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Sample records for platinum-based doublet chemotherapy

  1. Platinum-based doublet chemotherapy plus bevacizumab without bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC)

    DEFF Research Database (Denmark)

    Nørøxe, Dorte Schou; Wallerek, Sandra; Sørensen, Jens Benn

    2013-01-01

    We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance.......We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance....

  2. Platinum-based doublet chemotherapy plus bevacizumab without bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC)

    DEFF Research Database (Denmark)

    Nørøxe, Dorte Schou; Wallerek, Sandra; Sørensen, Jens Benn

    2013-01-01

    We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance.......We report on a retrospective, consecutive non-randomized group of patients who received bevacizumab plus chemotherapy without bevazicumab maintenance....

  3. Sequential treatment of tyrosine kinase inhibitor and platinum-based doublet chemotherapy on EGFR mutant non-small cell lung cancer: a meta-analysis of randomized controlled clinical trials

    Science.gov (United States)

    Qiao, Lifen; Wang, Jin; Long, Guoxian; Jiang, Yueqiang

    2017-01-01

    There is debate surrounding which treatment is superior in overall survival (OS) rates in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC); first-line tyrosine kinase inhibitor (TKI) followed by second-line platinum-based doublet chemotherapy (PCT), or the reverse sequence. Cross treatment of first- and second-line TKI and PCT makes it difficult to deduce which sequence (TKI-PCT or PCT-TKI) is better for OS. Using the keywords “lung cancer” and “EGFR” we identified clinical trials within the PubMed database which were published between January 2006 and November 2016. Basic characteristics and OS with hazard ratio and 95% confidence intervals were searched and analyzed. In total, 457 articles were reviewed and nine clinical trials with 1,876 patients were of sufficient quality for further analysis. Fixed effects models were performed to pool the data in this meta-analysis. All nine studies were open-labeled, multicenter, Phase III randomized controlled clinical trials. The pooled hazard ratio was 0.96 (95% confidence interval: 0.84–1.10) for OS between first-line TKI followed by second-line PCT compared to the reverse sequence. No statistically significant heterogeneity (I2=0, P=0.553) nor publication bias (Egger’s P=0.991) was observed among these studies. In conclusion, there was no OS benefit between first-line TKI followed by second-line PCT compared to the reverse sequence in EGFR mutant NSCLC patients. Chemotherapy was still useful and irreplaceable for the treatment of NSCLC, especially for those patients with EGFR unavailable for testing. PMID:28280362

  4. SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

    NARCIS (Netherlands)

    SCHRODER, CP; VANDERGRAAF, WTA; KEMA, IP; GROENEWEGEN, A; SLEIJFER, DT; DEVRIES, EGE

    1995-01-01

    The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3 antag

  5. [Comparison of the effectiveness of platinum-based chemotherapy versus non-platinum-based chemotherapy for triple-negative breast cancer with metastases confined to the lungs].

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    Hong, Ruoxi; Ma, Fei; Shi, Xiuqing; Li, Qing; Zhang, Pin; Yuan, Peng; Wang, Jiayu; Fan, Ying; Cai, Ruigang; Li, Qiao; Xu, Binghe

    2014-10-01

    To compare the effect of first-line treatment with platinum-based chemotherapy and non-platinum-based chemotherapy in patients with lung metastases from triple negative breast cancer (TNBC). Sixty-five eligible patients were divided into platinum-treated group and non-platinum-treated group according to the first-line therapy. Factors predicting the chemotherapeutic efficacy included overall survival (OS), progression-free survival (PFS) and objective response (OR). In the platinum-treated group of 32 patients, 2 cases (6.3%) achieved CR, 16 cases (50.0%) achieved PR, 11 (34.4%) cases achieved SD, and 3 patients (9.4%) achieved PD. In the non-platinum-treated group of 33 patients, 2 cases (6.1%) achieved CR, 6 cases (18.2%) achieved PR, 16 cases (48.5%) achieved SD, and 9 cases (27.3%) achieved PD. Median PFS was significantly longer in the platinum-treated group than in the non-platinum-treated group (10 months vs. 6.0 months, P = 0.012), and OS was also improved (32 months vs. 22 months, P = 0.006). Multivariate analysis of several factors including local-regional lymph node involvement, lung metastasis-related symptoms, first-line platinum-based chemotherapy, disease-free interval, size and number of lung lesions, showed that first-line platinum-based chemotherapy was an independent prognostic factor for TNBC patients with lung metastases. Compared with non-platinum-based chemotherapy, the first-line platinum-based chemotherapy can improve PFS and OS in TNBC patients with metastases confined to the lungs.

  6. Overexpression of MAC30 is Resistant to Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer.

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    Chen, Ruhua; Fen, Yan; Lin, Xubo; Ma, Tieliang; Cai, Hourong; Ding, Hui

    2016-12-01

    Adjuvant platinum-based chemotherapy has developed its stability as the first-line treatment in advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the prognostic value of meningioma-associated protein (MAC30) on adjuvant platinum-based chemotherapeutic response and survival in patients with NSCLC. A total of 174 retrospective stage III B to IV Chinese patients with NSCLC were enrolled in the study. Among all cases, 85 patients were given platinum-based chemotherapy and another 89 patients received molecularly targeted therapy. The expression of MAC30 in tumor samples was confirmed via immunohistochemical staining to correlate with the therapeutic response and survival of patients. Patients having NSCLC with MAC30 overexpression showed a poorer response to platinum-based chemotherapy, while there was no prognostic value of MAC30 expression on molecularly targeted therapy. Further, patients receiving platinum-based chemotherapy with enhanced MAC30 expression exhibited shorter survival. A multivariate analysis exhibited that increased MAC30 expression was an independent prognostic factor for overall survival in patients having NSCLC with platinum-based chemotherapy. In conclusion, patients having NSCLC with higher MAC30 expression resisted to platinum-based chemotherapy and exhibited worse survival. © The Author(s) 2015.

  7. Relationship between BRCA1 Expression and Efifcacy of Platinum-based Chemotherapy in Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Xu Guanghui; Li Yu; Liu Yi

    2014-01-01

    Objective:To explore the expression of breast cancer susceptibility gene 1 (BRCA1) in human colorectal cancer and its correlation with efifcacy of platinum-based chemotherapy. Methods:A total of 78 samples from patients with colorectal cancer and receiving platinum-based chemotherapy were selected, and meanwhile 14 cases of normal colonic mucosa samples were selected as a normal control, 12 cases of non-cancerous tissue in colorectal cancer samples were selected as a pericarcinorma control. The expression of BRCA1 in these tissues was detected using immunohistochemical S-P method, and all patients treated with drugs were followed-up for survival time. Results: The positive rate of BRCA1 expression in colorectal cancer tissue was 52.6%, signiifcantly lower than that in the control groups. BRCA1 expression was closely associated with histological differentiation degrees (χ2=14.16,P=0.001), but not with the age, gender, local inifltration, lymph node metastasis and TNM staging. Comparing with those with positive BRCA1 expression, the patients with negative BRCA1 expression after oxaliplatin-based chemotherapy had signiifcantly longer disease-free survival (DFS) (P=0.032). Conclusion:Application of oxaliplatin-based chemotherapy in the patients with negative BRCA1 expression can obtain the survival beneift, and the level of BRCA1 expression can be useful in the selection of chemotherapy regimens and evaluation of prognosis for patients with colorectal cancer after surgery.

  8. ERCC1 Expression in Metastatic Triple Negative Breast Cancer Patients Treated with Platinum-Based Chemotherapy

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    EL Baiomy, Mohamed Ali; El Kashef, Wagdi F

    2017-02-01

    Background: Possible targeted therapies for metastatic triple negative breast cancer (TNBC) include cytotoxic chemotherapy that causes interstrand breaks (platinum-based drugs). The excision repair cross-complementation 1 (ERCC1) enzyme plays an essential role in the nucleotide excision repair pathway, removing platinum-induced DNA adducts and contributing to cisplatin resistance. Detecting ERCC1 overexpression is important in considering treatment options for metastatic TNBC, including individualized approaches to therapy, and may facilitate improved responses or reduction of unnecessary toxicity. We hypothesized that assigning cisplatin based on pretreatment ERCC1 expression would improve response and survival. This study was conducted to assess the impact of ERCC1 expression on PFS, OS and response rates in metastatic triple negative breast cancer patients treated with platinum-based chemotherapy. Methods: From June 2012 to November 2013, 52 metastatic triple negative breast cancer patients were enrolled. ERCC1 protein expression was detected from pretreatment biopsies by Immunohistochemistry. All patients received cisplatin plus paclitaxel. The primary end point was the impact of ERCC1 expression on PFS and OS. Results: 34 patients (65.4%) showed positive ERCC1 expression while 18 (34.6%) proved negative. Positive ERCC1 expression was associated with short PFS (median, 5 months vs. 7 months; P = 0.043), short OS (median, 9 months vs. 11 months; P = 0.033) and poor response to cisplatin based chemotherapy (P = 0.046). Conclusions: This prospective study further validated ERCC1 as a reliable biomarker for customized chemotherapy in metastatic triple negative breast cancer patients. High expression of ERCC1 was thereby fond to be significantly associated with poor outcome in patients treated with platinum based chemotherapy.

  9. Pharmacogenomics of platinum-based chemotherapy sensitivity in NSCLC: toward precision medicine.

    Science.gov (United States)

    Yin, Ji-Ye; Li, Xi; Zhou, Hong-Hao; Liu, Zhao-Qian

    2016-08-01

    Lung cancer is one of the leading causes of cancer-related death in the world. Platinum-based chemotherapy is the first-line treatment for non-small-cell lung cancer (NSCLC), however, the therapeutic efficiency varies remarkably among individuals. A large number of pharmacogenomics studies aimed to identify genetic variations which can be used to predict platinum response. Those studies are leading NSCLC treatment to the new era of precision medicine. In the current review, we provided a comprehensive update on the main recent findings of genetic variations which can be used to predict platinum sensitivity in the NSCLC patients.

  10. Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer

    DEFF Research Database (Denmark)

    Rossi, Antonio; Chiodini, Paolo; Sun, Jong-Mu;

    2014-01-01

    BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare ...

  11. Randomized pharmacokinetic study comparing subcutaneous and intravenous palonosetron in cancer patients treated with platinum based chemotherapy.

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    Belen Sadaba

    Full Text Available BACKGROUND: Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV or oral routes, but subcutaneous (SC administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron. PATIENTS AND METHODS: Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA. RESULTS: From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p=0.160. Bioavalability of SC palonosetron was 118% (95% IC: 69-168. Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration. CONCLUSIONS: Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01046240.

  12. Calpain-2 expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer

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    Storr, Sarah J; Safuan, Sabreena; Woolston, Caroline M; Abdel-Fatah, Tarek; Deen, Suha; Chan, Stephen Y; Martin, Stewart G

    2012-01-01

    Ovarian cancer is routinely treated with surgery and platinum-based chemotherapy. Resistance is a major obstacle in the efficacy of this chemotherapy regimen and the ability to identify those patients at risk of developing resistance is of considerable clinical importance. The expression of calpain-1, calpain-2 and calpastatin were determined using standard immunohistochemistry on a tissue microarray of 154 primary ovarian carcinomas from patients subsequently treated with platinum-based adjuvant chemotherapy. High levels of calpain-2 expression was significantly associated with platinum resistant tumours (P = 0.031). Furthermore, high expression of calpain-2 was significantly associated with progression-free (P = 0.049) and overall survival (P = 0.006) in this cohort. The association between calpain-2 expression and overall survival remained significant in multivariate analysis accounting for tumour grade, stage, optimal debulking and platinum sensitivity (hazard ratio = 2.174; 95% confidence interval = 1.144–4.130; P = 0.018). The results suggest that determining calpain-2 expression in ovarian carcinomas may allow prognostic stratification of patients treated with surgery and platinum-based chemotherapy. The findings of this study warrant validation in a larger clinical cohort. PMID:22435971

  13. Piroxicam and intracavitary platinum-based chemotherapy for the treatment of advanced mesothelioma in pets: preliminary observations

    OpenAIRE

    2008-01-01

    Abstract Malignant Mesothelioma is an uncommon and very aggressive tumor that accounts for 1% of all the deaths secondary to malignancy in humans. Interestingly, this neoplasm has been occasionally described in companion animals as well. Aim of this study was the preclinical evaluation of the combination of piroxicam with platinum-based intracavitary chemotherapy in pets. Three companion animals have been treated in a three years period with this combination. Diagnosis was obtained by ultraso...

  14. Platinum-Based Chemotherapy for Variant Castrate-Resistant Prostate Cancer

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    Aparicio, Ana M.; Harzstark, Andrea L.; Corn, Paul G.; Wen, Sijin; Araujo, John C.; Tu, Shi-Ming; Pagliaro, Lance C.; Kim, Jeri; Millikan, Randall E.; Ryan, Charles J.; Tannir, Nizar M.; Zurita, Amado J.; Mathew, Paul; Arap, Wadih; Troncoso, Patricia; Thall, Peter F.; Logothetis, Christopher J.

    2013-01-01

    Purpose Clinical features characteristic of small-cell prostate carcinoma (SCPC), (““anaplastic””) often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined “anaplastic” clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low PSA levels relative to tumor burden or short response to androgen deprivation therapy. Experimental Design A 120-patient phase II trial of frontline carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity. Results Seventy-four of 113 (65.4%) and 24 of 71 (33.8%) were progression free after 4 cycles of CD and EP, respectively. Median overall survival (OS) was 16 months (95% CI, 13.6-19.0 months). Of the 7 “anaplastic” criteria, bulky tumor mass was significantly associated with poor outcome. Lactic acid dehydrogenase (LDH) strongly predicted for OS and rapid progression. Serum carcinoembryonic antigen (CEA) concentration strongly predicted OS but not rapid progression. Neuroendocrine markers did not predict outcome or response to therapy. Conclusion Our findings support the hypothesis that patients with “anaplastic” prostate cancer are a recognizable subset characterized by a high response rate of short duration to platinum-containing chemotherapies, similar to SCPC. Our results suggest that CEA is useful for selecting therapy in men with CRPC and consolidative therapies to bulky high-grade tumor masses should be considered in this patient population. PMID:23649003

  15. EMT-like circulating tumor cells in ovarian cancer patients are enriched by platinum-based chemotherapy.

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    Chebouti, Issam; Kasimir-Bauer, Sabine; Buderath, Paul; Wimberger, Pauline; Hauch, Siegfried; Kimmig, Rainer; Kuhlmann, Jan Dominik

    2017-07-25

    Assuming that tumor cell dissemination requires a shift to a mesenchymal phenotype, we analyzed the incidence of epithelial-to-mesenchymal-transition (EMT)-like circulating tumor cells (CTCs) in ovarian cancer patients and inquired, how their molecular phenotypes respond to platinum-based chemotherapy and influence outcome. Before surgery, overall detection rate for epithelial CTCs was 18%. EMT-like CTCs were more frequently observed (30%) and were mutually exclusive to epithelial CTCs in the majority of patients (82%). After chemotherapy, EMT-like CTCs increased up to 52%, accompanied by the "de novo" emergence of PI3Kα+/Twist+ EMT-like CTCs. Before surgery, PI3K+ EMT-like CTCs in combination with epithelial CTCs indicated decreased OS (p = 0.02) and FIGO I-III patients with residual tumor burden after surgery were more likely to be positive for EMT-like CTCs after chemotherapy (p = 0.02). In the latter group, epithelial CTCs alone significantly correlated with decreased PFS and OS (p = 0.02, p = 0.002), supported by an additional inclusion of PI3K+ CTCs (OS, p = 0.001). Blood samples of 91 ovarian cancer patients before surgery and 31 matched samples after adjuvant chemotherapy were evaluated for CTCs with the AdnaTest ovarian cancer and EMT-1, analyzing the epithelial-associated transcripts EpCAM, Muc-1 and CA125 and the EMT-associated transcripts PI3Kα, Akt-2 and Twist. Platinum-based chemotherapy seems to select for EMT-like CTCs in ovarian cancer patients and provokes a shift towards PI3Kα and Twist expressing CTCs, which may reflect clonal tumor evolution towards therapy resistance. It has to be determined, whether this CTC subgroup may serve as a biomarker to identify patients at high risk.

  16. Correlation of rs1799793 polymorphism in ERCC2 and the clinical response to platinum-based chemotherapy in patients with triple negative breast cancer.

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    Lu, Jun; Zhao, Haitao; Li, Sha; Tian, Zhongze; Zhu, Xianghui; Wang, Hongyi; Fu, Hua

    2015-01-01

    Polymorphisms of DNA repair genes may affect the repair capacity of DNA damages and cause different responses towards chemotherapy. Excision repair cross-complementing group 2 (ERCC2) plays an important role in the nucleotide excision repair. The aim of this study was to investigate the association between ERCC2 single nucleotide polymorphisms (SNPs) and the response to platinum-based chemotherapy among patients with triple negative breast cancer. In total, 60 triple negative breast cancer patients treated with platinum-based chemotherapy were studied. The clinical, pathological and treatment data of them were collected. Sequenom's MassARRAY system was used in the detection of the SNPs of ERCC2. Finally, the association between genotypes and different clinical responses among patients was analyzed. All of the patients received a platinum-based chemotherapy for 4 cycles in median and achieved an overall response rate of 66.7%, showing a comparative good response towards platinum-based chemotherapy among triple negative breast cancer. Fifty-three of the 60 patients had got the results of ERCC2 rs1799793 polymorphisms after MassARRAY detection. The proportion of GG genotype and GA genotype was 81.1% and 18.9% respectively. The response rate of the rs1799793 GG genotype group was 69.8%, while the GA genotype group only had a response rate of 30.0%. It turned out that the GG genotype was associated with better response towards platinum-based chemotherapy (P=0.030). ERCC2 rs1799793 polymorphism may be associated with the clinical sensitivity of platinum-based chemotherapy and could be a potential predictive biomarker for triple negative breast cancer patients treated with platinum compounds.

  17. Platinum-based chemotherapy: gastrointestinal immunomodulation and enteric nervous system toxicity.

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    Stojanovska, Vanesa; Sakkal, Samy; Nurgali, Kulmira

    2015-02-15

    The efficacy of chemotherapeutic treatment of colorectal cancer is challenged by severe gastrointestinal side effects, which include nausea, vomiting, constipation, and diarrhea. These symptoms can persist long after the treatment has been ceased. An emerging concept is the ability of platinum-based drugs to stimulate immunity, which is in contrast to conventional chemotherapeutic agents that are immunosuppressive. Here, we review the immunomodulatory aspects of platinum-based anticancer chemotherapeutics and their impact on gastrointestinal innervation. Given the bidirectional communication between the enteric nervous system and gastrointestinal immune system; exploring the consequences of platinum-induced immunogenicity will facilitate better understanding of gut dysfunction caused by chemotherapeutic agents. We propose that the development of future successful chemotherapeutics should rely on targeting the mechanisms underlying long-term gastrointestinal side effects.

