    PubMed

    Sarsam, Sinan; Sidiqi, Ibrahim; Shah, Dipak; Zughaib, Marcel

    2015-12-11

    Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common form of supraventricular tachycardia. In contrast, Wolff-Parkinson-White (WPW) pattern consists of an accessory pathway, which may result in the development of ventricular arrhythmias. Frequent tachycardia caused by AVNRT and accessory pathways may play a role in left ventricular systolic dysfunction. A 54-year-old man presented with palpitations and acute decompensated congestive heart failure. His baseline EKG showed Wolff-Parkinson-White (WPW) pattern. While hospitalized, he had an episode of atrioventricular nodal reentrant tachycardia (AVNRT). He underwent radiofrequency catheter ablation for AVNRT, and his accessory pathway was also ablated even though its conduction was found to be weak. He was clinically doing well on follow-up visit, with resolution of his heart failure symptoms and normalization of left ventricular function on echocardiography. This case raises the question whether the accessory pathway plays a role in the development of systolic dysfunction, and if there is any role for ablation in patients with asymptomatic WPW pattern.

  5. Sweetwater, Texas Large N Experiment

    NASA Astrophysics Data System (ADS)

    Sumy, D. F.; Woodward, R.; Barklage, M.; Hollis, D.; Spriggs, N.; Gridley, J. M.; Parker, T.

    2015-12-01

    From 7 March to 30 April 2014, NodalSeismic, Nanometrics, and IRIS PASSCAL conducted a collaborative, spatially-dense seismic survey with several thousand nodal short-period geophones complemented by a backbone array of broadband sensors near Sweetwater, Texas. This pilot project demonstrates the efficacy of industry and academic partnerships, and leveraged a larger, commercial 3D survey to collect passive source seismic recordings to image the subsurface. This innovative deployment of a large-N mixed-mode array allows industry to explore array geometries and investigate the value of broadband recordings, while affording academics a dense wavefield imaging capability and an operational model for high volume instrument deployment. The broadband array consists of 25 continuously-recording stations from IRIS PASSCAL and Nanometrics, with an array design that maximized recording of horizontal-traveling seismic energy for surface wave analysis over the primary target area with sufficient offset for imaging objectives at depth. In addition, 2639 FairfieldNodal Zland nodes from NodalSeismic were deployed in three sub-arrays: the outlier, backbone, and active source arrays. The backbone array consisted of 292 nodes that covered the entire survey area, while the outlier array consisted of 25 continuously-recording nodes distributed at a ~3 km distance away from the survey perimeter. Both the backbone and outlier array provide valuable constraints for the passive source portion of the analysis. This project serves as a learning platform to develop best practices in the support of large-N arrays with joint industry and academic expertise. Here we investigate lessons learned from a facility perspective, and present examples of data from the various sensors and array geometries. We will explore first-order results from local and teleseismic earthquakes, and show visualizations of the data across the array. Data are archived at the IRIS DMC under stations codes XB and 1B.

  6. Estimate of production of gaseous nitrogen in the human body based on (15)N analysis of breath N2 after administration of [(15)N2]urea.

    PubMed

    Junghans, Peter

    2013-01-01

    After oral administration of [(15)N2]urea (1.5 mmol, 95 atom% (15)N), we found that breath N2 was significantly (15)N-labelled. The result suggests that molecular nitrogen in breath must be partly produced endogenously. Based on a metabolic model, the endogenous N2 production was estimated to be 0.40±0.25 mmol kg(-1) d(-1) or 2.9±1.8 % of the total (urinary and faecal) N excretion in fasted healthy subjects (n=4). In patients infected with Helicobacter pylori (n=5), the endogenous N2 production was increased to 1.24±0.59 mmol kg(-1) d(-1) or 9.0±4.3 % of the total N excretion compared to the healthy controls (p<0.05). We conclude that N balance and gas exchange measurements may be affected by endogenously produced nitrogen, especially in metabolic situations with elevated nitrosation, for instance in oxidative and nitrosative stress-related diseases such as H. pylori infections.

  7. Dietary n-6 and n-3 fatty acids in immunity and autoimmune disease.

    PubMed

    Harbige, L S

    1998-11-01

    Clearly there is much evidence to show that under well-controlled laboratory and dietary conditions fatty acid intake can have profound effects on animal models of autoimmune disease. Studies in human autoimmune disease have been less dramatic; however, human trials have been subject to uncontrolled dietary and genetic backgrounds, infection and other environmental influences, and basic trial designs have been inadequate. The impact of dietary fatty acids on animal autoimmune disease models appears to depend on the animal model and the type and amount of fatty acids fed. Diets low in fat, essential fatty acid-deficient, or high in n-3 fatty acids from fish oils increase the survival and reduce disease severity in spontaneous autoantibody-mediated disease, whilst linoleic acid-rich diets appear to increase disease severity. In experimentally-induced T-cell-mediated autoimmune disease, essential fatty acid-deficient diets or diets supplemented with n-3 fatty acids appear to augment disease, whereas n-6 fatty acids prevent or reduce the severity. In contrast, in both T-cell and antibody-mediated auto-immune disease the desaturated and elongated metabolites of linoleic acid are protective. Suppression of autoantibody and T lymphocyte proliferation, apoptosis of autoreactive lymphocytes, and reduced pro-inflammatory cytokine production by high-dose fish oils are all likely mechanisms by which n-3 fatty acids ameliorate autoimmune disease. However, these could be undesirable long-term effects of high-dose fish oil which may compromise host immunity. The protective mechanism(s) of n-6 fatty acids in T-cell- mediated autoimmune disease are less clear, but may include dihomo-gamma-linolenic acid- and arachidonic acid-sensitive immunoregulatory circuits such as Th1 responses, TGF beta 1-mediated effects and Th3-like responses. It is often claimed that n-6 fatty acids promote autoimmune and inflammatory disease based on results obtained with linoleic acid only. It should be

  8. Functional variants in the LRRK2 gene confer shared effects on risk for Crohn's disease and Parkinson's disease.

    PubMed

    Hui, Ken Y; Fernandez-Hernandez, Heriberto; Hu, Jianzhong; Schaffner, Adam; Pankratz, Nathan; Hsu, Nai-Yun; Chuang, Ling-Shiang; Carmi, Shai; Villaverde, Nicole; Li, Xianting; Rivas, Manual; Levine, Adam P; Bao, Xiuliang; Labrias, Philippe R; Haritunians, Talin; Ruane, Darren; Gettler, Kyle; Chen, Ernie; Li, Dalin; Schiff, Elena R; Pontikos, Nikolas; Barzilai, Nir; Brant, Steven R; Bressman, Susan; Cheifetz, Adam S; Clark, Lorraine N; Daly, Mark J; Desnick, Robert J; Duerr, Richard H; Katz, Seymour; Lencz, Todd; Myers, Richard H; Ostrer, Harry; Ozelius, Laurie; Payami, Haydeh; Peter, Yakov; Rioux, John D; Segal, Anthony W; Scott, William K; Silverberg, Mark S; Vance, Jeffery M; Ubarretxena-Belandia, Iban; Foroud, Tatiana; Atzmon, Gil; Pe'er, Itsik; Ioannou, Yiannis; McGovern, Dermot P B; Yue, Zhenyu; Schadt, Eric E; Cho, Judy H; Peter, Inga

    2018-01-10

    Crohn's disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2066 CD cases and 3633 healthy controls. We detected association signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 × 10 -10 ) or protection from CD (N551K variant, tagging R1398H-associated haplotype, P = 3.3 × 10 -8 ). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinson's disease (PD), and healthy controls revealed extensive pleiotropy, with shared genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant was associated with increased kinase activity, whereas neither N551K nor R1398H variants on the protective haplotype altered kinase activity. We also confirmed that R1398H, but not N551K, increased guanosine triphosphate binding and hydrolyzing enzyme (GTPase) activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  9. Incidental nodal metastasis of differentiated thyroid carcinoma in neck dissection specimens from head and neck cancer patients.

    PubMed

    Lenzi, R; Marchetti, M; Muscatello, L

    2017-04-01

    Occult differentiated thyroid carcinomas are not uncommon. The initial presentation of a thyroid carcinoma is often detection of a metastatic cervical lymph node. A retrospective review was performed of the medical records of 304 patients who underwent neck dissection between 1996 and 2008 for squamous cell carcinoma of the head and neck. Ten patients (3.3 per cent) had nodal metastasis originating from papillary thyroid cancer. All of these patients underwent thyroidectomy and post-operative 131iodine radiometabolic therapy. No patient developed a thyroid tumour after surgery. Despite its metastatic spread, thyroid cancer does not affect the overall prognosis of patients who are already being treated for a more aggressive malignancy. However, in otherwise healthy patients, it is worth treating this second malignancy to avoid potential complications related to local disease or metastatic thyroid cancer.

  10. Micropropagation of Calophyllum brasiliense (Cambess.) from nodal segments.

    PubMed

    Silveira, S S; Cordeiro-Silva, R; Degenhardt-Goldbach, J; Quoirin, M

    2016-05-03

    Micropropagation of Calophyllum brasiliense Cambess. (Clusiaceae) is a way to overcome difficulties in achieving large-scale plant production, given the recalcitrant nature of the seeds, irregular fructification and absence of natural vegetative propagation of the species. Cultures were established using nodal segments 2 cm in length, obtained from 1-2 year old seedlings, maintained in a greenhouse. Mercury chloride and Plant Preservative Mixture™ were used in the surface sterilizing stage, better results being achieved with Plant Preservative Mixture™ incorporation in culture medium, at any concentration. Polyvinylpyrrolidone, activated charcoal, cysteine, ascorbic acid or citric acid were added to the culture medium to avoid oxidation. After 30 days of culture, polyvinylpirrolidone and ascorbic acid gave better results, eliminating oxidation in most explants. For shoot multiplication, benzylaminopurine was used in concentrations of 4.4 and 8.8 µM in Woody Plant Medium, resulting in an average of 4.43 and 4.68 shoots per explant, respectively, after 90 days. Indole-3-butyric acid and α-naphthalene acetic acid were used to induce root formation, reaching a maximum rooting rate of 24% with 20µM α-naphthalene acetic acid. For acclimatization. the rooted plants were transferred to Plantmax® substrate and cultured in a greenhouse, reaching 79% of survival after 30 days and 60% after one year.

  11. Nuclear movement regulated by non-Smad Nodal signaling via JNK is associated with Smad signaling during zebrafish endoderm specification.

    PubMed

    Hozumi, Shunya; Aoki, Shun; Kikuchi, Yutaka

    2017-11-01

    Asymmetric nuclear positioning is observed during animal development, but its regulation and significance in cell differentiation remain poorly understood. Using zebrafish blastulae, we provide evidence that nuclear movement towards the yolk syncytial layer, which comprises extraembryonic tissue, occurs in the first cells fated to differentiate into the endoderm. Nodal signaling is essential for nuclear movement, whereas nuclear envelope proteins are involved in movement through microtubule formation. Positioning of the microtubule-organizing center, which is proposed to be crucial for nuclear movement, is regulated by Nodal signaling and nuclear envelope proteins. The non-Smad JNK signaling pathway, which is downstream of Nodal signaling, regulates nuclear movement independently of the Smad pathway, and this nuclear movement is associated with Smad signal transduction toward the nucleus. Our study provides insight into the function of nuclear movement in Smad signaling toward the nucleus, and could be applied to the control of TGFβ signaling. © 2017. Published by The Company of Biologists Ltd.

  12. Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus

    PubMed Central

    Noble, Fergus; Nolan, Luke; Bateman, Adrian C; Byrne, James P; Kelly, Jamie J; Bailey, Ian S; Sharland, Donna M; Rees, Charlotte N; Iveson, Timothy J; Underwood, Tim J; Bateman, Andrew R

    2013-01-01

    AIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy. METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ≤ 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics. RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to

  13. Serum decoy receptor 3 level: a predictive marker for nodal metastasis and survival among oral cavity cancer patients.

    PubMed

    Tu, Hsi-Feng; Liu, Chung-Ji; Liu, Shyun-Yeu; Chen, Yu-Ping; Yu, En-Hao; Lin, Shu-Chun; Chang, Kuo-Wei

    2011-03-01

    Validating markers for prediction of nodal metastasis could be beneficial in treatment of oral cavity cancer. Decoy receptor 3 (DcR3), locus on 20q13, functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor (TNFR) family. This study analyzed the serum level of DcR3 in relationship to the clinical parameters of oral cavity cancer patients together with detection of DcR3 genomic copy number in primary and recurrent tumors. Elevated serum DcR3 was associated with nodal metastasis and worse prognosis. Gain of DcR3 copy number was detected in 17% of primary tumor tissue but not found in healthy areca chewers. Tissue from recurrent tumors showed more frequent DcR3 copy number alteration (48%) than the paired primary tumor tissue. Serum DcR3 level is a predictor for the nodal metastasis and survival among oral cavity cancer patients and the DcR3 copy number alteration could underlie oral carcinogenesis progression. Copyright © 2010 Wiley Periodicals, Inc.

  14. Nodal Gap” induced by the incommensurate diagonal spin density modulation in underdoped high- T c superconductors

    DOE PAGES

    Zhou, Tao; Gao, Yi; Zhu, Jian -Xin

    2015-03-07

    Recenmore » tly it was revealed that the whole Fermi surface is fully gapped for several families of underdoped cuprates. The existence of the finite energy gap along the d -wave nodal lines (nodal gap) contrasts the common understanding of the d -wave pairing symmetry, which challenges the present theories for the high- T c superconductors. Here we propose that the incommensurate diagonal spin-density-wave order can account for the above experimental observation. The Fermi surface and the local density of states are also studied. Our results are in good agreement with many important experiments in high- T c superconductors.« less

  15. Impact of [18F]fluorodeoxyglucose PET-CT staging on treatment planning in radiotherapy incorporating elective nodal irradiation for non-small-cell lung cancer: a prospective study.

    PubMed

    Kolodziejczyk, Milena; Kepka, Lucyna; Dziuk, Miroslaw; Zawadzka, Anna; Szalus, Norbert; Gizewska, Agnieszka; Bujko, Krzysztof

    2011-07-15

    To evaluate prospectively how positron emission tomography (PET) information changes treatment plans for non-small-cell lung cancer (NSCLC) patients receiving or not receiving elective nodal irradiation (ENI). One hundred consecutive patients referred for curative radiotherapy were included in the study. Treatment plans were carried out with CT data sets only. For stage III patients, mediastinal ENI was planned. Then, patients underwent PET-CT for diagnostic/planning purposes. PET/CT was fused with the CT data for final planning. New targets were delineated. For stage III patients with minimal N disease (N0-N1, single N2), the ENI was omitted in the new plans. Patients were treated according to the PET-based volumes and plans. The gross tumor volume (GTV)/planning tumor volume (PTV) and doses for critical structures were compared for both data sets. The doses for areas of potential geographical misses derived with the CT data set alone were compared in patients with and without initially planned ENI. In the 75 patients for whom the decision about curative radiotherapy was maintained after PET/CT, there would have been 20 cases (27%) with potential geographical misses by using the CT data set alone. Among them, 13 patients would receive ENI; of those patients, only 2 patients had the PET-based PTV covered by 90% isodose by using the plans based on CT alone, and the mean of the minimum dose within the missed GTV was 55% of the prescribed dose, while for 7 patients without ENI, it was 10% (p = 0.006). The lung, heart, and esophageal doses were significantly lower for plans with ENI omission than for plans with ENI use based on CT alone. PET/CT should be incorporated in the planning of radiotherapy for NSCLC, even in the setting of ENI. However, if PET/CT is unavailable, ENI may to some extent compensate for an inadequate dose coverage resulting from diagnostic uncertainties. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. On the correct representation of bending and axial deformation in the absolute nodal coordinate formulation with an elastic line approach

    NASA Astrophysics Data System (ADS)

    Gerstmayr, Johannes; Irschik, Hans

    2008-12-01

    In finite element methods that are based on position and slope coordinates, a representation of axial and bending deformation by means of an elastic line approach has become popular. Such beam and plate formulations based on the so-called absolute nodal coordinate formulation have not yet been verified sufficiently enough with respect to analytical results or classical nonlinear rod theories. Examining the existing planar absolute nodal coordinate element, which uses a curvature proportional bending strain expression, it turns out that the deformation does not fully agree with the solution of the geometrically exact theory and, even more serious, the normal force is incorrect. A correction based on the classical ideas of the extensible elastica and geometrically exact theories is applied and a consistent strain energy and bending moment relations are derived. The strain energy of the solid finite element formulation of the absolute nodal coordinate beam is based on the St. Venant-Kirchhoff material: therefore, the strain energy is derived for the latter case and compared to classical nonlinear rod theories. The error in the original absolute nodal coordinate formulation is documented by numerical examples. The numerical example of a large deformation cantilever beam shows that the normal force is incorrect when using the previous approach, while a perfect agreement between the absolute nodal coordinate formulation and the extensible elastica can be gained when applying the proposed modifications. The numerical examples show a very good agreement of reference analytical and numerical solutions with the solutions of the proposed beam formulation for the case of large deformation pre-curved static and dynamic problems, including buckling and eigenvalue analysis. The resulting beam formulation does not employ rotational degrees of freedom and therefore has advantages compared to classical beam elements regarding energy-momentum conservation.

  17. Scattering on a rectangular potential barrier in nodal-line Weyl semimetals

    NASA Astrophysics Data System (ADS)

    Khokhlov, D. A.; Rakhmanov, A. L.; Rozhkov, A. V.

    2018-06-01

    We investigate single-particle ballistic scattering on a rectangular barrier in the nodal-line Weyl semimetals. Since the system under study has a crystallographic anisotropy, the scattering properties are dependent on mutual orientation of the crystalline axis and the barrier. To account for the anisotropy, we examine two different barrier orientations. It is demonstrated that, for certain angles of incidence, the incoming particle passes through the barrier with probability of unity. This is a manifestation of the Klein tunneling, a familiar phenomenon in the context of graphene and semimetals with Weyl points. However, the Klein tunneling in the Weyl-ring systems is observed when the angle of incidence differs from 90∘, unlike the cases of graphene and Weyl-point semimetals. The reflectionless transmission also occurs for the so-called "magic angles." The values of the magic angles are determined by geometrical resonances between the barrier width and the de Broglie length of the scattered particle. In addition, we show that under certain conditions the wave function of the transmitted and reflected particles may be a superposition of two plane waves with unequal momenta. Such a feature is a consequence of the nontrivial structure of the isoenergy surfaces of the nodal-line semimetals. Conductance of the barrier is briefly discussed.

  18. The Role of Cerl2 in the Establishment of Left-Right Asymmetries during Axis Formation and Heart Development

    PubMed Central

    2017-01-01

    The formation of the asymmetric left-right (LR) body axis is one of the fundamental aspects of vertebrate embryonic development, and one still raising passionate discussions among scientists. Although the conserved role of nodal is unquestionable in this process, several of the details around this signaling cascade are still unanswered. To further understand this mechanism, we have been studying Cerberus-like 2 (Cerl2), an inhibitor of Nodal, and its role in the generation of asymmetries in the early vertebrate embryo. The absence of Cerl2 results in a wide spectrum of malformations commonly known as heterotaxia, which comprises defects in either global organ position (e.g., situs inversus totalis), reversed orientation of at least one organ (e.g., situs ambiguus), and mirror images of usually asymmetric paired organs (e.g., left or right isomerisms of the lungs). Moreover, these laterality defects are frequently associated with congenital heart diseases (e.g., transposition of the great arteries, or atrioventricular septal defects). Here, reviewing the knowledge on the establishment of LR asymmetry in mouse embryos, the emerging conclusion is that as necessary as is the activation of the Nodal signaling cascade, the tight control that Cerl2-mediates on Nodal signaling is equally important, and that generates a further regionalized LR genetic program in the proper time and space. PMID:29367552

  19. Performance of a recoverable tug for planetary missions including use of perigee propulsion and corrections for nodal regression

    NASA Technical Reports Server (NTRS)

    Borsody, J.

    1976-01-01

    Mathematical equations are derived by using the Maximum Principle to obtain the maximum payload capability of a reusable tug for planetary missions. The mathematical formulation includes correction for nodal precession of the space shuttle orbit. The tug performs this nodal correction in returning to this precessed orbit. The sample case analyzed represents an inner planet mission as defined by the declination (fixed) and right ascension of the outgoing asymptote and the mission energy. Payload capability is derived for a typical cryogenic tug and the sample case with and without perigee propulsion. Optimal trajectory profiles and some important orbital elements are also discussed.

  20. Topological insulating phases from two-dimensional nodal loop semimetals

    NASA Astrophysics Data System (ADS)

    Li, Linhu; Araújo, Miguel A. N.

    2016-10-01

    Starting from a minimal model for a two-dimensional nodal loop semimetal, we study the effect of chiral mass gap terms. The resulting Dirac loop anomalous Hall insulator's Chern number is the phase-winding number of the mass gap terms on the loop. We provide simple lattice models, analyze the topological phases, and generalize a previous index characterizing topological transitions. The responses of the Dirac loop anomalous Hall and quantum spin Hall insulators to a magnetic field's vector potential are also studied both in weak- and strong-field regimes, as well as the edge states in a ribbon geometry.

  1. Mechanism of polyuria and natriuresis in atrioventricular nodal tachycardia.

    PubMed Central

    Canepa-Anson, R; Williams, M; Marshall, J; Mitsuoka, T; Lightman, S; Sutton, R

    1984-01-01

    A woman with tachycardia associated with polyuria was investigated. Electrophysiological analysis showed that the tachycardia was an atrioventricular nodal re-entrant tachycardia. Programmed stimulation was then used to provoke and sustain the tachycardia for 40 minutes. Polyuria, with an appreciable increase in free water clearance, was observed. This was associated with reduction in plasma and urinary arginine vasopressin concentrations. Appreciable natriuresis also developed. These results support the hypothesis that the polyuria with increased free water clearance and the natriuresis occurring during sustained tachycardia in man are due to inhibition of secretion of vasopressin and the release of natriuretic factor. PMID:6434116

  2. The General-Use Nodal Network Solver (GUNNS) Modeling Package for Space Vehicle Flow System Simulation

    NASA Technical Reports Server (NTRS)

    Harvey, Jason; Moore, Michael

    2013-01-01

    The General-Use Nodal Network Solver (GUNNS) is a modeling software package that combines nodal analysis and the hydraulic-electric analogy to simulate fluid, electrical, and thermal flow systems. GUNNS is developed by L-3 Communications under the TS21 (Training Systems for the 21st Century) project for NASA Johnson Space Center (JSC), primarily for use in space vehicle training simulators at JSC. It has sufficient compactness and fidelity to model the fluid, electrical, and thermal aspects of space vehicles in real-time simulations running on commodity workstations, for vehicle crew and flight controller training. It has a reusable and flexible component and system design, and a Graphical User Interface (GUI), providing capability for rapid GUI-based simulator development, ease of maintenance, and associated cost savings. GUNNS is optimized for NASA's Trick simulation environment, but can be run independently of Trick.

  3. Study of flow over object problems by a nodal discontinuous Galerkin-lattice Boltzmann method

    NASA Astrophysics Data System (ADS)

    Wu, Jie; Shen, Meng; Liu, Chen

    2018-04-01

    The flow over object problems are studied by a nodal discontinuous Galerkin-lattice Boltzmann method (NDG-LBM) in this work. Different from the standard lattice Boltzmann method, the current method applies the nodal discontinuous Galerkin method into the streaming process in LBM to solve the resultant pure convection equation, in which the spatial discretization is completed on unstructured grids and the low-storage explicit Runge-Kutta scheme is used for time marching. The present method then overcomes the disadvantage of standard LBM for depending on the uniform meshes. Moreover, the collision process in the LBM is completed by using the multiple-relaxation-time scheme. After the validation of the NDG-LBM by simulating the lid-driven cavity flow, the simulations of flows over a fixed circular cylinder, a stationary airfoil and rotating-stationary cylinders are performed. Good agreement of present results with previous results is achieved, which indicates that the current NDG-LBM is accurate and effective for flow over object problems.