  18. Shenqi fuzheng, an injection concocted from chinese medicinal herbs, combined with platinum-based chemotherapy for advanced non-small cell lung cancer: a systematic review

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    Wang Min-Yan

    2010-10-01

    Full Text Available Abstract Background Platinum-based chemotherapy has been a standard therapy for advanced non-small cell lung cancer (NSCLC, but it has high toxicity. In China, Shenqi Fuzheng, a newly developed injection concocted from Chinese medicinal herbs has been reported that may increase efficacy and reduce toxicity when combined with platinum-based chemotherapy, but little is known about it outside of China. The aim of this study was to systematically review the existing clinical evidence on Shenqi Fuzheng Injection(SFI combined with platinum-based chemotherapy for advanced NSCLC. Methods Pubmed, Cochrane Library, EMBASE, CNKI, and CBM search were organized for all documents published, in English and Chinese, until April 2010. The randomized controlled clinical trials were selected based on specific criteria, in which a SFI plus platinum-based chemotherapy treatment group was compared with a platinum-based chemotherapy control group for patients with advanced NSCLC. The quality of studies was assessed by modified Jadad's scale, and Revman 4.2 software was used for data syntheses and analyses. Results Twenty nine studies were included in this review based on our selection criteria. Of them, ten studies were of high quality and the rest were of low quality, according to the modified Jadad scale. The meta-analysis showed there was a statistically significant higher tumor response (RR, 1.19; 95% CI, 1.07 to 1.32; P = 0.001 and performance status ((RR, 1.57; 95% CI, 1.45 to 1.70; P P = 0.016. Conclusions SFI intervention appears to be useful to increase efficacy and reduce toxicity when combined with platinum-based chemotherapy for advanced NSCLC, although this result needs to be further verified by more high-quality trials.

  19. Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study

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    Chen JH

    2016-04-01

    Full Text Available Jianhua Chen,1 Shengqi Wu,2 Chenping Hu,3 Yicheng Yang,4 Narayan Rajan,5 Yun Chen,4 Canjuan Yang,6 Jianfeng Li,6 Wendong Chen7 1Department of Medical Oncology, 2Department of Research and Education, Hunan Province Tumor Hospital, 3Department of Respiratory, Xiangya Hospital, Central South University, Changsha, Hunan, 4Lilly Suzhou Pharmaceutical Co., Ltd. Shanghai Branch, Shanghai, People's Republic of China; 5Global Health Outcomes Research, Eli Lilly and Co, Indianapolis, IN, USA; 6Division of Health Outcome Research, Normin Health Changsha Representative Office, Changsha, Hunan, People's Republic of China; 7Normin Health, Toronto, ON, Canada Objective: The objective of this study was to compare hospital costs per treatment cycle (HCTC for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC in Chinese patients. Methods: Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results: Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs, paclitaxel–platinum (39 pairs, gemcitabine–platinum (93 pairs, and vinorelbine–platinum (73 pairs, respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient –0.174, P=0.015, which included patients experiencing

  20. Research progress in the use of combinations of platinum-based chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors

    Institute of Scientific and Technical Information of China (English)

    Chi Pan; Suzhan Zhang; Jianjin Huang

    2013-01-01

    In the past decade, the advent of the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has dramatically influenced the therapeutic strategies for treating lung cancer, but with tumor progression and drug resistance, patients will ultimately develop reduced sensitivity to EGFR-TKIs. How can we delay the emergence of drug resistance? What is the next strategy after drug resistance? How to reasonably combine platinum-based chemotherapy and EGFR-TKIs? These questions are currently the focus of lung cancer research. Clinical studies have reported that platinum-based chemotherapy can increase the sensitivity to EGFR-TKIs. However, results of pre-clinical and clinical studies have been inconsistent. The mechanisms of platinum chemotherapy and EGFR-TKIs are still unknown due to the lack of systematic research. Therefore, systematic studies are required to show the mechanisms of EGFR-TKIs and chemotherapy agents and define the markers sensitive to their combinations when given concurrently or sequentially.

  1. The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Jian-Wei Zhang; Wen-Feng Fang; Yu-Xiang Ma; Li Zhang; Yuan-Yuan Zhao; Ying Guo; Cong Xue; Zhi-Huang Hu; Yan Huang; Hong-Yun Zhao; Jing Zhang; Xuan Wu

    2014-01-01

    Both platinum-based doublet chemotherapy (PBC) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival (OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials-involving 11,456 adult patients in 32 arms-were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian (predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs (r = 0.797,P < 0.001). The correlation was obvious in the trials in Asian populations (r = 0.936,P < 0.001) but was not statisticaly significant in the trials in predominantly Caucasian populations (r = 0.116,P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.

  2. Heat shock protein 70 as a predictive marker for platinum-based adjuvant chemotherapy in patients with resected non-small cell lung cancer.

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    Park, Tai Sun; Kim, Hye-Ryoun; Koh, Jae Soo; Jang, Seung Hun; Hwang, Yong Il; Yoon, Ho Il; Chung, Jin-Haeng; Kim, Cheol Hyeon; Kim, Sung-Soo; Kim, Woo Sung; Jo, Jungmin; Lee, Jae Cheol; Choi, Chang-Min

    2014-11-01

    Although adjuvant platinum-based chemotherapy improves survival in completely resected non-small cell lung cancer (NSCLC), its effect is limited. We evaluated whether the expression of heat shock protein 70 (Hsp70) is associated with clinical outcomes in patients with completely resected NSCLC who were treated with or without adjuvant platinum-based chemotherapy. Patients who underwent curative resection for NSCLC and diagnosed as stage IIA through IIIA were included. Immunohistochemical staining for Hsp70 was performed on surgical specimens and survival rates were compared by Hsp70 expression and adjuvant platinum-based chemotherapy. Of 327 enrolled patients, Hsp70 expression was positive in 220 (67.3%). For patients who did not receive adjuvant chemotherapy, Hsp70 expression did not significantly affect survival. However, for patients who received adjuvant chemotherapy, those with Hsp70-positive tumors had a longer disease-free survival outcome than cases with Hsp70-negative tumors (not reached vs. 27.3 months; P=0.002), although there was no significant difference in overall survival (97.0 vs. 58.9 months, P=0.080). In the adjuvant chemotherapy group, multivariate modeling showed that patients with Hsp70-postitive tumors had a lower risk of recurrence and death after adjusting for age, sex, performance status, pathologic stage, and histological type (disease-free survival: adjusted hazard ratio, 0.537; 95% CI, 0.362-0.796; P=0.002; overall survival: adjusted hazard ratio, 0.663; 95% CI, 0.419-1.051; P=0.080). Hsp70 is a positive predictive factor in completely resected NSCLC with received platinum-based adjuvant chemotherapy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies.

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    Williams, J I; Weitman, S; Gonzalez, C M; Jundt, C H; Marty, J; Stringer, S D; Holroyd, K J; Mclane, M P; Chen, Q; Zasloff, M; Von Hoff, D D

    2001-03-01

    Squalamine, an antiangiogenic aminosterol, is presently undergoing Phase II clinical trials in cancer patients. To broaden our understanding of the clinical potential for squalamine, this agent was evaluated in nu/nu mouse xenograft models using the chemoresistant MV-522 human non-small cell lung carcinoma and the SD human neuroblastoma lines. Squalamine was studied alone and in combination with either cisplatin or paclitaxel plus carboplatin. Squalamine alone produced a modest MV-522 tumor growth inhibition (TGI) and yielded a TGI with cisplatin that was better than cisplatin alone. Squalamine also significantly enhanced the activity of paclitaxel/carboplatin combination therapy in the MV-522 tumor model. Squalamine similarly improved the effectiveness of cisplatin in producing TGI when screened against the SD human neuroblastoma xenograft. Xenograft tumor shrinkage was seen for the MV-522 tumor in combination treatments including squalamine, whereas no tumor shrinkage was seen when squalamine was omitted from the treatment regimen. To gain a greater understanding of the mechanism by which squalamine inhibited tumor growth in the xenograft studies, in vitro experiments were carried out with vascular endothelial growth factor-stimulated human umbilical vein endothelial cells in culture exposed to squalamine. Squalamine treatment was found to retard two cellular events necessary for angiogenesis, inducing disorganization of F-actin stress fibers and causing a concomitant reduction of detectable cell the surface molecular endothelial cadherin (VE-cadherin). We propose that the augmentation by squalamine of cytotoxicity from platinum-based therapies is attributable to interference by squalamine with the ability of stimuli to promote endothelial cell movement and cell-cell communication necessary for growth of new blood vessels in xenografts after chemotherapeutic injury to the tumor.

  4. Treatment outcome in performance status 2 advanced NSCLC patients administered platinum-based combination chemotherapy

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    Helbekkmo, Nina; Aasebø, Ulf; Sundstrøm, Stein H

    2008-01-01

    BACKGROUND: There is no consensus regarding chemotherapy to patients with advanced NSCLC (ANSCLC) and performance status (PS) 2. Using data from a national multicenter study comparing two third-generation carboplatin-based regimens in ANSCLC patients, we evaluated the outcome of PS 2 patients...

  5. XRCC3 Thr241Met polymorphism and clinical outcomes of NSCLC patients receiving platinum-based chemotherapy: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xiao-yong Shen

    Full Text Available INTRODUCTION: X-ray repair cross-complementing protein 3 (XRCC3 is an essential gene involved in the double-strand break repair pathway. Published evidence has shown controversial results about the relationship between XRCC3 Thr241Met polymorphism and clinical outcomes of non-small cell lung cancer (NSCLC patients receiving platinum-based chemotherapy. METHODS: A systematic review and meta-analysis was performed to evaluate the predictive value of XRCC3 Thr241Met polymorphism on clinical outcomes of advanced NSCLC receiving platinum-based chemotherapy. Response to chemotherapy, overall survival (OS and progression-free survival (PFS were analyzed. RESULTS: A number of 11 eligible studies were identified according to the inclusion criteria. Carriers of the variant XRCC3 241Met allele were significantly associated with good response to platinum-based chemotherapy (ThrMet/MetMet vs. ThrThr: OR  = 1.509, 95% CI: 1.099-2.072, Pheterogeneity  = 0.618. The XRCC3 Thr241Met polymorphism was not associated with OS (MetMet vs. ThrThr, HR  = 0.939, 95% CI:0.651-1.356, Pheterogeneity  = 0.112 or PFS (MetMet vs. ThrThr, HR  = 0.960, 95% CI: 0.539-1.710, Pheterogeneity  = 0.198. Additionally, no evidence of publication bias was observed. CONCLUSIONS: This systematic review and meta-analysis shows that carriers of the XRCC3 241Met allele are associated with good response to platinum-based chemotherapy in advanced NSCLC, while the XRCC3 Thr241Met polymorphism is not associated with OS or PFS.

  6. Cost-effectiveness of adding cetuximab to platinum-based chemotherapy for first-line treatment of recurrent or metastatic head and neck cancer.

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    Malek B Hannouf

    Full Text Available PURPOSE: To assess the cost effectiveness of adding cetuximab to platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC from the perspective of the Canadian public healthcare system. METHODS: We developed a Markov state transition model to project the lifetime clinical and economic consequences of recurrent or metastatic HNSCC. Transition probabilities were derived from a phase III trial of cetuximab in patients with recurrent or metastatic HNSCC. Cost estimates were obtained from London Health Sciences Centre and the Ontario Case Costing Initiative, and expressed in 2011 CAD. A three year time horizon was used. Future costs and health benefits were discounted at 5%. RESULTS: In the base case, cetuximab plus platinum-based chemotherapy compared to platinum-based chemotherapy alone led to an increase of 0.093 QALY and an increase in cost of $36,000 per person, resulting in an incremental cost effectiveness ratio (ICER of $386,000 per QALY gained. The cost effectiveness ratio was most sensitive to the cost per mg of cetuximab and the absolute risk of progression among patients receiving cetuximab. CONCLUSION: The addition of cetuximab to standard platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic HNSCC has an ICER that exceeds $100,000 per QALY gained. Cetuximab can only be economically attractive in this patient population if the cost of cetuximab is substantially reduced or if future research can identify predictive markers to select patients most likely to benefit from the addition of cetuximab to chemotherapy.

  7. Piroxicam and intracavitary platinum-based chemotherapy for the treatment of advanced mesothelioma in pets: preliminary observations

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    Citro Gennaro

    2008-05-01

    Full Text Available Abstract Malignant Mesothelioma is an uncommon and very aggressive tumor that accounts for 1% of all the deaths secondary to malignancy in humans. Interestingly, this neoplasm has been occasionally described in companion animals as well. Aim of this study was the preclinical evaluation of the combination of piroxicam with platinum-based intracavitary chemotherapy in pets. Three companion animals have been treated in a three years period with this combination. Diagnosis was obtained by ultrasonographic exam of the body cavities that evidenced thickening of the mesothelium. A surgical biopsy further substantiated the diagnosis. After drainage of the malignant effusion from the affected cavity, the patients received four cycles of intracavitary CDDP at the dose of 50 mg/m2 every three weeks if dogs or four cycles of intracavitary carboplatin at the dose of 180 mg/m2 (every 3 weeks if cats, coupled with daily administration of piroxicam at the dose of 0.3 mg/kg. The therapy was able to arrest the effusion in all patients for variable remission times: one dog is still in remission after 3 years, one dog died of progressive disease after 8 months and one cat died due to progressive neoplastic growth after six months, when the patient developed a mesothelial cuirass. The combination showed remarkable efficacy at controlling the malignant effusion secondary to MM in our patients and warrants further investigations.

  8. Reactive Oxygen Species Modulator 1 (Romo1) Predicts Poor Outcomes in Advanced Non-small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy.

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    Lee, Seung Hyeun; Choi, Sue In; Lee, Ji Sung; Kim, Chul Hwan; Jung, Won Jai; Lee, Eun Joo; Min, Kyung Hoon; Hur, Gyu Young; Lee, Seung Heon; Lee, Sung Yong; Kim, Je Hyeong; Lee, Sang Yeub; Shin, Chol; Shim, Jae Jeong; Kang, Kyung Ho; In, Kwang Ho

    2017-01-01

    Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated. A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting.

  9. Effect of the XRCC1 and XRCC3 Genetic Polymorphisms on the Efficacy of Platinum-based Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer

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    Chong’an XU

    2011-12-01

    Full Text Available Background and objective DNA repair gene polymorphisms can be used to predict the sensitivity of platinum-based chemotherapy. Thus, such polymorphisms are important for the individual treatment of non-small cell lung cancer (NSCLC. The aim of this study is to investigate the relationship between X-ray repair cross complementing protein 1 (XRCC1 and X-ray repair cross complementing protein 3 (XRCC3 gene polymorphisms and the chemosensitivity of platinum-based chemotherapy in patients with advanced NSCLC. Methods Genomic DNA were extracted from the sera of a total of 130 patients with advanced NSCLC who received platinum-based chemotherapy. XRCC1 Arg194 Trp, Arg399 Gln, and XRCC3 Thr241 Met were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method, and the relationship between XRCC1 and XRCC3 polymorphisms and chemotherapy sensitivity was analyzed. Results A total of 130 patients with advanced NSCLC received platinum-based chemotherapy, with an overall response rate of 33.8% after two chemotherapy cycles. The XRCC1 194 and 399 genetic polymorphisms, but not XRCC3 241, were found to be related to the chemosensitivity. The objective response rate of the patients with at least one XRCC1 194 Trp allele was 2.5 times higher than that of Arg/Arg genotype carriers (42.1% vs 22.2%, OR=2.545, 95%CI: 1.159-5.590, P=0.020. The objective response rate of the XRCC1 399 Arg/Arg genotype carriers was significantly higher than that of the patients with at least one Gln allele (45.5% vs 21.9%, OR=0.336, 95%CI: 0.156-0.722, P=0.005. Combined effects between XRCC1 194 and XRCC1 399 were observed. The objective response rate of the patients with at least one XRCC1 194 Trp allele and a 399 Arg/Arg genotype was significantly higher than that of patients with 194 Arg/Arg and 399 Arg/Gln genotypes (44.4% vs 18.8%, OR=3.467, 95%CI: 1.223-9.782, P=0.019. Moreover, XRCC1 and XRCC3 have a combined effect in predicting chemosensitivity

  10. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy

    DEFF Research Database (Denmark)

    Bellmunt, J; Fougeray, R; Rosenberg, J E

    2013-01-01

    To compare long-term, updated overall survival (OS) of patients with advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine plus best supportive care (BSC) or BSC alone, after failure of platinum-based chemotherapy....

  11. Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis

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    Xiao HQ

    2016-03-01

    Full Text Available Huai-Qing Xiao,1 Rong-Hua Tian,2 Zhi-Hao Zhang,1 Kai-Qi Du,1 Yi-Ming Ni3 1Department of Cardiothoracic Surgery, Zhejiang Corps Hospital, Chinese People’s Armed Police Force, Jiaxing, Zhejiang Province, People’s Republic of China; 2Department of Respiratory, Affiliated Haian People’s Hospital of Nantong University, Haian, Jiangsu, People’s Republic of China; 3Department of Cardiothoracic Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Purpose: To assess the efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell lung cancer (NSCLC through a trial-level meta-analysis. Methods: Trials published between 1990 and 2015 were identified by an electronic search of public databases (Medline, Embase, and Cochrane Library. All clinical studies were independently identified by two authors. Demographic data, treatment regimens, objective response rate (ORR, progression-free survival (PFS, and overall survival (OS were extracted and analyzed using comprehensive meta-analysis software (version 2.0. Results: A total of 2,551 patients with advanced nonsquamous NSCLC from ten trials were included for analysis: 1,565 patients were treated with pemetrexed plus platinum doublet chemotherapy and 986 with platinum plus other first-line chemotherapy. Pooled ORR for pemetrexed plus platinum chemotherapy was 37.8% (95% confidence interval [CI]: 31.7%–44.3%, with median PFS and OS of 5.7 and 16.05 months, respectively. When compared to other platinum-based doublet chemotherapies, the use of pemetrexed plus platinum chemotherapy significantly improved OS (hazard ratio [HR] =0.86, 95% CI: 0.77–0.97, P=0.01 but not PFS (HR =0.90, 95% CI: 0.80–1.01, P=0.084 in advanced nonsquamous NSCLC patients. Conclusion: Pemetrexed plus platinum doublet regimen is an efficacious treatment for advanced nonsquamous NSCLC patients. Our

  12. Elevated serum levels of vascular endothelial growth factor predict a poor prognosis of platinum-based chemotherapy in non-small cell lung cancer

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    Zang JL

    2017-01-01

    Full Text Available Jialan Zang,1–3,* Yong Hu,1,2,* Xiaoyue Xu,1,2 Jie Ni,1,2 Dali Yan,1,2 Siwen Liu,4 Jieyu He,5 Jing Xue,4 Jianzhong Wu,4 Jifeng Feng2 1The Fourth Clinical School of Nanjing Medical University, 2Department of Chemotherapy, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 3Department of Oncology, The First Hospital of Harbin City, Harbin, 4Center of Clinical Laboratory, Nanjing Medical University Affiliated Cancer Hospital, 5Department of Public Health, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Aim: This study was designed to investigate the predictive and prognostic values of serum vascular endothelial growth factor (VEGF level in non-small cell lung cancer (NSCLC patients treated with platinum-based chemotherapy. Methods: Patients’ peripheral blood samples were collected prior to chemotherapy and after 1 week of the third cycle of combination chemotherapy. Serum VEGF levels were evaluated through Luminex multiplex technique. Between September 2011 and August 2015, a total of 135 consecutive advanced or recurrent histologically verified NSCLC patients were enrolled in the study. Moreover, all the patients received platinum-based combination chemotherapy as a first-line treatment. Results: No significant associations were found between pretreatment serum VEGF levels and clinical characteristics, such as sex (P=0.0975, age (P=0.2522, stage (P=0.1407, lymph node metastasis (P=0.6409, tumor location (P=0.3520, differentiated degree (P=0.5608, pathological (histological type (P=0.4885, and response to treatment (P=0.9859. The VEGF load per platelet (VEGFPLT levels were not correlated with sex, age, primary tumor site, and pathological type in NSCLC patients (all P>0.05. The median survival time of progression-free survival (PFS was 6.407 and 5.29 months in the low and high groups, respectively, when using 280 pg/mL VEGF level as the cutoff point (P=0.024. Conclusion

  13. Echocardiography and cardiac biomarkers in patients with non-small cell lung cancer treated with platinum-based chemotherapy

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    Omersa, Daniel; Cufer, Tanja; Marcun, Robert

    2017-01-01

    Abstract Background Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains an important cause of cancer death worldwide. Platinum-based chemotherapy (PBC) for NSCLC can modify outcome while the risk of cardiotoxicity remains poorly researched. We aimed to evaluate the incidence and severity of cardiac injury during PBC in patients with NSCLC and to identify patients at risk. Methods This was a single-centre, prospective, observational study of patients with early and advanced stage NSCLC referred for PBC. In addition to standard care, patients were examined and evaluated for cardiotoxicity before the first dose (visit 1), at the last dose (visit 2) and 6 months after the last dose of PBC (visit 3). Cardiotoxicity (at visit 2 and 3) was defined as increase in the ultrasensitive troponin T, N-terminal pro-B type natriuretic peptide or decrease in left ventricular ejection fraction (LVEF). Results Overall, 41 patients (mean age 61 ± 9; 54% men; 68% advanced lung cancer) were included. The median number of PBC cycles was 4. During the study period, there were no incidents of heart failure, and 3 deaths caused by tumour progression were recorded. The mean values of biomarkers and LVEF did not change significantly (p > 0.20). However, 10 (25%) had cardiotoxicity which was independently associated with a history of ischemic heart disease (p = 0.026). Conclusions In NSCLC, cardiac assessment and lifestyle modifications may be pursued in patients with a history of cardiac disease and in patients with longer life expectancy.

  14. Variation of adverse drug reaction profile of platinum-based chemotherapy with body mass index in patients with solid tumors: An observational study

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    Dattatreyo Chatterjee

    2014-01-01

    Full Text Available Objectives: Toxicity of cancer chemotherapy may be affected by nutritional status of patients which is reflected in the body mass index (BMI. We sought to assess whether the adverse drug reaction (ADR profile of platinum-based chemotherapy varies with BMI status. Materials and Methods: Adult patients of either sex, suffering from a solid tumor (lung, head and neck, ovary, gall bladder, stomach, colon and started on platinum-based chemotherapy as initial treatment were included. BMI at chemotherapy commencement was obtained from medical records. Events were recorded and graded as per Eastern Co-operative Oncology Group Common Toxicity Criteria-patients′ complaints; clinically evident signs and laboratory reports were considered. Frequencies of individual adverse events were compared between low BMI (<18.5 kg/m 2 and satisfactory BMI groups. Similar comparisons were done for events with grades 2 or 3 severities. Results: A total of 50 patients were observed over a 3-month period of whom 17 (34% belonged to the low BMI group. Nausea, vomiting, diarrhea, stomatitis, anemia, alopecia, tinnitus and paresthesia were the commonly observed ADRs. The frequencies of anemia (P = 0.152 and vomiting (P = 0.140 and severity of grades of nausea (P = 0.066, anemia (P = 0.120 and paresthesia (P = 0.128 showed a higher trend in the low BMI group though differences were not statistically significant. The frequencies of tinnitus (P = 0.021 and paresthesia overall (P = 0.036 were significantly higher in the low BMI group. Conclusion: ADR profile of primary platinum-based chemotherapy appears to be partly influenced by BMI. This suggests the importance of maintaining adequate nutrition in patients and the need for greater vigilance in those with low BMI.

  15. Prognostic impact of 18F-FDG uptake on PET in non-small cell lung cancer patients with postoperative recurrence following platinum-based chemotherapy.

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    Kaira, Kyoichi; Yamamoto, Nobuyuki; Kenmotsu, Hirotsugu; Murakami, Haruyasu; Ono, Akira; Naito, Tateaki; Endo, Masahiro; Takahashi, Toshiaki

    2014-03-01

    Whether fluorine-18-fluorodeoxyglucose ((18)F-FDG) uptake within tumor cells differs between primary and recurrent lung cancers is unknown. The aim of this study was to investigate the prognostic significance of (18)F-FDG uptake by comparing that measured preoperatively at the primary site to that measured postoperatively at sites of non-small cell lung cancer (NSCLC) recurrence. Only patients with postoperative recurrences who received platinum-based chemotherapy as the initial treatment after recurrence were included in the study. Fifty-two patients underwent (18)F-FDG positron emission tomography (PET) examinations before thoracotomy and at the time of recurrence after curative surgery. All recurrences were treated with platinum-based chemotherapy. (18)F-FDG uptake in the preoperative primary tumors was significantly higher than that in the recurrent tumors (p=0.028), demonstrating a statistically significant correlation (Pearson's correlation coefficient γ=0.482, precurrence. In NSCLC patients treated by chemotherapy for recurrence, preoperative measurements of (18)F-FDG uptake may be a more powerful surrogate marker for predicting outcome when measured preoperatively at the primary tumor site rather than postoperatively at sites of recurrence. © 2013 Published by The Japanese Respiratory Society on behalf of The Japanese Respiratory Society.

  16. Pemetrexed had significantly better clinical efficacy in patients with stage IV lung adenocarcinoma with susceptible EGFR mutations receiving platinum-based chemotherapy after developing resistance to the first-line gefitinib treatment

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    Yang CJ

    2016-03-01

    study. The overall response rate of second salvage therapy is 13%, and none of them received erlotinib. Patients who received chemotherapy had a trend for better PFS2 than those who received erlotinib (4.3 months vs 3.0 months, P=0.1417 but not in OS. Furthermore, patients who received platinum-based doublet had a trend for better PFS2 and a significantly better OS2 than those who received chemotherapy without platinum (PFS2: 4.9 months vs 2.6 months, P=0.0584; OS2: 16.1 months vs 6.7 months, P=0.0007. Analyses of the patients receiving platinum-based doublet showed that patients receiving pemetrexed had a significantly better PFS2 (6.4 months vs 4.1 months, P=0.0083 and a trend for better OS2 than those without pemetrexed treatment.Conclusion: Pemetrexed-based platinum chemotherapy may be the most optimal therapy in acquired resistance to gefitinib. Further prospective randomized controlled study is needed urgently. Keywords: epidermal growth factor receptor, gefitinib, acquired resistance, pemetrexed, chemotherapy

  17. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are predictive of chemotherapeutic response and prognosis in epithelial ovarian cancer patients treated with platinum-based chemotherapy.

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    Miao, Yi; Yan, Qin; Li, Shuangdi; Li, Bilan; Feng, Youji

    2016-06-07

    The aim of present study was to investigate the role of preoperative neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) used as prognostic markers for predicting chemotherapeutic response and survival outcomes in patients with epithelial ovarian cancer (EOC) who are receiving platinum-based chemotherapy. A total of 344 patients diagnosed with EOC who are receiving platinum-based chemotherapy from 2005 to 2010 in the hospital were enrolled. NLR and PLR were calculated from complete blood cell count taken before operation. The patients were divided into platinum-resistant (P-R) group and platinum-sensitive (P-S) group according to chemotherapeutic response. Clinicopathologic variables and outcomes were retrospectively collected and compared among groups. We used receiver operating characteristic (ROC) curves to calculate optimal cut-off values for NLR and PLR to predict chemotherapeutic response and prognosis. The AUC, sensitivity, specificity of NLR > 3.02 to predict platinum resistance were 0.819, 75.0% and 81.45%, respectively. The corresponding values of PLR > 207 were 0.727, 60.42% and 85.48%, respectively. Patients with lower value of NLR (NLR platinum resistance in patients with EOC.

  18. Clinical Significance of Long Non-Coding RNA CASC8 rs10505477 Polymorphism in Lung Cancer Susceptibility, Platinum-Based Chemotherapy Response, and Toxicity

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    Lei Hu

    2016-05-01

    Full Text Available Long non-coding RNA (lncRNA CASC8 rs10505477 polymorphism has been identified to be related to risk of many kinds of cancers, such as colorectal cancer, gastric cancer, and invasive ovarian cancer, and it may be involved in the prognosis of gastric cancer patients who have received platinum-based chemotherapy after surgical treatment. So far, there is no study investigating the clinical significance of lncRNA CASC8 rs10505477 in lung cancer susceptibility and treatment. In this study, we genotyped 498 lung cancer patients and 213 healthy control subjects to explore the correlation between the rs10505477 polymorphism and lung cancer risk in a Chinese population. Among the 498 patients, 467 were selected for the chemotherapy response and toxicity study. We found that the single nucleotide polymorphisms (SNP rs10505477 was greatly related to lung cancer risk in male and adenocarcinoma subgroups in recessive model (adjusted OR = 0.51, 95%CI = 0.29–0.90, p = 0.02; adjusted OR = 0.52, 95%CI = 0.30–0.89, p = 0.02, respectively. It was also closely correlated with platinum-based chemotherapy response in dominant model (adjusted OR = 1.58, 95%CI = 1.05–2.39, p = 0.03. Additionally, we observed that CASC8 rs10505477 polymorphism was significantly relevant to severe hematologic toxicity in non-small-cell lung cancer (NSCLC subgroup in dominant model (adjusted OR = 0.59, 95%CI = 0.35–0.98, p = 0.04 and in additive model (adjusted OR = 0.62, 95%CI = 0.43–0.90, p = 0.01. Furthermore, it was found that rs10505477 polymorphism was greatly associated with gastrointestinal toxicity in SCLC and cisplatin subgroups in dominant model (adjusted OR = 7.82, 95%CI = 1.36–45.07, p = 0.02; adjusted OR = 1.94, 95%CI = 1.07–3.53, p = 0.03, respectively. Thus, lncRNA CASC8 rs10505477 could serve as a possible risk marker for diagnosing lung cancer, and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients.

  19. XRCC3 Thr241Met is associated with response to platinum-based chemotherapy but not survival in advanced non-small cell lung cancer.

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    Mantang Qiu

    Full Text Available BACKGROUND: A lot of studies have investigated the correlation between x-ray repair cross-complementing group 3 (XRCC3 Thr241Met polymorphism and clinical outcomes in non-small cell cancer (NSCLC, while the conclusion is still conflicting. MATERIALS AND METHODS: We conducted this meta-analysis to evaluate the predictive value of XRCC3 Thr241Met polymorphism on response and overall survival of patients with NSCLC. Pooled odds ratios (ORs and hazard ratios (HRs and corresponding 95% confidence intervals (95% CIs were used to estimate the association strength. RESULTS: A total of 14 eligible studies with 2828 patients were identified according to our inclusion criteria. Meta-analysis results showed that carriers of the variant 241Met allele were significantly associated with good response, compared with those harboring the wild 241Thr allele (Met vs. Thr, OR = 1.453, 95% CI: 1.116-1.892, Pheterogeneity = 0.968 and ThrMet+MetMet vs. ThrThr, OR = 1.476, 95% CI: 1.087-2.004, Pheterogeneity = 0.696. This significant association was observed in Caucasian population but not in Asian population. On the other hand, there was no significant association of XRCC3 Thr241Met polymorphism with survival (ThrMet+MetMet vs. ThrThr, HR = 1.082, 95% CI: 0.929-1.261, Pheterogeneity = 0.564, and there was no difference between Asian and Caucasian population. CONCLUSIONS: These findings suggest a predictive role of XRCC3 Thr241Met polymorphism on response to platinum-based chemotherapy in patients with advanced NSCLC. Additionally, we first report that the XRCC3 Thr241Met polymorphism is associated with response to platinum-based chemotherapy and highlights the prognostic value of the XRCC3 Thr241Met polymorphism.

  20. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study).

    Science.gov (United States)

    Cicènas, Saulius; Geater, Sarayut Lucien; Petrov, Petar; Hotko, Yevgeniy; Hooper, Gregory; Xia, Fan; Mudie, Nadejda; Wu, Yi-Long

    2016-12-01

    The phase III IUNO trial assessed the benefit of maintenance erlotinib versus erlotinib at progression in advanced/metastatic non-small-cell lung cancer (NSCLC) that had not progressed following four cycles of platinum-based chemotherapy. Patients had stage IIIB/IV NSCLC, no known epidermal growth factor receptor (EGFR)-activating mutation, and objective response or disease stabilization after platinum-based induction chemotherapy. Central EGFR-mutation testing was undertaken on tumors from patients with unknown or wild-type EGFR status following local testing. Patients were randomized to receive blinded maintenance erlotinib 150mg/day ('early erlotinib') or placebo. Those who progressed on placebo received open-label erlotinib ('late erlotinib'); patients who progressed on erlotinib received approved second-line chemotherapy or best supportive care. Primary endpoint: overall survival (OS). 643 patients were randomized to receive maintenance erlotinib (n=322) or placebo (n=321). As of March 23, 2015, 242 (75.2%) OS events had occurred with 'early erlotinib' versus 235 (73.2%) with 'late erlotinib'. Median OS was 9.7 and 9.5 months with 'early erlotinib' and 'late erlotinib', respectively (HR, 1.02, 95% CI: 0.85-1.22; log-rank p=0.82). No progression-free survival, objective response rate, or disease control rate benefit was observed with maintenance erlotinib. 410 patients entered the second-line phase of the study: 160 patients (50%) from the maintenance erlotinib arm and 250 patients (78%) from the maintenance placebo arm. The pattern of adverse events (AEs) was consistent with previous trials; 11 patients who received blinded erlotinib and 3 who received placebo died during the blinded maintenance phase due to nontreatment-related AEs. OS with maintenance erlotinib was not superior to second-line treatment in patients whose tumor did not harbor an EGFR-activating mutation. Safety results were consistent with the established safety profile of erlotinib. Thus

  1. A research of platinum-based dual drugs versus single agent chemotherapy for elderly and comorbidity patients with advanced non-small cell lung cancer%存在内科合并症的老年晚期非小细胞肺癌患者一线含铂双药与单药方案化疗的对照研究

    Institute of Scientific and Technical Information of China (English)

    张琼妍; 李大鹏; 陶敏

    2012-01-01

    目的 探讨含铂双药与第3代化疗药物单药方案化疗在有内科合并症的老年晚期非小细胞肺癌(NSCLC)患者中的疗效和安全性.方法 回顾性分析150例有内科合并症(依据察尔森指数筛选)经细胞学或病理组织学确诊的老年晚期NSCLC患者.按照接受一线化疗方案分为第3代化疗药物单药组(28例)和含铂双药组(122例),比较两组的疗效及不良反应.结果 所有患者均可评价疗效.单药组获PR 6例(21.4%),SD 2例(7.1%),PD 20例(71.4%),有效率为21.4%;双药组获PR 48例(39.3%),SD 10例(8.2%),PD 64例(52.5%),有效率为39.3%,两组有效率差异无统计学意义(P>0.05).单药组和双药组的中位无进展时间(PFS)分别为5.0个月和7.0个月(P =0.617),中位总生存期(OS)分别为7.4个月和10.7个月(P =0.473).经年龄、ECOG评分和察尔森指数1~2分分层后发现,单药组与双药组的PFS或OS差异均无统计学意义(P>0.05);而经察尔森指数3-4分分层后发现,单药组和双药组的中位PFS分别为3.5个月和8.3个月(P=0.001),中位OS为5.0个月和8.3个月(P=0.019).不良反应主要包括中性粒细胞减少、贫血、血小板减少和恶心呕吐,单药组不良反应基本为1~2级,双药组3~4级不良反应发生率较单药组高.结论 含铂双药方案一线治疗有内科合并症的老年晚期NSCLC的疗效与第3代化疗药物单药方案类似,而在察尔森指数3~4分患者中前者远期疗效更好,但总体不良反应发生率略高.%Objective To investigate the efficacy and toxicity of single agent and platinum-based dual drugs chemotherapy for elderly and comorbidity patients with advanced non-small cell lung cancer (NSCLC). Methods A total of 150 cases of elderly NSCLC patients with cytological or pathological diagnosis were retrospectively reviwed. Doublet chemotherapy group was treated with platinum-based dual drugs, and single agent chemotherapy group was treated with the third

  2. Association of POLK polymorphisms with platinum-based chemotherapy response and severe toxicity in non-small cell lung cancer patients.

    Science.gov (United States)

    Shao, Minhua; Jin, Bo; Niu, Yanjie; Ye, Junyi; Lu, Daru; Han, Baohui

    2014-11-01

    Lung cancer is the leading cause of tumor-derived death. Although target therapy is proven very efficient, traditionally platinum-based chemotherapies are still primary treatment for most patients. Platinum can suppress the tumor growth and impair normal cells together. The primary aim of the present study was to study the potential role of translesion synthesis (TLS) that might play in platinum-chemotherapy tolerance and side-effect. In present study, a total of 663 patients who were newly histologically diagnosed with advanced NSCLC (aNSCLC) were enrolled. Treatment response was classified into four categories: complete response, partial response, stable disease, and progressive disease. Incidence of gastrointestinal and hematological toxicities was assessed twice a week during the whole first-line treatment. Eleven SNPs of POLK were genotyped. The associations between SNPs and treatment response or toxicity were analyzed with logistic regression model. Cox regression was used for survival analysis between SNPs and progression-free survival or overall survival. We identified that rs3213801 and rs5744533 showed complete linkage in the present study, and they were significantly associated with treatment response (adjusted P = 0.044), together with rs5744655 (adjusted P = 0.039). rs1018119 was correlated with gastrointestinal toxicity in smokers specially (adjusted P = 0.041). Besides, rs3756558 was associated with hematological toxicity and overall toxicity in smokers and combined cohort with additive model. We also identified the significant association between two SNPs, rs10077427 and rs5744545, and PFS. The polymorphism of POLK, an important gene in TLS, participates in platinum-chemotherapy tolerance and side-effect.

  3. Can Aidi injection restore cellular immunity and improve clinical efficacy in non-small-cell lung cancer patients treated with platinum-based chemotherapy? A meta-analysis of 17 randomized controlled trials following the PRISMA guidelines.