  4. Primary radiotherapy with surgery in reserve for advanced laryngeal carcinoma. Results and complications.

    PubMed

    Croll, G A; Gerritsen, G J; Tiwari, R M; Snow, G B

    1989-08-01

    A retrospective study of a selected group of 58 patients with T3 and T4 squamous cell carcinomas of the larynx presenting between 1974 and 1984 was undertaken. These patients were treated primarily with radical radiotherapy and salvage surgery in reserve. The aim of this study was to examine survival, recurrence rate and the complications after salvage surgery. In 30 patients the tumor was classified as a T3 and in 28 as a T4. In 14 patients (24%) nodal disease in the neck was present prior to the radiotherapy. Follow-up in all patients continued for at least 3 years or until death. Nineteen patients (33%) developed locally recurrent tumor and five (9%) developed nodal metastases to the neck. The recurrence in almost every patient was detected within 2 years after completion of the irradiation. Thirty patients (52%) are alive of whom 29 have no evidence of disease. Of these 30 patients 22 (73%) have their larynx intact and functioning. The 5-year adjusted acturial survival for the whole group of patients is 73%, for the T3N0 group 87% and for the T4N0 group 75%. Patients with nodal disease responded poorly. After salvage surgery severe postoperative complications developed in 37% of the patients. There were no deaths following salvage surgery.

  5. [Parahisian atrial tachycardia or atrioventricular nodal reentrant tachycardia with tendon of Todaro breakthrough?].

    PubMed

    Orczykowski, Michał; Jaworska-Wilczyńska, Maria; Urbanek, Piotr; Bodalski, Robert; Derejko, Paweł; Gajek, Jacek; Hryniewiecki, Tomasz; Szumowski, Lukasz; Walczak, Franciszek

    2010-08-01

    We present a case of a 61 year-old woman with tachycardia originating close to the His bundle where radiofrequency (RF) ablation may bear potential risk of atrioventricular (AV) block. In this case report we discuss the possibility of a AV nodal reciprocating tachycardia with tendon of Todaro breakthrough. Patient was safely and effectively treated with RF catheter ablation.

  6. The structure, stability, and infrared spectrum of B 2N, B 2N +, B 2N -, BO, B 2O and B 2N 2.

    NASA Astrophysics Data System (ADS)

    Martin, J. M. L.; François, J. P.; Gijbels, R.

    1992-05-01

    The structure, infrared spectrum, and heat of formation of B 2N, B 2N -, BO, and B 2O have been studied ab initio. B 2N is very stable; B 2O even more so. B 2N, B 2N -, B 2O, and probably B 2N + have symmetric linear ground-state structures; for B 2O, an asymmetric linear structure lies about 12 kcal/mol above the ground state. B 2N +, B 2N - and B 2O have intense asymmetric stretching frequencies, predicted near 870, 1590 and 1400 cm -1, respectively. Our predicted harmonic frequencies and isotopic shifts for B 2O confirm the recent experimental identification by Andrews and Burkholder. Absorptions at 1889.5 and 1998.5 cm -1 in noble-gas trapped boron nitride vapor belong the BNB and BNBN ( 3Π), respectively; a tentative assignment of 882.5 cm -1 to BNB + is proposed. Total atomization energies Σ De (Σ D0) are computed (accuracy ±2 kcal/mol) as: BO 193.1 (190.4), B 2O 292.5 (288.7), B 2N 225.0 (250.3) kcal/mol. The ionization potential and electron affinity of B 2N are predicted to be 8.62±0.1 and 3.34±0.1 eV. The MP4-level additivity approximations involved in G1 theory results in errors on the order of 1 kcal/mol in the Σ De values.

  7. A randomized controlled trial of the effect of prednisone omission from a multidrug chemotherapy protocol on treatment outcome in dogs with peripheral nodal lymphomas.

    PubMed

    Childress, Michael O; Ramos-Vara, José A; Ruple, Audrey

    2016-11-01

    OBJECTIVE To determine the effect of prednisone omission from a multidrug chemotherapy protocol on outcome in dogs with peripheral nodal lymphomas. DESIGN Single-center, nonblinded, parallel-group, randomized, controlled trial. ANIMALS 40 client-owned dogs with a histopathologically confirmed diagnosis of peripheral nodal lymphoma and an expected survival time of > 4 weeks with treatment. PROCEDURES Treatment consisted of a combination of L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone (L-CHOP) or an identical protocol except for the omission of prednisone (L-CHO). The primary outcome of interest was progression-free survival time. Veterinary caregivers and assessors of outcome were not blinded to treatment assignment. Treatment assignment was concealed from the owners of study dogs prior to enrollment, but was revealed after written informed consent was provided. RESULTS The trial was terminated early because of slow enrollment. The 40 dogs successfully enrolled in the study were randomly assigned to the L-CHOP (n = 18) or L-CHO (22) group; results for all 40 dogs were analyzed with respect to the primary outcome. Median progression-free survival time was 142.5 days for dogs receiving L-CHO and 292 days for dogs receiving L-CHOP (hazard ratio, 1.79; 95% confidence interval, 0.85 to 3.75). Serious adverse events were more common among dogs receiving L-CHO. However, this difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE The exclusion of prednisone from the L-CHOP protocol did not appear to result in improved progression-free survival time for dogs with peripheral nodal lymphomas. However, the present trial was likely underpowered to detect a clinically meaningful difference in progression-free survival time between groups.

  8. A nodally condensed SUPG formulation for free-surface computation of steady-state flows constrained by unilateral contact - Application to rolling

    NASA Astrophysics Data System (ADS)

    Arora, Shitij; Fourment, Lionel

    2018-05-01

    In the context of the simulation of industrial hot forming processes, the resultant time-dependent thermo-mechanical multi-field problem (v →,p ,σ ,ɛ ) can be sped up by 10-50 times using the steady-state methods while compared to the conventional incremental methods. Though the steady-state techniques have been used in the past, but only on simple configurations and with structured meshes, and the modern-days problems are in the framework of complex configurations, unstructured meshes and parallel computing. These methods remove time dependency from the equations, but introduce an additional unknown into the problem: the steady-state shape. This steady-state shape x → can be computed as a geometric correction t → on the domain X → by solving the weak form of the steady-state equation v →.n →(t →)=0 using a Streamline Upwind Petrov Galerkin (SUPG) formulation. There exists a strong coupling between the domain shape and the material flow, hence, a two-step fixed point iterative resolution algorithm was proposed that involves (1) the computation of flow field from the resolution of thermo-mechanical equations on a prescribed domain shape and (2) the computation of steady-state shape for an assumed velocity field. The contact equations are introduced in the penalty form both during the flow computation as well as during the free-surface correction. The fact that the contact description is inhomogeneous, i.e., it is defined in the nodal form in the former, and in the weighted residual form in the latter, is assumed to be critical to the convergence of certain problems. Thus, the notion of nodal collocation is invoked in the weak form of the surface correction equation to homogenize the contact coupling. The surface correction algorithm is tested on certain analytical test cases and the contact coupling is tested with some hot rolling problems.

  9. Occurrence of a pig respiratory disease associated with swine influenza A (H1N2) virus in Tochigi Prefecture, Japan.

    PubMed

    Yoneyama, Shuji; Hayashi, Tsuyoshi; Kojima, Hirokazu; Usami, Yoshihide; Kubo, Masanori; Takemae, Nobuhiro; Uchida, Yuko; Saito, Takehiko

    2010-04-01

    In February 2008, a feeder pig herd of the affected farm in Tochigi Prefecture, Japan, showed increasing respiratory symptoms; by April, the situation worsened with 12-16 pigs dying daily. Diagnostic tests revealed the presence of H1N2 subtype of swine influenza virus (SIV) and Pasteurella multocida from nasal swab and lung emulsion. Serological tests by hemagglutination inhibition method and enzyme-linked immunosorbent assay method (ELISA; imported from U.S.A.) indicated the spread of SIV into the pig herds of the affected farm around April 2008. The severe infection and subsequent damage were considered as a result of the combined infection of SIV (H1N2) and bacteria that may have been prevalent in the pig farm. Genetic homology search of sequences for the hemagglutinin (HA) and neuraminidase (NA) genes of A/swine/Tochigi/1/08 showed high homology to Japanese SIVs (H1N2) isolated in the 2000s. Therefore, we considered that Japanese SIV (H1N2) has established an independent stable lineage and participated in infecting pig populations as one of the factors of the pig respiratory disease complex. Consistent surveillance would contribute to clarifying the prevalence of dominant SIVs.

  10. Can axial-based nodal size criteria be used in other imaging planes to accurately determine "enlarged" head and neck lymph nodes?

    PubMed

    Bartlett, Eric S; Walters, Thomas D; Yu, Eugene

    2013-01-01

    Objective. We evaluate if axial-based lymph node size criteria can be applied to coronal and sagittal planes. Methods. Fifty pretreatment computed tomographic (CT) neck exams were evaluated in patients with head and neck squamous cell carcinoma (SCCa) and neck lymphadenopathy. Axial-based size criteria were applied to all 3 imaging planes, measured, and classified as "enlarged" if equal to or exceeding size criteria. Results. 222 lymph nodes were "enlarged" in one imaging plane; however, 53.2% (118/222) of these were "enlarged" in all 3 planes. Classification concordance between axial versus coronal/sagittal planes was poor (kappa = -0.09 and -0.07, resp., P < 0.05). The McNemar test showed systematic misclassification when comparing axial versus coronal (P < 0.001) and axial versus sagittal (P < 0.001) planes. Conclusion. Classification of "enlarged" lymph nodes differs between axial versus coronal/sagittal imaging planes when axial-based nodal size criteria are applied independently to all three imaging planes, and exclusively used without other morphologic nodal data.

  11. An Improved Micropropagation Protocol by Ex Vitro Rooting of Passiflora edulis Sims. f. flavicarpa Deg. through Nodal Segment Culture.

    PubMed

    Shekhawat, Mahipal S; Manokari, M; Ravindran, C P

    2015-01-01

    A procedure for rapid clonal propagation of Passiflora edulis Sims. f. flavicarpa Deg. (Passifloraceae) has been developed in this study. Nodal explants were sterilized with 0.1% HgCl2 and inoculated on Murashige and Skoog (MS) basal medium. The addition of 2.0 mgL(-1) 6-benzylaminopurine (BAP) to MS medium caused an extensive proliferation of multiple shoots (8.21 ± 1.13) primordial from the nodal meristems. Subculturing of these multiple shoots on the MS medium augmented with 1.0 mgL(-1) of each BAP and Kinetin (Kin) was successful for the multiplication of the shoots in vitro with maximum numbers of shoots (25.73 ± 0.06) within four weeks of incubation. Shoots were rooted best (7.13 ± 0.56 roots/shoots) on half strength MS medium supplemented with 2.0 mgL(-1) indole-3 butyric acid (IBA). All in vitro regenerated shoots were rooted by ex vitro method, and this has achieved 6-7 roots per shoot by pulsing of cut ends of the shoots using 200 as well as 300 mgL(-1) IBA. The plantlets were hardened in the greenhouse for 4-5 weeks. The hardened plantlets were shifted to manure containing nursery polybags after five weeks and then transferred to a sand bed for another four weeks for acclimatization before field planting with 88% survival rate.

  12. Early-stage Node-negative (T1-T2N0) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy.

    PubMed

    Franco, Pierfrancesco; Arcadipane, Francesca; Ragona, Riccardo; Mistrangelo, Massimiliano; Cassoni, Paola; Rondi, Nadia; Morino, Mario; Racca, Patrizia; Ricardi, Umberto

    2016-04-01

    To report clinical outcomes of a consecutive series of patients with early-stage (T1-T1N0) anal cancer treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial. A cohort of 43 patients underwent SIB-IMRT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumor volume and 42 Gy/28 fractions to the elective nodal volumes for cT1N0 cases, and 54 Gy/30 fractions and 45 Gy/30 fractions to the same volumes for cT2N0 cases. Chemotherapy was administered concurrently following Nigro's regimen. The primary endpoint was colostomy-free survival (CFS). Secondary endpoints were locoregional control (LRC), disease-free (DFS), cancer-specific (CSS) and overall (OS) survival. Median follow-up was 39.7 months. The actuarial 3-year CFS was 79.4% [95% confidence interval (CI)=61.4-89.7%]. Actuarial 3-year OS and CSS were 90.8% (95% CI=74.1-96.9%) and 93.8% (95% CI=77.3-98.4%), while DFS was 75.5% (95% CI=56.4-87.1%). Actuarial 3-year LRC was 86.1% (95% CI=69.6-94%). On multivariate analysis, tumor size >3 cm showed a trend towards significance in predicting CFS [hazard ratio (HR)=8.6, 95% CI=84.7-88.1%; p=0.069]. Maximum detected adverse events included: skin (G3): 18%; gastrointestinal tract (G2): 67%; genitourinary tract (G3): 3%; genitalia (G2): 30%; anemia (G2): 7%; leukopenia (G3): 26%, leukopenia (G4):7%; neutropenia (G3): 15%; neutropenia (G4): 12%; thrombocytopenia (G3): 9%. Our clinical results support the use of SIB-IMRT in the combined modality treatment of patients with anal cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  13. Prognostic Significance of the Number of Metastatic pN2 Lymph Nodes in Stage IIIA-N2 Non-Small-Cell Lung Cancer After Curative Resection.

    PubMed

    Yoo, Changhoon; Yoon, Shinkyo; Lee, Dae Ho; Park, Seung-Il; Kim, Dong Kwan; Kim, Yong-Hee; Kim, Hyeong Ryul; Choi, Se Hoon; Kim, Woo Sung; Choi, Chang-Min; Jang, Se Jin; Song, Si Yeol; Kim, Su Ssan; Choi, Eun Kyung; Lee, Jae Cheol; Suh, Cheolwon; Lee, Jung-Shin; Kim, Sang-We

    2015-11-01

    Stage IIIA-N2 non-small cell lung cancer (NSCLC) shows prognostic heterogeneity. We investigated the prognostic relevance of the number of metastatic pN2 nodes in patients with IIIA-N2 NSCLC. The criteria for the number of pN2 used in this study were significantly associated with the survival outcomes after surgery and may improve the accuracy of prognostic prediction in this subgroup of patients. There have been controversies regarding the prognostic relevance of the number of positive N2 nodes in pathologic stage IIIA-N2 non-small-cell lung cancer (NSCLC). We examine prognosis of patients with pathologic stage IIIA-N2 with classifying the number of positive N2 nodes into subgroups. From January 1997 to December 2004, 250 patients were diagnosed with pathologic stage IIIA-N2 disease. All patients underwent mediastinal lymph node dissection. After excluding 44 patients with preoperative chemotherapy, incomplete resection, and postsurgical mortality, 206 patients were included in the analysis. Patients were classified according to the number of positive N2 lymph nodes (N2a: 1 [n = 83], N2b: 2-4 [n = 82], N2c: ≥ 5 [n = 41]), and its correlation with survival outcomes were investigated. With a median follow-up of 96.3 months, 5-year disease-free survival (DFS) was 27.2% (95% confidence interval [CI], 21.6-33.7), and 5-year overall survival (OS) was 37.7% (95% CI, 31.5-44.7) in all patients. The number of metastatic N2 lymph nodes was associated with DFS (P < .001) and OS (P = .01). In the N2a, N2b, and N2c groups, 5-year DFS rates were 38%, 24%, and 5%, respectively, and 5-year OS rates were 47%, 35%, and 24%, respectively. In a multivariate analysis, the number of metastatic N2 lymph nodes was an independent prognostic factor for DFS and OS. Stratification of patients according to the number of metastatic N2 lymph nodes may improve the accuracy of prognostic prediction among patients with curatively resected stage IIIA-N2 NSCLC. Copyright © 2015 Elsevier Inc. All

  14. Preoperative Prediction of Node-Negative Disease After Neoadjuvant Chemotherapy in Patients Presenting with Node-Negative or Node-Positive Breast Cancer.

    PubMed

    Murphy, Brittany L; L Hoskin, Tanya; Heins, Courtney Day N; Habermann, Elizabeth B; Boughey, Judy C

    2017-09-01

    Axillary node status after neoadjuvant chemotherapy (NAC) influences the axillary surgical staging procedure as well as recommendations regarding reconstruction and radiation. Our aim was to construct a clinical preoperative prediction model to identify the likelihood of patients being node negative after NAC. Using the National Cancer Database (NCDB) from January 2010 to December 2012, we identified cT1-T4c, N0-N3 breast cancer patients treated with NAC. The effects of patient and tumor factors on pathologic node status were assessed by multivariable logistic regression separately for clinically node negative (cN0) and clinically node positive (cN+) disease, and two models were constructed. Model performance was validated in a cohort of NAC patients treated at our institution (January 2013-July 2016), and model discrimination was assessed by estimating the area under the curve (AUC). Of 16,153 NCDB patients, 6659 (41%) were cN0 and 9494 (59%) were cN+. Factors associated with pathologic nodal status and included in the models were patient age, tumor grade, biologic subtype, histology, clinical tumor category, and, in cN+ patients only, clinical nodal category. The validation dataset included 194 cN0 and 180 cN+ patients. The cN0 model demonstrated good discrimination, with an AUC of 0.73 (95% confidence interval [CI] 0.72-0.74) in the NCDB and 0.77 (95% CI 0.68-0.85) in the external validation, while the cN+ patient model AUC was 0.71 (95% CI 0.70-0.72) in the NCDB and 0.74 (95% CI 0.67-0.82) in the external validation. We constructed two models that showed good discrimination for predicting ypN0 status following NAC in cN0 and cN+ patients. These clinically useful models can guide surgical planning after NAC.

  15. Correlation of Various Biomarkers with Axillary Nodal Metastases: Can a Panel of Such Biomarkers Guide Selective Use of Axillary Surgery in T1 Breast Cancer?

    PubMed

    Dass, Tufale A; Rakesh, Sharma; Prakash, K Patil; Singh, Chandraveer

    2015-12-01

    To evaluate the correlation of various clinic-pathological variables with axillary nodal involvement in T1 breast cancer & to identify a sub-group of T1 cancers, on the basis of observed variables, with a low risk of axillary nodal metastases. Clinico-pathological variables observed included tumor size, lymphovascular invasion (LVI), histological grade of tumor, tumor palpability, estrogen/progesterone (ER/PR) & her2/neu receptors, age, family history, histological type of tumor, axillary nodal metastases for 100 patients without clinically palpable nodes who underwent axillary lymph node dissection in Bombay Hospital & Medical Research Center from March, 2009. Data compiled was analyzed by univariate & multivariate analysis. All the variables viz. tumor size, LVI, histological grade, tumor palpability & ER/PR/Her2 receptor profile, which were found to be significantly associated with axillary lymph node involvement (ALNI) on univariate analysis were also found to be independent predictors of ALNI on multivariate analysis. Age of the patient, family history & histological type of tumor were not significantly correlated with ALNI. None of the 12 patients with tumor biomarker profile of T1a-b tumors without LVI & with histological grade I, had ALNI. The risk of ALNI can be predicted by using various tumor biomarker variables. Based on the predicted risk of ALNI, the management strategy for axilla can be individualized. The omission of operative axillary staging may be considered in patients with low predictive risk of ALNI.

  16. High-dose therapy and autologous stem cell transplantation for extra-nodal NK/T lymphoma in patients from the Western hemisphere: a study from the European Society for Blood and Marrow Transplantation.

    PubMed

    Fox, Christopher P; Boumendil, Ariane; Schmitz, Norbert; Finel, Herve; Luan, Jian J; Sucak, Gülsan; Blaise, Didier; Finke, Jürgen; Pflüger, Karl-Heinz; Veelken, Hendrik; Gorin, Norbert-Claude; Poiré, Xavier; Ganser, Arnold; Dreger, Peter; Sureda, Anna

    2015-01-01

    Extra-nodal NK/T lymphoma (ENKTL) is rare and more frequently encountered in East Asia. The role of high-dose therapy and autologous stem cell transplantation (HDT-ASCT) for ENKTL is unclear. Twenty-eight evaluable patients who had undergone HDT-ASCT in Europe from 2000-2009 were studied. The median age was 47 years and patients had received a median of two lines of prior therapy. Some 57% of patients were not in complete remission or beyond first complete remission at HDT-ASCT. The 1-year non-relapse mortality (NRM) was 11%; 2-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 52%, respectively. Notably, the 2-year PFS and OS for those with stage III/IV disease were 33% and 40%, respectively, with no relapses beyond 1-year post-HDT-ASCT. This is the largest analysis of HDT-ASCT for patients with ENKTL reported from the Western hemisphere. Survival is comparable to East Asian cohorts and outcomes are encouraging for patients with advanced disease.

  17. The Accuracy of Integrated [18F] Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Detection of Pelvic and Para-aortic Nodal Metastasis in Patients with High Risk Endometrial Cancer

    PubMed Central

    Gholkar, Nikhil Shirish; Saha, Subhas Chandra; Prasad, GRV; Bhattacharya, Anish; Srinivasan, Radhika; Suri, Vanita

    2014-01-01

    Lymph nodal (LN) metastasis is the most important prognostic factor in high-risk endometrial cancer. However, the benefit of routine lymphadenectomy in endometrial cancer is controversial. This study was conducted to assess the accuracy of [18F] fluorodeoxyglucose-positron emission tomography/computed tomography ([18F] FDG-PET/CT) in detection of pelvic and para-aortic nodal metastases in high-risk endometrial cancer. 20 patients with high-risk endometrial carcinoma underwent [18F] FDG-PET/CT followed by total abdominal hysterectomy, bilateral salpingo-oophorectomy and systematic pelvic lymphadenectomy with or without para-aortic lymphadenectomy. The findings on histopathology were compared with [18F] FDG-PET/CT findings to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of [18F] FDG-PET/CT. The pelvic nodal findings were analyzed on a patient and nodal chain based criteria. The para-aortic nodal findings were reported separately. Histopathology documented nodal involvement in two patients (10%). For detection of pelvic nodes, on a patient based analysis, [18F] FDG-PET/CT had a sensitivity of 100%, specificity of 61.11%, PPV of 22.22%, NPV of 100% and accuracy of 65% and on a nodal chain based analysis, [18F] FDG-PET/CT had a sensitivity of 100%, specificity of 80%, PPV of 20%, NPV of 100%, and accuracy of 80.95%. For detection of para-aortic nodes, [18F] FDG-PET/CT had sensitivity of 100%, specificity of 66.67%, PPV of 20%, NPV of 100%, and accuracy of 69.23%. Although [18F] FDG-PET/CT has high sensitivity for detection of LN metastasis in endometrial carcinoma, it had moderate accuracy and high false positivity. However, the high NPV is important in selecting patients in whom lymphadenectomy may be omitted. PMID:25538488

  18. Inland waterway ports nodal attraction indices relevant in development strategies on regional level

    NASA Astrophysics Data System (ADS)

    Dinu, O.; Burciu, Ş.; Oprea, C.; Ilie, A.; Rosca, M.

    2016-08-01

    Present paper aims to propose a set of ranking indices and related criteria, concerning mainly spatial analysis, for the inland waterway port, with special view on inland ports of Danube. Commonly, the attraction potential of a certain transport node is assessed by its spatial accessibility indices considering both spatial features of the location provided by the networks that connect into that node and its economic potential defining the level of traffic flows depending on the economic centers of its hinterland. Paper starts with a overview of the critical needs that are required for potential sites to become inland waterway ports and presents nodal functions that coexist at different levels, leading to a port hierarchy from the points of view of: capacity, connection to hinterland, traffic structure and volume. After a brief review of the key inland waterway port ranking criterion, a selection of nodal attraction measures is made. Particular considerations for the Danube inland port case follows proposed methodology concerning indices of performance for network scale and centrality. As expected, the shorter the distance from an inland port to the nearest access point the greater accessibility. Major differences in ranking, dependent on selected criterion, were registered.

  19. Plasticity in nodal root elongation through the hardpan triggered by rewatering during soil moisture fluctuation stress in rice.

    PubMed

    Suralta, Roel Rodriguez; Niones, Jonathan Manito; Kano-Nakata, Mana; Thi Tran, Thiem; Mitsuya, Shiro; Yamauchi, Akira

    2018-03-12

    Rainfed lowland (RFL) rice fields have hardpans and experience soil moisture fluctuations (SMF) stress, which influence root system development. Here, we clarify the expression and timing of the plasticity in nodal root elongation through the hardpan under SMF and its contribution to shoot growth using a shallow-rooting IR64 and its deep-rooting introgression line, YTH304. Under SMF, soil moisture content had negative relationship with soil penetration resistance, regardless of hardpan bulk densities. YTH304 had greater root system below the hardpan than IR64 in hardpan with 1.50 but not in 1.70 g cm -3 bulk density (BD). YTH304 had greater plasticity in nodal root elongation through the hardpan than IR64 under SMF, which was clearly expressed during rewatering. YTH304 also had greater soil water uptake below the hardpan during drought and greater shoot growth than IR64. The results imply that deep root system development during SMF was due to the plasticity in nodal root elongation through the hardpan expressed during rewatering rather than during drought periods. This is against the long standing belief that active root elongation through the hardpan happens during drought. This also implies a need to revisit current root screening methods to identify rice lines with good hardpan penetration ability.

  20. Functional Brain Connectome and Its Relation to Hoehn and Yahr Stage in Parkinson Disease.

    PubMed

    Suo, Xueling; Lei, Du; Li, Nannan; Cheng, Lan; Chen, Fuqin; Wang, Meiyun; Kemp, Graham J; Peng, Rong; Gong, Qiyong

    2017-12-01

    Purpose To use resting-state functional magnetic resonance (MR) imaging and graph theory approaches to investigate the brain functional connectome and its potential relation to disease severity in Parkinson disease (PD). Materials and Methods This case-control study was approved by the local research ethics committee, and all participants provided informed consent. There were 153 right-handed patients with PD and 81 healthy control participants recruited who were matched for age, sex, and handedness to undergo a 3-T resting-state functional MR examination. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 90 brain regions, and the topologic properties were analyzed by using graph theory approaches. Nonparametric permutation tests were used to compare topologic properties, and their relationship to disease severity was assessed. Results The functional connectome in PD showed abnormalities at the global level (ie, decrease in clustering coefficient, global efficiency, and local efficiency, and increase in characteristic path length) and at the nodal level (decreased nodal centralities in the sensorimotor cortex, default mode, and temporal-occipital regions; P < .001, false discovery rate corrected). Further, the nodal centralities in left postcentral gyrus and left superior temporal gyrus correlated negatively with Unified Parkinson's Disease Rating Scale III score (P = .038, false discovery rate corrected, r = -0.198; and P = .009, false discovery rate corrected, r = -0.270, respectively) and decreased with increasing Hoehn and Yahr stage in patients with PD. Conclusion The configurations of brain functional connectome in patients with PD were perturbed and correlated with disease severity, notably with those responsible for motor functions. These results provide topologic insights into understanding the neural functional changes in relation to disease severity of PD. © RSNA, 2017 Online supplemental material

  1. External validation of the proposed T and N categories of squamous cell carcinoma of the penis.

    PubMed

    Al-Najar, Amr; Alkatout, Ibrahim; Al-Sanabani, Sakhr; Korda, Joanna Beate; Hegele, Axel; Bolenz, Christian; Jünemann, Klaus-Peter; Naumann, Carsten Maik

    2011-04-01

    The aim of this study was to validate recently proposed modifications to the current TNM classification of penile squamous cell carcinoma (PSCC) by using data from four German urological centers. We identified 89 patients treated for histologically confirmed PSCC between 1996 and 2008 and reclassified them according to the proposed TNM staging revisions. The proposed changes restricted T2 to tumoral invasion of the corpus spongiosum, whereas invasion of the corpus cavernosum was considered as T3. No changes were made to T1 and T4. Furthermore, N1 was limited to unilateral and N2 to bilateral inguinal lymph node involvement regardless of their number. Pelvic lymph node involvement and fixed lymph node were considered as N3 tumors. The range of follow up after initial treatment was 1-142 months (mean 38). Node-negative cases following the current classification were 65.2% (30/46), 48.5% (16/33) and 87.5% (7/8) for T1, T2 and T3, respectively. According to the proposed classification, N0 cases were markedly reduced in the T3 group (55.5%, 10/18) and relatively changed in the T2 group (56.5%, 13/23). T4 patients had no negative disease status. The 3-year disease-specific survival (DSS) rates for the proposed categories were 85.4%, 71.6% and 62.4% for T1, T2 and T3, respectively. For the current categories, the 3-year DSS rates were 85.4%, 66.9% and 100% for T1, T2 and T3, respectively. The 3-year DSS of the current N categories was 78.7%, 51% and 13.3% for N1, N2 and N3, respectively. According to the newly proposed categories, the 3-year DSS was 70%, 50% and 13.3% for N1, N2 and N3, respectively. Tumor and nodal staging of the newly proposed TNM classification show a more distinctive survival compared to the current one. However, a multi-institutional validation is still required to further corroborate the proposed modifications. © 2011 The Japanese Urological Association.

  2. Association of N-acetyltransferase-2 polymorphism with an increased risk of coronary heart disease in a Chinese population.

    PubMed

    Sun, J D; Yuan, H; Hu, H Q; Yu, H M

    2016-03-04

    We investigated the possible correlations between N-acetyltransferase-2 (NAT2) gene polymorphisms and the risk of coronary heart disease (CHD). CHD patients (113) and healthy controls (118) were enrolled from the First People's Hospital of Yuhang between January 2013 and June 2014. The patients were divided into mild CHD (N = 72) and severe CHD (N = 41) subgroups. DNA samples were extracted and the distributions of NAT2 polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Clinical characteristic indexes of severe CHD patients were also examined for relevant statistical analysis. WT, M1, M2, and M3 alleles were observed in both case and control groups. PCR-RFLP identified a wild-type homozygote, WT/WT; a mutant heterozygote, WT/Mx; and a mutant homozygote, Mx/Mx (x = 1, 2, and 3) variant of the NAT2 genotype. Mx/Mx differed significantly between case and control groups (P < 0.05); the frequencies of all four alleles did not differ significantly between case and control groups (P > 0.05). Slow acetylator genotype frequencies were notably higher in the case group than in the control group (P < 0.05). Individuals with the slow acetylator genotype were at 1.97-times higher risk of CHD and also displayed higher triglyceride and lower high-density lipoprotein cholesterol levels than those with the rapid acetylator genotype (P < 0.05). Therefore, the NAT2 polymorphism was believed to be associated with increased risk of CHD, with the NAT2 slow acetylator genotype serving as a risk factor for severe CHD in a Chinese population.

  3. Blood N-terminal Pro-brain Natriuretic Peptide and Interleukin-17 for Distinguishing Incomplete Kawasaki Disease from Infectious Diseases.

    PubMed

    Wu, Ling; Chen, Yuanling; Zhong, Shiling; Li, Yunyan; Dai, Xiahua; Di, Yazhen

    2015-06-01

    To explore the diagnostic value of blood N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin-17(IL-17) for incomplete Kawasaki disease. Patients with Kawasaki disease, Incomplete Kawasaki disease and unclear infectious fever were included in this retrospective study. Their clinical features, and laboratory test results of blood NT-proBNP and IL-17 were collected and compared. 766 patients with complete clinical information were recruited, consisting of 291 cases of Kawasaki disease, 74 cases of incomplete Kawasaki disease, and 401 cases of unclear infectious diseases. When the consistency with indicator 2 and 3 in Kawasaki disease diagnosis criteria was assessed with blood IL-17 ?11.55 pg/mL and blood NT-proBNP ? 225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases reached 86.5% and 94.8%, respectively. When we chose the consistency with indicator 1 and 2 in Kawasaki disease diagnosis criteria, the appearance of decrustation and/or the BCG erythema, blood IL-17 ?11.55 pg/mL and blood NT-Pro BNP ?225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases was 43.2% and 100%, respectively. Blood NT-proBNP and IL-17 are useful laboratory indicators for distinguishing incomplete Kawasaki disease and infectious diseases at the early stage.

  4. Infrared spectra of seeded hydrogen clusters: (para-H2)N-N2O and (ortho-H2)N-N2O, N = 2-13.

    PubMed

    Tang, Jian; McKellar, A R W

    2005-09-15

    High-resolution infrared spectra of clusters containing para-H2 and/or ortho-H2 and a single nitrous oxide molecule are studied in the 2225-cm(-1) region of the upsilon1 fundamental band of N2O. The clusters are formed in pulsed supersonic jet expansions from a cooled nozzle and probed using a tunable infrared diode laser spectrometer. The simple symmetric rotor-type spectra generally show no resolved K structure, with prominent Q-branch features for ortho-H2 but not para-H2 clusters. The observed vibrational shifts and rotational constants are reported. There is no obvious indication of superfluid effects for para-H2 clusters up to N=13. Sharp transitions due to even larger clusters are observed, but no definite assignments are possible. Mixed (para-H2)N-(ortho-H2)M-N2O cluster line positions can be well predicted by linear interpolation between the corresponding transitions of the pure clusters.

  5. Symmetry-guaranteed nodal-line semimetals in an fcc lattice

    NASA Astrophysics Data System (ADS)

    Kawakami, Takuto; Hu, Xiao

    2017-12-01

    We demonstrate theoretically that nodal-line semimetals (NLSs) can be realized in an fcc lattice with orbitals belonging to the same irreducible representation, such as {px,py,pz} or {dx y,dy z,dz x} orbitals on every lattice site. The three orbitals are divided into two subgroups in terms of the parity with respect to the mirror reflections on high-symmetry planes of the fcc lattice, which, with rotation symmetry, endows symmetry-guaranteed NL passing through W points in the Brillouin zone. Depending on the parameters, there also appears an accidental NL around the Γ point. We notice that the symmetry-guaranteed NL addressed in the present work can be found in band structures of elemental solids taking the fcc structure, such as Cu, Ag, Au, In, Ga, etc., as well as opal, which is an fcc photonic crystal of SiO2 spheres. Furthermore, we clarify that the fcc lattice of Si spheres exhibits a NL in a frequency band where no other photonic band exists, which provides a unique platform to realize topological NLSs under intensive search, and can be explored for achieving slow light.

  6. Outcomes after primary chemoradiotherapy for N3 (>6 cm) head and neck squamous cell carcinoma after an FDG-PET--guided neck management policy.

    PubMed

    Adams, Gerard; Porceddu, Sandro V; Pryor, David I; Panizza, Benedict; Foote, Matthew; Rowan, Ann; Burmeister, Bryan

    2014-08-01

    The purpose of this study was to assess whether a positron emission tomography (PET)-directed policy remains appropriate for managing neck nodes (N3; >6 cm) in head and neck squamous cell carcinoma (HNSCC). All patients with N3 (>6 cm) HNSCC treated with definitive chemoradiotherapy (CRT) at our institution between 2005 and 2012 were included in the analysis. Patients underwent PET assessment before and 12 weeks after CRT. Neck dissections were performed for PET-avid residual nodal abnormalities after complete response at the primary site. Rate of isolated nodal failure (INF) was the primary outcome. Median follow-up from diagnosis for 33 patients was 30 months (range, 6-76 months). INF occurred in 2 patients (6%) with neck dissections performed in 4 cases (12%). First failure was predominantly distant metastatic (10; 30%). The rate of INF remains low when following a PET-directed neck management policy after definitive CRT for N3 (>6 cm) HNSCC. Copyright © 2013 Wiley Periodicals, Inc.

  7. Sensitive molecular detection of small nodal metastasis in uterine cervical cancer using HPV16-E6/CK19/MUC1 cancer biomarkers

    PubMed Central

    Samouëlian, Vanessa; Mechtouf, Nawel; Leblanc, Eric; Cardin, Guillaume B.; Lhotellier, Valérie; Querleu, Denis; Révillion, Françoise; Rodier, Francis

    2018-01-01

    Metastatic nodal involvement is a critical prognostic factor in uterine cervical cancer (UCC). To improve current methods of detecting UCC metastases in lymph nodes (LNs), we used quantitative PCR (qPCR) to assess mRNA expression of potential metastatic biomarkers. We found that expression of HPV16-E6, cytokeratin19 (CK19), and mucin1 (MUC1) is consistently upregulated in tumors and metastatic tissues, supporting a role for these genes in UCC progression. These putative biomarkers were able to predict the presence of histologically positive metastatic LNs with respective sensitivities and specificities of 82% and 99% (CK19), 76% and 95% (HPV16-E6), and 76% and 78% (MUC1). While the biomarkers failed to detect 1.7% to 2.2% of the histologically positive LNs when used individually, combining CK19 and HPV16-E6 enhanced sensitivity and specificity to 100% and 94%, respectively. To explore the sensitivity of qPCR-based detection of varying proportions of invading HPV16-positive UCC cells, we designed a LN metastasis model that achieved a fresh cell detection limit of 0.008% (1:12500 HPV16-positive to HPV16-negative cells), and a paraffin-embedded, formalin-fixed (PEFF) detection limit of 0.02% (1:5000 HPV16-positive to HPV16-negative cells), both of which are within the theoretical detection limit for micrometastasis. Thus, HPV E6/E7 oncogenes may be useful targets for the ultrasensitive detection of nodal involvements like micrometastases in fresh or archived tissue samples. Moreover, our results suggest that the biomarker combination of CK19/HPV-E6 could support a real-time intraoperative strategy for the detection of small, but potentially lethal, metastatic nodal involvements in fresh UCC tissues. PMID:29774091

  8. Sensitive molecular detection of small nodal metastasis in uterine cervical cancer using HPV16-E6/CK19/MUC1 cancer biomarkers.

    PubMed

    Samouëlian, Vanessa; Mechtouf, Nawel; Leblanc, Eric; Cardin, Guillaume B; Lhotellier, Valérie; Querleu, Denis; Révillion, Françoise; Rodier, Francis

    2018-04-24

    Metastatic nodal involvement is a critical prognostic factor in uterine cervical cancer (UCC). To improve current methods of detecting UCC metastases in lymph nodes (LNs), we used quantitative PCR (qPCR) to assess mRNA expression of potential metastatic biomarkers. We found that expression of HPV16-E6, cytokeratin19 (CK19), and mucin1 (MUC1) is consistently upregulated in tumors and metastatic tissues, supporting a role for these genes in UCC progression. These putative biomarkers were able to predict the presence of histologically positive metastatic LNs with respective sensitivities and specificities of 82% and 99% (CK19), 76% and 95% (HPV16-E6), and 76% and 78% (MUC1). While the biomarkers failed to detect 1.7% to 2.2% of the histologically positive LNs when used individually, combining CK19 and HPV16-E6 enhanced sensitivity and specificity to 100% and 94%, respectively. To explore the sensitivity of qPCR-based detection of varying proportions of invading HPV16-positive UCC cells, we designed a LN metastasis model that achieved a fresh cell detection limit of 0.008% (1:12500 HPV16-positive to HPV16-negative cells), and a paraffin-embedded, formalin-fixed (PEFF) detection limit of 0.02% (1:5000 HPV16-positive to HPV16-negative cells), both of which are within the theoretical detection limit for micrometastasis. Thus, HPV E6/E7 oncogenes may be useful targets for the ultrasensitive detection of nodal involvements like micrometastases in fresh or archived tissue samples. Moreover, our results suggest that the biomarker combination of CK19/HPV-E6 could support a real-time intraoperative strategy for the detection of small, but potentially lethal, metastatic nodal involvements in fresh UCC tissues.

  9. An Improved Micropropagation Protocol by Ex Vitro Rooting of Passiflora edulis Sims. f. flavicarpa Deg. through Nodal Segment Culture

    PubMed Central

    Shekhawat, Mahipal S.; Manokari, M.; Ravindran, C. P.

    2015-01-01

    A procedure for rapid clonal propagation of Passiflora edulis Sims. f. flavicarpa Deg. (Passifloraceae) has been developed in this study. Nodal explants were sterilized with 0.1% HgCl2 and inoculated on Murashige and Skoog (MS) basal medium. The addition of 2.0 mgL−1 6-benzylaminopurine (BAP) to MS medium caused an extensive proliferation of multiple shoots (8.21 ± 1.13) primordial from the nodal meristems. Subculturing of these multiple shoots on the MS medium augmented with 1.0 mgL−1 of each BAP and Kinetin (Kin) was successful for the multiplication of the shoots in vitro with maximum numbers of shoots (25.73 ± 0.06) within four weeks of incubation. Shoots were rooted best (7.13 ± 0.56 roots/shoots) on half strength MS medium supplemented with 2.0 mgL−1 indole-3 butyric acid (IBA). All in vitro regenerated shoots were rooted by ex vitro method, and this has achieved 6-7 roots per shoot by pulsing of cut ends of the shoots using 200 as well as 300 mgL−1 IBA. The plantlets were hardened in the greenhouse for 4-5 weeks. The hardened plantlets were shifted to manure containing nursery polybags after five weeks and then transferred to a sand bed for another four weeks for acclimatization before field planting with 88% survival rate. PMID:26273489

  10. H9N2 avian influenza transmission and antigenicity

    USDA-ARS?s Scientific Manuscript database

    Low pathogenic H9N2 avian influenza has become endemic in parts of Asia, the Middle East and North Africa causing respiratory disease with occasional mortality. The use of vaccination has become common to try and control the clinical disease, but vaccination has not been shown to be an effective er...

  11. Immunohistochemical assessment of the diagnostic utility of PD-L1: a preliminary analysis of anti-PD-L1 antibody (SP142) for lymphoproliferative diseases with tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells.

    PubMed

    Sakakibara, Ayako; Kohno, Kei; Eladl, Ahmed E; Klaisuwan, Teerada; Ishikawa, Eri; Suzuki, Yuka; Shimada, Satoko; Nakaguro, Masato; Shimoyama, Yoshie; Takahara, Taishi; Kato, Seiichi; Asano, Naoko; Nakamura, Shigeo; Satou, Akira

    2018-06-01

    The programmed death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important role in tumour cells escape from immune control. PD-L1 immunohistochemistry is a useful predictor of immunotherapy response, but is still not used widely in the diagnostic setting. Here we describe results using PD-L1 immunohistochemistry during routine diagnostics in lymphoma. Ninety-one lymphoproliferative disease cases sharing tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells with and without Epstein-Barr virus (EBV) association were investigated by immunohistochemistry for PD-L1 (clone SP142). PD-L1 expression was present in more than 5% of tumour or non-malignant HRS-like cells in 100% of EBV + classical (C) Hodgkin lymphoma (HL) (n = 10) and EBV-negative nodular sclerosis CHL (n = 8); 40% of EBV + diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) (n = 20); and 4% of nodal peripheral T cell lymphoma of follicular helper T cell type (PTCL-TFH) (n = 22). In contrast, nodular lymphocyte-predominant HL (n = 4), lymphocyte-rich CHL (n = 6), EBV + hyperplasia (n = 8), plasmablastic lymphoma (n = 3) and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (n = 5) seldom exhibited PD-L1 in their large cells. Assessing PD-L1 positivity in tumour and non-malignant large cells was helpful in differentiating between CHL versus nodal PTCL-TFH (P < 0.0001) or EBV + DLBCL-NOS (P = 0.0052) and between EBV + DLBCL-NOS versus nodal PTCL-TFH (P = 0.0052), with PD-L1 expression indicating the first diagnosis in each of those sets. Immunohistochemical evaluation of PD-L1 expression in tumour and non-malignant HRS-like large cells may be useful for assessing either immune escape or immunodeficiency in their pathogenesis. © 2018 John Wiley & Sons Ltd.

  12. Toxicity and quality of life after choline-PET/CT directed salvage lymph node dissection and adjuvant radiotherapy in nodal recurrent prostate cancer.

    PubMed

    Jilg, Cordula A; Leifert, Anja; Schnell, Daniel; Kirste, Simon; Volegova-Neher, Natalia; Schlager, Daniel; Wieser, Gesche; Henne, Karl; Schultze-Seemann, Wolfgang; Grosu, Anca-L; Rischke, Hans Christian

    2014-08-12

    In a previous study we demonstrated that, based on 11C/18 F-choline positron emission tomography-computerized-tomography as a diagnostic tool, salvage lymph node dissection (LND) plus adjuvant radiotherapy (ART) is feasible for treatment of pelvic/retroperitoneal nodal recurrence of prostate cancer (PCa). However, the toxicity of this combined treatment strategy has not been systematically investigated before. The aim of the current study was to evaluate the acute and late toxicity and quality of life of ART after LND in pelvic/retroperitoneal nodal recurrent PCa. 43 patients with nodal recurrent PCa were treated with 46 LND followed by ART (mean 49.6 Gy total dose) at the sites of nodal recurrence. Toxicity of ART was analysed by physically examination (31/43, 72.1%), by requesting 15 frequent items of adverse events from the Common-Terminology-Criteria for Adverse Events Version 4.0-catalogue and by review of medical records. QLQ-C30 (EORTC quality of life assessment) and PR25 (prostate cancer module) questionnaires were used to investigate quality of life. Toxicity was evaluated before starting of ART, during ART (acute toxicity), after ART (mean 2.3 months) and at end of follow up (mean 3.2 years after end of ART) reflecting late toxicity. 71.7% (33/46) of 46 ART were treatment of pelvic, 10.9% (5/46) of retroperitoneal only and 28.3% (13/46) of pelvic and retroperitoneal regions. Overall 52 symptoms representing toxicities were observed before ART, 107 during ART, 88 after end of ART and 52 at latest follow up. Leading toxicities during ART were diarrhoea (19%, 20/107), urinary incontinence (16%, 17/107) and fatigue (16%, 17/107). The spectrum of late toxicities was almost equal to those before beginning of ART. No grade 3 adverse events or chronic lymphedema at extremities were observed. We observed no clear correlation between localisation of treated regions, technique of ART and frequency or severity of toxicities. Mean quality of life at final

  13. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer.

    PubMed

    Castro, Elena; Goh, Chee; Olmos, David; Saunders, Ed; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Sawyer, Emma; Wilkinson, Rosemary; Ardern-Jones, Audrey; Ellis, Steve; Frost, Debra; Peock, Susan; Evans, D Gareth; Tischkowitz, Marc; Cole, Trevor; Davidson, Rosemarie; Eccles, Diana; Brewer, Carole; Douglas, Fiona; Porteous, Mary E; Donaldson, Alan; Dorkins, Huw; Izatt, Louise; Cook, Jackie; Hodgson, Shirley; Kennedy, M John; Side, Lucy E; Eason, Jacqueline; Murray, Alex; Antoniou, Antonis C; Easton, Douglas F; Kote-Jarai, Zsofia; Eeles, Rosalind

    2013-05-10

    To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.

  14. Depth of invasion, size and number of metastatic nodes predicts extracapsular spread in early oral cancers with occult metastases.