    Science.gov (United States)

    Xiao, Zheng; Wang, Chengqiong; Sun, Yongping; Li, Nana; Li, Jing; Chen, Ling; Yao, Xingsheng; Ding, Jie; Ma, Hu

    2016-11-01

    Aidi injection is an adjuvant chemotherapy drug commonly used in China. Can Aidi injection restore the cellular immunity and improve the clinical efficacy in non-small-cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy? There is a lack of strong evidence to prove it. To further reveal it, we systematically evaluated all related studies. We collected all studies about the clinical efficacy and cellular immunity of Aidi injection plus platinum-based chemotherapy for NSCLC in Medline, Embase, Web of Science, China national knowledge infrastructure database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang, China biological medicine database (CBM) (established to June 2015), Cochrane Central Register of Controlled Trials (CCRCT) (June 2015), Chinese clinical trial registry, and US-clinical trials (June 2015). We evaluated their quality according to the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0), extracted data following the patient intervention control group outcomes principles and synthesized the data by meta-analysis. Seventeen (RCTs) with 1390 NSCLC patients were included, with general methodological quality in most trials. The merged relative risk (RR) values and their 95% CI of meta-analysis for objective response rate (ORR) and disease control rate (DCR) were as follows: 1.26 (1.12, 1.42) and 1.11(1.04, 1.17). The merged standardized mean difference (SMD) values and their 95% CI of meta-analysis for the percentage of CD3T cells, CD4T cells, CD8T cells, natural killer (NK) cells, and CD4/CD8 T cell ratio were as follows: 1.41, (0.89, 1.92), 1.59, (1.07, 2.11), 0.85, (0.38, 1.33), 1.64 (0.89, 2.39) and 0.91, (0.58, 1.24). Compared with platinum-based chemotherapy alone, all differences were statistically significant. These results might be overestimated or underestimated. Aidi injection plus platinum-based chemotherapy can improve the clinical efficacy of patients with NSCLC. Aidi

  4. Relationship of Insulin-like Growth Factor Receptor Single Nucleotide 
Polymorphism (SNP with Platinum-based Chemotherapy Outcomes in Advanced Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yusheng CHEN

    2012-02-01

    Full Text Available Background and objective It has been proven that the insulin-like growth factor 1 receptor (IGF-1R gene is an important regulator of many aspects of growth, differentiation, and development. The insulin-like growth factor 2 receptor (IGF-2R gene is a negative mediator for carcinogenesis. The aim of this study is to investigate the relationship of IGF-1R+1013(G/A and IGF-2R+1619(G/A single nucleotide polymorphism (SNP with platinum-based chemotherapy outcomes in advanced non-small cell lung cancer (NSCLC. Methods A total of 132 patients with NSCLC were routinely treated with platinum-based chemotherapy, and their clinical responses were evaluated after four cycles of chemotherapy. IGF-1R+1013(G/A and IGF-2R+1619(G/A were genotyped using polymerase chain reaction-restrictive fragment length polymorphism. The relationship between IGF-1R+1013(G/A and IGF-2R+1619(G/A genotypes and the clinical benefit rate, as well as the median survival time (MST, was analyzed. Results No significant association was found between IGF-1R+1013(G/A and IGF-2R+1619(G/A polymorphisms with clinical benefit (P>0.05. Further, we found that the two SNPs could not work together (P=0.975. The MST of patients with IGF-1R+1013(G/A genotypes with A allele (GA+AA was significantly shorter than that of GG genotype carriers (P=0.017. There was no significant difference in MST in patients with IGF-2R+1619(G/A A allele (GA+AA carrier and GG genotype carrier (P=0.575. The two SNPs showed a synergistic effect on MST. Patients who carried a mutant allele A of IGF-1R+1013(G/A and a mutant allele A of IGF-2R+1619(G/A had a MST of 12 months, which was significantly shorter than that of patients with other genotypes (P<0.05. Estimation by the Cox proportional hazards model showed that IGF-1R+1013(G/A polymorphism is an independent prognostic factor (P=0.020, and IGF-1R+1013(G/A polymorphism in combination with IGF-2R +1619(G/A polymorphism is an independent prognostic factor in advanced

  5. Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer

    Science.gov (United States)

    Jia, Ming; Zhu, Meiling; Wang, Mengyun; Sun, Menghong; Qian, Ji; Ding, Fei; Chang, Jianhua; Wei, Qingyi

    2016-01-01

    The JNK and P38α pathways play a crucial role in tissue homeostasis, apoptosis and autophagy under genotoxic stresses, but it is unclear whether single nucleotide polymorphisms (SNPs) of genes in these pathways play a role in platinum-based chemotherapy-induced toxicities in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 11 selected, independent, potentially functional SNPs of nine genes in the JNK and P38α pathways in 689 patients with advanced NSCLC treated with platinum-combination chemotherapy regimens. Associations between these SNPs and chemotherapy toxicities were tested in a discovery group of 345 patients and then validated in a replication group of 344 patients. In both discovery and validation groups as well as their pooled analysis, carriers of GADD45B rs2024144T variant allele had a significantly higher risk for severe hematologic toxicity and carriers of MAPK14 rs3804451A variant allele had a significantly higher risk for both overall toxicity and gastrointestinal toxicity. In addition, carriers of GADD45A rs581000C had a lower risk of anemia, while carriers of GADD45B rs2024144T had a significantly higher risk for leukocytopenia or agranulocytosis. The present study provides evidence that genetic variants in genes involved in the JNK and P38α pathways may predict platinum-based chemotherapy toxicity outcomes in patients with advanced NSCLC. Larger studies of other patient populations are needed to validate our findings. PMID:26993769

  6. Phase I/II study of docetaxel combined with resminostat, an oral hydroxamic acid HDAC inhibitor, for advanced non-small cell lung cancer in patients previously treated with platinum-based chemotherapy.

    Science.gov (United States)

    Tambo, Yuichi; Hosomi, Yukio; Sakai, Hiroshi; Nogami, Naoyuki; Atagi, Shinji; Sasaki, Yasutsuna; Kato, Terufumi; Takahashi, Toshiaki; Seto, Takashi; Maemondo, Makoto; Nokihara, Hiroshi; Koyama, Ryo; Nakagawa, Kazuhiko; Kawaguchi, Tomoya; Okamura, Yuta; Nakamura, Osamu; Nishio, Makoto; Tamura, Tomohide

    2017-04-01

    Objectives To determine the recommended dose and efficacy/safety of docetaxel combined with resminostat (DR) in non-small cell lung cancer (NSCLC) patients with previous platinum-based chemotherapy. Materials and Methods A multicenter, open-label, phase I/II study was performed in Japanese patients with stage IIIB/IV or recurrent NSCLC and prior platinum-based chemotherapy. The recommended phase II dose was determined using a standard 3 + 3 dose design in phase I part. Resminostat was escalated from 400 to 600 mg/day and docetaxel fixed at 75 mg/m(2). In phase II part, the patients were randomly assigned to docetaxel alone (75 mg/m(2)) or DR therapy. Docetaxel was administered on day 1 and resminostat on days 1-5 in the DR group. Treatment was repeated every 21 days until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Results A total of 117 patients (phase I part, 9; phase II part, 108) were enrolled. There was no dose-limiting toxicity in phase I part; the recommended dose for resminostat was 600 mg/day with 75 mg/m(2) of docetaxel. In phase II part, median PFS (95% confidence interval [CI]) was 4.2 (2.8-5.7) months with docetaxel group and 4.1 (1.5-5.4) months with DR group (hazard ratio [HR]: 1.354, 95% CI: 0.835-2.195; p = 0.209). Grade ≥ 3 adverse events significantly more common with DR group than docetaxel group were leukopenia, febrile neutropenia, thrombocytopenia, and anorexia. Conclusion In Japanese NSCLC patients previously treated with platinum-based chemotherapy, DR therapy did not improve PFS compared with docetaxel alone and increased toxicity.

  7. A phase 2 randomized study of TAS-102 versus topotecan or amrubicin in patients requiring second-line chemotherapy for small cell lung cancer refractory or sensitive to frontline platinum-based chemotherapy.

    Science.gov (United States)

    Scagliotti, Giorgio; Nishio, Makoto; Satouchi, Miyako; Valmadre, Giuseppe; Niho, Seiji; Galetta, Domenico; Cortinovis, Diego; Benedetti, Fabio; Yoshihara, Eiji; Makris, Lukas; Inoue, Akira; Kubota, Kaoru

    2016-10-01

    TAS-102 is an oral combination treatment comprised of an antimetabolite, trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, at a molar ratio of 1:0.5. This antimetabolite has demonstrated efficacy in clinical trials, including a global phase 3 trial in metastatic colorectal cancer. As this agent has shown activity greater than cisplatin in small cell lung cancer xenograft mouse models, the objective of this study was to evaluate TAS-102 in the second-line treatment of small cell lung cancer. This was a multicenter, open-label, two-arm, randomized phase 2 study designed to compare oral TAS-102 (35mg/m(2)/dose twice daily) versus control (topotecan or amrubicin). Patients requiring second-line chemotherapy for treatment of small cell lung cancer, either refractory or sensitive to frontline platinum-based chemotherapy, were enrolled. Eighteen patients were enrolled. Eight of nine patients receiving TAS-102 discontinued treatment due to progressive disease and one patient died due to clinical progression during the safety follow-up. Unplanned interim futility considerations were made, and the study was terminated early because it was unlikely that superiority of TAS-102 versus comparator could be demonstrated. Six control patients discontinued therapy due to progressive disease and one due to an adverse event. Median progression-free survival was 1.4 months (range 0.9-1.8) versus 2.7 months (range 1.0-6.8) for TAS-102 and control, respectively, with a hazard ratio of 3.76 (80% CI, 1.68-8.40) favoring control. The most common adverse events with TAS-102 were neutropenia, diarrhea, anemia, anorexia, and fatigue, each in three patients. TAS-102 showed no evidence of activity in second-line small cell lung cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Prophylactic G-CSF and antibiotics enable a significant dose-escalation of triplet-chemotherapy in non-small cell lung cancer.

    NARCIS (Netherlands)

    Timmer-Bonte, J.N.H.; Punt, C.J.A.; Heijden, H.F.M. van der; Die, C.E. van; Bussink, J.; Beijnen, J.H.; Huitema, A.D.; Tjan-Heijnen, V.C.

    2008-01-01

    In advanced non-small cell lung cancer (NSCLC) the clinical benefit of a platinum-based doublet is only modest, therefore, attenuated dosed three-drug combinations are investigated. We hypothesized that with adequate support a full dosed chemotherapy triplet is feasible. The study was designed as a

  9. The impact of common and rare EGFR mutations in response to EGFR tyrosine kinase inhibitors and platinum-based chemotherapy in patients with non-small cell lung cancer.

    Science.gov (United States)

    Arrieta, Oscar; Cardona, Andrés Felipe; Corrales, Luis; Campos-Parra, Alma Delia; Sánchez-Reyes, Roberto; Amieva-Rivera, Eduardo; Rodríguez, July; Vargas, Carlos; Carranza, Hernán; Otero, Jorge; Karachaliou, Nikki; Astudillo, Horacio; Rosell, Rafael

    2015-02-01

    In non-small cell lung cancer (NSCLC), the association between common EGFR mutations (Del EX19/L858R) with EGFR tyrosine kinase inhibitors (EGFR-TKIs) has been well established. However, this has not been investigated for rare EGFR mutations or their impact on treatment response and outcome to EGFR TKIs (primary objective) and chemotherapy (secondary objective). In an observational prospective cohort, we analyzed 188 NSCLC patients from Mexico, Colombia and Costa Rica with EGFR mutations. As a first line of treatment, 66.5% received platinum-based chemotherapy. All patients received TKIs in first-line treatment or after progression to chemotherapy. The clinical-pathological characteristics as well as the f of common and rare EGFR mutations associated with treatment response were analyzed. Of all patients, 79.5% had common and 20.5% had rare EGFR mutations. Lepidic and acinar adenocarcinomas were associated with common EGFR mutations (p=0.010). Patients with common EGFR mutations had higher response rates to EGFR-TKIs than those who had rare EGFR mutations (63.8 vs 32.4%, p<0.001). Women had increased progression-free survival (PFS) to EGFR-TKIs than men (16.4 vs 9.5 months, p=0.02). The median PFS and overall survival (OS) were better in patients with common EGFR mutations (15.5 vs 3.9 months, p<0.001; and 37.3 vs 17.4 months, p<0.001) respectively. Our findings suggested that only patients with rare EGFR mutations could receive platinum-based chemotherapy as a first-line treatment, due to their low response rates and short PFS in response to EGFR-TKIs. Consequently, EGFR-TKIs could be reserved as a second- or third-line treatment. In patients with EGFR mutations, women have better PFS to EGFR-TKIs than men, and rare EGFR mutations are more frequent in high grade adenocarcinomas than in low grade tumors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. On the Effect of Triplet or Doublet Chemotherapy in Advanced Gastric Cancer: Results From a National Cancer Registry.

    Science.gov (United States)

    Carmona-Bayonas, Alberto; Jiménez-Fonseca, Paula; Lorenzo, Maria Luisa Sánchez; Ramchandani, Avinash; Martínez, Elena Asensio; Custodio, Ana; Garrido, Marcelo; Echavarría, Isabel; Cano, Juana María; Barreto, Jose Enrique Lorenzo; García, Teresa García; Manceñido, Felipe Álvarez; Lacalle, Alejandra; Cardona, Marta Ferrer; Mangas, Monserrat; Visa, Laura; Buxó, Elvira; Azkarate, Aitor; Díaz-Serrano, Asunción; Montes, Ana Fernández; Rivera, Fernando

    2016-11-01

    There is currently no consensus regarding first-line chemotherapy for patients with advanced gastric cancer (AGC) who are ineligible to receive trastuzumab. The objective of this study was to evaluate the efficacy and tolerance of triplets versus doublets by analyzing a national gastric cancer registry. Patients with AGC treated with polychemotherapy without associating trastuzumab were included from 2008 through 2016. The effect of triplets versus doublets was compared using 3 methods: Cox proportional hazards regression, propensity score matching (PSM), and coarsened exact matching (CEM). A total of 970 patients were recruited (doublets: n=569; triplets: n=401). In the multivariate Cox model, the use of triplets was associated with better overall survival (OS), with a hazard ratio (HR) of 0.84 (95% CI, 0.72-0.98; P=.035). After PSM, the sample contained 340 pairs. A significant increase in OS, 11.14 months (95% CI, 9.60-12.68) versus 9.60 months (95% CI, 8.44-10.75), was seen in favor of triplets (HR, 0.77; 95% CI, 0.65-0.92; stratified log-rank test, P=.004). The effect appeared to be comparable for anthracycline-based (HR, 0.78; 95% CI, 0.64-0.94) or docetaxel-based triplets (HR, 0.78; 95% CI, 0.60-1.009). The trend was similar after applying the CEM algorithm, with an HR of 0.78 (95% CI, 0.63-0.97; P=.03). Triplet therapy was viable and relative dose intensities exceeded 85%, except for cisplatin in DCX (docetaxel, cisplatin, capecitabine). Triplets had more severe toxicity overall, especially hematologic, hepatic, and mucosal adverse events. With the limitations of a retrospective study that examines a heterogeneous set of chemotherapy regimens, we found that triplets are feasible in daily practice and are associated with a discreet benefit in efficacy at the expense of a moderate increase in toxicity. Copyright © 2016 by the National Comprehensive Cancer Network.

  11. A feasibility study of the use of saliva as an alternative to leukocytes as a source of DNA for the study of Pt-DNA adducts in cancer patients receiving platinum-based chemotherapy.

    Science.gov (United States)

    Taylor, Sarah E; Wood, Joanna P; Thomas, Anne L; Jones, George D D; Reid, Helen J; Sharp, Barry L

    2014-12-01

    This note presents a comparison of the use of saliva versus leukocytes for the determination of Pt-DNA adducts obtained from patients undergoing platinum-based chemotherapy. Samples of both blood and saliva were taken pre- and post-treatment and were analysed via sector-field inductively coupled plasma mass spectrometry (SF-ICP-MS) to determine the level of Pt-DNA adducts formed. As expected, significant inter-patient variability was seen; however, a lack of correlation between the levels of adducts observed in saliva and blood samples was also observed (Pearson correlation coefficient r = -0.2598). A high yield of DNA was obtained from saliva samples, but significant difficulties were experienced in obtaining patient adherence to the saliva sampling procedure. In both leukocyte and saliva samples, not only was Pt from previous chemotherapy cycles detected, but the rapid appearance of Pt in the DNA was noted in both sample types 1 h after treatment.

  12. Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial.

    Science.gov (United States)

    Heigener, David F; Pereira, José Rodrigues; Felip, Enriqueta; Mazal, Juraj; Manzyuk, Lyudmila; Tan, Eng Huat; Merimsky, Ofer; Sarholz, Barbara; Esser, Regina; Gatzemeier, Ulrich

    2015-06-01

    The First-Line Erbitux in Lung Cancer (FLEX) trial showed that the addition of cetuximab to chemotherapy followed by weekly cetuximab maintenance significantly improved survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC). The phase IIIb NSCLC Erbitux Trial (NEXT) trial (NCT00820755) investigated the efficacy and safety of weekly and every 2 weeks cetuximab maintenance therapy in this setting. Patients were treated with platinum-based chemotherapy plus cetuximab, and those progression-free after four to six cycles were randomized to every 2 weeks (500 mg/m(2)) or weekly (250 mg/m(2)) cetuximab maintenance. Randomization was stratified for tumor histology and response status. The primary endpoint for a regimen would be reached if the lower boundary of the 95 % confidence interval (CI) for the 1-year survival rate exceeded 55 %. A planned 480 patients were to be randomized. However, enrollment was curtailed following a negative opinion from the European Medicines Agency with regard to the use of cetuximab in this setting. After combination therapy, 311/583 (53.3 %) patients without progression were randomized to maintenance therapy: 157 to every 2 weeks cetuximab and 154 to weekly cetuximab. Baseline characteristics were balanced between these groups and exposure to cetuximab was similar. The 1-year survival rate was 62.8 % (95 % CI, 54.7-70.0) for every 2 weeks cetuximab and 64.4 % (95 % CI, 56.2-71.4) for weekly cetuximab. Safety profiles were similar, manageable, and in line with expectations. Therefore, in patients with advanced NSCLC who were progression-free after four to six cycles of first-line chemotherapy plus cetuximab, weekly and every 2 weeks cetuximab maintenance therapy were associated with similar survival outcomes.

  13. Anti-tumor activity of an anti-DR5 monoclonal antibody, TRA-8, in combination with taxane/platinum-based chemotherapy in an ovarian cancer model.

    Science.gov (United States)

    Bevis, Kerri S; McNally, Lacey R; Sellers, Jeffery C; Della Manna, Deborah; Londoño Joshi, Angelina; Amm, Hope; Straughn, J Michael; Buchsbaum, Donald J

    2011-04-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates apoptosis via binding to death receptors and enhances the anti-tumor effect of conventional cancer therapies. We evaluated the efficacy of TRA-8, an agonistic antibody to DR5, combined with docetaxel and carboplatin in vitro in an intraperitoneal (IP) ovarian cancer model. Luciferase positive ES2 cells (ES2H) were treated in 96 well plates with TRA-8, carboplatin, docetaxel, and combination therapy. Cell viability was assessed using ATP-lite assay. Apoptosis was confirmed via Western blot analysis. ES2H cells were injected IP into female athymic nude mice. Animals were sorted based on bioluminescent signal with the following treatments: 1) untreated; 2) TRA-8 alone; 3) docetaxel+carboplatin; and 4) docetaxel+carboplatin+TRA-8. Animals receiving TRA-8 antibody were injected IP with 200 μg of TRA-8 twice weekly until death. Animals receiving docetaxel+carboplatin were injected IP with 5mg/kg and 15 mg/kg respectively every 3 weeks until death. Animals were assessed for tumor burden using bioluminescence imaging and overall survival. Combination therapy reduced viability of ES2H cells in vitro over single agent therapy. Tumor burden was lowest in the chemotherapy+TRA-8 group at days 23 (pTRA-8 group (41 days) compared to the chemotherapy only group (34 days) and control group (27 days) as determined by Kaplan-Meier analysis (pTRA-8 reduced cell-viability via activation of apoptotic pathways, reduced tumor burden and improved survival in this ovarian cancer model. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a retrospective study in a single comprehensive European cancer institution.