    PubMed

    Mair, Manish D; Shetty, Rathan; Nair, Deepa; Mathur, Yash; Nair, Sudhir; Deshmukh, Anuja; Thiagarajan, Shiva; Pantvaidya, Gouri; Lashkar, Sarbani; Prabhash, Kumar; Chaukar, Devendra; Pai, Prathmesh; Cruz, Anil D; Chaturvedi, Pankaj

    2018-06-01

    Presence of extracapsular spread (ECS) significantly decreases survival in oral cancer patients. Considering its prognostic impact, we have studied the incidence and factors predicting ECS in clinically node negative early oral cancers. We performed a retrospective chart review of 354 treatment naïve clinically node negative early oral cancer patients operated between 2012 and 2014. Chi-square test and logistic regression were used for identifying predictors of ECS, while cox-regression test was used for survival analysis. The incidence of occult nodal metastasis was 28.5% (101/354). Among them, ECS was seen in 15.3%(54/354) patients. The incidence of ECS in T1 and T2 lesion was 13.4% (21/157) and 16.8% (33/197), respectively. The overall incidence of ECS was 48% and 29% in lymph nodes smaller than 10 mm and 5 mm respectively. We found that tumor depth of invasion (>5 mm; p-0.027) and node (metastatic) size >15 mm (p-0.018) were significant predictors of ECS. p N2b disease was seen in 41/354 (11.6%) of which 31/354 (8.7%) had ECS, i.e. 75.6% of pN2b patients been ECS positive (p-0.000). The 3-year OS of patients without nodal metastasis, nodal metastasis without ECS and nodal metastasis with ECS was 88.4%, 66.9% and 59.2% (p-0.000) respectively. A significant number of patients with metastatic nodal size less than 1 cm have ECS which suggests aggressive behavior of the primary tumor. Thus, elective neck dissection is the only way of detecting ECS in these patients which may warrant treatment intensification. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Programming and Isolation of Highly Pure Physiologically and Pharmacologically Functional Sinus-Nodal Bodies from Pluripotent Stem Cells

    PubMed Central

    Jung, Julia Jeannine; Husse, Britta; Rimmbach, Christian; Krebs, Stefan; Stieber, Juliane; Steinhoff, Gustav; Dendorfer, Andreas; Franz, Wolfgang-Michael; David, Robert

    2014-01-01

    Summary Therapeutic approaches for “sick sinus syndrome” rely on electrical pacemakers, which lack hormone responsiveness and bear hazards such as infection and battery failure. These issues may be overcome via “biological pacemakers” derived from pluripotent stem cells (PSCs). Here, we show that forward programming of PSCs with the nodal cell inducer TBX3 plus an additional Myh6-promoter-based antibiotic selection leads to cardiomyocyte aggregates consisting of >80% physiologically and pharmacologically functional pacemaker cells. These induced sinoatrial bodies (iSABs) exhibited highly increased beating rates (300–400 bpm), coming close to those found in mouse hearts, and were able to robustly pace myocardium ex vivo. Our study introduces iSABs as highly pure, functional nodal tissue that is derived from PSCs and may be important for future cell therapies and drug testing in vitro. PMID:24936448

  16. Prior infection of chickens with H1N1 or H1N2 avian influenza elicits partial heterologous protection against highly pathogenic H5N1.

    PubMed

    Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn

    2012-01-01

    There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70-80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody.

  17. Prior Infection of Chickens with H1N1 or H1N2 Avian Influenza Elicits Partial Heterologous Protection against Highly Pathogenic H5N1

    PubMed Central

    Nfon, Charles; Berhane, Yohannes; Pasick, John; Embury-Hyatt, Carissa; Kobinger, Gary; Kobasa, Darwyn; Babiuk, Shawn

    2012-01-01

    There is a critical need to have vaccines that can protect against emerging pandemic influenza viruses. Commonly used influenza vaccines are killed whole virus that protect against homologous and not heterologous virus. Using chickens we have explored the possibility of using live low pathogenic avian influenza (LPAI) A/goose/AB/223/2005 H1N1 or A/WBS/MB/325/2006 H1N2 to induce immunity against heterologous highly pathogenic avian influenza (HPAI) A/chicken/Vietnam/14/2005 H5N1. H1N1 and H1N2 replicated in chickens but did not cause clinical disease. Following infection, chickens developed nucleoprotein and H1 specific antibodies, and reduced H5N1 plaque size in vitro in the absence of H5 neutralizing antibodies at 21 days post infection (DPI). In addition, heterologous cell mediated immunity (CMI) was demonstrated by antigen-specific proliferation and IFN-γ secretion in PBMCs re-stimulated with H5N1 antigen. Following H5N1 challenge of both pre-infected and naïve controls chickens housed together, all naïve chickens developed acute disease and died while H1N1 or H1N2 pre-infected chickens had reduced clinical disease and 70–80% survived. H1N1 or H1N2 pre-infected chickens were also challenged with H5N1 and naïve chickens placed in the same room one day later. All pre-infected birds were protected from H5N1 challenge but shed infectious virus to naïve contact chickens. However, disease onset, severity and mortality was reduced and delayed in the naïve contacts compared to directly inoculated naïve controls. These results indicate that prior infection with LPAI virus can generate heterologous protection against HPAI H5N1 in the absence of specific H5 antibody. PMID:23240067

  18. Developmental effects of tobacco smoke exposure during human embryonic stem cell differentiation are mediated through the transforming growth factor-β superfamily member, Nodal

    PubMed Central

    Liszewski, Walter; Ritner, Carissa; Aurigui, Julian; Wong, Sharon S. Y.; Hussain, Naveed; Krueger, Winfried; Oncken, Cheryl; Bernstein, Harold S.

    2012-01-01

    While the pathologies associated with in utero smoke exposure are well established, their underlying molecular mechanisms are incompletely understood. We differentiated human embryonic stem cells in the presence of physiological concentrations of tobacco smoke and nicotine. Using post hoc microarray analysis, quantitative PCR, and immunoblot analysis, we demonstrated that tobacco smoke has lineage- and stage-specific effects on human embryonic stem cell differentiation, through both nicotine-dependent and -independent pathways. We show that three major stem cell pluripotency/differentiation pathways, Notch, canonical Wnt, and transforming growth factor-β, are affected by smoke exposure, and that Nodal signaling through SMAD2 is specifically impacted by effects on Lefty1, Nodal, and FoxH1. These events are associated with upregulation of microRNA-302a, a post-transcriptional silencer of Lefty1. The described studies provide insight into the mechanisms by which tobacco smoke influences fetal development at the cellular level, and identify specific transcriptional, post-transcriptional, and signaling pathways by which this likely occurs. PMID:22381624

  19. A study of the radiative transfer equation using a spherical harmonics-nodal collocation method

    NASA Astrophysics Data System (ADS)

    Capilla, M. T.; Talavera, C. F.; Ginestar, D.; Verdú, G.

    2017-03-01

    Optical tomography has found many medical applications that need to know how the photons interact with the different tissues. The majority of the photon transport simulations are done using the diffusion approximation, but this approximation has a limited validity when optical properties of the different tissues present large gradients, when structures near the photons source are studied or when anisotropic scattering has to be taken into account. As an alternative to the diffusion model, the PL equations for the radiative transfer problem are studied. These equations are discretized in a rectangular mesh using a nodal collocation method. The performance of this model is studied by solving different 1D and 2D benchmark problems of light propagation in tissue having media with isotropic and anisotropic scattering.

  20. Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns Tell Us?

    PubMed

    Schweickert, Axel; Ott, Tim; Kurz, Sabrina; Tingler, Melanie; Maerker, Markus; Fuhl, Franziska; Blum, Martin

    2017-12-29

    Laterality of inner organs is a wide-spread characteristic of vertebrates and beyond. It is ultimately controlled by the left-asymmetric activation of the Nodal signaling cascade in the lateral plate mesoderm of the neurula stage embryo, which results from a cilia-driven leftward flow of extracellular fluids at the left-right organizer. This scenario is widely accepted for laterality determination in wildtype specimens. Deviations from this norm come in different flavors. At the level of organ morphogenesis, laterality may be inverted (situs inversus) or non-concordant with respect to the main body axis (situs ambiguus or heterotaxia). At the level of Nodal cascade gene activation, expression may be inverted, bilaterally induced, or absent. In a given genetic situation, patterns may be randomized or predominantly lacking laterality (absence or bilateral activation). We propose that the distributions of patterns observed may be indicative of the underlying molecular defects, with randomizations being primarily caused by defects in the flow-generating ciliary set-up, and symmetrical patterns being the result of impaired flow sensing, on the left, the right, or both sides. This prediction, the reasoning of which is detailed in this review, pinpoints functions of genes whose role in laterality determination have remained obscure.

  1. Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns Tell Us?

    PubMed Central

    Schweickert, Axel; Ott, Tim; Kurz, Sabrina; Tingler, Melanie; Maerker, Markus; Fuhl, Franziska; Blum, Martin

    2017-01-01

    Laterality of inner organs is a wide-spread characteristic of vertebrates and beyond. It is ultimately controlled by the left-asymmetric activation of the Nodal signaling cascade in the lateral plate mesoderm of the neurula stage embryo, which results from a cilia-driven leftward flow of extracellular fluids at the left-right organizer. This scenario is widely accepted for laterality determination in wildtype specimens. Deviations from this norm come in different flavors. At the level of organ morphogenesis, laterality may be inverted (situs inversus) or non-concordant with respect to the main body axis (situs ambiguus or heterotaxia). At the level of Nodal cascade gene activation, expression may be inverted, bilaterally induced, or absent. In a given genetic situation, patterns may be randomized or predominantly lacking laterality (absence or bilateral activation). We propose that the distributions of patterns observed may be indicative of the underlying molecular defects, with randomizations being primarily caused by defects in the flow-generating ciliary set-up, and symmetrical patterns being the result of impaired flow sensing, on the left, the right, or both sides. This prediction, the reasoning of which is detailed in this review, pinpoints functions of genes whose role in laterality determination have remained obscure. PMID:29367579

  2. Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression.

    PubMed

    Santos, Rosângela Portilho Costa; Benvenuti, Ticiana Thomazine; Honda, Suzana Terumi; Del Valle, Paulo Roberto; Katayama, Maria Lucia Hirata; Brentani, Helena Paula; Carraro, Dirce Maria; Rozenchan, Patrícia Bortman; Brentani, Maria Mitzi; de Lyra, Eduardo Carneiro; Torres, César Henrique; Salzgeber, Marcia Batista; Kaiano, Jane Haruko Lima; Góes, João Carlos Sampaio; Folgueira, Maria Aparecida Azevedo Koike

    2011-02-01

    Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor.

  3. Is there a role for pre-operative contrast-enhanced magnetic resonance imaging for radical surgery in malignant pleural mesothelioma?

    PubMed

    Stewart, Duncan; Waller, David; Edwards, John; Jeyapalan, Kanagaratnam; Entwisle, James

    2003-12-01

    To assess the use of contrast-enhanced magnetic resonance imaging (CEMRI) in addition to computed tomography in the pre-operative assessment of patients for radical surgery in malignant pleural mesothelioma. Over a 45-month period, 51 of 76 patients assessed (69 men and seven women), underwent extra-pleural pneumonectomy or radical pleurectomy/decortication. Post-operative pathological stage was correlated with radiological staging, with particular emphasis on tumour resectability. Seventeen (22%) patients were found on CEMRI to have unresectable, but histologically unconfirmed disease, not previously seen on CT. Fifty-one (67%) patients proceeded to radical surgery, but pathological nodal data were incomplete in three, so excluding these patients from further analyses. The median pre-operative interval after CEMRI was 17 days. Two patients were found to have unexpectedly extensive disease at thoracotomy, thus the sensitivity of CEMRI for prediction of resectability was 97%. Using the International Mesothelioma Interest Group system, tumour stage was correctly predicted by CEMRI in 48% of patients, but understaged in 50% of cases, largely due to the underestimation of pericardial involvement, but this did not affect resectability and had no significant effect on prognosis. Nodal stage was correctly identified in 60% of patients. CEMRI was successful in predicting pathological tumour stage T3 or less (sensitivity of 85%; specificity of 100%), but less so in identifying tumour stage T2 or less (sensitivity of 23%; specificity of 96%) or N2 nodal disease (sensitivity 66%; specificity 73%). CEMRI is most useful in the differentiation of T3 and T4 disease and may be unnecessary at earlier stages. Its multiplanar tumour localisation abilities are of value in the assessment of resectability. It is unlikely to contribute significantly to nodal staging, but it remains a valuable adjunct in the selection of patients for radical surgery.

  4. Preparation of mucosal nanoparticles and polymer-based inactivated vaccine for Newcastle disease and H9N2 AI viruses

    PubMed Central

    Naggar, Heba M. El; Madkour, Mohamed Sayed; Hussein, Hussein Ali

    2017-01-01

    Aim: To develop a mucosal inactivated vaccines for Newcastle disease (ND) and H9N2 viruses to protect against these viruses at sites of infections through mucosal immunity. Materials and Methods: In this study, we prepared two new formulations for mucosal bivalent inactivated vaccine formulations for Newcastle and Avian Influenza (H9N2) based on the use of nanoparticles and polymer adjuvants. The prepared vaccines were delivered via intranasal and spray routes of administration in specific pathogen-free chickens. Cell-mediated and humoral immune response was measured as well as challenge trial was carried out. In addition, ISA71 water in oil was also evaluated. Results: Our results showed that the use of spray route as vaccination delivery method of polymer and nanoparticles Montanide™ adjuvants revealed that it enhanced the cell mediated immune response as indicated by phagocytic activity, gamma interferon and interleukin 6 responses and induced protection against challenge with Newcastle and Avian Influenza (H9N2) viruses. Conclusion: The results of this study demonstrate the potentiality of polymer compared to nanoparticles adjuvantes when used via spray route. Mass application of such vaccines will add value to improve the vaccination strategies against ND virus and Avian influenza viruses. PMID:28344402

  5. Clinical features of patients with nodal marginal zone lymphoma compared to follicular lymphoma: similar presentation, but differences in prognostic factors and rate of transformation.

    PubMed

    van den Brand, Michiel; van der Velden, Walter J F M; Diets, Illja J; Ector, Geneviève I C G; de Haan, Anton F J; Stevens, Wendy B C; Hebeda, Konnie M; Groenen, Patricia J T A; van Krieken, Han J M

    2016-07-01

    Nodal marginal zone lymphoma (NMZL) is a rare type of B-cell non-Hodgkin lymphoma. This study assessed the clinical features of 56 patients with NMZL in comparison to 46 patients with follicular lymphoma (FL). Patients with NMZL and FL had a largely similar clinical presentation, but patients with FL had a higher disease stage at presentation, more frequent abdominal lymphadenopathy and bone marrow involvement, and showed more common transformation into diffuse large B-cell lymphoma (DLBCL) during the course of disease. Overall survival and event-free survival were similar for patients with NMZL and FL, but factors associated with worse prognosis differed between the two groups. Transformation into DLBCL was associated with a significantly poorer outcome in both groups, but the phenotypes were different: DLBCL arising in FL was mainly of germinal center B-cell phenotype, whereas DLBCL arising in NMZL was mainly of non-germinal center B-cell phenotype.

  6. A case of nodal malignant lymphoma presenting with arterial bleeding related to its duodenal penetration.

    PubMed

    Miyake, Takakazu; Iida, Tomoya; Masaki, Yoshiharu; Onodera, Kei; Kubo, Toshiyuki; Yamashita, Kentaro; Yamano, Hiroo; Nakase, Hiroshi

    2018-06-01

    A 62-year-old man with a chief complaint of dysphagia visited our hospital. Enhanced computed tomography showed the tumor near the duodenal wall and lymphadenopathy in the left supraclavicular fossa and para-aortic lymph node. Upper gastrointestinal endoscopy showed an ulcer accompanied with a fistula in the anterior wall of duodenal bulb, suggesting that the tumor penetrated into duodenal wall. Biopsy from the lymph node in the left supraclavicular fossa indicated diffuse large B-cell lymphoma. Although chemotherapy was planned, massive arterial bleeding occurred from the part of duodenal penetration. Endoscopic hemostasis was unsuccessfully performed. Therefore, we performed transcathether arterial embolization for hemostasis. After the procedure, the patient received six cycles of chemotherapy, and he achieved complete response. He has been alive 5 years without recurrence. There were many cases of gastrointestinal bleeding from primary gastrointestinal lymphomas, while there were few cases with nodal involvement by malignant lymphoma resulting in bleeding from gastrointestinal tract. We herein report a case of duodenal bleeding by nodal involvement of diffuse large B-cell lymphoma with review of literature.

  7. Presence of DQ2.2 Associated with DQ2.5 Increases the Risk for Celiac Disease

    PubMed Central

    Almeida, Lucas Malta; Gandolfi, Lenora; Pratesi, Riccardo; Uenishi, Rosa Harumi; de Almeida, Fernanda Coutinho; Selleski, Nicole

    2016-01-01

    Background. Celiac disease (CD) is a genetically determined immune-mediated disorder in which gluten immunogenic peptides are presented to CD4 T cells by HLA-DQ2.5, DQ8, DQ2.2, and their combinations. Our aim is to establish a risk gradient for celiac disease based on HLA-DQ profile in a brazilian representative population and the relevance of DQ2.2 in celiac disease development. Materials and Methods. 237 celiac patients and 237 controls (both groups with 164 females and 73 males) were included. All samples were tested for the presence of predisposing HLA-DQ alleles using the PCR-SSP method. Results were considered significant when p < 0.05. Disease risk was expressed as 1 : N for each HLA-DQ category described at this study. Results. DQ2.5 and/or DQ8 were detected in 224 celiac patients (94.5%) and 84 controls (35.4%). Eight celiac patients (3.4%) and 38 controls (16%) disclosed only DQ2.2. Even though DQ2.222 or β2/x) showed a low CD risk of 1 : 251 and 1 : 550, respectively, the genotype DQ2.5/DQ2.222) showed high CD risk of 1 : 10 (p < 0.0001). The disease risk gradient ranged from 1 : 3014 to 1 : 7. Conclusion. Our study allowed the determination of a risk gradient for celiac disease development in at-risk population, showing that DQ2.2 variant was relevant when associated with DQ2.5. PMID:28042478

  8. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease.

    PubMed

    Khurana, Surender; Loving, Crystal L; Manischewitz, Jody; King, Lisa R; Gauger, Phillip C; Henningson, Jamie; Vincent, Amy L; Golding, Hana

    2013-08-28

    Vaccine-induced disease enhancement has been described in connection with several viral vaccines in animal models and in humans. We investigated a swine model to evaluate mismatched influenza vaccine-associated enhanced respiratory disease (VAERD) after pH1N1 infection. Vaccinating pigs with whole inactivated H1N2 (human-like) virus vaccine (WIV-H1N2) resulted in enhanced pneumonia and disease after pH1N1 infection. WIV-H1N2 immune sera contained high titers of cross-reactive anti-pH1N1 hemagglutinin (HA) antibodies that bound exclusively to the HA2 domain but not to the HA1 globular head. No hemagglutination inhibition titers against pH1N1 (challenge virus) were measured. Epitope mapping using phage display library identified the immunodominant epitope recognized by WIV-H1N2 immune sera as amino acids 32 to 77 of pH1N1-HA2 domain, close to the fusion peptide. These cross-reactive anti-HA2 antibodies enhanced pH1N1 infection of Madin-Darby canine kidney cells by promoting virus membrane fusion activity. The enhanced fusion activity correlated with lung pathology in pigs. This study suggests a role for fusion-enhancing anti-HA2 antibodies in VAERD, in the absence of receptor-blocking virus-neutralizing antibodies. These findings should be considered during the evaluation of universal influenza vaccines designed to elicit HA2 stem-targeting antibodies.

  9. Infrared spectra of N2O-(ortho-D2)N and N2O-(HD)N clusters trapped in bulk solid parahydrogen.

    PubMed

    Lorenz, Britney D; Anderson, David T

    2007-05-14

    High-resolution infrared spectra of the clusters N2O-(ortho-D2)N and N2O-(HD)N, N=1-4, isolated in bulk solid parahydrogen at liquid helium temperatures are studied in the 2225 cm-1 region of the nu3 antisymmetric stretch of N2O. The clusters form during vapor deposition of separate gas streams of a precooled hydrogen mixture (ortho-D2para-H2 or HDpara-H2) and N2O onto a BaF2 optical substrate held at approximately 2.5 K in a sample-in-vacuum liquid helium cryostat. The cluster spectra reveal the N2O nu3 vibrational frequency shifts to higher energy as a function of N, and the shifts are larger for ortho-D2 compared to HD. These vibrational shifts result from the reduced translational zero-point energy for N2O solvated by the heavier hydrogen isotopomers. These spectra allow the N=0 peak at 2221.634 cm-1, corresponding to the nu3 vibrational frequency of N2O isolated in pure solid parahydrogen, to be assigned. The intensity of the N=0 absorption feature displays a strong temperature dependence, suggesting that significant structural changes occur in the parahydrogen solvation environment of N2O in the 1.8-4.9 K temperature range studied.

  10. Simple vector bundles on a nodal Weierstrass cubic and quasi-trigonometric solutions of the classical Yang-Baxter equation

    NASA Astrophysics Data System (ADS)

    Burban, Igor; Galinat, Lennart; Stolin, Alexander

    2017-11-01

    In this paper we study the combinatorics of quasi-trigonometric solutions of the classical Yang-Baxter equation, arising from simple vector bundles on a nodal Weierstraß cubic. Dedicated to the memory of Petr Petrovich Kulish.

  11. Intensity-Modulated Proton Therapy for Elective Nodal Irradiation and Involved-Field Radiation in the Definitive Treatment of Locally Advanced Non-Small Cell Lung Cancer: A Dosimetric Study

    PubMed Central

    Kesarwala, Aparna H.; Ko, Christine J.; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E.; O’Meara, William P.; Simone, Charles B.; Rengan, Ramesh

    2015-01-01

    Background Photon involved-field radiation therapy (IFRT), the standard for locally advanced non-small cell lung cancer (LA-NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Given the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. Materials and Methods IMPT IFRT plans were generated to the same total dose of 66.6–72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 CGE to elective nodal (EN) planning treatment volumes (PTV) plus 24 CGE to involved field (IF)-PTVs. Results Proton IFRT and ENI both improved D95 involved field (IF)-PTV coverage by 4% (p<0.01) compared to photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. Lung V20 and mean lung dose decreased 18% (p<0.01) and 36% (p<0.01), respectively, with proton IFRT and 11% (p=0.03) and 26% (p<0.01) with ENI. Mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all p<0.01). Conclusions This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates IMPT could allow ENI while maintaining a favorable therapeutic ratio compared to photon IFRT. PMID:25604729

  12. Intensity-modulated proton therapy for elective nodal irradiation and involved-field radiation in the definitive treatment of locally advanced non-small-cell lung cancer: a dosimetric study.

    PubMed

    Kesarwala, Aparna H; Ko, Christine J; Ning, Holly; Xanthopoulos, Eric; Haglund, Karl E; O'Meara, William P; Simone, Charles B; Rengan, Ramesh

    2015-05-01

    Photon involved-field (IF) radiation therapy (IFRT), the standard for locally advanced (LA) non-small cell lung cancer (NSCLC), results in favorable outcomes without increased isolated nodal failures, perhaps from scattered dose to elective nodal stations. Because of the high conformality of intensity-modulated proton therapy (IMPT), proton IFRT could increase nodal failures. We investigated the feasibility of IMPT for elective nodal irradiation (ENI) in LA-NSCLC. IMPT IFRT plans were generated to the same total dose of 66.6-72 Gy received by 20 LA-NSCLC patients treated with photon IFRT. IMPT ENI plans were generated to 46 cobalt Gray equivalent (CGE) to elective nodal planning treatment volumes (PTV) plus 24 CGE to IF-PTVs. Proton IFRT and ENI improved the IF-PTV percentage of volume receiving 95% of the prescribed dose (D95) by 4% (P < .01) compared with photon IFRT. All evaluated dosimetric parameters improved significantly with both proton plans. The lung percentage of volume receiving 20 Gy/CGE (V20) and mean lung dose decreased 18% (P < .01) and 36% (P < .01), respectively, with proton IFRT, and 11% (P = .03) and 26% (P < .01) with ENI. The mean esophagus dose decreased 16% with IFRT and 12% with ENI; heart V25 decreased 63% with both (all P < .01). This study demonstrates the feasibility of IMPT for LA-NSCLC ENI. Potential decreased toxicity indicates that IMPT could allow ENI while maintaining a favorable therapeutic ratio compared with photon IFRT. Published by Elsevier Inc.

  13. Can Axial-Based Nodal Size Criteria Be Used in Other Imaging Planes to Accurately Determine “Enlarged” Head and Neck Lymph Nodes?

    PubMed Central

    Bartlett, Eric S.; Walters, Thomas D.; Yu, Eugene

    2013-01-01

    Objective. We evaluate if axial-based lymph node size criteria can be applied to coronal and sagittal planes. Methods. Fifty pretreatment computed tomographic (CT) neck exams were evaluated in patients with head and neck squamous cell carcinoma (SCCa) and neck lymphadenopathy. Axial-based size criteria were applied to all 3 imaging planes, measured, and classified as “enlarged” if equal to or exceeding size criteria. Results. 222 lymph nodes were “enlarged” in one imaging plane; however, 53.2% (118/222) of these were “enlarged” in all 3 planes. Classification concordance between axial versus coronal/sagittal planes was poor (kappa = −0.09 and −0.07, resp., P < 0.05). The McNemar test showed systematic misclassification when comparing axial versus coronal (P < 0.001) and axial versus sagittal (P < 0.001) planes. Conclusion. Classification of “enlarged” lymph nodes differs between axial versus coronal/sagittal imaging planes when axial-based nodal size criteria are applied independently to all three imaging planes, and exclusively used without other morphologic nodal data. PMID:23984099

  14. Functional properties of LRRK2 mutations in Taiwanese Parkinson disease.

    PubMed

    Chang, Kuo-Hsuan; Chen, Chiung-Mei; Lin, Chih-Hsin; Chang, Wen-Teng; Jiang, Pei-Ru; Hsiao, Ya-Chin; Wu, Yih-Ru; Lee-Chen, Guey-Jen

    2017-03-01

    Leucine-rich repeat kinase 2 (LRRK2) is a large protein encoding multiple functional domains. Mutations within different LRRK2 domains have been considered to be involved in the development of Parkinson disease by different mechanisms. Our previous study found three LRRK2 mutations-p.R767H, p.S885N, and p.R1441H-in Taiwanese patients with Parkinson disease. We evaluated the functional properties of LRRK2 p.R767H, p.S885N, and p.R1441H mutations by overexpressing them in human embryonic kidney 293 and neuroblastoma SK-N-SH cells. The common p.G2019S mutation in the kinase domain was included for comparison. In 293 cells, overexpressed p.R1441H-but not p.R767H, p.S885N, or p.G2019-increased GTP binding affinity to prolong the active state. Overexpressed p.R1441H and p.G2019S generated inclusions in 293 cells. In SK-N-SH cells, the α-synuclein was coexpressed with wild type as well as mutated p.R767H, p.S885N, p.R1441H, and p.G2019 LRRK2 proteins. Part of the perinuclear inclusions formed by p.R1441H and p.G2019S were colocalized with α-synuclein. Additionally, p.S885N and p.R1441H mutations caused reduced interaction between LRRK2 and ARHGEF7, a putative guanine nucleotide exchange factor for LRRK2, whereas this interaction was well preserved in p.R767H and p.G2019S mutations. Our study suggests that p.R1441H protein facilitates the formation of intracellular inclusions, compromises GTP hydrolysis by increasing its affinity for GTP, and reduces its interaction with ARHGEF7. Copyright © 2016. Published by Elsevier B.V.

  15. Nodal Analysis Optimization Based on the Use of Virtual Current Sources: A Powerful New Pedagogical Method

    ERIC Educational Resources Information Center

    Chatzarakis, G. E.

    2009-01-01

    This paper presents a new pedagogical method for nodal analysis optimization based on the use of virtual current sources, applicable to any linear electric circuit (LEC), regardless of its complexity. The proposed method leads to straightforward solutions, mostly arrived at by inspection. Furthermore, the method is easily adapted to computer…

  16. The First Molybdenum(VI) and Tungsten(VI) Oxoazides MO2(N3)2, MO2(N3)22 CH3CN, (bipy)MO2(N3)2, and [MO2(N3)4](2-) (M=Mo, W).

    PubMed

    Haiges, Ralf; Skotnitzki, Juri; Fang, Zongtang; Dixon, David A; Christe, Karl O

    2015-08-10

    Molybdenum(VI) and tungsten(VI) dioxodiazide, MO2(N3)2 (M=Mo, W), were prepared through fluoride-azide exchange reactions between MO2F2 and Me3SiN3 in SO2 solution. In acetonitrile solution, the fluoride-azide exchange resulted in the isolation of the adducts MO2(N3)22 CH3CN. The subsequent reaction of MO2(N3)2 with 2,2'-bipyridine (bipy) gave the bipyridine adducts (bipy)MO2(N3)2. The hydrolysis of (bipy)MoO2(N3)2 resulted in the formation and isolation of [(bipy)MoO2N3]2O. The tetraazido anions [MO2(N3)4](2-) were obtained by the reaction of MO2(N3)2 with two equivalents of ionic azide. Most molybdenum(VI) and tungsten(VI) dioxoazides were fully characterized by their vibrational spectra, impact, friction, and thermal sensitivity data and, in the case of (bipy)MoO2(N3)2, (bipy)WO2(N3)2, [PPh4]2[MoO2(N3)4], [PPh4]2[WO2(N3)4], and [(bipy)MoO2N3]2O by their X-ray crystal structures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease.

    PubMed

    Anguiano, Lidia; Riera, Marta; Pascual, Julio; Valdivielso, José Manuel; Barrios, Clara; Betriu, Angels; Mojal, Sergi; Fernández, Elvira; Soler, María José

    2015-07-01

    Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc

  18. Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer

    PubMed Central

    Castro, Elena; Goh, Chee; Olmos, David; Saunders, Ed; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Sawyer, Emma; Wilkinson, Rosemary; Ardern-Jones, Audrey; Ellis, Steve; Frost, Debra; Peock, Susan; Evans, D. Gareth; Tischkowitz, Marc; Cole, Trevor; Davidson, Rosemarie; Eccles, Diana; Brewer, Carole; Douglas, Fiona; Porteous, Mary E.; Donaldson, Alan; Dorkins, Huw; Izatt, Louise; Cook, Jackie; Hodgson, Shirley; Kennedy, M. John; Side, Lucy E.; Eason, Jacqueline; Murray, Alex; Antoniou, Antonis C.; Easton, Douglas F.; Kote-Jarai, Zsofia; Eeles, Rosalind

    2013-01-01

    Purpose To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. Patients and Methods This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). Results PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Conclusion Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients. PMID:23569316

  19. The CD200-tolerance signaling molecule associated with pregnancy success is present in patients with early-stage breast cancer but does not favor nodal metastasis.

    PubMed

    Clark, David A; Dhesy-Thind, Sukhbinder; Ellis, Peter; Ramsay, Jennifer

    2014-11-01

    The CD200-tolerance signaling molecule prevents pregnancy failure and is also expressed by a wide variety of malignant tumors. The effect of CD200 mRNA expression on progression of human tumors has been variable. A cross-sectional study was performed to examine the correlation between CD200 protein expression in the primary tumors from postoperative Stage I-IIIA human breast cancer and the likelihood of regional lymph node metastasis. Fifty-eight percentage of patients had strong CD200(+) tumor staining (71% of Stage I and 53% Stage II-IIIA). Strong staining was associated with large T2-3 primary tumors compared to T1 tumors (64 versus 50%) and T2-3 N(+) versus T1 N(-) tumors (70 versus 63%), but this was not statistically significant. Nodal metastases were not more frequent in patients with strong CD200(+) staining (57% compared to 58% for weak/negative staining cases), and the metastatic tumor cells in regional lymph nodes were often CD200(-) when the primary tumor was CD200(+). CD200 expression by early-stage human breast cancer cells in primary tumors did not correlate with increased regional lymph node metastasis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Selective Encaging of N2O in N2O-N2 Binary Gas Hydrates via Hydrate-Based Gas Separation.

    PubMed

    Yang, Youjeong; Shin, Donghoon; Choi, Seunghyun; Woo, Yesol; Lee, Jong-Won; Kim, Dongseon; Shin, Hee-Young; Cha, Minjun; Yoon, Ji-Ho

    2017-03-21

    The crystal structure and guest inclusion behaviors of nitrous oxide-nitrogen (N 2 O-N 2 ) binary gas hydrates formed from N 2 O/N 2 gas mixtures are determined through spectroscopic analysis. Powder X-ray diffraction results indicate that the crystal structure of all the N 2 O-N 2 binary gas hydrates is identified as the structure I (sI) hydrate. Raman spectra for the N 2 O-N 2 binary gas hydrate formed from N 2 O/N 2 (80/20, 60/40, 40/60 mol %) gas mixtures reveal that N 2 O molecules occupy both large and small cages of the sI hydrate. In contrast, there is a single Raman band of N 2 O molecules for the N 2 O-N 2 binary gas hydrate formed from the N 2 O/N 2 (20/80 mol %) gas mixture, indicating that N 2 O molecules are trapped in only large cages of the sI hydrate. From temperature-dependent Raman spectra and the Predictive Soave-Redlich-Kwong (PSRK) model calculation, we confirm the self-preservation of N 2 O-N 2 binary gas hydrates in the temperature range of 210-270 K. Both the experimental measurements and the PSRK model calculations demonstrate the preferential occupation of N 2 O molecules rather than N 2 molecules in the hydrate cages, leading to a possible process for separating N 2 O from gas mixtures via hydrate formation. The phase equilibrium conditions, pseudo-pressure-composition (P-x) diagram, and gas storage capacity of N 2 O-N 2 binary gas hydrates are discussed in detail.

  1. SU-F-P-52: A Meta-Analysis of Controlled Clinical Trials Comparing Elective Nodal Irradiation with Involved-Field Irradiation for Conformal Or Intensity-Modulated Radiotherapy in Patients with Esophageal Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bai, W; Zhang, R; Zhou, Z

    Purpose: To compare elective nodal irradiation with involved-field irradiation for three-dimensional conformal radiotherapy or intensity-modulated radiotherapy in patients with esophageal cancer by a metaanalysis. Methods: Wanfang, CNKI, VIP, CBM databases, PubMed, Embase and Cochrane Library were searched to identify the controlled clinical trials of elective nodal irradiation with involved-field irradiation for three-dimensional conformal radiotherapy or intensity-modulated radiotherapy in patients with esophageal cancer. The obtained data were analyzed using Stata 11.0. The difference between two groups was estimated by calculating the odds ratio (OR) with 95% confidence interval (95% CI). Results: A total of 12 controlled clinical trials involving 1095 esophagealmore » cancer patients, which were selected according to inclusion and exclusion criteria, were included in this meta-analysis. The meta-analysis showed that the elective nodal irradiation group reduced the rates of out-field failure comparing with involved-field irradiation group (OR=3.727, P=0.007). However, the rates of ≥grades 3 acute radiation pneumonitis and esophagitis were significantly higher in the elective nodal irradiation group than in the involved-field irradiation group (OR=0.348, P=0.001, OR=0.385, P=0.000). 1-, 2-, 3-year local control rates (OR=0.966, P=0.837, OR=0.946, P=0.781; OR=0.732P=0.098) and 1-, 3-, 5-year survival rates were similar in the two groups ( OR=0.966, P=0.837; OR=0.946, P=0.781; OR=0.732, P=0.098; OR=0.952, P=0.756; OR=1.149, P=0.422; OR=0.768, P=0.120). It is the same with the rates of distant metastasis (OR=0.986, P=0.937). Conclusion: Compared with involved-field irradiation, the elective nodal irradiation can reduce the rates of out-field failure for three-dimensional conformal radiotherapy or intensity-modulated radiotherapy in patients with esophageal cancer. However, its advantage of local control and survival rates is not obvious and it increases the

  2. Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression

    PubMed Central

    Santos, Rosângela Portilho Costa; Benvenuti, Ticiana Thomazine; Honda, Suzana Terumi; Del Valle, Paulo Roberto; Katayama, Maria Lucia Hirata; Brentani, Helena Paula; Carraro, Dirce Maria; Rozenchan, Patrícia Bortman; Brentani, Maria Mitzi; de Lyra, Eduardo Carneiro; Torres, César Henrique; Salzgeber, Marcia Batista; Kaiano, Jane Haruko Lima; Góes, João Carlos Sampaio

    2010-01-01

    Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor. Electronic supplementary material The online version of this article (doi:10.1007/s13277-010-0108-7) contains supplementary material, which is available to authorized users. PMID:20820980

  3. Delineation of Supraclavicular Target Volumes in Breast Cancer Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brown, Lindsay C.; Diehn, Felix E.; Boughey, Judy C.

    Purpose: To map the location of gross supraclavicular metastases in patients with breast cancer, in order to determine areas at highest risk of harboring subclinical disease. Methods and Materials: Patients with axial imaging of gross supraclavicular disease were identified from an institutional breast cancer registry. Locations of the metastatic lymph nodes were transferred onto representative axial computed tomography images of the supraclavicular region and compared with the Radiation Therapy Oncology Group (RTOG) breast cancer atlas for radiation therapy planning. Results: Sixty-two patients with 161 supraclavicular nodal metastases were eligible for study inclusion. At the time of diagnosis, 117 nodal metastasesmore » were present in 44 patients. Forty-four nodal metastases in 18 patients were detected at disease recurrence, 4 of whom had received prior radiation to the supraclavicular fossa. Of the 161 nodal metastases, 95 (59%) were within the RTOG consensus volume, 4 nodal metastases (2%) in 3 patients were marginally within the volume, and 62 nodal metastases (39%) in 30 patients were outside the volume. Supraclavicular disease outside the RTOG consensus volume was located in 3 regions: at the level of the cricoid and thyroid cartilage (superior to the RTOG volume), in the posterolateral supraclavicular fossa (posterolateral to the RTOG volume), and in the lateral low supraclavicular fossa (lateral to the RTOG volume). Only women with multiple supraclavicular metastases had nodal disease that extended superiorly to the level of the thyroid cartilage. Conclusions: For women with risk of harboring subclinical supraclavicular disease warranting the addition of supraclavicular radiation, coverage of the posterior triangle and the lateral low supraclavicular region should be considered. For women with known supraclavicular disease, extension of neck coverage superior to the cricoid cartilage may be warranted.« less

  4. Histogram Analysis of Apparent Diffusion Coefficients for Occult Tonsil Cancer in Patients with Cervical Nodal Metastasis from an Unknown Primary Site at Presentation.

    PubMed

    Choi, Young Jun; Lee, Jeong Hyun; Kim, Hye Ok; Kim, Dae Yoon; Yoon, Ra Gyoung; Cho, So Hyun; Koh, Myeong Ju; Kim, Namkug; Kim, Sang Yoon; Baek, Jung Hwan

    2016-01-01

    To explore the added value of histogram analysis of apparent diffusion coefficient (ADC) values over magnetic resonance (MR) imaging and fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) for the detection of occult palatine tonsil squamous cell carcinoma (SCC) in patients with cervical nodal metastasis from a cancer of an unknown primary site. The institutional review board approved this retrospective study, and the requirement for informed consent was waived. Differences in the bimodal histogram parameters of the ADC values were assessed among occult palatine tonsil SCC (n = 19), overt palatine tonsil SCC (n = 20), and normal palatine tonsils (n = 20). One-way analysis of variance was used to analyze differences among the three groups. Receiver operating characteristic curve analysis was used to determine the best differentiating parameters. The increased sensitivity of histogram analysis over MR imaging and (18)F-FDG PET/CT for the detection of occult palatine tonsil SCC was evaluated as added value. Histogram analysis showed statistically significant differences in the mean, standard deviation, and 50th and 90th percentile ADC values among the three groups (P < .0045). Occult palatine tonsil SCC had a significantly higher standard deviation for the overall curves, mean and standard deviation of the higher curves, and 90th percentile ADC value, compared with normal palatine tonsils (P < .0167). Receiver operating characteristic curve analysis showed that the standard deviation of the overall curve best delineated occult palatine tonsil SCC from normal palatine tonsils, with a sensitivity of 78.9% (15 of 19 patients) and a specificity of 60% (12 of 20 patients). The added value of ADC histogram analysis was 52.6% over MR imaging alone and 15.8% over combined conventional MR imaging and (18)F-FDG PET/CT. Adding ADC histogram analysis to conventional MR imaging can improve the detection sensitivity for occult

  5. Long-time stability effects of quadrature and artificial viscosity on nodal discontinuous Galerkin methods for gas dynamics

    NASA Astrophysics Data System (ADS)

    Durant, Bradford; Hackl, Jason; Balachandar, Sivaramakrishnan

    2017-11-01

    Nodal discontinuous Galerkin schemes present an attractive approach to robust high-order solution of the equations of fluid mechanics, but remain accompanied by subtle challenges in their consistent stabilization. The effect of quadrature choices (full mass matrix vs spectral elements), over-integration to manage aliasing errors, and explicit artificial viscosity on the numerical solution of a steady homentropic vortex are assessed over a wide range of resolutions and polynomial orders using quadrilateral elements. In both stagnant and advected vortices in periodic and non-periodic domains the need arises for explicit stabilization beyond the numerical surface fluxes of discontinuous Galerkin spectral elements. Artificial viscosity via the entropy viscosity method is assessed as a stabilizing mechanism. It is shown that the regularity of the artificial viscosity field is essential to its use for long-time stabilization of small-scale features in nodal discontinuous Galerkin solutions of the Euler equations of gas dynamics. Supported by the Department of Energy Predictive Science Academic Alliance Program Contract DE-NA0002378.

  6. Preoperative N Staging of Gastric Cancer by Stomach Protocol Computed Tomography

    PubMed Central

    Kim, Se Hoon; Kim, Jeong Jae; Lee, Jeong Sub; Kim, Seung Hyoung; Kim, Bong Soo; Maeng, Young Hee; Hyun, Chang Lim; Kim, Min Jeong

    2013-01-01

    Purpose Clinical stage of gastric cancer is currently assessed by computed tomography. Accurate clinical staging is important for the tailoring of therapy. This study evaluated the accuracy of clinical N staging using stomach protocol computed tomography. Materials and Methods Between March 2004 and November 2012, 171 patients with gastric cancer underwent preoperative stomach protocol computed tomography (Jeju National University Hospital; Jeju, Korea). Their demographic and clinical characteristics were reviewed retrospectively. Two radiologists evaluated cN staging using axial and coronal computed tomography images, and cN stage was matched with pathologic results. The diagnostic accuracy of stomach protocol computed tomography for clinical N staging and clinical characteristics associated with diagnostic accuracy were evaluated. Results The overall accuracy of stomach protocol computed tomography for cN staging was 63.2%. Computed tomography images of slice thickness 3.0 mm had a sensitivity of 60.0%; a specificity of 89.6%; an accuracy of 78.4%; and a positive predictive value of 78.0% in detecting lymph node metastases. Underestimation of cN stage was associated with larger tumor size (P<0.001), undifferentiated type (P=0.003), diffuse type (P=0.020), more advanced pathologic stage (P<0.001), and larger numbers of harvested and metastatic lymph nodes (P<0.001 each). Tumor differentiation was an independent factor affecting underestimation by computed tomography (P=0.045). Conclusions Computed tomography with a size criterion of 8 mm is highly specific but relatively insensitive in detecting nodal metastases. Physicians should keep in mind that computed tomography may not be an appropriate tool to detect nodal metastases for choosing appropriate treatment. PMID:24156034

  7. Therapeutic potential of n-3 polyunsaturated fatty acids in disease.

    PubMed

    Fetterman, James W; Zdanowicz, Martin M

    2009-07-01

    The potential therapeutic benefits of supplementation with n-3 polyunsaturated fatty acids (PUFAs) in various diseases are reviewed, and the antiinflammatory actions, activity, and potential drug interactions and adverse effects of n-3 PUFAs are discussed. Fish oils are an excellent source of long-chain n-3 PUFAs, such as eicosapentaenoic acid and docosahexaenoic acid. After consumption, n-3 PUFAs can be incorporated into cell membranes and reduce the amount of arachidonic acid available for the synthesis of proinflammatory eicosanoids (e.g., prostaglandins, leukotrienes). Likewise, n-3 PUFAs can also reduce the production of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1, and interleukin-6. Considerable research has been conducted to evaluate the potential therapeutic effects of fish oils in numerous conditions, including arthritis, coronary artery disease, inflammatory bowel disease, asthma, and sepsis, all of which have inflammation as a key component of their pathology. Additional investigations into the use of supplementation with fish oils in patients with neural injury, cancer, ocular diseases, and critical illness have recently been conducted. The most commonly reported adverse effects of fish oil supplements are a fishy aftertaste and gastrointestinal upset. When recommending an n-3 PUFA, clinicians should be aware of any possible adverse effect or drug interaction that, although not necessarily clinically significant, may occur, especially for patients who may be susceptible to increased bleeding (e.g., patients taking warfarin). The n-3 PUFAs have been shown to be efficacious in treating and preventing various diseases. The wide variation in dosages and formulations used in studies makes it difficult to recommend dosages for specific treatment goals.

  8. Nodal bilayer-splitting controlled by spin-orbit interactions in underdoped high-T c cuprates

    DOE PAGES

    Harrison, N.; Ramshaw, B. J.; Shekhter, A.

    2015-06-03

    The highest superconducting transition temperatures in the cuprates are achieved in bilayer and trilayer systems, highlighting the importance of interlayer interactions for high T c. It has been argued that interlayer hybridization vanishes along the nodal directions by way of a specific pattern of orbital overlap. Recent quantum oscillation measurements in bilayer cuprates have provided evidence for a residual bilayer-splitting at the nodes that is sufficiently small to enable magnetic breakdown tunneling at the nodes. Here we show that several key features of the experimental data can be understood in terms of weak spin-orbit interactions naturally present in bilayer systems,more » whose primary effect is to cause the magnetic breakdown to be accompanied by a spin flip. These features can now be understood to include the equidistant set of three quantum oscillation frequencies, the asymmetry of the quantum oscillation amplitudes in c-axis transport compared to ab-plane transport, and the anomalous magnetic field angle dependence of the amplitude of the side frequencies suggestive of small effective g-factors. We suggest that spin-orbit interactions in bilayer systems can further affect the structure of the nodal quasiparticle spectrum in the superconducting phase. PACS numbers: 71.45.Lr, 71.20.Ps, 71.18.+y« less

  9. Thyroid cancer in Graves' disease: is surgery the best treatment for Graves' disease?

    PubMed

    Tamatea, Jade A U; Tu'akoi, Kelson; Conaglen, John V; Elston, Marianne S; Meyer-Rochow, Goswin Y

    2014-04-01

    Graves' disease is a common cause of thyrotoxicosis. Treatment options include anti-thyroid medications or definitive therapy: thyroidectomy or radioactive iodine (I(131) ). Traditionally, I(131) has been the preferred definitive treatment for Graves' disease in New Zealand. Reports of concomitant thyroid cancer occurring in up to 17% of Graves' patients suggest surgery, if performed with low morbidity, may be the preferred option. The aim of this study was to determine the rate of thyroid cancer and surgical outcomes in a New Zealand cohort of patients undergoing thyroidectomy for Graves' disease. This study is a retrospective review of Waikato region patients undergoing thyroid surgery for Graves' disease during the 10-year period prior to 1 December 2011. A total of 833 patients underwent thyroid surgery. Of these, 117 were for Graves' disease. Total thyroidectomy was performed in 82, near-total in 33 and subtotal in 2 patients. Recurrent thyrotoxicosis developed in one subtotal patient requiring I(131) therapy. There were two cases of permanent hypoparathyroidism and one of permanent recurrent laryngeal nerve palsy. Eight patients (6.8%) had thyroid cancer detected, none of whom had overt nodal disease. Five were papillary microcarcinomas (one of which was multifocal), two were papillary carcinomas (11 mm and 15 mm) and one was a minimally invasive follicular carcinoma. Thyroid cancer was identified in approximately 7% of patients undergoing surgery for Graves' disease. A low complication rate (<2%) of permanent hypoparathyroidism and nerve injury (<1%) supports surgery being a safe alternative to I(131) especially for patients with young children, ophthalmopathy or compressive symptoms. © 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.