    Directory of Open Access Journals (Sweden)

    Ramon Andrade de Mello

    Full Text Available BACKGROUND: The use of cetuximab in combination with platinum (P plus 5-fluorouracil (F has previously been demonstrated to be effective in the treatment of metastatic squamous cell cancer of head and neck (SCCHN. We investigated the efficacy and outcome of this protocol as a first-line treatment for patients with recurrent or metastatic disease. We evaluated overall-survival (OS, progression-free-survival (PFS, overall response rate (ORR and the treatment toxicity profile in a retrospective cohort. PATIENTS AND METHODS: This study enrolled 121 patients with untreated recurrent or metastatic SCCHN. The patients received PF+ cetuximab every 3 weeks for a maximum of 6 cycles. Patients with stable disease who received PF+ cetuximab continued to receive cetuximab until disease progressed or unacceptable toxic effects were experienced, whichever occurred first. RESULTS: The median patient age was 53 (37-78 years. The patient cohort was 86.8% male. The addition of cetuximab to PF in the recurrent or metastatic setting provided an OS of 11 months (Confidential Interval, CI, 95%, 8.684-13.316 and PFS of 8 months (CI 95%, 6.051-9.949. The disease control rate was 48.9%, and the ORR was 23.91%. The most common grade 3 or 4 adverse events in the PF+ cetuximab regimen were febrile neutropenia (5.7%, skin rash (3.8% and mucosistis (3.8%. CONCLUSIONS: The results of this study suggest that cetuximab plus platinum-fluorouracil chemotherapy is a good option for systemic treatment in advanced SSCHN patients. This regimen has a well-tolerated toxicity profile.

  15. Influence of comorbidity on survival, toxicity and health-related quality of life in patients with advanced non-small-cell lung cancer receiving platinum-doublet chemotherapy

    DEFF Research Database (Denmark)

    Grønberg, Bjørn H; Sundstrøm, Stein; Kaasa, Stein;

    2010-01-01

    AIM OF THE STUDY: To investigate whether patients with severe comorbidity receiving platinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC) have a shorter overall survival, experience more toxicity or more deterioration of health-related quality of life (HRQoL) than other....... Comorbidity was assessed from hospital medical records using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Toxicity was graded using the CTCAE v3.0 and the patients reported HRQoL on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30...... neutropenic fevers (12% versus 5%; p=.012) and deaths from neutropenic infections (3% versus 0%; p=.027). They had more thrombocytopenia (46% versus 36%; p=.03), but not more thrombocytopenic bleedings (3% versus 4%; p=.65). In general, the patients with severe comorbidity reported poorer HRQoL...

  16. Cetuximab plus platinum-based chemotherapy in head and neck squamous cell carcinoma: a randomized, double-blind safety study comparing cetuximab produced from two manufacturing processes using the EXTREME study regimen.

    Science.gov (United States)

    Soulières, Denis; Aguilar, Jose Luis; Chen, Eric; Misiukiewicz, Krzysztof; Ernst, Scott; Lee, Hyun Jung; Bryant, Katherine; He, Shuang; Obasaju, Coleman K; Chang, Shao-Chun; Chin, Steve; Adkins, Douglas

    2016-01-14

    Cetuximab, in combination with platinum chemotherapy plus 5-fluoruracil (5-FU), is approved for the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). Cetuximab manufactured by ImClone (US commercial cetuximab) potentially results in higher systemic exposures than cetuximab manufactured by Boehringer Ingelheim (BI-manufactured cetuximab). This prospective, randomized, double-blind study compared the safety profiles of the two cetuximab formulations. Patients with previously untreated locoregionally recurrent and/or metastatic SCCHN were randomly assigned to receive the same dose of US commercial cetuximab (Arm A) or BI-manufactured cetuximab (Arm B), each in combination with cisplatin or carboplatin plus 5-FU. The primary outcome was all-grade, all-cause treatment-emergent adverse events (TEAEs). The majority of patients experienced ≥ 1 TEAE, regardless of causality (Arm A: 75/77 patients, 97.4%; Arm B: 68/71 patients, 95.8%). TEAEs with the highest incidence included nausea, fatigue, and hypomagnesemia in both arms. The absolute risk difference between the two arms for patients experiencing at least one adverse event (AE) was 0.029 (p = 0.281, 95% confidence interval [CI]: -0.024, 0.082) for AEs regardless of causality and 0.005 (p = 0.915, 95% CI: -0.092, 0.103) for AEs possibly related to study drug. There were no significant differences between the two arms in the incidence of acneiform rash, cardiac events, infusion reactions, or hypomagnesemia. Overall survival, progression-free survival, and overall response rates were similar in the two arms. There were no clinically meaningful differences in safety between US commercial cetuximab and BI-manufactured cetuximab in combination with platinum-based therapy with 5-FU in patients with locoregionally recurrent and/or metastatic SCCHN. The use of US commercial cetuximab in this combination chemotherapy regimen did not result in any unexpected safety signals. The

  17. High plasma exposure to pemetrexed leads to severe hyponatremia in patients with advanced non small cell lung cancer receiving pemetrexed-platinum doublet chemotherapy

    Directory of Open Access Journals (Sweden)

    Gota V

    2014-06-01

    Full Text Available Vikram Gota,1 Krunal Kavathiya,1 Kartik Doshi,1 Murari Gurjar,1 Solai E Damodaran,1 Vanita Noronha,2 Amit Joshi,2 Kumar Prabhash2 1Department of Clinical Pharmacology, Advanced Centre for Treatment Research and Education in Cancer, 2Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India Background: Pemetrexed-platinum doublet therapy is a standard treatment for stage IIIb/IV nonsquamous non small cell lung cancer (NSCLC. While the regimen is associated with several grade ≥3 toxicities, hyponatremia is not a commonly reported adverse effect. Here we report an unusually high incidence of grade ≥3 hyponatremia in Indian patients receiving pemetrexed-platinum doublet, and the pharmacological basis for this phenomenon. Methods: Forty-six patients with advanced NSCLC were enrolled for a bioequivalence study of two pemetrexed formulations. All patients received the pemetrexed-platinum doublet for six cycles followed by single-agent pemetrexed maintenance until progression. Pharmacokinetic blood samples were collected at predefined time points during the first cycle and the concentration-time profile of pemetrexed was investigated by noncompartmental analysis. Hyponatremic episodes were investigated with serum electrolytes, serum osmolality, urinary sodium, and urine osmolality. Results: Sixteen of 46 patients (35% had at least one episode of grade ≥3 hyponatremia. Twenty-four episodes of grade ≥3 hyponatremia were observed in 200 cycles of doublet chemotherapy. Plasma exposure to pemetrexed was significantly higher in patients with high-grade hyponatremia than in those with low-grade or no hyponatremia (P=0.063 and P=0.001, respectively. Pemetrexed clearance in high-grade hyponatremia was quite low compared with normal and low-grade hyponatremia (P=0.001 and P=0.055, respectively. Median pemetrexed exposure in this cohort was much higher than that reported in the literature from Western studies. Conclusion: Higher exposure to

  18. ERCC1和XPD基因SNPs与晚期NSCLC含铂类药物化疗敏感性的关系%Association between polymorphisms of ERCC1 and XPD and sensitivity to platinum-based chemotherapy in advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    张胜利; 张增利; 施敏骅

    2013-01-01

    Objective To investigate whether SNPs of ERCCKC118T) and XPD(Lys751Gln) were associated with the sensitivity of non-small-cell lung cancer ( NSCLC) to platinum-based chemotherapy in the patients with advanced NSCLC. Methods Polymorphisms of ERCC1 and XPD were detected by PCR-restrictive fragment length polymorphism (PCR-RFLP) method in 78 cases. Results No association was detected between polymorphisms of ERCC1 and XPD and age, sex, histologic type,ECOG performance status,smoking history and clinical stage of tumor. The difference of clinical response was not found among age, sex, ECOG performance status and smoking history (P>0. 05). The polymorphic genotypes of ERCCl (C118T) were related to the sensitivity to platinum-based chemotherapy. Conclusion The patients carrying at least 1 T allele(T/T+C/T) may be taken as a marker to predict the sensitivity of NSCLC to platinum-based chemotherapy.%目的 探讨切除修复交叉互补基因1(ERCC1)第118位密码子(C118T)和着色性干皮病基因D(XPD)第751位密码子(Lys751Gln)的单核苷酸多态性(SNPs)与晚期非小细胞肺癌(NSCLC)患者含铂类药物化疗疗效的关系.方法 用PCR-限制性片段长度多态性(PCR-RFLP)技术检测78例NSCLC患者的ERCC1 (C118T)和XPD(Lys751Gln)基因型.结果 ERCC1(C118T)、XPD(Lys751Gln) SNPs不受年龄、性别、吸烟史、临床分期、体力状况评分(ECOG)和病理类型影响;ERCC1 (C118T)中不同的年龄、性别、吸烟史和ECOG评分之间化疗疗效差异无统计学意义.ERCC1(C118T) SNPs与含铂类药物化疗疗效有关.结论 含有T等位基因可作为预测晚期NSCLC患者铂类药物化疗敏感性的预测指标.

  19. XRCC1和XRCC3单核苷酸多态性与晚期非小细胞肺癌铂类药物化疗疗效的相关性%Effect of the XRCC1 and XRCC3 Genetic Polymorphisms on the Efficacy of Platinum-based Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    许崇安; 王小杰; 张晔; 李琳

    2011-01-01

    背景与目的 DNA修复基因多态性预测铂类药物化疗敏感性对非小细胞肺癌(non-small cell lung cancer,NSCLC)个体化治疗具有重要意义.本研究旨在探讨X线修复交错互补基因1(X-ray repair cross complementing gene 1,XRCC1)和X线修复交错互补基因3(X-ray repair cross complementing gene 3,XRCC3)单核苷酸多态性与晚期NSCLC患者对铂类药物化疗疗效的关系.方法 采用PCR-RFLP方法检测130例以含铂方案化疗的晚期NSCLC患者外周血DNA中XRCC1 Arg194 Trp、Arg399 Gln和XRCC3 Thr241 Met基因多态性,分析其基因型与化疗疗效的关系.结果 130例晚期NSCLC患者采用含铂方案化疗2个周期后,化疗总有效率为33.8%.XRCC1 194和399基因多态性与铂类药物化疗敏感性相关,而XRCC3 241基因多态性与化疗敏感性无关(P=0.145).携带至少1个XRCC1 194 Trp等位基因者化疗有效率至少是携带Arg/Arg基因型患者的2.5倍(42.1%vs22.2%,OR=2.545,95%CI:1.159-5.590,P=0.020).携带XRCC1399 Arg/Arg基因型者的化疗有效率为45.5%,明显高于携带至少1个Gln等位基因者(21.9%)(OR=0.336,95%CI:0.156-0.722,P=0.005).XRCC1 194和399基因多态性之间存在联合作用,同时携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg基因型者的化疗有效率明显高于同时携带194 Arg/Arg和399 Arg/Gln基因型者(44.4% vs 18.8%,OR=3.467,95%CI:1.223-9.782,P=0.019).XRCC1和XRCC3基因多态性在化疗敏感性方面存在一定的联合作用,携带至少1个XRCC1 194 Trp等位基因和399 Arg/Arg野生型基因同时又携带XRCC3 241 Thr/Met基因型者的化疗有效率明显高于其它基因型携带者.结论 XRCC1和XRCC3的多态联合可能与晚期NSCLC患者对铂类药物化疗疗效具有相关性.%Background and objective DNA repair gene polymorphisms can be used to predict the sensitivity of platinum-based chemotherapy. Thus, such polymorphisms are important for the individual treatment of non-small cell lung

  20. Time-Series Modeling and Simulation for Comparative Cost-Effective Analysis in Cancer Chemotherapy: An Application to Platinum-Based Regimens for Advanced Non-small Cell Lung Cancer.

    Science.gov (United States)

    Chisaki, Yugo; Nakamura, Nobuhiko; Yano, Yoshitaka

    2017-01-01

    The purpose of this study was to propose a time-series modeling and simulation (M&S) strategy for probabilistic cost-effective analysis in cancer chemotherapy using a Monte-Carlo method based on data available from the literature. The simulation included the cost for chemotherapy, for pharmaceutical care for adverse events (AEs) and other medical costs. As an application example, we describe the analysis for the comparison of four regimens, cisplatin plus irinotecan, carboplatin plus paclitaxel, cisplatin plus gemcitabine (GP), and cisplatin plus vinorelbine, for advanced non-small cell lung cancer. The factors, drug efficacy explained by overall survival or time to treatment failure, frequency and severity of AEs, utility value of AEs to determine QOL, the drugs' and other medical costs in Japan, were included in the model. The simulation was performed and quality adjusted life years (QALY) and incremental cost-effectiveness ratios (ICER) were calculated. An index, percentage of superiority (%SUP) which is the rate of the increased cost vs. QALY-gained plots within the area of positive QALY-gained and also below some threshold values of the ICER, was calculated as functions of threshold values of the ICER. An M&S process was developed, and for the simulation example, the GP regimen was the most cost-effective, in case of threshold values of the ICER=$70000/year, the %SUP for the GP are more than 50%. We developed an M&S process for probabilistic cost-effective analysis, this method would be useful for decision-making in choosing a cancer chemotherapy regimen in terms of pharmacoeconomic.

  1. A pooled exploratory analysis of the effect of tumor size and KRAS mutations on survival benefit from adjuvant platinum-based chemotherapy in node-negative non-small cell lung cancer.

    Science.gov (United States)

    Cuffe, Sinead; Bourredjem, Abderrahmane; Graziano, Stephen; Pignon, Jean-Pierre; Domerg, Caroline; Ezzalfani, Monia; Seymour, Lesley; Strevel, Elizabeth; Burkes, Ronald; Capelletti, Marzia; Jänne, Pasi A; Tsao, Ming-Sound; Shepherd, Frances A

    2012-06-01

    The staging of node-negative non-small-cell lung cancer is modified in the 7th edition TNM classification. Here, we pool data from the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial and the Cancer and Leukemia Group B-9633 trial to explore the prognostic and predictive effects of the new T-size descriptors and KRAS mutation status. Node-negative patients were reclassified as T2a (>3-≤5 cm), T2b (>5-≤7 cm), T3 (>7 cm) or T ≤ 3 cm (≤3 cm, but other T2 characteristics). Of 538 eligible patients, 288 (53.5%) were T2a, 111 (21%) T2b, 62 (11.5%) T3, whereas 77 (14%) T≤3 cm were excluded to avoid confounding. KRAS mutations were detected in 104 of 390 patients (27%). T-size was prognostic for disease-free survival (p = 0.03), but borderline for overall survival (OS; p = 0.10), on multivariable analysis. Significant interaction between the prognostic value of KRAS and tumor size was observed for OS (p = 0.01), but not disease-free survival (p = 0.10). There was a nonsignificant trend (p = 0.24) for increased chemotherapy effect on OS with advancing T-size (hazard ratio [HR] T2a 0.90, [0.63-1.30]; T2b 0.69, [0.38-1.24]; and T3 0.57, [0.28-1.17]). The HR for chemotherapy effect on OS in T2a patients with KRAS wild-type tumors was 0.81 (p = 0.36), whereas a trend for detrimental effect was observed in those with mutant tumors (HR 2.11; p = 0.09; interaction p = 0.05). Similar trends were observed in T2b to T3 patients with wild-type (HR 0.86; p = 0.62), and KRAS mutant tumors (HR 1.16; p = 0.74; interaction p = 0.58). Chemotherapy effect seems to increase with tumor size. However, this small study could not identify subgroups of patients who did or did not derive significant benefit from adjuvant chemotherapy based on T-size or KRAS status.

  2. Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy.

    Science.gov (United States)

    Felip, Enriqueta; Hirsh, Vera; Popat, Sanjay; Cobo, Manuel; Fülöp, Andrea; Dayen, Charles; Trigo, José M; Gregg, Richard; Waller, Cornelius F; Soria, Jean-Charles; Goss, Glenwood D; Gordon, James; Wang, Bushi; Palmer, Michael; Ehrnrooth, Eva; Gadgeel, Shirish M

    2017-06-23

    In the phase III LUX-Lung 8 trial, afatinib significantly improved progression-free survival (PFS) and overall survival (OS) versus erlotinib in patients with squamous cell carcinoma (SCC) of the lung progressing during or after platinum-based chemotherapy. Patient-reported outcomes (PROs) and health-related quality of life (QoL) in these patients are presented. Patients (n = 795) were randomized 1:1 to oral afatinib (40 mg/d) or erlotinib (150 mg/d). PROs were collected (baseline, every 28 days until progression, 28 days after discontinuation) using the European Organization for Research and Treatment of Cancer QoL questionnaire and lung cancer-specific module. The percentage of patients improved during therapy, time to deterioration (TTD), and changes over time were analyzed for prespecified lung cancer-related symptoms and global health status (GHS)/QoL. Questionnaire compliance was 77.3% to 99.0% and 68.7% to 99.0% with afatinib and erlotinib, respectively. Significantly more patients who received afatinib versus erlotinib experienced improved scores for GHS/QoL (36% vs. 28%; P = .041) and cough (43% vs. 35%; P = .029). Afatinib significantly delayed TTD in dyspnea (P = .008) versus erlotinib, but not cough (P = .256) or pain (P = .869). Changes in mean scores favored afatinib for cough (P = .0022), dyspnea (P = .0007), pain (P = .0224), GHS/QoL (P = .0320), and all functional scales. Differences in adverse events between afatinib and erlotinib, specifically diarrhea, did not affect GHS/QoL. In patients with SCC of the lung, second-line afatinib was associated with improved prespecified disease-related symptoms and GHS/QoL versus erlotinib, complementing PFS and OS benefits with afatinib. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. An Analysis on Prognosis of Locoregionally Advanced Nasopharyngeal Carcinoma Treated with IMRT and Platinum-based Chemotherapy%调强放射治疗联合铂类化疗治疗局部晚期鼻咽癌预后分析

    Institute of Scientific and Technical Information of China (English)

    郭文杰; 许建华; 卞秀华; 姜雪松; 郭业松; 王雪; 宗丹; 何侠

    2012-01-01

    [目的]评价调强放射治疗联合铂类化疗治疗不同亚组局部晚期鼻咽癌的预后.[方法]将181例连续收治经病理学确诊的初治局部晚期鼻咽癌分为3组,以局部扩展为主要特征的T3~4N0~1M066例,以区域淋巴结转移为主要特征的T1~2N2~3M0 42例及混合型T3~4N2~3M0 73例,均采用调强放射治疗合并以铂类为基础的诱导化疗及同步化疗.中位随访24个月.[结果]局部扩展型、区域淋巴结转移型和混合型2年局部区域控制率分别为92.3%、100%及97.2% (P=0.32);2年无远处转移生存率分别为91.1%,78.2%和76.3% (P=0.016);2年无进展生存率分别为86.7%,78.2%和77.0%(P=0.095).COX多因素分析示N分期是局部晚期鼻咽癌远处转移及疾病相关死亡的独立的危险因素(HR=2.99,95 %CI:1.65~5.44;HR=3.20,95%CI:1.58~6.49).[结论]在调强放疗联合铂类化疗的治疗背景下,局部及区域晚期鼻咽癌中N2~3亚组预相对较差,远处转移率及疾病相关死亡率上升.%[Purpose] To investigate the prognosis of locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and platinum-based chemotherapy. [Methods] One hundred eighty-one patients with locally advanced nasopharyngeal carcinoma were retrospectively divided into three subgroups: locally advanced (T3-4N0-1M0) group(n =66), regionally advanced (T1-2N2-3M0)group (n= 42) and the mixed group(T3-4V2-3,M0)(n=73). The patients were all treated with definitive intensity-modulated radiotherapy and platinum-based chemotherapy with median follow-up of 24 months. [Results] The 2-year locoregional control (LRC) rate for locally advanced group,regionally advanced group,and the mixed type group was 92.3%, 100% and 97.2% respectively(P=0.32),the 2-year distant metastasis free survival(DMFS) rate was 91.1%,78.2% and 76.3% repectively (P=0.016),the 2-year progress free survival (PFS) rate was 86.7%,78.2% and 77