  10. PREVALENCE OF CELIAC DISEASE PREDISPOSING GENOTYPES, INCLUDING HLA-DQ2.2 VARIANT, IN BRAZILIAN CHILDREN.

    PubMed

    Selleski, Nicole; Almeida, Lucas Malta; Almeida, Fernanda Coutinho de; Pratesi, Claudia Beatriz; Nóbrega, Yanna Karla de Medeiros; Gandolfi, Lenora

    2018-01-01

    Celiac disease is an autoimmune enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. Almost all celiac patients carry immune recognition genes coding for HLA-DQ2.5 and DQ8 heterodimers. Over the last few years, great importance has been given to HLA-DQ2.2 as probable predisposing variant, although controversies still exist regarding its relevance. The aim of our study was to determine the possible existence of an association between HLA-DQ2.2 and celiac disease in Brazilian children by analyzing the prevalence of the predisposing variants for celiac disease in a representative group of children of a population in which this determination is still missing. HLA-DQ typing was performed in samples from a group of celiac (n=100) and non-celiac children (n=110). All samples were tested for the presence of the following variants: DQA1*05-DQB1*02 (DQ2.5), DQA1*03-DQB1*03:02 (DQ8) and DQA1*02:01-DQB1*02:02 (DQ2.2). Fisher`s exact test was used for statistical analysis. In the group of 100 celiac children, 78 (78%) were positive for DQ2, 13 (13 %) were DQ2/DQ8 and 6 (6%) were DQ8 positives. The HLA-DQ pattern in the 110 non-celiac children was as follows: positive for DQ2 in 33 (29.9%) samples, in 2 (1.8 %) was positive for DQ2/DQ8 and in 15 (13.6%) was positive for DQ8. We found significant differences between the distribution of some but not all of the analyzed alleles when comparing celiac and non-celiac children. The genotyping of celiac disease HLA-DQ predisposing alleles showed similarities with HLA-DQ patterns found in both European and non-European populations, which may be a reflection of the miscegenation, which gave origin to the current Brazilian population. No significant association was found between DQ2.2 variant and celiac disease in the studied population.

  11. Electrical Analysis of B-52/FB-111 AMAC and Release Circuitry Utilizing Sneak Circuit Analysis Techniques. Volume 2. B-52 Network Trees.

    DTIC Science & Technology

    1975-10-31

    A335 Line c~ O AF " Par, Rt ,; L109 4F PFrs, Release. A116 e AM SolIeAoid- $’,’&t &Np "A uG6 4 )6 JI -4? 7*4 194 -S~2-23 A .o0 PROJECT TITLE " 2 -P...ra, DATE ANLYST DATE NODAL SET "od#0 Afff Wf AINOSPACI COMPANY. - ousoN. TtxM B-79 D2-118576 2 SNEAK CIRCUITS NETWORK TREE REV t .10 PROJECT TITLE...TITLE QcDATE ANALYST DATE ]NODAL ...... H0U4705 AIMm fC $FAC( COMPANY NqOU$1Ct., :TM.’$ B-1 22 cc 10~ z -1 in ’ cz d q’ 1.4’ %On 4C -JJ J51r4 =oPc s-e

  12. Theoretical study of the interaction of N/sub 2/ with water molecules. (H/sub 2/O)/sub n/:N/sub 2/, n = 1--8

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Curtiss, L.A.; Eisgruber, C.L.

    1984-03-01

    Ab initio molecular orbital calculations including correlation energy have been carried out on the interaction of a single H/sub 2/O molecule with N/sub 2/. The potential energy surface for H/sub 2/O:N/sub 2/ is found to have a minimum corresponding to a HOH xxx N/sub 2/ structure with a weak (<2 kcal mol/sup -1/) hydrogen bond. A second, less stable, configuration corresponding to a H/sub 2/O xxx N/sub 2/ structure with N/sub 2/ bonded side on to the oxygen of H/sub 2/O was found to be either a minimum or a saddle point in the potential energy surface depending on themore » level of calculation. The minimal STO-3G basis set was used to investigate the interaction of up to eight H/sub 2/O molecules with N/sub 2/. Two types of clusters, one containing only HOH xxx N/sub 2/ interactions and the other containing both HOH xxxN/sub 2/ and H/sub 2/O xxx N/sub 2/ interactions, were investigated for (N/sub 2/:(H/sub 2/O)/sub n/, n = 2--8).« less

  13. Anderson's disease (chylomicron retention disease): a new mutation in the SARA2 gene associated with muscular and cardiac abnormalities.

    PubMed

    Silvain, M; Bligny, D; Aparicio, T; Laforêt, P; Grodet, A; Peretti, N; Ménard, D; Djouadi, F; Jardel, C; Bégué, J M; Walker, F; Schmitz, J; Lachaux, A; Aggerbeck, L P; Samson-Bouma, M E

    2008-12-01

    Anderson's disease (AD) or chylomicron retention disease (CMRD) is a rare hereditary lipid malabsorption syndrome linked to SARA2 gene mutations. We report in this study a novel mutation in two sisters for which the Sar1b protein is predicted to be truncated by 32 amino acids at its carboxyl-terminus. Because the SARA2 gene is also expressed in the muscle, heart, liver and placenta, extraintestinal clinical manifestations may exist. For the first time, we describe in this study in the two sisters muscular as well as cardiac abnormalities that could be related to the reported expression of SARA2 in these tissues. We also evaluated six other patients for potential manifestations of the SARA2 mutation. The creatine phosphokinase levels were increased in all patients [1.5-9.4 x normal (N)] and transaminases were moderately elevated in five of the eight patients (1.2-2.6 x N), probably related to muscle disease rather than to liver dysfunction. A decreased ejection fraction occurred in one patient (40%, N: 60%). The muscle, liver and placental tissues that were examined had no specific abnormalities and, in particular, no lipid accumulation. These results suggest that myolysis and other extraintestinal abnormalities can occur in AD/CMRD and that the clinical evaluation of patients should reflect this.

  14. Survival significance of coexisting chronic obstructive pulmonary disease in patients with early lung cancer after curative surgery

    PubMed Central

    Miyazawa, Tomoyuki; Sakai, Hiroki; Kimura, Yusuke; Tsuda, Masataka; Wakiyama, Yoichi; Marushima, Hideki; Kojima, Koji; Nakamura, Haruhiko

    2017-01-01

    Background The impact of chronic obstructive pulmonary disease (COPD) severity on survival after curative resection of early‐stage lung cancer (NSCLC) has not been sufficiently elucidated. Methods We retrospectively reviewed 250 consecutive patients who underwent lobectomy with lymph nodal dissection for pathological stage I–II NSCLC. Results Among the COPD patients, 28 were classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1, 21 as GOLD 2, and one as GOLD 3. The cumulative overall survival (OS) of the non‐COPD, GOLD 1, and GOLD 2–3 groups at five years was 90.7%, 85.7%, and 55.3%, respectively, (P < 0.0001), while recurrence‐free survival (RFS) between the groups at five years was 84.7%, 80.7%, and 72.9%, respectively. Although RFS in the GOLD 2–3 group tended to indicate a poor prognosis, there was no statistical difference between the groups (P = 0.385). In multivariate analysis, age ≥75 years, pN1, and GOLD 2–3 COPD were independent factors for a poor prognosis (P = 0.034, P = 0.010, and P = 0.030, respectively). Conclusions Our results indicate that early stage NSCLC patients with COPD had a significantly increased risk of poorer OS and potentially an increased risk of poor RFS. PMID:28976075

  15. Ab initio studies of Th3N4, Th2N3 and Th2N2(NH)

    NASA Astrophysics Data System (ADS)

    Obodo, K. O.; Chetty, N.

    2014-09-01

    Using density functional theory within the Perdew-Burke-Ernzerhof generalized gradient approximation [GGA (PBE)] implemented in the VASP codes, we investigate the structural, elastic and electronic properties of Th3N4, Th2N3 and Th2N2(NH). The calculated structural properties of these thorium-based nitrides are in good agreement with experimental data. We observe that all the Th-N based compounds that we considered are energetically favorable and elastically stable. We find that Th3N4 is semiconducting with a band gap of 1.59 eV, which compares well with the experimental band gap of 1.7 eV and we find Th2N3 to be metallic. Th2N2(NH), which is crystallographically equivalent to Th2N3, is insulating with a band gap of 2.12 eV. This is due to the -(NH) group that effects a shifting of the energy bands that results in the opening of a gap at the Fermi-level. The Th-N based compounds that we considered are predominantly ionic.

  16. Rapid clinical diagnosis of Legionnaires' disease during the "herald wave" of the swine influenza (H1N1) pandemic: the Legionnaires' disease triad.

    PubMed

    Cunha, Burke A; Mickail, Nardeen; Syed, Uzma; Strollo, Stephanie; Laguerre, Marianne

    2010-01-01

    simplified diagnostic swine influenza (H1N1) triad was developed for the rapid clinical diagnosis of probable H1N1 pneumonia, which also differentiated it from its mimics as well as from bacterial pneumonia, eg, Legionnaires' disease. During the "herald wave" of the H1N1 pandemic, we noticed an unexplained increase in Legionnaires' disease CAPs. Because clinical resources were stressed to the maximum during the pandemic, it was critically important to rapidly identify patients rapidly with Legionnaire's disease who did not require influenza precautions or oseltamivir, but who did require anti-Legionella antimicrobial therapy. Based on the Winthrop-University Hospital Infectious Disease Division's diagnostic weighted point score system for Legionnaires' disease (modified), key indicators were identified and became the basis for the diagnostic Legionnaires' disease triad. The diagnostic Legionnaires' disease triad was used to make a clinical diagnosis of Legionnaires' disease until the results of Legionella diagnostic tests were reported. The diagnostic Legionnaires' disease triad diagnosed Legionnaires' disease in hospitalized adults with CAPs with extrapulmonary findings (atypical CAP) and relative bradycardia, accompanied by any three (ie, a triad) of the following: otherwise unexplained relative lymphopenia, early/mildly elevated serum transaminases (SGOT/SGPT), highly increased ferritin levels (> or =2 x n), or hypophosphatemia. The diagnostic Legionnaires' disease triad provides clinicians with a rapid way to clinically diagnose Legionnaires' disease, pending Legionella test results. The accuracy of the diagnostic Legionnaires' disease triad was confirmed in our 9 cases of Legionnaires' disease by subsequent Legionella diagnostic testing. The diagnostic Legionnaires' disease triad is particularly useful in situations where a rapid clinical syndromic diagnosis is needed, ie, during an H1N1 pandemic. Copyright 2010 Elsevier Inc. All rights reserved.

  17. R47H TREM2 variant increases risk of typical early-onset Alzheimer’s disease but not of prion or frontotemporal dementia

    PubMed Central

    CF, Slattery; J, Beck; L, Harper; G, Adamson; Z, Abdi; J, Uphill; T, Campbell; R, Druyeh; CJ, Mahoney; JD, Rohrer; J, Kenny; J, Lowe; KK, Leung; J, Barnes; SL, Clegg; M, Blair; JM, Nicholas; RJ, Guerreiro; JB, Rowe; C, Ponto; I, Zerr; H, Kretzschmar; P, Gambetti; SJ, Crutch; JD, Warren; MN, Rossor; NC, Fox; J, Collinge; JM, Schott; S, Mead

    2015-01-01

    Background Rare TREM2 variants are significant risk factors for Alzheimer’s disease. Methods We used next generation sequencing of the whole gene (n=700), exon 2 Sanger sequencing (n=2634), p.R47H genotyping (n=3518) and genome wide association study imputation (n=13048) to determine whether TREM2 variants are risk factors or phenotypic modifiers in patients with Alzheimer’s disease (n=1002), frontotemporal dementia (n=358), sporadic (n=2500) and variant (n=115) Creutzfeldt-Jakob disease. Results We confirm only p.R47H as a risk factor for Alzheimer’s disease (OR=2.19; 95%CI=1.04-4.51; P=0.03). p.R47H does not significantly alter risk for frontotemporal dementia (OR=0.81), variant or sporadic Creutzfeldt-Jakob disease (OR=1.06 95%CI=0.66-1.69) in our cohorts. Individuals with p.R47H associated Alzheimer’s (n=12) had significantly earlier symptom onset than individuals with no TREM2 variants (n=551) (55.2years vs. 61.7years, P=0.02). We note that heterozygous p.R47H Alzheimer’s disease is memory led and otherwise indistinguishable from “typical” sporadic Alzheimer’s. Conclusion We find p.R47H is a risk factor for Alzheimer’s disease, but not frontotemporal dementia or prion disease. PMID:25160042

  18. Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease

    PubMed Central

    Westerlund, Marie; Behbahani, Homira; Gellhaar, Sandra; Forsell, Charlotte; Belin, Andrea Carmine; Anvret, Anna; Zettergren, Anna; Nissbrandt, Hans; Lind, Charlotta; Sydow, Olof; Graff, Caroline; Olson, Lars; Ankarcrona, Maria; Galter, Dagmar

    2011-01-01

    The serine-protease OMI/HTRA2, required for several cellular processes, including mitochondrial function, autophagy, chaperone activity, and apoptosis, has been implicated in the pathogenesis of both Alzheimer's disease (AD) and Parkinson's disease (PD). Western blot quantification of OMI/HTRA2 in frontal cortex of patients with AD (n=10) and control subjects (n=10) in two separate materials indicated reduced processed (active, 35 kDa) OMI/HTRA2 levels, whereas unprocessed (50 kDa) enzyme levels were not significantly different between the groups. Interestingly, the specific protease activity of OMI/HTRA2 was found to be significantly increased in patients with AD (n=10) compared to matched control subjects (n=10) in frontal cortex in two separate materials. Comparison of OMI/HTRA2 mRNA levels in frontal cortex and hippocampus, two brain areas particularly affected by AD, indicated similar levels in patients with AD (n=10) and matched control subjects (n=10). In addition, we analyzed the occurrence of the OMI/HTRA2 variants A141S and G399S in Swedish case-control materials for AD and PD and found a weak association of A141S with AD, but not with PD. In conclusion, our genetic, histological, and biochemical findings give further support to an involvement of OMI/HTRA2 in the pathology of AD; however, further studies are needed to clarify the role of this gene in neurodegeneration.—Westerlund, M., Behbahani, H., Gellhaar, S., Forsell, C., Carmine Belin, A., Anvret, A., Zettergren, A., Nissbrandt, H., Lind, C., Sydow, O., Graff, C., Olson, L., Ankarcrona, M., Galter, D. Altered enzymatic activity and allele frequency of OMI/HTRA2 in Alzheimer's disease. PMID:21163861

  19. Recombinant Newcastle Disease Virus Expressing H9 HA Protects Chickens against Heterologous Avian Influenza H9N2 Virus Challenge

    PubMed Central

    Nagy, Abdou; Lee, Jinhwa; Mena, Ignacio; Henningson, Jamie; Li, Yuhao; Ma, Jingjiao; Duff, Michael; Li, Yonghai; Lang, Yuekun; Yang, Jianmei; Abdallah, Fatma; Richt, Juergen; Ali, Ahmed; García-Sastre, Adolfo; Ma, Wenjun

    2017-01-01

    In order to produce an efficient poultry H9 avian influenza vaccine that provides cross-protection against multiple H9 lineages, two Newcastle Disease Virus (NDV) LaSota vaccine strain recombinant viruses were generated using reverse genetics. The recombinant NDV-H9Con virus expresses a consensus-H9 hemagglutinin (HA) that is designed based on available H9N2 sequences from Chinese and Middle Eastern isolates. The recombinant NDV-H9Chi virus expresses a chimeric-H9 HA in which the H9 ectodomain of A/Guinea Fowl/Hong Kong/WF10/99 was fused with the cytoplasmic and transmembrane domain of the fusion protein (F) of NDV. Both recombinant viruses expressed the inserted HA stably and grew to high titers. An efficacy study in chickens showed that both recombinant viruses were able to provide protection against challenge with a heterologous H9N2 virus. In contrast to the NDV-H9Chi virus, the NDV-H9Con virus induced a higher hemagglutination inhibition titer against both NDV and H9 viruses in immunized birds, and efficiently inhibited virus shedding through the respiratory route. Moreover, sera collected from birds immunized with either NDV-H9Con or NDV-H9Chi were able to cross-neutralize two different lineages of H9N2 viruses, indicating that NDV-H9Con and NDV-H9Chi are promising vaccine candidates that could provide cross-protection among different H9N2 lineage viruses. PMID:27102817

  20. Sentinel lymph node biopsy in early-stage cervical cancer: utility of intraoperative versus postoperative assessment.

    PubMed

    Fader, A Nickles; Edwards, R P; Cost, M; Kanbour-Shakir, A; Kelley, J L; Schwartz, B; Sukumvanich, P; Comerci, J; Sumkin, J; Elishaev, E; Rohan, L Cencia

    2008-10-01

    To determine the diagnostic accuracy of sentinel lymph node (SLN) detection using lymphoscintigraphy, intraoperative blue dye, and radiocolloid in patients with early-stage cervical cancer. Intra-cervical injection of technetium-99 sulfur colloid and lymphoscintigraphy were performed preoperatively. Isosulfan blue was injected intra-cervically immediately prior to surgery. SLNs were excised and examined intraoperatively (imprint cytology and frozen section) and postoperatively (H and E histology and immunohistochemistry (IHC) for cytokeratin). Thirty eight patients were evaluable. Laparoscopy and laparotomy were performed in 28.9% and 71.1%, respectively. Subjects had squamous cell carcinoma (n=26), adenocarcinoma (n=10) or adenosquamous (n=2) histologies. 55.3% had cervical tumors <2 cm. The overall SLN detection rate was 92.1%. The external iliac region just distal to the common iliac bifurcation was the most common SLN location. A mean of 2.1 SLNs were detected per patient with bilateral SLNs observed in 47.4%. On final pathology, metastatic nodal disease was identified in 15.7% of patients. Of these, 83.3% were detected in the SLNs. Sensitivity of SLN detection of metastasis was 100% for patients with cervical tumors <2 cm. However intraoperative evaluation by imprint cytology and frozen section correctly identified lymph node metastasis in only 33.3%. SLN detection is feasible and accurately reflects pelvic nodal basin status when performed in early-stage cervical cancer patients. However, while current intraoperative pathology techniques for assessing nodal metastases reliably detect metastases larger than 2 mm, they lack sufficient sensitivity to detect micrometastasis and isolated tumor cells.

  1. The Electronic Spectra of CaN2(+) and Ca(N2)2(+)

    NASA Technical Reports Server (NTRS)

    Rodriguez-Santiago, Luis; Bauschlicher, Charles W., Jr.; Arnold, James (Technical Monitor)

    1998-01-01

    The ground and low-lying electronic states of CaN2(+) are studied at several levels of theory. The results for the X(sup 2)Sigma(+) state and the excited (2)(sup 2)Pi state, arising from occupying the Ca 4p orbital, are in good agreement with experiment. The analogous states of Ca(N2)2(+) are studied using the same theoretical approaches, and predictions are made as to the changes caused by the addition of the second N2 ligand.

  2. Volumetric tumor burden and its effect on brachial plexus dosimetry in head and neck intensity-modulated radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Romesser, Paul B.; Qureshi, Muhammad M.; Kovalchuk, Nataliya

    2014-07-01

    To determine the effect of gross tumor volume of the primary (GTV-P) and nodal (GTV-N) disease on planned radiation dose to the brachial plexus (BP) in head and neck intensity-modulated radiotherapy (IMRT). Overall, 75 patients underwent definitive IMRT to a median total dose of 69.96 Gy in 33 fractions. The right BP and left BP were prospectively contoured as separate organs at risk. The GTV was related to BP dose using the unpaired t-test. Receiver operating characteristics curves were constructed to determine optimized volumetric thresholds of GTV-P and GTV-N corresponding to a maximum BP dose cutoff of > 66 Gy.more » Multivariate analyses were performed to account for factors associated with a higher maximal BP dose. A higher maximum BP dose (> 66 vs ≤ 66 Gy) correlated with a greater mean GTV-P (79.5 vs 30.8 cc; p = 0.001) and ipsilateral GTV-N (60.6 vs 19.8 cc; p = 0.014). When dichotomized by the optimized nodal volume, patients with an ipsilateral GTV-N ≥ 4.9 vs < 4.9 cc had a significant difference in maximum BP dose (64.2 vs 59.4 Gy; p = 0.001). Multivariate analysis confirmed that an ipsilateral GTV-N ≥ 4.9 cc was an independent predictor for the BP to receive a maximal dose of > 66 Gy when adjusted individually for BP volume, GTV-P, the use of a low anterior neck field technique, total planned radiation dose, and tumor category. Although both the primary and the nodal tumor volumes affected the BP maximal dose, the ipsilateral nodal tumor volume (GTV-N ≥ 4.9 cc) was an independent predictor for high maximal BP dose constraints in head and neck IMRT.« less

  3. The edematous toddler: a case of pediatric Ménétrier disease.

    PubMed

    Blackstone, Mercedes M; Mittal, Manoj K

    2008-10-01

    nétrier disease is a protein-losing gastroenteropathy, characterized clinically by nonspecific gastrointestinal symptoms and generalized edema, biochemically by hypoalbuminemia, and pathologically by enlarged gastric folds. Distinct from its adult counterpart, Ménétrier disease of childhood usually remits spontaneously and has a very good prognosis. We present a case report of Ménétrier disease in an edematous toddler and a brief review.

  4. Outbreaks of avian influenza A (H5N2), (H5N8), and (H5N1) among birds--United States, December 2014-January 2015.

    PubMed

    Jhung, Michael A; Nelson, Deborah I

    2015-02-06

    During December 15, 2014-January 16, 2015, the U.S. Department of Agriculture received 14 reports of birds infected with Asian-origin, highly pathogenic avian influenza A (HPAI) (H5N2), (H5N8), and (H5N1) viruses. These reports represent the first reported infections with these viruses in U.S. wild or domestic birds. Although these viruses are not known to have caused disease in humans, their appearance in North America might increase the likelihood of human infection in the United States. Human infection with other avian influenza viruses, such as HPAI (H5N1) and (H5N6) viruses and (H7N9) virus, has been associated with severe, sometimes fatal, disease, usually following contact with poultry.

  5. Is the non-sentinel lymph node compartment the next site for melanoma progression from the sentinel lymph node compartment in the regional nodal basin?