  4. GSTP1 Ile105Val(A/G)多态性与进展期胃癌铂类药物化疗敏感性的Meta分析%Association between Ile105Val polymorphism of GSTP1 and sensitivity to platinum-based chemotherapy in advanced gastric cancer: a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    邓成辉; 关泉林; 姜雷; 李小奇; 甘亮亮; 魏孔孔

    2014-01-01

    目的 定量评价进展期胃癌患者中谷胱甘肽S转移酶pi(GSTP1)基因105氨基酸位点Ile/Val多态性与铂类药物化疗敏感性的关系.方法 检索中国期刊全文数据库(CNKI)、中文科技期刊全文数据库(VIP)、中国生物医学文献数据库(CBM)、万方数据库、PubMed、EMBASE、Cochrane Library,收集国内外公开发表的关于GSTP1 Ilel05Val基因多态性与胃癌铂类药物化疗敏感性关系的文献.临床有效(完全缓解+部分缓解)作为评价化疗敏感性的指标.运用RevMan 5.2进行Meta分析,计算合并比值比(OR)及95%可信区间(CI),运用Stata 12.0识别是否存在发表偏倚.结果 本研究纳入6项研究共计病例724例,Meta分析结果显示,各基因型间(GG+GAvs AA:OR=2.38,95% CI为1.29~4.38;GG vs GA+ AA:OR=3.66,95% CI为1.18 ~ 11.39;GG vs AA:OR=4.42,95% CI为1.28~15.26)以及亚洲人群亚组(GG+ GA vs AA:OR=2.93,95%CI为1.33 ~ 6.48)中GSTP1 Ilel05Val多态性与化疗敏感性的差异有统计学意义.结论 GSTP1 Ile105VaI(A/G)基因多态性可能与进展期胃癌铂类化疗药物敏感性相关.%Objective To quantitatively evaluate the association between Ile105Val polymorphism of glutathione S-transferase pi (GSTP1) and sensitivity to platinum-based chemotherapy in advanced gastric cancer.Methods The relevant published literatures about Ile105Val polymorphism of GSTP1 and sensitivity to platinum-based chemotherapy in gastric cancer were retrieved from China National Knowledge Internet (CNKI),VIP,Chinese Biomedical Literature Data (CBM),Wan-Fang databases,PubMed,EMBASE and Cochrane Library.Clinical response (complete response and partial response) was employed to estimate chemosensitivity.Meta-analysis was conducted by the RevMan 5.2 software,odds ratio (OR) with 95% confidence interval (CI) were calculated.Publication bias was identified using Stata 12.0 software.Results A total of 724 cases from 6 case-control trials were included.The results of

  5. Effectiveness and safety of triplet combination chemotherapy compared to doublet combination chemotherapy for advanced gastric cancer: a meta-analysis%晚期胃癌化疗三药联合方案对比两药联合方案有效性及安全性meta分析

    Institute of Scientific and Technical Information of China (English)

    刘宁; 陆建伟; 丁选胜

    2012-01-01

    OBJECTIVE To perform a systematic review of the randomized controlled trials in advanced gastric cancer for comparing the effectiveness and safety between triplet combination chemotherapy and doublet combination chemotherapy. METHODS Cochrane strategy in combination with manual search was used to identify previously published randomized controlled trials in advanced gastric cancer by searching Cochrane library. PubMed. EMBase, China Journal Full-text Database. RESULTS Twelve randomized controlled trials were studied. The overall response rate in triplet combination chemotherapy was higher than that in doublet combination chemotherapy(OR= 1. 36,95% CI 1. 10 - 1.67. P=0.004), In subgroup analy sis, the overall response rate in taxanes based triplet combination chemotherapy was higher than that in doublet combination chemotherapy (OR = 1. 50,95% Cl 1. 14 - 1. 97, P = 0. 01)0 4), the tendency was not observed in antitumor antibiotic based triplet combination chemotherapy(OR = 1. 21,95% Cl 0. 85 - 1. 72. P= 0. 68). In adverse events of grade 3/4, there was no statistical significance between the triplet combination chemotherapy and doublet combination chemothcrapy(P> 05). In subgroup analysis, the incidence of diarrhea of grades 3 to 4 was higher in taxanes based triplet combination chemotherapy than that in doublet combination chemotherapy(OR= 3. 19.95% CI 1. 92-5.30. P<0. 05), the tendency was also not observed in antitumor antibiotic based triplet combination chemotherapy(()R = 0. 96.95% CI 0. 35 - 2. 63, P = 0. 94). CONCLUSION In advanced gastric cancer, triplet combination chemotherapy was more effective than that in doublet combination chemotherapy, especially in taxanes based triplet combination chemotherapy. In adverse events of grade 3/4. there was no statistical significance between the triplet combination chemotherapy and doublet combination chemotherapy%目的:系统评价晚期胃癌化疗三药联合方案对比两药联合方案的随机对照试验结

  6. Chemical Imaging of Platinum-Based Drugs and their Metabolites.

    Science.gov (United States)

    Liu, Xin; Hummon, Amanda B

    2016-12-05

    Platinum-based drugs (cisplatin, carboplatin, and oxaliplatin) are widely used therapeutic agents for cancer treatment. Even though the platinum (Pt)-drugs are routinely used clinically, a clear picture of their distribution within tumor tissues is lacking. The current methods to image the distribution of Pt drugs are limited and do not enable the discrimination of the drug from its metabolites. In this manuscript, we demonstrate a methodology that enables chemical imaging of a Pt drug and its metabolites simultaneously and specifically. Matrix-Assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry Imaging (MSI) is combined with an on-tissue chemical derivatization using diethyldithiocarbamate (DDTC). DDTC abstracts the Pt atom to generate ionizable complexes that can be imaged by MALDI MSI. We demonstrate that Pt drugs and their metabolites can be specifically imaged. This approach was successfully applied to map the penetration and metabolism of oxaliplatin in hyperthermic intraperitoneal chemotherapy (HIPEC)-like treated 3D colorectal tumor mimics. The distribution of cisplatin and carboplatin was mapped in additional 3D tumor mimics. We demonstrate that the approach can also be used to image the distribution of copper ions in cells. This method has the potential to be used to evaluate the penetration and distribution of a wide range of compounds.

  7. Olaparib for Maintenance Treatment of BRCA 1 or 2 Mutated, Relapsed, Platinum-Sensitive Ovarian, Fallopian Tube and Peritoneal Cancer in People Whose Relapsed Disease has Responded to Platinum-Based Chemotherapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Tappenden, Paul; Harnan, Sue; Ren, Shijie; Thokala, Praveen; Wong, Ruth; Mukuria, Clara; Green, Clare; Pledge, Simon; Tidy, John

    2017-01-01

    As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of olaparib (AstraZeneca) to submit evidence on the clinical and cost effectiveness of olaparib for the maintenance treatment of BRCA1/2 mutated (BRCAm), platinum-sensitive relapsed (PSR) ovarian, fallopian tube and peritoneal cancer in people whose relapsed disease has responded to platinum-based chemotherapy. The Evidence Review Group (ERG) produced a critical review of the evidence contained within the company's submission (CS) to NICE. The clinical evidence related to one phase II, double-blind randomised controlled trial that recruited 265 patients with PSR serous ovarian cancer (OC) regardless of BRCAm status. Patients received olaparib 400 mg twice daily (b.i.d.) or matched placebo. In the whole population, the primary endpoint of progression-free survival (PFS) was met (hazard ratio [HR] 0.35; 95 % confidence interval [CI] 0.25-0.49, p group (HR 0.88; 95 % CI 0.64-1.21; p = 0.44) or the BRCAm subgroup (0.73; 95 % CI 0.45-1.17; p = 0.19), though treatment switching may have confounded results. The exclusion of data from sites allowing crossover resulted in an HR for overall survival (OS) of 0.52 (95 % CI 0.28-0.97, p = 0.039) in the BRCAm group. Health-related quality-of-life measures were not significantly different between groups. All post hoc exploratory outcomes (time to treatment discontinuation/death, time to first subsequent therapy/death, and time to second subsequent therapy/death) were statistically significantly better in the olaparib arm in the whole population and the BRCAm subgroup analyses. Adverse events were more frequent for olaparib but were largely minor or manageable. The company's semi-Markov model assessed the cost effectiveness of olaparib versus routine surveillance in patients with BRCAm PSR OC from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a

  8. Biomarkers to assess the efficiency of treatment with platinum-based drugs: what can metallomics add?

    Science.gov (United States)

    Araujo, Thiago de O; Costa, Lilian T; Fernandes, Janaina; Aucélio, Ricardo Queiroz; de Campos, Reinaldo Calixto

    2014-12-01

    Since the approval of cisplatin as an antineoplastic drug, the medical and the scientific communities have been concerned about the side effects of platinum-based drugs, and this has been the dose-limiting factor that leads to reduced treatment efficiency. Another important issue is the intrinsic or acquired resistance of some patients to treatment. Identifying proper biomarkers is crucial in evaluating the efficiency of a treatment, assisting physicians in determining, at early stages, whether or not the patient presents resistance to the drug, minimizing severe side effects, and allowing them to redirect the established course of chemotherapy. A great effort is being made to identify biomarkers that can be used to predict the outcome of the treatment of cancer patients with platinum-based drugs. In this context, the metallomic approach has not yet been used to its full potential. Since the basis of these drugs is platinum, the monitoring of biomarkers containing this metal should be the natural approach to evaluate treatment progress. This review intends to show where the research in this field stands and points out some gaps that can be filled by metallomics.

  9. Molecular pathways: the immunogenic effects of platinum-based chemotherapeutics

    NARCIS (Netherlands)

    Hato, S.V.; Khong, A.; Vries, I.J.M. de; Lesterhuis, W.J.

    2014-01-01

    The platinum-based drugs cisplatin, carboplatin, and oxaliplatin belong to the most widely used chemotherapeutics in oncology, showing clinical efficacy against many solid tumors. Their main mechanism of action is believed to be the induction of cancer cell apoptosis as a response to their covalent

  10. Clinical progression of lobaplatin in combination chemotherapy for patients with recurrence or metastatic cancer

    Institute of Scientific and Technical Information of China (English)

    Yu Peng; Jiangkui Liu; Qiang Lin

    2014-01-01

    The-platinum-based-combination-chemotherapy-has-become-one-of-the-major-modalities-in-anti-cancer-treatment.-After-the-first-line-chemotherapy,-many-patients-need-further-chemotherapy-because-of-recurrence-or-metastasis.-Lobaplatin-is-one-of-the-third-generation-platinum-drugs,and-this-article-briefly-reviews-the-clinical-progression-of-lobaplatin-in-combination-chemotherapy-for-patients-with-recurrence-or-metastatic-cancer.

  11. Origins of inert Higgs doublets

    Directory of Open Access Journals (Sweden)

    Thomas W. Kephart

    2016-05-01

    Full Text Available We consider beyond the standard model embedding of inert Higgs doublet fields. We argue that inert Higgs doublets can arise naturally in grand unified theories where the necessary associated Z2 symmetry can occur automatically. Several examples are discussed.

  12. Long noncoding RNA expression signature to predict platinum-based chemotherapeutic sensitivity of ovarian cancer patients.

    Science.gov (United States)

    Liu, Rong; Zeng, Ying; Zhou, Cheng-Fang; Wang, Ying; Li, Xi; Liu, Zhao-Qian; Chen, Xiao-Ping; Zhang, Wei; Zhou, Hong-Hao

    2017-12-01

    Dysregulated long noncoding RNAs (lncRNAs) are potential markers of several tumor prognoses. This study aimed to develop a lncRNA expression signature that can predict chemotherapeutic sensitivity for patients with advanced stage and high-grade serous ovarian cancer (HGS-OvCa) treated with platinum-based chemotherapy. The lncRNA expression profiles of 258 HGS-OvCa patients from The Cancer Genome Atlas were analyzed. Results revealed that an eight-lncRNA signature was significantly associated with chemosensitivity in the multivariate logistic regression model, which can accurately predict the chemosensitivity of patients [Area under curve (AUC) = 0.83]. The association of a chemosensitivity predictor with molecular subtypes indicated the excellent prognosis performance of this marker in differentiated, mesenchymal, and immunoreactive subtypes (AUC > 0.8). The significant correlation between ZFAS1 expression and chemosensitivity was confirmed in 233 HGS-OvCa patients from the Gene Expression Omnibus datasets (GSE9891, GSE63885, and GSE51373). In vitro experiments demonstrated that the ZFAS1 expression was upregulated by cisplatin in A2008, HeyA8, and HeyC2 cell lines. This finding suggested that ZFAS1 may participate in platinum resistance. Therefore, the evaluation of the eight-lncRNA signature may be clinically implicated in the selection of platinum-resistant HGS-OvCa patients. The role of ZFAS1 in platinum resistance should be further investigated.

  13. American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer.

    Science.gov (United States)

    Azzoli, Christopher G; Baker, Sherman; Temin, Sarah; Pao, William; Aliff, Timothy; Brahmer, Julie; Johnson, David H; Laskin, Janessa L; Masters, Gregory; Milton, Daniel; Nordquist, Luke; Pfister, David G; Piantadosi, Steven; Schiller, Joan H; Smith, Reily; Smith, Thomas J; Strawn, John R; Trent, David; Giaccone, Giuseppe

    2009-12-20

    The purpose of this article is to provide updated recommendations for the treatment of patients with stage IV non-small-cell lung cancer. A literature search identified relevant randomized trials published since 2002. The scope of the guideline was narrowed to chemotherapy and biologic therapy. An Update Committee reviewed the literature and made updated recommendations. One hundred sixty-two publications met the inclusion criteria. Recommendations were based on treatment strategies that improve overall survival. Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life. For first-line therapy in patients with performance status of 0 or 1, a platinum-based two-drug combination of cytotoxic drugs is recommended. Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy. For patients with performance status of 2, a single cytotoxic drug is sufficient. Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment. Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy. The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor (EGFR) mutation; for negative or unknown EGFR mutation status, cytotoxic chemotherapy is preferred. Bevacizumab is recommended with carboplatin-paclitaxel, except for patients with certain clinical characteristics. Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry. Docetaxel, erlotinib, gefitinib, or pemetrexed is recommended as second-line therapy. Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib. Data are insufficient to recommend the routine third-line use of cytotoxic drugs. Data are insufficient to recommend routine use of molecular markers to select chemotherapy.

  14. Compressing the Inert Doublet Model

    CERN Document Server

    Blinov, Nikita; Morrissey, David E; de la Puente, Alejandro

    2015-01-01

    The Inert Doublet Model relies on a discrete symmetry to prevent couplings of the new scalars to Standard Model fermions. This stabilizes the lightest inert state, which can then contribute to the observed dark matter density. In the presence of additional approximate symmetries, the resulting spectrum of exotic scalars can be compressed. Here, we study the phenomenological and cosmological implications of this scenario. We derive new limits on the compressed Inert Doublet Model from LEP, and outline the prospects for exclusion and discovery of this model at dark matter experiments, the LHC, and future colliders.

  15. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy

    DEFF Research Database (Denmark)

    Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek;

    2010-01-01

    To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.......To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy....

  16. Convection-enhancement delivery of platinum-based drugs and Lipoplatin™ to optimize the concomitant effect with radiotherapy in F98 glioma rat model

    Science.gov (United States)

    Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

    2015-01-01

    The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin™-liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later. PMID:25784204

  17. Convection-enhancement delivery of platinum-based drugs and Lipoplatin(TM) to optimize the concomitant effect with radiotherapy in F98 glioma rat model.

    Science.gov (United States)

    Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

    2015-06-01

    The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum-based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin(TM) - liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later.

  18. Doublet chemotherapy with cisplatin and pemetrexed is associated with a favorable outcome in patients with advanced non-squamous non-small-cell lung cancer who are eligible for bevacizumab and maintenance therapy.

    Science.gov (United States)

    Nakashima, Kazuhisa; Murakami, Haruyasu; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Endo, Masahiro; Takahashi, Toshiaki

    2016-11-01

    The previous AVAPERL trial demonstrated that induction therapy with first-line cisplatin (CDDP), pemetrexed (PEM) and bevacizumab (BEV), followed by continuation maintenance therapy with PEM+BEV, improved the progression-free survival (PFS) and overall survival (OS) compared with BEV alone (median PFS, 10.2 vs. 6.6 months and median OS, 19.8 vs. 15.9 months, respectively) in patients with advanced non-squamous non-small-cell lung cancer (non-Sq NSCLC). However, those findings were based on selected patients who were eligible for BEV and maintenance therapy. To assess the efficacy of CDDP+PEM as first-line therapy in selected patients depending on their eligibility for BEV and maintenance therapy, consecutive patients with non-Sq NSCLC who received first-line chemotherapy with CDDP+PEM at the Shizuoka Cancer Center (Shizuoka, Japan) between July, 2009 and December, 2013 were retrospectively reviewed. A total of 160 patients were assessed, including 92 who were eligible and 68 who were not eligible for BEV treatment. In the BEV-eligible group, CDDP+PEM treatment followed by maintenance PEM exhibited significantly superior efficacy compared with that in the BEV-ineligible group (median PFS, 5.8 vs. 4.8 months, respectively, P=0.013; and median OS, 21.3 vs. 12.6 months, respectively, P=0.0025). In the BEV-eligible group, 60 patients were suitable for maintenance therapy with PEM (group A) and 32 patients were unsuitable (group B). In the BEV-ineligible group, 31 patients were suitable for maintenance therapy with PEM (group C) and 37 patients were unsuitable (group D). In group A, the median PFS and OS were 6.9 and 31.8 months, respectively, compared with 2.4 and 10.5 months in group B, 6.1 and 18.5 months in group C, and 2.8 and 7.7 months in group D. The PFS and OS in group A were significantly better compared with those in the other groups. Thus, the PFS and OS with CDDP+PEM were favorable among patients with advanced non-Sq NSCLC who were eligible for BEV and

  19. Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, M.; Jeppesen, Ulla

    2007-01-01

    The response of tumor cells to platinum-based chemotherapy involves DNA repair mechanisms. Excision repair cross-complementation group 1 (ercc1) is one of the leading genes involved in DNA repair, and several studies have linked ercc1 to platinum resistance in cell lines and in human cancers....... A common single nucleotide polymorphism (SNP) of ercc1 at codon 118 has been proposed to impair ercc1 translation and reduce ERCC1 protein expression and consequently influence the response to platinum-based chemotherapy. The primary aim of the present study was to evaluate ERCC1 expression and ercc1 codon...... 118 polymorphism in epithelial ovarian cancer (EOC) and their possible predictive value in patients treated with platinum-based chemotherapy. Formalin-fixed, paraffin-embedded tissue sections from 159 patients with advanced EOC were used for immunohistochemistry. Ercc1 codon 118 SNP genotyping...

  20. The role of support and promoter on the oxidation of sulfur dioxide using platinum based catalysts

    DEFF Research Database (Denmark)

    Koutsopoulos, Sotiris; Rasmussen, Søren Birk; Eriksen, Kim Michael

    2006-01-01

    The catalytic oxidation of SO2 to SO3 was studied over platinum based catalysts in the absence and the presence of dopants. The active metal was supported on silica gel or titania (anatase) by impregnation. The activities of the silica supported catalysts were found to follow the order PtRh/SiO2...

  1. Structure of matrix metalloproteinase-3 with a platinum-based inhibitor.

    Science.gov (United States)

    Belviso, Benny Danilo; Caliandro, Rocco; Siliqi, Dritan; Calderone, Vito; Arnesano, Fabio; Natile, Giovanni

    2013-06-18

    An X-ray investigation has been performed with the aim of characterizing the binding sites of a platinum-based inhibitor (K[PtCl3(DMSO)]) of matrix metalloproteinase-3 (stromelysin-1). The platinum complex targets His224 in the S1' specificity loop, representing the first step in the selective inhibition process (PDB ID code 4JA1).

  2. The interaction of platinum-based drugs with native biologically relevant proteins

    NARCIS (Netherlands)

    Brauckmann, Christine; Wehe, Christoph A.; Kieshauer, Michael; Lanvers-Kaminsky, Claudia; Sperling, Michael; Karst, Uwe

    2013-01-01

    This study focuses on the identification of the products that are formed upon binding of therapeutically relevant platinum complexes to proteins like beta-lactoglobulin A (LGA), human serum albumin (HSA), or human hemoglobin (HB). The respective proteins were incubated with the platinum-based antica

  3. THROMBOCYTOSIS AS PROGNOSTIC FACTOR FOR SURVIVAL IN PATIENTS WITH ADVANCED NON SMALL CELL LUNG CANCER TREATED WITH FIRST- LINE CHEMOTHERAPY.

    Directory of Open Access Journals (Sweden)

    Deyan Davidov

    2014-12-01

    Full Text Available Objective: The aim of this study was to evaluate elevated platelet count as a prognostic factor for survival in patients with advanced (stage IIIB/ IV non- small cell lung cancer (NSCLC receiving first- line chemotherapy. Methods: From 2005 to 2009 three hundreds forty seven consecutive patients with stage IIIB or IV NSCLC, treated in Department of Medical Oncology, UMHAT "Dr Georgi Stranski" entered the study. The therapeutic regimens included intravenous administration of platinum- based doublets. Survival analysis was evaluated by Kaplan- Meier test. The influence of pretreatment thrombocytosis as prognostic factor for survival was analyzed using multivariate stepwise Cox regression analyses. Results: Elevated platelet counts were found in 78 patients. The overall survival for patients without elevated platelet counts was 9,6 months versus 6,9 months for these with thrombocytosis. In multivariate analysis as independent poor prognostic factors were identified: stage, performance status and elevated platelet counts. Conclusions: These results indicated that platelet counts as well as some clinical pathologic characteristics could be useful prognostic factors in patients with unresectable NSCLC.

  4. Doublet method for very fast autocoding

    Directory of Open Access Journals (Sweden)

    Berman Jules J

    2004-09-01

    Full Text Available Abstract Background Autocoding (or automatic concept indexing occurs when a software program extracts terms contained within text and maps them to a standard list of concepts contained in a nomenclature. The purpose of autocoding is to provide a way of organizing large documents by the concepts represented in the text. Because textual data accumulates rapidly in biomedical institutions, the computational methods used to autocode text must be very fast. The purpose of this paper is to describe the doublet method, a new algorithm for very fast autocoding. Methods An autocoder was written that transforms plain-text into intercalated word doublets (e.g. "The ciliary body produces aqueous humor" becomes "The ciliary, ciliary body, body produces, produces aqueous, aqueous humor". Each doublet is checked against an index of doublets extracted from a standard nomenclature. Matching doublets are assigned a numeric code specific for each doublet found in the nomenclature. Text doublets that do not match the index of doublets extracted from the nomenclature are not part of valid nomenclature terms. Runs of matching doublets from text are concatenated and matched against nomenclature terms (also represented as runs of doublets. Results The doublet autocoder was compared for speed and performance against a previously published phrase autocoder. Both autocoders are Perl scripts, and both autocoders used an identical text (a 170+ Megabyte collection of abstracts collected through a PubMed search and the same nomenclature (neocl.xml, containing over 102,271 unique names of neoplasms. In side-by-side comparison on the same computer, the doublet method autocoder was 8.4 times faster than the phrase autocoder (211 seconds versus 1,776 seconds. The doublet method codes 0.8 Megabytes of text per second on a desktop computer with a 1.6 GHz processor. In addition, the doublet autocoder successfully matched terms that were missed by the phrase autocoder, while the

  5. Chemotherapy and quality of life in NSCLC PS 2 patients

    DEFF Research Database (Denmark)

    Helbekkmo, Nina; Strøm, Hans H; Sundstrøm, Stein H

    2009-01-01

    INTRODUCTION: Nearly 40% of patients with advanced NSCLC are in performance status (PS) 2. These patients have a shorter life expectancy than PS 0/1 patients and they are underrepresented in clinical trials. Data on how platinum-based combination chemotherapy affects Health Related Quality of Life...... (HRQOL) of patients with PS 2 are scarce and the treatment of this important group of patients is controversial. METHODS: A national multicenter phase III study on platinum based chemotherapy to 432 advanced NSCLC patients included 123 patients with PS 2. To explore the treatment impact on HRQOL......: Whereas the demographic data at baseline were well balanced between the groups, the PS 2 patients had significantly worse function and more severe symptoms than the PS 0/1 patients. In response to combination chemotherapy, the PS 2 patients had a more profound improvement of global QOL, cognitive function...

  6. Doublet-Triplet Splitting and Fat Branes

    CERN Document Server

    Maru, N

    2001-01-01

    We consider the doublet-triplet splitting problem in supersymmetric SU(5) grand unified theory in five dimensions where the fifth dimension is non-compact. We point out that an unnatural fine-tuning of parameters in order to obtain the light Higgs doublets is not required due to the exponential suppression of the overlap of the wave functions.

  7. Symmetries in multi-Higgs-doublet models

    CERN Document Server

    Ivanov, I P

    2012-01-01

    We report the recent progress in understanding of symmetries which can be implemented in the scalar sector of electroweak symmetry breaking models with several Higgs doublets. In particular we present the list of finite reparametrization symmetry groups which can appear in the three-Higgs-doublet models.

  8. Neoadjuvant intraarterial chemotherapy and embolization in treatment of advanced ovarian epithelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    刘恩令; 糜若然

    2004-01-01

    Background The purpose of the study was to evaluate the role of neoadjuvant chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries in treating patients with advanced ovarian epithelial carcinoma.Methods Forty-two patients with advanced ovarian epithelial carcinoma (study group) were treated via the anterior branches of the bilateral internal iliac arteries after cytoreductive surgery and 7 courses of adjuvant platinum-based combination chemotherapy. Primary cytoreductive surgery was performed in 43 patients with advanced ovarian epithelial carcinoma (control group), and then followed by 8 courses of adjuvant platinum-based combination chemotherapy. The rate of optimal cytoreductive surgery, survival rate, blood loss during operation and operative time were investigated in the two groups. Statistical significance was asessed using Student's t test, the Chi-squre test and the log-rank test. Results In the study group, the rate of optimum debulking after platinum-based chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries was 71.43%(30/42) (χ2=10.06, P0.05).Conclusions Neoadjuvant platinum-based combination chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries is an alternative treatment for patients with advanced ovarian epithelial carcinoma, in whom the chance of optimal cytoreductive surgery is low. The treatment can reduce blood loss, decrease operative time, and increase the rate of optimal cytoreductive surgery; but the median survival can't be improved significantly.

  9. Singlet-Doublet Dark Matter

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Timothy; /SLAC /Michigan U., MCTP; Kearney, John; Pierce, Aaron; /Michigan U., MCTP; Tucker-Smith, David; /Williams Coll.

    2012-02-15

    In light of recent data from direct detection experiments and the Large Hadron Collider, we explore models of dark matter in which an SU(2){sub L} doublet is mixed with a Standard Model singlet. We impose a thermal history. If the new particles are fermions, this model is already constrained due to null results from XENON100. We comment on remaining regions of parameter space and assess prospects for future discovery. We do the same for the model where the new particles are scalars, which at present is less constrained. Much of the remaining parameter space for both models will be probed by the next generation of direct detection experiments. For the fermion model, DeepCore may also play an important role.

  10. Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer

    DEFF Research Database (Denmark)

    Dahl Steffensen, Karina; Waldstrøm, Marianne; Jeppesen, Ulla;

    -complementation group 1 (ERCC1) is one of the genes that encode the proteins of the NER complex and several studies have linked ERCC1 to platinum resistance in cell lines and in human cancers. Cells with a high repair capacity, e.g. high level of ERCC1 expression may therefore be resistant to platinum......Background: The response of tumor cells to platinum-based drugs involves DNA repair mechanisms. Platinum-DNA adducts are repaired by nucleotide excision repair (NER) enzymes that recognize the DNA damage and excise the platinum-DNA adducts from the injured DNA strand. Excision repair cross...... the response to platinum based chemotherapy. The aim of this study was to evaluate ERCC1 expression and ERCC1 118 polymorphism in epithelial ovarian cancer and the potential association with response to platinum-based chemotherapy. Methods: Formalin-fixed, paraffin-embedded tissue sections from 159 patients...

  11. Higgs properties in the Stealth Doublet Model

    Directory of Open Access Journals (Sweden)

    Wouda Glenn

    2013-11-01

    Full Text Available I present a model with two scalar doublets and a softly broken ℤ2 symmetry, where only one of the doublets gets a vacuum expectation value and couples to fermions at tree-level. The softly broken ℤ2 symmetry leads to interesting phenomenology such as mixing between the two doublets and a charged scalar H± which can be light and dominantly decays into Hγ. The model can also naturally reproduce an enhanced γγ signal of the newly observed Higgs boson at the LHC with mass 125 GeV.

  12. Vacuum stability in neutrinophilic Higgs doublet model

    Energy Technology Data Exchange (ETDEWEB)

    Haba, Naoyuki [Department of Physics, Osaka University, Toyonaka, Osaka 560-0043 (Japan); Horita, Tomohiro, E-mail: tomohiro@het.phys.sci.osaka-u.ac.jp [Department of Physics, Osaka University, Toyonaka, Osaka 560-0043 (Japan)

    2011-11-03

    A neutrinophilic Higgs model has tiny vacuum expectation value (VEV), which can naturally explain tiny masses of neutrinos. There is a large energy scale hierarchy between a VEV of the neutrinophilic Higgs doublet and that of usual standard model-like Higgs doublet. In this Letter we at first analyze vacuum structures of Higgs potential in both supersymmetry (SUSY) and non-SUSY neutrinophilic Higgs models, and next investigate a stability of this VEV hierarchy against radiative corrections. We will show that the VEV hierarchy is stable against radiative corrections in both Dirac neutrino and Majorana neutrino scenarios in both SUSY and non-SUSY neutrinophilic Higgs doublet models.

  13. Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer

    NARCIS (Netherlands)

    Frielink, L.M.; Pijlman, B.M.; Ezendam, N.P.; Pijnenborg, J.M.A.

    2016-01-01

    BACKGROUND: Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. METHODS: All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The perc

  14. Prevention of chemotherapy-induced peripheral neuropathy by the small-molecule inhibitor pifithrin-mu

    NARCIS (Netherlands)

    Krukowski, Karen; Nijboer, Cora H.; Huo, XiaoJiao; Kavelaars, Annemieke; Heijnen, Gobi J.

    2015-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. It is the most frequent cause of dose reduction or treatment discontinuation in patients treated for cancer with commonly used drugs including taxanes and platinum-based compounds. No FDA-approved treatmen

  15. TP53 status and taxane-platinum versus platinum-based therapy in ovarian cancer patients: A non-randomized retrospective study

    Directory of Open Access Journals (Sweden)

    Markowska Janina

    2008-01-01

    Full Text Available Abstract Background Taxane-platinum therapy (TP has replaced platinum-based therapy (PC or PAC, DNA damaging chemotherapy in the postoperative treatment of ovarian cancer patients; however, it is not always effective. TP53 protein plays a differential role in response to DNA-damaging agents and taxanes. We sought to define profiles of patients who benefit the most from TP and also of those who can be treated with PC. Methods We compared the effectiveness of PC/PAC (n = 253 and TP (n = 199 with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease; this was a non-randomized retrospective study. Immunohistochemical analysis was performed on 452 archival tumors; univariate and multivariate analysis by the Cox's and logistic regression models was performed in all patients and in subgroups with [TP53(+] and without TP53 accumulation [TP53(-]. Results The advantage of taxane-platinum therapy over platinum-based therapy was seen in the TP53(+, and not in the TP53(- group. In the TP53(+ group taxane-platinum therapy enhanced the probability of complete remission (p = .018, platinum sensitivity (p = .014, platinum highly sensitive response (p = .038 and longer survival (OS, p = .008. Poor tumor differentiation diminished the advantage from taxane-platinum therapy in the TP53(+ group. In the TP53(- group PC/PAC was at least equally efficient as taxane-platinum therapy and it enhanced the chance of platinum highly sensitive response (p = .010. However, in the TP53(- group taxane-platinum therapy possibly diminished the risk of death in patients over 53 yrs (p = .077. Among factors that positively interacted with taxane-platinum therapy in some analyses were endometrioid and clear cell type, FIGO III stage, bulky residual tumor, more advanced age of patient and moderate tumor differentiation. Conclusion Our results suggest that taxane-platinum therapy is particularly justified in patients with TP53(+ tumors or older

  16. Customized Adjuvant Chemotherapy Based on Biomarker Examination May Improve Survival of Patients Completely Resected for Non-small-cell Lung Cancer.

    Science.gov (United States)

    Liu, Dage; Nakashima, Nariyasu; Nakano, Jun; Tarumi, Shintaro; Matsuura, Natsumi; Nakano, Takayuki; Nii, Kazuhito; Tokunaga, Yoshimasa; Go, Tetsuhiko; Yokomise, Hiroyasu

    2017-05-01

    Adjuvant platinum-based chemotherapy is recommended for patients with completely resected stage II (N1) or III (N2) non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is difficult to predict for individual patients. Our previous prospective study on individualized treatment according to biomarker status, such as excision repair cross-complementing 1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase M1 (RRM1), achieved encouraging results in patients with advanced NSCLC. The present study further examined the effect of biomarker-based adjuvant chemotherapy in patients with completely resected NSCLC. Between January 2006 and December 2014, 66 patients with localized (stage I-IIIA) NSCLC who underwent R0 operation received 2-4 cycles of platinum doublet adjuvant chemotherapy: Platinum plus docetaxel, platinum plus pemetrexed for adenocarcinoma, and platinum plus tegafur/gimeracil/oteracil combination (TS-1) for squamous cell carcinoma (SCC) were selected according to the registered protocol at each period. Immunohistochemistry was used to evaluate the biomarkers: ERCC1 status for platinum, tubulin for docetaxel, and TYMS for pemetrexed and TS-1. A matched chemotherapy regimen meant that platinum plus docetaxel was administered in patients negative for ERCC1 and negative for tubulin, platinum plus pemetrexed in patients with adenocarcinoma positive for tubulin, negative for ERCC1 and negative for TYMS, and platinum plus TS-1 in those with SCC positive for tubulin, negative for ERCC1 and negative for TYMS. The 5-year survival rate was 77.5% considering all 66 patients, and 85.7%, 71.8%, and 78.8% for those with p-stage I, II, and III, respectively. Patients who received a matched chemotherapy regimen (n=13; platinum plus docetaxel in eight, platinum plus pemetrexed in five) had significantly better 5-year survival than patients with unmatched biomarker status (n=53) (100% vs. 71.0%, p=0

  17. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  18. Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

    Directory of Open Access Journals (Sweden)

    Hohenforst-Schmidt W

    2013-07-01

    through passive transport within the tumor. Recent advances have enhanced the diffusion of pharmaceuticals through active transport by using pharmaceuticals designed to target the genome of tumors. In the present study, five patients with non-small cell lung cancer epidermal growth factor receptor (EGFR negative stage IIIa–IV International Union Against Cancer 7 (UICC-7, and with Eastern Cooperative Oncology Group (ECOG 2 scores were administered platinum-based doublet chemotherapy using combined intratumoral-regional and intravenous route of administration. Cisplatin analogues were injected at 0.5%–1% concentration within the tumor lesion and proven malignant lymph nodes according to pretreatment histological/cytological results and the concentration of systemic infusion was decreased to 70% of a standard protocol. This combined intravenous plus intratumoral-regional chemotherapy is used as a first line therapy on this short series of patients. To the best of our knowledge this is the first report of direct treatment of involved lymph nodes with cisplatin by endobronchial ultrasound drug delivery with a needle without any adverse effects. The initial overall survival and local response are suggestive of a better efficacy compared to established doublet cisplatin–based systemic chemotherapy in (higher standard concentrations alone according to the UICC 7 database expected survival. An extensive search of the literature was performed to gather information of previously published literature of intratumoral chemo-drug administration and formulation for this treatment modality. Our study shows a favorable local response, more than a 50% reduction, for a massive tumor mass after administration of five sessions of intratumoral chemotherapy plus two cycles of low-dose intravenous chemotherapy according to our protocol. These encouraging results (even in very sick ECOG 2 patients with central obstructive non-small cell lung cancer having a worse prognosis and quality of

  19. The Efficacy and Safety of Chemotherapy in Patients With Nonsmall Cell Lung Cancer and Interstitial Lung Disease: A PRISMA-Compliant Bayesian Meta-Analysis and Systematic Review.

    Science.gov (United States)

    Chen, Yu Jie; Chen, Ling Xiao; Han, Mei Xiang; Zhang, Tian Song; Zhou, Zhi Rui; Zhong, Dian Sheng

    2015-09-01

    Chemotherapy plays a critical and venturous role against the co-morbidity of nonsmall cell lung cancer and interstitial lung disease (NSCLC-ILD).We performed a Bayesian meta-analysis and systematic review to evaluate the safety and efficacy of the chemotherapy in NSCLC-ILD patients.EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (up to January 2015).We included all study designs except case reports, all studies with NSCLC-ILD patients and all the possible chemotherapy regimens.Quality was assessed by a components approach. We derived summary estimates using Bayesian method through WinBUGS (version 1.4.3, MRC Biostatistics Unit, Cambridge, UK).Seven studies involving 251 patients with NSCLC-ILD were included in the meta-analysis. The treatment response (complete remission, 0; [partial remission, 39.1%; 95% credible interval [CrI], 32.6-45.7]; [stable disease, 36%; 95% CrI, 29.6-42.2]; [PD, 15.4%; 95% CrI, 11.3-19.8]; [nonevaluable, 6.4%; 95% CrI, 2.7-10.1]; [overall response rate, 41.3%; 95% CrI, 35.3-47.4]; [disease control rate, 77.7%; 95% CrI, 72.2-82.7]) were comparable to that of patients with NSCLC alone; the survival outcomes (median overall survival, median progression-free survival, and 1-year survival rate) were slightly worse, especially the lower 1-year survival rate. Platinum-based doublets as first-line chemotherapy may be related to higher incidence of acute exacerbation-ILD in first line chemotherapy (AE, 8.47%; 95% CrI, 5.04-12.6).The data selection bias and small patient number make the meta-analysis of treatment response and conclusions generated from these data inaccurate.The present meta-analysis suggests that chemotherapy might be an effective therapy for patients with NSCLC-ILD, but it might be associated with higher incidence of acute exacerbation.