    PubMed

    Rios-Cantu, Andrei; Lu, Ying; Melendez-Elizondo, Victor; Chen, Michael; Gutierrez-Range, Alejandra; Fadaki, Niloofar; Thummala, Suresh; West-Coffee, Carla; Cleaver, James; Kashani-Sabet, Mohammed; Leong, Stanley P L

    2017-06-01

    Melanoma patients with additional positive lymph nodes in the completion lymph node dissection (CLND) following a positive sentinel lymph node (SLN) biopsy would have a poorer prognosis than patients with no additional positive lymph nodes. We hypothesize that the progression of disease from the SLN to the non-SLN compartment is orderly and is associated with the worsening of the disease status. Thus, the SLN and non-SLN compartments are biologically different in that cancer cells, in general, arrive in the SLN compartment before spreading to the non-SLN compartment. To validate this concept, we used a large cohort of melanoma patients from our prospective SLN database in an academic tertiary medical center. Adult cutaneous melanoma patients (n = 291) undergoing CLND after a positive SLN biopsy from 1994 to 2009 were analyzed. Comparison of 5-year disease-free survival and 5-year overall survival between positive (n = 66) and negative (n = 225) CLND groups was made. The 5-year disease-free survival rates were 55% (95% CI 49-62%) for patients with no additional LN on CLND versus 14% (95% CI 8-26%) in patients with positive LN on CLND (p < 0.0001, log-rank test). The median disease-free survival time was 7.4 years with negative CLND (95% CI 4.4-15+ years) and 1.2 years with positive CLND (95% CI 1.0-1.8 years). The 5-year overall survival rates were 67% (95% CI 61-74%) for negative CLND versus 38% (95% CI 28-52%) for positive CLND (p < 0.0001, log-rank test). The median overall survival time was 12.1 years for negative CLND (95% CI 9.3-15+ years) and 2.5 years for positive CLND (95% CI 2.2-5.7 years). This study shows that CLND status is a significant prognostic factor for patients with positive SLNs undergoing CLND. Also, it suggests an orderly progression of metastasis from the SLN to the non-SLN compartment. Thus, the SLN in the regional nodal basin draining the primary melanoma may serve as an important gateway for metastasis to the non

  6. Gallbladder Cancer: expert consensus statement

    PubMed Central

    Aloia, Thomas A; Járufe, Nicolas; Javle, Milind; Maithel, Shishir K; Roa, Juan C; Adsay, Volkan; Coimbra, Felipe J F; Jarnagin, William R

    2015-01-01

    An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists was convened on 15 January 2014 to review current evidence on the management of gallbladder carcinoma in order to establish practice guidelines. In summary, within high incidence areas, the assessment of routine gallbladder specimens should include the microscopic evaluation of a minimum of three sections and the cystic duct margin; specimens with dysplasia or proven cancer should be extensively sampled. Provided the patient is medically fit for surgery, data support the resection of all gallbladder polyps of >1.0 cm in diameter and those with imaging evidence of vascular stalks. The minimum staging evaluation of patients with suspected or proven gallbladder cancer includes contrasted cross-sectional imaging and diagnostic laparoscopy. Adequate lymphadenectomy includes assessment of any suspicious regional nodes, evaluation of the aortocaval nodal basin, and a goal recovery of at least six nodes. Patients with confirmed metastases to N2 nodal stations do not benefit from radical resection and should receive systemic and/or palliative treatments. Primary resection of patients with early T-stage (T1b–2) disease should include en bloc resection of adjacent liver parenchyma. Patients with T1b, T2 or T3 disease that is incidentally identified in a cholecystectomy specimen should undergo re-resection unless this is contraindicated by advanced disease or poor performance status. Re-resection should include complete portal lymphadenectomy and bile duct resection only when needed to achieve a negative margin (R0) resection. Patients with preoperatively staged T3 or T4 N1 disease should be considered for clinical trials of neoadjuvant chemotherapy. Following R0 resection of T2–4 disease in N1 gallbladder cancer, patients should be considered for adjuvant systemic chemotherapy and/or chemoradiotherapy. PMID:26172135

  7. Gallbladder cancer: expert consensus statement.

    PubMed

    Aloia, Thomas A; Járufe, Nicolas; Javle, Milind; Maithel, Shishir K; Roa, Juan C; Adsay, Volkan; Coimbra, Felipe J F; Jarnagin, William R

    2015-08-01

    An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists was convened on 15 January 2014 to review current evidence on the management of gallbladder carcinoma in order to establish practice guidelines. In summary, within high incidence areas, the assessment of routine gallbladder specimens should include the microscopic evaluation of a minimum of three sections and the cystic duct margin; specimens with dysplasia or proven cancer should be extensively sampled. Provided the patient is medically fit for surgery, data support the resection of all gallbladder polyps of >1.0 cm in diameter and those with imaging evidence of vascular stalks. The minimum staging evaluation of patients with suspected or proven gallbladder cancer includes contrasted cross-sectional imaging and diagnostic laparoscopy. Adequate lymphadenectomy includes assessment of any suspicious regional nodes, evaluation of the aortocaval nodal basin, and a goal recovery of at least six nodes. Patients with confirmed metastases to N2 nodal stations do not benefit from radical resection and should receive systemic and/or palliative treatments. Primary resection of patients with early T-stage (T1b-2) disease should include en bloc resection of adjacent liver parenchyma. Patients with T1b, T2 or T3 disease that is incidentally identified in a cholecystectomy specimen should undergo re-resection unless this is contraindicated by advanced disease or poor performance status. Re-resection should include complete portal lymphadenectomy and bile duct resection only when needed to achieve a negative margin (R0) resection. Patients with preoperatively staged T3 or T4 N1 disease should be considered for clinical trials of neoadjuvant chemotherapy. Following R0 resection of T2-4 disease in N1 gallbladder cancer, patients should be considered for adjuvant systemic chemotherapy and/or chemoradiotherapy. © 2015 International Hepato-Pancreato-Biliary Association.

  8. Are Radiation Therapy Oncology Group Para-aortic Contouring Guidelines for Pancreatic Neoplasm Applicable to Other Malignancies—Assessment of Nodal Distribution in Gynecological Malignancies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kabolizadeh, Peyman; Fulay, Suyash; Beriwal, Sushil, E-mail: beriwals@upmc.edu

    Purpose: Intensity modulated radiation therapy is used to reduce dose to adjacent critical structures while maintaining adequate target coverage, but it requires precise target localization. We report the 3-dimensional distribution of para-aortic (PA) lymph nodes (LN) in pelvic malignancies. We propose a guideline to accurately define the PA LN by anatomic landmarks and compare our data with published guidelines for pancreatic cancer. Methods and Materials: A retrospective analysis was performed on 46 patients with pelvic malignancies and positive PA LNs. Positive LNs were defined based on size and morphology or fluorodeoxyglucose avidity. All PA LNs were characterized into 3 groupsmore » based on location: left PA (between aorta and left psoas muscle), aortocaval (between aorta and inferior vena cava), and right paracaval (between inferior vena cava and right psoas muscle). Patients with retrocrural LNs were also analyzed. Results: One hundred thirty-three positive PA LNs were evaluated. The majority of the PA LNs were in the left PA (59%) and aortocaval (35) regions, and only 8% were in the right paracaval region. All patients with positive right paracaval LNs also had involved left PA LNs, with only 1 exception. The highest PA LN involvement was at the level of the renal vessels and was seen in 28% of patients. Of these patients with disease extending to renal vessels, 38% had retrocrural LN involvement. Conclusions: The nodal contouring for the PA region should not be defined by a fixed circumferential margin around the vessels. The left PA and aortocaval spaces should be covered adequately because these are common locations of PA LNs. For microscopic disease superiorly, contouring should extend up to renal vessels rather than a fixed bony landmark. For patients who have nodal involvement at renal vessels, one can consider including retrocrural LNs. Radiation Therapy Oncology Group Para-aortic Contouring Guidelines for Pancreatic Neoplasm are not applicable

  9. Production of N2O/+/ by reaction of metastable O2/+/ ions with N2

    NASA Technical Reports Server (NTRS)

    Ajello, J. M.; Rayermann, P.

    1975-01-01

    Photoionization mass spectrometry examination of the production of N2O(+) was undertaken to determine whether N2(+) or O2(+) ions are responsible for onset of N2O(+). It appears that the N2(+) ion does not contribute significantly to the production of N2O(+) in this experiment. Therefore, it is clear that excited O2(+) is responsible for the formation of N2O(+) near the appearance potential of these ions.

  10. Does atrioventricular reentry tachycardia (AVRT) or atrioventricular nodal reentry tachycardia (AVNRT) in children affect their cognitive and emotional development?

    PubMed

    Maryniak, Agnieszka; Bielawska, Alicja; Bieganowska, Katarzyna; Miszczak-Knecht, Maria; Walczak, Franciszek; Szumowski, Lukasz

    2013-04-01

    The current study sought to assess cognitive and emotional functions among children and adolescents with atrioventricular reentry tachycardia (AVRT) and atrioventricular nodal reentry tachycardia (AVNRT). 113 patients (62 girls and 51 boys ages, 9-18 years) scheduled for radiofrequency ablation due to AVRT or AVNRT underwent neuropsychologic examination. The study excluded patients who had experienced cardiac arrest, congenital heart defects, neurologic disorders, or other diseases affecting cognitive or emotional development. Standardized tests for examining verbal and visual memory as well as visual-spatial functioning were performed. For patients exhibiting deficits in two or more tests, a diagnosis of "cognitive deficits" was determined. Levels of anxiety were tested using the State-Trait Anxiety Inventory. Cognitive deficits were found in 47.8 % of the patients. The age at first arrhythmia attack was related to memory dysfunction. The mean age at which the first symptoms occurred was significantly lower for patients with deficits (8.3 years) than for patients who had no deficit (10.2 years) (t = 2.15; p = 0.03). Boys exhibited a significantly higher level of trait anxiety than girls (t = 3.42; p = 0.0009). A significant negative correlation was found between anxiety and the age at appearance of the first symptoms (r = -0.26; p = 0.005). These findings led us to conclude that cognitive and emotional developments can be negatively affected by AVNRT and AVRT, particularly if tachycardia appears early in life.

  11. Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

    PubMed Central

    Monsalvo, Ana Clara; Batalle, Juan P.; Lopez, M. Florencia; Krause, Jens C.; Klemenc, Jennifer; Zea, Johanna; Maskin, Bernardo; Bugna, Jimena; Rubinstein, Carlos; Aguilar, Leandro; Dalurzo, Liliana; Libster, Romina; Savy, Vilma; Baumeister, Elsa; Aguilar, Liliana; Cabral, Graciela; Font, Julia; Solari, Liliana; Weller, Kevin P.; Johnson, Joyce; Echavarria, Marcela; Edwards, Kathryn M.; Chappell, James D.; Crowe, James E.; Williams, John V.; Melendi, Guillermina A.; Polack, Fernando P.

    2010-01-01

    Pandemic influenza viruses often cause severe disease in middle-aged adults without preexistent co-morbidities. The mechanism of illness associated with severe disease in this age group is not well understood1–10. Here, we demonstrate preexisting serum antibody that cross-reacts with, but does not protect against 2009 H1N1 influenza virus in middle-aged adults. Non-protective antibody is associated with immune complex(IC)-mediated disease after infection. High titers of serum antibody of low avidity for H1-2009 antigen, and low avidity pulmonary ICs against the same protein were detected in severely ill patients. Moreover, C4d deposition - a sensitive marker of complement activation mediated by ICs- was present in lung sections of fatal cases. Archived lung sections from adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a novel biological mechanism for the unusual age distribution of severe cases during influenza pandemics. PMID:21131958

  12. Laser detection of CO2 concentration in human breath at various diseases

    NASA Astrophysics Data System (ADS)

    Ageev, Boris G.; Nikiforova, Olga Y.

    2015-12-01

    Absorption spectra of human breath in 10 μm region were recorded by the use of intracavity laser photo-acoustic gas analyzer based on tunable waveguide CO2 laser. Healthy persons and patients with various diseases were studied. For determination of CO2 concentration in exhalation samples gas analyzer was calibrated by reference gaseous mixture CO2-N2. It was obtained that CO2 concentration values in human breath of healthy persons are greater than that of patients with various diseases.

  13. Mathematical Formalism for Designing Wide-Field X-Ray Telescopes: Mirror Nodal Positions and Detector Tilts

    NASA Technical Reports Server (NTRS)

    Elsner, R. F.; O'Dell, S. L.; Ramsey, B. D.; Weisskopf, M. C.

    2011-01-01

    We provide a mathematical formalism for optimizing the mirror nodal positions along the optical axis and the tilt of a commonly employed detector configuration at the focus of a x-ray telescope consisting of nested mirror shells with known mirror surface prescriptions. We adopt the spatial resolution averaged over the field-of-view as the figure of merit M. A more complete description appears in our paper in these proceedings.

  14. Sensitivity and Specificity of Cardiac Tissue Discrimination Using Fiber-Optics Confocal Microscopy.

    PubMed

    Huang, Chao; Sachse, Frank B; Hitchcock, Robert W; Kaza, Aditya K

    2016-01-01

    Disturbances of the cardiac conduction system constitute a major risk after surgical repair of complex cases of congenital heart disease. Intraoperative identification of the conduction system may reduce the incidence of these disturbances. We previously developed an approach to identify cardiac tissue types using fiber-optics confocal microscopy and extracellular fluorophores. Here, we applied this approach to investigate sensitivity and specificity of human and automated classification in discriminating images of atrial working myocardium and specialized tissue of the conduction system. Two-dimensional image sequences from atrial working myocardium and nodal tissue of isolated perfused rodent hearts were acquired using a fiber-optics confocal microscope (Leica FCM1000). We compared two methods for local application of extracellular fluorophores: topical via pipette and with a dye carrier. Eight blinded examiners evaluated 162 randomly selected images of atrial working myocardium (n = 81) and nodal tissue (n = 81). In addition, we evaluated the images using automated classification. Blinded examiners achieved a sensitivity and specificity of 99.2 ± 0.3% and 98.0 ± 0.7%, respectively, with the dye carrier method of dye application. Sensitivity and specificity was similar for dye application via a pipette (99.2 ± 0.3% and 94.0 ± 2.4%, respectively). Sensitivity and specificity for automated methods of tissue discrimination were similarly high. Human and automated classification achieved high sensitivity and specificity in discriminating atrial working myocardium and nodal tissue. We suggest that our findings facilitate clinical translation of fiber-optics confocal microscopy as an intraoperative imaging modality to reduce the incidence of conduction disturbances during surgical correction of congenital heart disease.

  15. NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

    PubMed

    Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

    2016-08-01

    Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

  16. Quantifying N2O reduction to N2 based on N2O isotopocules - validation with independent methods (helium incubation and 15N gas flux method)

    NASA Astrophysics Data System (ADS)

    Lewicka-Szczebak, Dominika; Augustin, Jürgen; Giesemann, Anette; Well, Reinhard

    2017-02-01

    Stable isotopic analyses of soil-emitted N2O (δ15Nbulk, δ18O and δ15Nsp = 15N site preference within the linear N2O molecule) may help to quantify N2O reduction to N2, an important but rarely quantified process in the soil nitrogen cycle. The N2O residual fraction (remaining unreduced N2O, rN2O) can be theoretically calculated from the measured isotopic enrichment of the residual N2O. However, various N2O-producing pathways may also influence the N2O isotopic signatures, and hence complicate the application of this isotopic fractionation approach. Here this approach was tested based on laboratory soil incubations with two different soil types, applying two reference methods for quantification of rN2O: helium incubation with direct measurement of N2 flux and the 15N gas flux method. This allowed a comparison of the measured rN2O values with the ones calculated based on isotopic enrichment of residual N2O. The results indicate that the performance of the N2O isotopic fractionation approach is related to the accompanying N2O and N2 source processes and the most critical is the determination of the initial isotopic signature of N2O before reduction (δ0). We show that δ0 can be well determined experimentally if stable in time and then successfully applied for determination of rN2O based on δ15Nsp values. Much more problematic to deal with are temporal changes of δ0 values leading to failure of the approach based on δ15Nsp values only. For this case, we propose here a dual N2O isotopocule mapping approach, where calculations are based on the relation between δ18O and δ15Nsp values. This allows for the simultaneous estimation of the N2O-producing pathways' contribution and the rN2O value.

  17. Immunoarchitectural patterns in nodal marginal zone B-cell lymphoma: a study of 51 cases.

    PubMed

    Salama, Mohamed E; Lossos, Izidore S; Warnke, Roger A; Natkunam, Yasodha

    2009-07-01

    Nodal marginal zone lymphoma (NMZL) represents a rare and heterogeneous group that lacks markers specific for the diagnosis. We evaluated morphologic and immunoarchitectural features of 51 NMZLs, and the following immunostains were performed: CD20, CD21, CD23, CD5, CD3, CD43, CD10, Ki-67, BCL1, BCL2, BCL6, HGAL, and LMO2. Four immunoarchitectural patterns were evident: diffuse (38 [75%]), well-formed nodular/follicular (5 [10%]), interfollicular (7 [14%]), and perifollicular (1 [2%]). Additional features included a monocytoid component (36 [71%]), admixed large cells (20 [39%]), plasma cells (24 [47%]), compartmentalizing stromal sclerosis (13 [25%]), and prominent blood vessel sclerosis (10 [20%]). CD21 highlighted disrupted follicular dendritic cell meshwork in 35 (71%) of 49 cases, and CD43 coexpression was present in 10 (24%) of 42 cases. A panel of germinal center-associated markers was helpful in eliminating cases of diffuse follicle center lymphoma. Our results highlight the histologic and immunoarchitectural spectrum of NMZL and the usefulness of immunohistochemical analysis for CD43, CD23, CD21, BCL6, HGAL, and LMO2 in the diagnosis of NMZL.

  18. Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes.

    PubMed

    Colombo, Marco; Looker, Helen C; Farran, Bassam; Agakov, Felix; Brosnan, M Julia; Welsh, Paul; Sattar, Naveed; Livingstone, Shona; Durrington, Paul N; Betteridge, D John; McKeigue, Paul M; Colhoun, Helen M

    2018-05-21

    Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded. Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2-77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction. Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745. The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  19. The bonding of FeN2, FeCO, and Fe2N2 - Model systems for side-on bonding of CO and N2

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Pettersson, Lars G. M.; Siegbahn, Per E. M.

    1987-01-01

    Qualitative calculations are performed to elucidate the nature of the side-on interaction of both N2 and CO with a single Fe atom. The systems are found to be quite similar, with bonding leading to an increase in the CO or N2 bond length and a decrease in the vibrational frequency. The CO or N2 stretching modes lead to a large dipole derivative along the metal-ligand bond axis. The populations show an almost identical, large donation from the Fe 3d orbitals into the CO or N2 Pi-asterisk. The larger system Fe2N2 is then considered, with the N2 bridging the Fe2, both parallel and perpendicular to the Fe2 bond axis for two different Fe-Fe distances. For FeN2, the shift in the observed N2 frequency is smaller than observed for the alpha state of N2/Fe(111). The shift in the N2 vibrational frequency increases when the N2 interacts with two Fe atoms, either at the Fe-Fe nearest neighbor distance or at the first layer Fe-Fe distance, when the side-on N2 axis is oriented perpendicular to an Fe-Fe bond.

  20. Varying the Lewis base coordination of the Y2N2 core in the reduced dinitrogen complexes {[(Me3Si)2N]2(L)Y}2(μ-η22-N2) (L = benzonitrile, pyridines, triphenylphosphine oxide, and trimethylamine N-oxide).

    PubMed

    Corbey, Jordan F; Farnaby, Joy H; Bates, Jefferson E; Ziller, Joseph W; Furche, Filipp; Evans, William J

    2012-07-16

    The effect of the neutral donor ligand, L, on the Ln(2)N(2) core in the (N═N)(2-) complexes, [A(2)(L)Ln](2)(μ-η(2):η(2)-N(2)) (Ln = Sc, Y, lanthanide; A = monoanion; L = neutral ligand), is unknown since all of the crystallographically characterized examples were obtained with L = tetrahydrofuran (THF). To explore variation in L, displacement reactions between {[(Me(3)Si)(2)N](2)(THF)Y}(2)(μ-η(2):η(2)-N(2)), 1, and benzonitrile, pyridine (py), 4-dimethylaminopyridine (DMAP), triphenylphosphine oxide, and trimethylamine N-oxide were investigated. THF is displaced by all of these ligands to form {[(Me(3)Si)(2)N](2)(L)Y}(2)(μ-η(2):η(2)-N(2)) complexes (L = PhCN, 2; py, 3; DMAP, 4; Ph(3)PO, 5; Me(3)NO, 6) that were fully characterized by analytical, spectroscopic, density functional theory, and X-ray crystallographic methods. The crystal structures of the Y(2)N(2) cores in 2-5 are similar to that in 1 with N-N bond distances between 1.255(3) Å and 1.274(3) Å, but X-ray analysis of the N-N distance in 6 shows it to be shorter: 1.198(3) Å.

  1. The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer.

    PubMed

    Evans, Christopher P; Higano, Celestia S; Keane, Thomas; Andriole, Gerald; Saad, Fred; Iversen, Peter; Miller, Kurt; Kim, Choung-Soo; Kimura, Go; Armstrong, Andrew J; Sternberg, Cora N; Loriot, Yohann; de Bono, Johann; Noonberg, Sarah B; Mansbach, Hank; Bhattacharya, Suman; Perabo, Frank; Beer, Tomasz M; Tombal, Bertrand

    2016-10-01

    Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer. To assess the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease. One thousand seven hundred and seventeen asymptomatic or minimally symptomatic patients were randomized to enzalutamide (n=872) or placebo (n=845). Subgroup analyses included nonvisceral (only bone and/or nodal; n=1513), visceral (lung and/or liver; n=204), low-volume bone disease (<4 bone metastases; n=867), high-volume bone disease (≥4 bone metastases; n=850), lymph node only disease (n=195). Oral enzalutamide (160mg) or placebo once daily while continuing androgen deprivation therapy. Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc. Enzalutamide improved rPFS versus placebo in patients with nonvisceral disease (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.14-0.22), visceral disease (HR, 0.28; 95% CI, 0.16-0.49), low- or high-volume bone disease (HR, 0.16; 95% CI, 0.11-0.22; HR, 0.22; 95% CI, 0.16-0.29, respectively), and lymph node only disease (HR, 0.09; 95% CI, 0.04-0.19). For OS, HRs favored enzalutamide (<1) across all disease subgroups, although 95% CI was >1 in patients with visceral disease (HR, 0.82; 95% CI, 0.55-1.23). Enzalutamide was well tolerated in patients with or without visceral disease. Enzalutamide provided clinically significant benefits in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only disease. Patients with metastatic castration-resistant prostate cancer-including those with or without visceral disease or widespread bone disease

  2. Regulation of salt marsh mosquito populations by the 18.6-yr lunar-nodal cycle.

    PubMed

    Rochlin, Ilia; Morris, James T

    2017-08-01

    The 18.6-yr lunar-nodal cycle drives changes in tidal amplitude globally, affecting coastal habitat formation, species and communities inhabiting rocky shores, and salt marsh vegetation. However, the cycle's influence on salt marsh fauna lacked sufficient long-term data for testing its effect. We circumvented this problem by using salt marsh mosquito records obtained over a period of over four decades in two estuaries in the northeastern USA. Salt marsh mosquito habitat is near the highest tide level where the impact of the nodal cycle on flood frequency is greatest. Wavelet spectral and cross-correlation analyses revealed periodicity in salt marsh mosquito abundance that was negatively correlated with tidal amplitude. Tidal amplitude was a significant predictor of salt marsh mosquito abundance with the cycle maxima coinciding with lower mosquito populations, possibly due to access by predatory fish. However, these effects were detected only at the location with extensive salt marsh habitat and astronomical tides and were weakened or lacked significance at the location with small microtidal salt marshes and wind-driven tides. Mosquitoes can serve as proxy indicators for numerous invertebrate species on the salt marsh. These predictable cycles and their effects need to be taken into consideration when investigating, restoring, or managing intertidal communities that are also facing sea-level rise. © 2017 by the Ecological Society of America.

  3. The lunar nodal tide and the distance to tne Moon during the Precambrian era

    NASA Technical Reports Server (NTRS)

    Walker, J. C. G.; Zahnle, K. J.

    1986-01-01

    The origin and early evolution of life on Earth occurred under physical and chemical conditions distinctly different from those of the present day. The broad goal of this research program is to characterize these conditions. One aspect involves the dynamics of the Earth-Moon system, the distance of the Moon from the Earth, and the length of the day. These have evolved during the course of Earth history as a result of the dissipation of tidal energy. As the moon has receded the amplitude of oceanic tides has decreased while the increasing length of the day should have influenced climate and the circulation of atmosphere and ocean. A 23.3 year periodicity preserved in a 2500 million year old banded iron-formation was interpreted as reflecting the climatic influence of the lunar nodal tide. The corresponding lunar distance would then have been approx. 52 Earth radii. The influence of the lunar nodal tide is also apparent in rocks with an age of 680 million years B.P. The derived value for lunar distance 2500 million years ago is the only datum on the dynamics of the Earth-Moon system during the Precambrian era of Earth history. The implied development of Precambrian tidal friction is in accord with more recent paleontological evidence as well as the long term stability of the lunar orbit.

  4. [Disease-free survival related factors in breast cancer].

    PubMed

    Dávila-Arias, Cristina; Ocón, Olga; Fernández, Mariana F; Arrebola, Juan Pedro; Sánchez, María José; Aneiros, José; Torné, Pablo; Olea, Nicolás

    2014-10-07

    To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  5. DYRK1A-mediated phosphorylation of GluN2A at Ser(1048) regulates the surface expression and channel activity of GluN1/GluN2A receptors.

    PubMed

    Grau, Cristina; Arató, Krisztina; Fernández-Fernández, José M; Valderrama, Aitana; Sindreu, Carlos; Fillat, Cristina; Ferrer, Isidre; de la Luna, Susana; Altafaj, Xavier

    2014-01-01

    N-methyl-D-aspartate glutamate receptors (NMDARs) play a pivotal role in neural development and synaptic plasticity, as well as in neurological disease. Since NMDARs exert their function at the cell surface, their density in the plasma membrane is finely tuned by a plethora of molecules that regulate their production, trafficking, docking and internalization in response to external stimuli. In addition to transcriptional regulation, the density of NMDARs is also influenced by post-translational mechanisms like phosphorylation, a modification that also affects their biophysical properties. We previously described the increased surface expression of GluN1/GluN2A receptors in transgenic mice overexpressing the Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), suggesting that DYRK1A regulates NMDARs. Here we have further investigated whether the density and activity of NMDARs were modulated by DYRK1A phosphorylation. Accordingly, we show that endogenous DYRK1A is recruited to GluN2A-containing NMDARs in the adult mouse brain, and we identify a DYRK1A phosphorylation site at Ser(1048) of GluN2A, within its intracellular C-terminal domain. Mechanistically, the DYRK1A-dependent phosphorylation of GluN2A at Ser(1048) hinders the internalization of GluN1/GluN2A, causing an increase of surface GluN1/GluN2A in heterologous systems, as well as in primary cortical neurons. Furthermore, GluN2A phosphorylation at Ser(1048) increases the current density and potentiates the gating of GluN1/GluN2A receptors. We conclude that DYRK1A is a direct regulator of NMDA receptors and we propose a novel mechanism for the control of NMDAR activity in neurons.

  6. DYRK1A-mediated phosphorylation of GluN2A at Ser1048 regulates the surface expression and channel activity of GluN1/GluN2A receptors

    PubMed Central

    Grau, Cristina; Arató, Krisztina; Fernández-Fernández, José M.; Valderrama, Aitana; Sindreu, Carlos; Fillat, Cristina; Ferrer, Isidre; de la Luna, Susana; Altafaj, Xavier

    2014-01-01

    N-methyl-D-aspartate glutamate receptors (NMDARs) play a pivotal role in neural development and synaptic plasticity, as well as in neurological disease. Since NMDARs exert their function at the cell surface, their density in the plasma membrane is finely tuned by a plethora of molecules that regulate their production, trafficking, docking and internalization in response to external stimuli. In addition to transcriptional regulation, the density of NMDARs is also influenced by post-translational mechanisms like phosphorylation, a modification that also affects their biophysical properties. We previously described the increased surface expression of GluN1/GluN2A receptors in transgenic mice overexpressing the Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), suggesting that DYRK1A regulates NMDARs. Here we have further investigated whether the density and activity of NMDARs were modulated by DYRK1A phosphorylation. Accordingly, we show that endogenous DYRK1A is recruited to GluN2A-containing NMDARs in the adult mouse brain, and we identify a DYRK1A phosphorylation site at Ser1048 of GluN2A, within its intracellular C-terminal domain. Mechanistically, the DYRK1A-dependent phosphorylation of GluN2A at Ser1048 hinders the internalization of GluN1/GluN2A, causing an increase of surface GluN1/GluN2A in heterologous systems, as well as in primary cortical neurons. Furthermore, GluN2A phosphorylation at Ser1048 increases the current density and potentiates the gating of GluN1/GluN2A receptors. We conclude that DYRK1A is a direct regulator of NMDA receptors and we propose a novel mechanism for the control of NMDAR activity in neurons. PMID:25368549

  7. α6β2* and α4β2* Nicotinic Acetylcholine Receptors As Drug Targets for Parkinson's Disease

    PubMed Central

    Wonnacott, Susan

    2011-01-01

    Parkinson's disease is a debilitating movement disorder characterized by a generalized dysfunction of the nervous system, with a particularly prominent decline in the nigrostriatal dopaminergic pathway. Although there is currently no cure, drugs targeting the dopaminergic system provide major symptomatic relief. As well, agents directed to other neurotransmitter systems are of therapeutic benefit. Such drugs may act by directly improving functional deficits in these other systems, or they may restore aberrant motor activity that arises as a result of a dopaminergic imbalance. Recent research attention has focused on a role for drugs targeting the nicotinic cholinergic systems. The rationale for such work stems from basic research findings that there is an extensive overlap in the organization and function of the nicotinic cholinergic and dopaminergic systems in the basal ganglia. In addition, nicotinic acetylcholine receptor (nAChR) drugs could have clinical potential for Parkinson's disease. Evidence for this proposition stems from studies with experimental animal models showing that nicotine protects against neurotoxin-induced nigrostriatal damage and improves motor complications associated with l-DOPA, the “gold standard” for Parkinson's disease treatment. Nicotine interacts with multiple central nervous system receptors to generate therapeutic responses but also produces side effects. It is important therefore to identify the nAChR subtypes most beneficial for treating Parkinson's disease. Here we review nAChRs with particular emphasis on the subtypes that contribute to basal ganglia function. Accumulating evidence suggests that drugs targeting α6β2* and α4β2* nAChR may prove useful in the management of Parkinson's disease. PMID:21969327

  8. Involved-Field Radiotherapy versus Elective Nodal Irradiation in Combination with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study

    PubMed Central

    Chen, Ming; Bao, Yong; Ma, Hong-Lian; Wang, Jin; Wang, Yan; Peng, Fang; Zhou, Qi-Chao; Xie, Cong-Hua

    2013-01-01

    This prospective randomized study is to evaluate the locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer. It appears that higher dose could be delivered in IFRT arm than that in ENI arm, and IFRT did not increase the risk of initially uninvolved or isolated nodal failures. Both a tendency of improved locoregional progression-free survival and a significant increased overall survival rate are in favor of IFRT arm in this study. PMID:23762840

  9. Correlation between the sudden jump-like increases of the atrio-Hisian interval induced during burst atrial pacing and during programmed atrial stimulation in patients with atrioventricular nodal reentrant tachycardia.

    PubMed

    Bayraktarova, Iskra H; Stoyanov, Milko K; Kunev, Boyan T; Shalganov, Tchavdar N

    To study the correlation between the sudden prolongations of the atrio-Hisian (AH) interval with ≥50 ms during burst and programmed atrial stimulation, and to define whether the AH jump during burst atrial pacing is a reliable diagnostic criterion for dual AV nodal physiology. Retrospective data on 304 patients with preliminary ECG diagnosis of AV nodal reentrant tachycardia (AVNRT), confirmed during electrophysiological study, was analyzed for the presence of AH jump during burst and programmed atrial stimulation, and for correlation between the pacing modes for inducing the jump. Wilcoxon signed-ranks test and Spearman's bivariate correlation coefficient were applied, significant was P-value <0.05. The population was aged 48.5 ± 15.7 (12-85) years; males were 38.5%. AH jump occurred during burst atrial pacing in 81% of the patients, and during programmed stimulation - in 78%, P = 0.366. In 63.2% AH jump was induced by both pacing modes; in 17.8% - only by burst pacing; in 14.8% - only by programmed pacing; in 4.2% there was no inducible jump. There was negative correlation between both pacing modes, ρ = -0.204, Р<0.001. Burst and programmed atrial stimulation separately prove the presence of dual AV nodal physiology in 81 and 78% of the patients with AVNRT, respectively. There is negative correlation between the two pacing modes, allowing the combination of the two methods to prove diagnostic in 95.8% of the patients. Copyright © 2017 Indian Heart Rhythm Society. Production and hosting by Elsevier B.V. All rights reserved.

  10. Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease

    PubMed Central

    Knott, L.; Avery, N.C.; Hollander, A.P.; Tarlton, J.F.

    2011-01-01

    Summary Objective To examine effects of high omega-3 (n-3) polyunsaturated fatty acid (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig model, and to further characterise pathogenesis in this model. Modern diets low in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly including OA. However, n-3 is also thought to increases bone density, which is a possible contributing factor in OA. Therefore we aim to determine the net influence of n-3 in disease development. Method OA-prone Dunkin-Hartley (DH) Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and subchondral bone pathology by histology, and biochemistry, including collagen cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase, glycosaminoglycan (GAG), and denatured type II collagen. Results Dietary n-3 reduced disease in OA-prone animals. Most cartilage parameters were modified by n-3 diet towards those seen in the non-pathological BS2 strain – significantly active MMP-2, lysyl-pyridinoline and total collagen cross-links – the only exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG content was higher and denatured type II lower in the n-3 group. Subchondral bone parameters in the DH n-3 group also changed towards those seen in the non-pathological strain, significantly calcium:phosphate ratios and epiphyseal bone density. Conclusion Dietary n-3 PUFA reduced OA in the prone strain, and most disease markers were modified towards those of the non-OA strain, though not all significantly so. Omega-3 did not increase markers of pathology in either strain. PMID:21723952

  11. N-terminal pro-brain natriuretic peptide in acute Kawasaki disease correlates with coronary artery involvement.

    PubMed

    Adjagba, Philippe M; Desjardins, Laurent; Fournier, Anne; Spigelblatt, Linda; Montigny, Martine; Dahdah, Nagib

    2015-10-01

    We have lately documented the importance of N-terminal pro-brain natriuretic peptide in aiding the diagnosis of Kawasaki disease. We sought to investigate the potential value of N-terminal pro-brain natriuretic peptide pertaining to the prediction of coronary artery dilatation (Z-score>2.5) and/or of resistance to intravenous immunoglobulin therapy. We hypothesised that increased serum N-terminal pro-brain natriuretic peptide level correlates with increased coronary artery dilatation and/or resistance to intravenous immunoglobulin. We carried out a prospective study involving newly diagnosed patients treated with 2 g/kg intravenous immunoglobulin within 5-10 days of onset of fever. Echocardiography was performed in all patients at onset, then weekly for 3 weeks, then at month 2, and month 3. Coronary arteries were measured at each visit, and coronary artery Z-score was calculated. All the patients had N-terminal pro-brain natriuretic peptide serum level measured at onset, and the Z-score calculated. There were 109 patients enrolled at 6.58±2.82 days of fever, age 3.79±2.92 years. High N-terminal pro-brain natriuretic peptide level was associated with coronary artery dilatation at onset in 22.2 versus 5.6% for normal N-terminal pro-brain natriuretic peptide levels (odds ratio 4.8 [95% confidence interval 1.05-22.4]; p=0.031). This was predictive of cumulative coronary artery dilatation for the first 3 months (p=0.04-0.02), but not during convalescence at 2-3 months (odds ratio 1.28 [95% confidence interval 0.23-7.3]; p=non-significant). Elevated N-terminal pro-brain natriuretic peptide levels did not predict intravenous immunoglobulin resistance, 15.3 versus 13.5% (p=1). Elevated N-terminal pro-brain natriuretic peptide level correlates with acute coronary artery dilatation in treated Kawasaki disease, but not with intravenous immunoglobulin resistance.

  12. Discriminatory Solutions for (n,n-2)-Games.

    DTIC Science & Technology

    An ( n ,m)-game is an n -person game in which all coalitions with less than m players are not vital. A p-discriminatory solution to a game is a von...for an arbitrary ( n , n -2)-game to have a k-discriminatory solution. These conditions are used to characterize all 2-discriminatory solutions for 4...person games, and for the simple ( n , n -2)-games in which all coalitions with at least n -2 players are winning coalitions. (Author)

  13. Patterns of failure after postoperative radiotherapy for incompletely resected (R1) non-small cell lung cancer: implications for radiation target volume design.

    PubMed

    Olszyna-Serementa, Marta; Socha, Joanna; Wierzchowski, Marek; Kępka, Lucyna

    2013-05-01

    Overall survival (OS) and pattern of failure in R1-resected non-small cell lung cancer (NSCLC) patients treated with 3D-planned postoperative radiotherapy (PORT) was retrospectively evaluated. The outcomes and patterns of failure in patients with (+) and without (-) extracapsular nodal extension (ECE) were compared and analyzed with respect to the radiation target volume design. Eighty R1-resected (37 ECE+ and 43 ECE-) patients received PORT (60Gy, 2Gy daily) between 2002 and 2011. Patients with N2 disease received limited elective nodal irradiation (ENI); for pN0-1 disease the use of ENI was optional. Among ECE- (extranodal-R1) patients there were 35 pN0-1 and eight pN2 cases; in pN0-1 patients, patterns of failure and outcomes were analyzed with respect to the use of ENI. Loco-regional failure (LRF) was defined as in-field relapse; isolated nodal failure (INF) was defined as out-of-field regional nodal recurrence occurring without LRF, irrespective of distant metastases. The actuarial 3-year OS rate was 36.3% (median: 30 months). Three-year OS rates in the ECE- and ECE+ group were 40.4% and 31.4%, with median OS of 31 and 24 months, respectively (p=0.43). In multivariate analysis, the presence of ECE was correlated with OS (HR=3.02; 95% CI: 1.00-9.16; p=0.05). Three-year cumulative incidence of LRF (CILRF) was 14.5% and 15.5% in the ECE- and ECE+ groups, respectively (p=0.98). Three-year cumulative incidence of INF (CIINF) was 14.1% in the ECE- group and 11.1% in the ECE+ group (p=0.76). For pN0-1 patients treated with and without ENI (13 and 22 patients) 3-year CILRF rates were 7.7% and 20.8%, respectively (p=0.20); 3-year CIINF rates were 9.1% and 16.3%, respectively (p=0.65). PORT resulted in a relatively good survival of R1-resected NSCLC patients. Relatively high incidence of INF was found in both ECE+ and ECE- patients. For ECE+ patients, treated with limited ENI, distant failure remains a major concern, so the design of ENI fields seems of lesser

  14. Probing lattice dynamics and electron-phonon coupling in the topological nodal-line semimetal ZrSiS

    NASA Astrophysics Data System (ADS)

    Singha, Ratnadwip; Samanta, Sudeshna; Chatterjee, Swastika; Pariari, Arnab; Majumdar, Dipanwita; Satpati, Biswarup; Wang, Lin; Singha, Achintya; Mandal, Prabhat

    2018-03-01

    Topological materials provide an exclusive platform to study the dynamics of relativistic particles in table-top experiments and offer the possibility of wide-scale technological applications. ZrSiS is a newly discovered topological nodal-line semimetal and has drawn enormous interests. In this paper, we have investigated the lattice dynamics and electron-phonon interaction in single-crystalline ZrSiS using Raman spectroscopy. Polarization and angle-resolved Raman data have been analyzed using crystal symmetries and theoretically calculated atomic vibrational patterns along with phonon dispersion spectra. Wavelength- and temperature-dependent measurements show the complex interplay of electron and phonon degrees of freedom, resulting in resonant phonon and quasielastic electron scattering through interband transition. Our high-pressure Raman studies reveal vibrational anomalies, which are the signature of structural phase transitions. Further investigations through high-pressure synchrotron x-ray diffraction clearly show pressure-induced structural transitions and coexistence of multiple phases, which also indicate possible electronic topological transitions in ZrSiS. This study not only provides the fundamental information on the phonon subsystem, but also sheds some light in understanding the topological nodal-line phase in ZrSiS and other isostructural systems.

  15. Human Lipooligosaccharide IGG That Prevents Endemic Meningococcal Disease Recognizes an Internal Lacto-N-neotetraose Structure*

    PubMed Central

    Cheng, Hui; Yang, Zhijie; Estabrook, Michele M.; John, Constance M.; Jarvis, Gary A.; McLaughlin, Stephanie; Griffiss, J. McLeod

    2011-01-01

    Antibodies that initiate complement-mediated killing of Neisseria meningitidis as they enter the bloodstream from the oropharynx protect against disseminated disease. Human IgGs that bind the neisserial L7 lipooligosaccharide (LOS) are bactericidal for L3,7 and L2,4 meningococci in the presence of human complement. These strains share a lacto-N-neotetraose (nLc4) LOS α chain. We used a set of mutants that have successive saccharide deletions from the nLc4 α chain to characterize further the binding and bactericidal activity of nLc4 LOS IgG. We found that the nLc4 α chain conforms at least four different antigens. We separately purified IgG that required the nLc4 (non-reducing) terminal galactose (Gal) for binding and IgG that bound the truncated nLc3 α chain that lacks this Gal residue. IgG that bound the internal nLc3 α chain killed both L3,7 and L2,4 strains, whereas IgG that required the nLc4 terminal Gal residue for binding killed L2,4 stains but not L3,7 strains. These results show that the diversity of LOS antibodies in human serum is as much a function of the conformation of multiple antigens by a single glycoform as of the production of multiple glycoforms. Differences in sensitivity to killing by human nLc4 LOS IgG may account for the fact that fully two-thirds of endemic group B meningococcal disease in infants and children is caused by L3,7 strains, but only 20% is caused by L2,4 stains. PMID:22027827

  16. Predictors of health-related quality of life in patients treated with neck dissection for head and neck cancer.

    PubMed

    Gane, Elise M; McPhail, Steven M; Hatton, Anna L; Panizza, Benedict J; O'Leary, Shaun P

    2017-12-01

    Patients with head and neck cancer can report reduced health-related quality of life several years after treatment. The aim of this study was to identify risk factors for reduced quality of life in patients up to 5 years following neck dissection. This cross-sectional study was conducted at two hospitals in Brisbane, Australia. Patients completed two measures of quality of life: the Neck Dissection Impairment Index (NDII), a region- and disease-specific tool, and the Assessment of Quality of Life-4 Domains, a general tool. Generalised linear modelling was used to determine which demographic and clinical variables were associated with quality of life. The cohort included n = 129 patients (71% male, median age 61, median 3 years since surgery). Positive nodal disease was associated with better quality of life on the NDII [e.g. N2 vs N0 coeff (95% CI) = 22.84 (7.33, 38.37)]. Worse quality of life was associated with adjuvant treatment [e.g. Independent Living domain model: surgery with chemoradiation vs surgery only coeff (95% CI) = -0.11 (-0.22, -0.01)]. Positive nodal disease was associated with better quality of life, which may be a reflection of response shift. Multimodality treatment leads to worse quality of life compared with surgery only.

  17. Effect of Radiotherapy Dose and Volume on Relapse in Merkel Cell Cancer of the Skin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Foote, Matthew, E-mail: matthew_foote@health.qld.gov.a; Harvey, Jennifer; Porceddu, Sandro

    Purpose: To assess the effect of radiotherapy (RT) dose and volume on relapse patterns in patients with Stage I-III Merkel cell carcinoma (MCC). Patients and Methods: This was a retrospective analysis of 112 patients diagnosed with MCC between January 2000 and December 2005 and treated with curative-intent RT. Results: Of the 112 evaluable patients, 88% had RT to the site of primary disease for gross (11%) or subclinical (78%) disease. Eighty-nine percent of patients had RT to the regional lymph nodes; in most cases (71%) this was for subclinical disease in the adjuvant or elective setting, whereas 21 patients (19%)more » were treated with RT to gross nodal disease. With a median follow-up of 3.7 years, the 2-year and 5-year overall survival rates were 72% and 53%, respectively, and the 2-year locoregional control rate was 75%. The in-field relapse rate was 3% for primary disease, and relapse was significantly lower for patients receiving {>=}50Gy (hazard ratio [HR] = 0.22; 95% confidence interval [CI], 0.06-0.86). Surgical margins did not affect the local relapse rate. The in-field relapse rate was 11% for RT to the nodes, with dose being significant for nodal gross disease (HR = 0.24; 95% CI, 0.07-0.87). Patients who did not receive elective nodal RT had a much higher rate of nodal relapse compared with those who did (HR = 6.03; 95% CI, 1.34-27.10). Conclusion: This study indicates a dose-response for subclinical and gross MCC. Doses of {>=}50Gy for subclinical disease and {>=}55Gy for gross disease should be considered. The draining nodal basin should be treated in all patients.« less

  18. Topological Nodal Cooper Pairing in Doped Weyl Metals

    NASA Astrophysics Data System (ADS)

    Li, Yi; Haldane, F. D. M.

    2018-02-01

    We generalize the concept of Berry connection of the single-electron band structure to that of a two-particle Cooper pairing state between two Fermi surfaces with opposite Chern numbers. Because of underlying Fermi surface topology, the pairing Berry phase acquires nontrivial monopole structure. Consequently, pairing gap functions have topologically protected nodal structure as vortices in the momentum space with the total vorticity solely determined by the pair monopole charge qp. The nodes of gap function behave as the Weyl-Majorana points of the Bogoliubov-de Gennes pairing Hamiltonian. Their relation with the connection patterns of the surface modes from the Weyl band structure and the Majorana surface modes inside the pairing gap is also discussed. Under the approximation of spherical Fermi surfaces, the pairing symmetry are represented by monopole harmonic functions. The lowest possible pairing channel carries angular momentum number j =|qp|, and the corresponding gap functions are holomorphic or antiholomorphic functions on Fermi surfaces. After projected on the Fermi surfaces with nontrivial topology, all the partial-wave channels of pairing interactions acquire the monopole charge qp independent of concrete pairing mechanism.

  19. A Web-based nomogram predicting para-aortic nodal metastasis in incompletely staged patients with endometrial cancer: a Korean Multicenter Study.

    PubMed

    Kang, Sokbom; Lee, Jong-Min; Lee, Jae-Kwan; Kim, Jae-Weon; Cho, Chi-Heum; Kim, Seok-Mo; Park, Sang-Yoon; Park, Chan-Yong; Kim, Ki-Tae

    2014-03-01

    The purpose of this study is to develop a Web-based nomogram for predicting the individualized risk of para-aortic nodal metastasis in incompletely staged patients with endometrial cancer. From 8 institutions, the medical records of 397 patients who underwent pelvic and para-aortic lymphadenectomy as a surgical staging procedure were retrospectively reviewed. A multivariate logistic regression model was created and internally validated by rigorous bootstrap resampling methods. Finally, the model was transformed into a user-friendly Web-based nomogram (http://http://www.kgog.org/nomogram/empa001.html). The rate of para-aortic nodal metastasis was 14.4% (57/397 patients). Using a stepwise variable selection, 4 variables including deep myometrial invasion, non-endometrioid subtype, lymphovascular space invasion, and log-transformed CA-125 levels were finally adopted. After 1000 repetitions of bootstrapping, all of these 4 variables retained a significant association with para-aortic nodal metastasis in the multivariate analysis-deep myometrial invasion (P = 0.001), non-endometrioid histologic subtype (P = 0.034), lymphovascular space invasion (P = 0.003), and log-transformed serum CA-125 levels (P = 0.004). The model showed good discrimination (C statistics = 0.87; 95% confidence interval, 0.82-0.92) and accurate calibration (Hosmer-Lemeshow P = 0.74). This nomogram showed good performance in predicting para-aortic metastasis in patients with endometrial cancer. The tool may be useful in determining the extent of lymphadenectomy after incomplete surgery.

  20. Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine

    PubMed Central

    de Andrade, Kívia Queiroz; Moura, Fabiana Andréa; dos Santos, John Marques; de Araújo, Orlando Roberto Pimentel; de Farias Santos, Juliana Célia; Goulart, Marília Oliveira Fonseca

    2015-01-01

    Liver disease is highly prevalent in the world. Oxidative stress (OS) and inflammation are the most important pathogenetic events in liver diseases, regardless the different etiology and natural course. N-acetyl-l-cysteine (the active form) (NAC) is being studied in diseases characterized by increased OS or decreased glutathione (GSH) level. NAC acts mainly on the supply of cysteine for GSH synthesis. The objective of this review is to examine experimental and clinical studies that evaluate the antioxidant and anti-inflammatory roles of NAC in attenuating markers of inflammation and OS in hepatic damage. The results related to the supplementation of NAC in any form of administration and type of study are satisfactory in 85.5% (n = 59) of the cases evaluated (n = 69, 100%). Within this percentage, the dosage of NAC utilized in studies in vivo varied from 0.204 up to 2 g/kg/day. A standard experimental design of protection and treatment as well as the choice of the route of administration, with a broader evaluation of OS and inflammation markers in the serum or other biological matrixes, in animal models, are necessary. Clinical studies are urgently required, to have a clear view, so that, the professionals can be sure about the effectiveness and safety of NAC prescription. PMID:26694382