  20. Structural insights into microtubule doublet interactions inaxonemes

    Energy Technology Data Exchange (ETDEWEB)

    Downing, Kenneth H.; Sui, Haixin

    2007-06-06

    Coordinated sliding of microtubule doublets, driven by dynein motors, produces periodic beating of the axoneme. Recent structural studies of the axoneme have used cryo-electron tomography to reveal new details of the interactions among some of the multitude of proteins that form the axoneme and regulate its movement. Connections among the several sets of dyneins, in particular, suggest ways in which their actions may be coordinated. Study of the molecular architecture of isolated doublets has provided a structural basis for understanding the doublet's mechanical properties that are related to the bending of the axoneme, and has also offered insight into its potential role in the mechanism of dynein activity regulation.

  1. Gauge coupling unification with extra Higgs doublets

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Junpei [Research Center for Higher Education, Health Sciences University of Hokkaido (Japan)

    2016-06-15

    Gauge coupling unification is studied within the framework where there are extra Higgs doublets and E{sub 6} exotic fields. Supersymmetric models and nonsupersymmetric models are investigated, and a catalog of models with gauge coupling unification is presented. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. A Three Doublet Lepton-Specific Model

    CERN Document Server

    Merchand, Marco

    2016-01-01

    In the lepton-specific version of two Higgs doublet models, a discrete symmetry is used to couple one Higgs, $\\Phi_2$, to quarks and the other, $\\Phi_1$, to leptons. The symmetry eliminates tree level flavor changing neutral currents (FCNC). Motivated by strong constraints on such currents in the quark sector from meson-antimeson mixing, and by hints of $h \\to \\mu\\tau$ in the lepton sector, we study a simple three Higgs doublet model in which one doublet couples to quarks and the other two to leptons. Unlike most other studies of three Higgs doublet models, we impose no flavor symmetry and just use a $Z_2$ symmetry to constrain the Yukawa couplings. We present the model and discuss the various mixing angles. Constraining the parameters to be consistent with observations of the Higgs boson at the LHC, we study the properties of the charged Higgs boson(s) in the model, focusing on the case in which the charged Higgs is above the top threshold. It is found that one can have the branching fraction of the charged ...

  3. Conventional Cisplatin-Based Combination Chemotherapy Is Effective in the Treatment of Metastatic Spermatocytic Seminoma with Extensive Rhabdomyosarcomatous Transformation.

    Science.gov (United States)

    Jeong, Yumun; Cheon, Jaekyung; Kim, Tae-Oh; Lim, Doo-Ho; Lee, Sunpyo; Cho, Young-Mi; Hong, Jun Hyuk; Lee, Jae Lyun

    2015-10-01

    A 52-year-old man was presented with a huge left testicular mass and palpable cervical lymphadenopathy with retroperitoneal lymph node enlargement on an abdominal computed tomography. A left radical orchiectomy and an ultrasound-guided neck node biopsy were performed. A pathological examination revealed spermatocytic seminoma with extensive rhabdomyosarcomatous transformation, a condition known to be highly resistant to platinum-based chemotherapy. The patient received four cycles of etoposide, ifosfamide and cisplatin (VIP) chemotherapy. A repeat computed tomography revealed a substantial regression consistent with a partial response. Retroperitoneal lymph node dissection was attempted, which revealed rhabdomyosarcoma; however, complete microscopic resection was not achieved. After surgery, the residual abdominal lymph node progressed and salvage paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy was employed, which again achieved a partial response. Here, we present a first case report of a spermatocytic seminoma with extensive rhabdomyosarcomatous transformation and multiple metastatic lymphadenopathies that showed a favorable response to platinum-based systemic chemotherapy.

  4. An ERK-dependent pathway to Noxa expression regulates apoptosis by platinum-based chemotherapeutic drugs.

    Science.gov (United States)

    Sheridan, C; Brumatti, G; Elgendy, M; Brunet, M; Martin, S J

    2010-12-09

    Cisplatin is a widely used cancer chemotherapeutic that promotes DNA damage-associated apoptosis. Although platinum compounds are known to form DNA adducts and provoke DNA damage, the molecular mechanism of cisplatin-induced cell death remains unclear. In this article, we show that the BH3-only protein Noxa is strongly transcriptionally upregulated in response to cisplatin and related platinum compounds. Cisplatin-induced Noxa expression was ERK dependent, but p53 independent, and inhibition of ERK activation markedly attenuated cisplatin-induced cell death, as well as Noxa expression. Furthermore, siRNA-mediated ablation of Noxa expression also inhibited cisplatin-induced cell death and permitted clonogenic survival. These observations reveal a novel ERK-regulated route to Noxa expression that is important for the cell killing activity of platinum-based chemotherapeutic drugs.

  5. Synthesis of nanosized platinum based catalyst using sol-gel process

    Science.gov (United States)

    Ingale, S. V.; Wagh, P. B.; Bandyopadhyay, D.; Singh, I. K.; Tewari, R.; Gupta, S. C.

    2015-02-01

    The nano-sized platinum based catalysts using high surface area silica support have been prepared by sol-gel method. Tetramethoxysilane (TMOS) diluted in methanol was hydrolyzed to form a porous silica gel. Platinum (2%) was loaded at sol state using platinum chloride solution. After gelation, the solvent from the gel pores was extracted at ambient temperature which resulted in porous silica matrix incorporated with nanosized platinum. X-ray diffraction studies indicated the presence of elemental platinum in the silica-platinum composites. Transmission electron microscopy of the platinum -silica composites revealed that nanosized platinum particles of about 5-10 nm are homogeneously dispersed in silica matrix. Chemisorptions studies showed high dispersion (more than 50%) of platinum on silica support with specific surface area of 400 m2/g which puts them as promising candidates as catalyst in heterogeneous reactions.

  6. Parabola-doublet aplanat becomes anastigmatic when second doublet is inserted near focus.

    Science.gov (United States)

    Blakley, Rick

    2004-08-01

    A doublet of choice glasses may be located in the converging focal cone of the infinity-focused parabola to yield an aplanatic telescope or camera. The resulting angular field is limited by high astigmatism but is significantly larger than that of the coma-limited parabola. The spherical and chromatic aberrations are so well corrected and the coma so well balanced that the doublet may be used unaltered with a parabola of arbitrary focal length and speed with excellent results for the unvignetted rays. A second doublet nearer to the focus and designed independently of the first corrects the system's astigmatism while preserving its aplanaticism. It may also be designed for flattening the field. This arrangement may allow for greater flexibility in the placing of optical elements than does Wynne's triplet for modest-aperture systems. Equations are presented for choosing candidate glasses for the first doublet from the very limited manifold of solving glasses.

  7. Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    Kayo OSAWA

    2009-01-01

    The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC) patients. CYP3A4*16B polymorphism was associated with decreased metabolism ofirrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin) are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinudeotide repeat (CA-SSR) showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR promoter activity

  8. Gene Polymorphisms and Chemotherapy in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Kayo OSAWA

    2009-08-01

    Full Text Available The phamacogenetics is being used to predict whether the selected chemotherapy will be really effective and tolerable to the patient. Irinotecan, oxidized by CYP3A4 to produce inactive compounds, is used for treatment of various cancers including advanced non small cell lung cancer (NSCLC patients. CYP3A4*16B polymorphism was associated with decreased metabolism of irrinotecan. Irinotecan is also metabolized by carboxylesterase to its principal active metabolite, SN-38, which is subsequently glucuronidated by UGT1As to form the inactive compound SN-38G. UGT1A1*28 and UGT1A1*6 polymorphisms were useful for predicting severe toxicity with NSCLC patients treated with irinotecan-based chemotherapy. Platinum-based compounds (cisplatin, carboplatin are being used in combination with new cytotoxic drugs such as gemcitabine, paclitaxel, docetaxel, or vinorelbine in the treatment of advanced NSCLC. Cisplatin activity is mediated through the formation of cisplatin-DNA adducts. Gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy. ERCC1, XRCC1 and XRCC3 gene polymorphisms were a useful marker for predicting better survival in advanced NSCLC patients treated with platinum-based chemotherapy. XPA and XPD polymorphisms significantly increased response to platinum-based chemotherapy. These DNA repair gene polymorphisms were useful as a predictor of clinical outcome to the platinum-based chemotherapy. EGFR kinase inhibitors induce dramatic clinical responses in NSCLC patients with advanced disease. EGFR gene polymorphism in intron 1 contains a polymorphic single sequence dinucleotide repeat (CA-SSR showed a statistically significant correlation with the gefitinib response and was appeared to be a useful predictive marker of the development of clinical outcome containing skin rashes with gefitinib treatment. The other polymorphisms of EGFR were also associated with increased EGFR

  9. Understanding Chemotherapy

    Science.gov (United States)

    N ational C ancer I nstitute Understanding Chemotherapy What is chemotherapy? Chemotherapy is a cancer treatment that uses drugs to destroy cancer cells. It is also called “chemo.” Today, there are ...

  10. Urinary excretion of platinum, arsenic and selenium of cancer patients from the Antofagasta region in Chile treated with platinum-based drugs

    Directory of Open Access Journals (Sweden)

    Román Domingo A

    2012-04-01

    Full Text Available Abstract Background Arsenic exposure increases the risk of non-cancerous and cancerous diseases. In the Antofagasta region in Chile, an established relationship exists between arsenic exposure and the risk of cancer of the bladder, lung and skin. Platinum-based drugs are first-line treatments, and many works recognise selenium as a cancer-fighting nutrient. We characterised the short-term urinary excretion amounts of arsenic, selenium and platinum in 24-h urine samples from patients with lung cancer and those with cancer other than lung treated with cisplatin or/and carboplatin. As - Se - Pt inter-element relationships were also investigated. Results The amounts of platinum excreted in urine were not significantly different between patients with lung cancer and those with other cancers treated with cisplatin, despite the significant variation in platinum amounts supplied from platinum-based drugs. In general, the analytical amounts of excreted selenium were greater than those for arsenic, which could imply that platinum favours the excretion of selenium. For other types of cancers treated with drugs without platinum, excretion of selenium was also greater than that of arsenic, suggesting an antagonist selenium-anti-cancer drug relationship. Conclusions Regards the baseline status of patients, the analytical amounts of excreted Se is greater than those for As, particularly, for cisplatin chemotherapy. This finding could imply that for over the As displacement Pt favours the excretion of Se. The analytical amounts of excreted Se were greater than those for As, either with and without Pt-containing drugs, suggesting an antagonist Se-anti-cancer drug relationship. However, it seemed that differences existed between As - Se - Pt inter-element associations in patients treated for lung cancer in comparison with those treated for cancer other than lung. Therefore, knowledge obtained in this work, can contribute to understanding the arsenic cancer

  11. Effective theory for electroweak doublet dark matter

    Science.gov (United States)

    Dedes, A.; Karamitros, D.; Spanos, V. C.

    2016-11-01

    We perform a detailed study of an effective field theory which includes the standard model particle content extended by a pair of Weyl fermionic SU(2) doublets with opposite hypercharges. A discrete symmetry guarantees that a linear combination of the doublet components is stable and can act as a candidate particle for dark matter. The dark sector fermions interact with the Higgs and gauge bosons through renormalizable d =4 operators, and nonrenormalizable d =5 operators that appear after integrating out extra degrees of freedom above the TeV scale. We study collider, cosmological and astrophysical probes for this effective theory of dark matter. We find that a weakly interacting dark matter particle with a mass nearby the electroweak scale, and thus observable at the LHC, is consistent with collider and astrophysical data only when fairly large magnetic dipole moment transition operators with the gauge bosons exist, together with moderate Yukawa interactions.

  12. Effective Theory for Electroweak Doublet Dark Matter

    CERN Document Server

    Dedes, Athanasios; Spanos, Vassilis C

    2016-01-01

    We perform a detailed study of an effective field theory which includes the Standard Model particle content extended by a pair of Weyl fermionic SU(2)-doublets with opposite hypercharges. A discrete symmetry guarantees that a linear combination of the doublet components is stable and can act as a candidate particle for Dark Matter. The dark sector fermions interact with the Higgs and gauge bosons through renormalizable $d=4$ operators, and non-renormalizable $d=5$ operators that appear after integrating out extra degrees of freedom above the TeV scale. We study collider, cosmological and astrophysical probes for this effective theory of Dark Matter. We find that a WIMP with a mass nearby to the electroweak scale, and thus observable at LHC, is consistent with collider and astrophysical data only when fairly large magnetic dipole moment transition operators with the gauge bosons exist, together with moderate Yukawa interactions.

  13. Effective Field Theory with Two Higgs Doublets

    CERN Document Server

    Crivellin, Andreas; Procura, Massimiliano

    2016-01-01

    In this article we extend the effective field theory framework describing new physics effects to the case where the underlying low-energy theory is a Two-Higgs-Doublet model. We derive a complete set of independent operators up to dimension six assuming a $Z_2$-invariant CP-conserving Higgs potential. The effects on Higgs and gauge boson masses, mixing angles in the Higgs sector as well as couplings to fermions and gauge bosons are computed. At variance with the case of a single Higgs doublet, we find that pair production of SM-like Higgses, arising through dimension-six operators, is not fixed by fermion-fermion-Higgs couplings and can therefore be sizable.

  14. Progress in Personalizing Chemotherapy for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    James S. Chang

    2012-01-01

    Full Text Available Platinum-based chemotherapy is commonly used for the treatment of locally advanced and metastatic bladder cancer. However, there are currently no methods to predict chemotherapy response in this disease setting. A better understanding of the biology of bladder cancer has led to developments of molecular biomarkers that may help guide clinical decision making. These biomarkers, while promising, have not yet been validated in prospective trials and are not ready for clinical applications. As alkylating agents, platinum drugs kill cancer cells mainly through induction of DNA damage. A microdosing approach is currently being tested to determine if chemoresistance can be identified by measuring platinum-induced DNA damage using highly sensitive accelerator mass spectrometry technology. The hope is that these emerging strategies will help pave the road towards personalized therapy in advanced bladder cancer.

  15. ROLE OF TRANSPORTERS IN THE DISTRIBUTION OF PLATINUM-BASED DRUGS

    Directory of Open Access Journals (Sweden)

    Saliha eHarrach

    2015-04-01

    Full Text Available Platinum derivatives used as chemotherapeutic drugs such as cisplatin and oxaliplatin have a potent antitumor activity. However, severe side effects such as nephro-, oto-, and neurotoxicity are associated with their use. Effects and side effects of platinum-based drugs are in part caused by their transporter-mediated uptake in target and non target cells. In this mini review, the transport systems involved in cellular handling of platinum derivatives are illustrated, focusing on transporters for cisplatin. The copper transporter 1 seems to be of particular importance for cisplatin uptake in tumor cells, while the organic cation transporter (OCT 2, due to its specific organ distribution, may play a major role in the development of undesired cisplatin side effects. In polarized cells, e.g. in renal proximal tubule cells, apically expressed transporters, such as multidrug and toxin extrusion protein 1, mediate secretion of cisplatin and in this way contribute to the control of its toxic effects. Specific inhibition of cisplatin uptake transporters such as the OCTs may be an attractive therapeutic option to reduce its toxicity, without impairing its antitumor efficacy.

  16. Acetaldehyde behavior over platinum based catalyst in hydrogen stream generated by ethanol reforming

    Energy Technology Data Exchange (ETDEWEB)

    de Lima, Adriana F.F. [Laboratorio de Catalise, Instituto Nacional de Tecnologia, Av. Venezuela 82/507, 20081-310 Rio de Janeiro, RJ (Brazil); Instituto de Quimica e INOG (Instituto Nacional de Oleo Gas), UERJ-CNPq, FAPERJ, Universidade do Estado do Rio de Janeiro, Rua Sao Francisco Xavier, 524, 20550-900 Rio de Janeiro, RJ (Brazil); Colman, Rita C. [Departamento de Engenharia Quimica e de Petroleo, Universidade Federal Fluminense, Av. Passos da Patria, 156/bl E/240, 24210-240 Niteroi, RJ (Brazil); Zotin, Fatima M.Z. [Instituto de Quimica e INOG (Instituto Nacional de Oleo Gas), UERJ-CNPq, FAPERJ, Universidade do Estado do Rio de Janeiro, Rua Sao Francisco Xavier, 524, 20550-900 Rio de Janeiro, RJ (Brazil); CETEM-MCT, Av. Pedro Calmon, 900, Cidade Universitaria, 21941-908 Rio de Janeiro, RJ (Brazil); Appel, Lucia G. [Laboratorio de Catalise, Instituto Nacional de Tecnologia, Av. Venezuela 82/507, 20081-310 Rio de Janeiro, RJ (Brazil)

    2010-12-15

    Due to the greenhouse effect, hydrogen production from bioethanol reforming is a very important subject in heterogeneous catalysis research. Pt based catalysts are employed in H{sub 2} purification processes and also as electrocatalysts of PEM (''Proton Exchange Membrane'') fuel cells. Hydrogen obtained from ethanol reforming may contain, as contaminants, acetaldehyde and small amounts of CO. This aldehyde can be decarbonylated on Pt based catalysts generating carbon monoxide and methane, rendering the hydrogen purification more challenging. Moreover, acetaldehyde might also change the electrocatalyst behavior. Therefore, this contribution aims at studying the acetaldehyde behavior in the presence of platinum based catalysts in hydrogen atmosphere. The Pt/SiO{sub 2}, Pt/USY catalysts and an electrocatalyst were characterized by n-butylamine, H{sub 2} and CO{sub 2} adsorption, ATG/DTG measurements and cyclohexane dehydrogenation reaction. It was observed that the acid-basic properties of the supports promote condensation reactions. When in contact with Pt based catalysts, acetaldehyde undergoes C-C and C=O bond scissions. The former occurs at a wide range of temperatures, whereas the latter only at low temperatures (<200 C). The C-C bond scission (decarbonylation) produces methane and CO. The C=O bond scission generates carbon residues on the catalyst as well as oxygen species, which in turn is able to eliminate CO from the catalytic surface. The data also show that decarbonylation is not a structure-sensitive reaction. (author)

  17. Aged nano-structured platinum based catalyst: effect of chemical treatment on adsorption and catalytic activity.

    Science.gov (United States)

    Shim, Wang Geun; Nahm, Seung Won; Park, Hyuk Ryeol; Yun, Hyung Sun; Seo, Seong Gyu; Kim, Sang Chai

    2011-02-01

    To examine the effect of chemical treatment on the adsorption and catalytic activity of nanostructured platinum based catalyst, the aged commercial Pt/AC catalyst was pretreated with sulfuric acid (H2SO4) and a cleaning agent (Hexane). Several reliable methods such as nitrogen adsorption, X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and inductively coupled plasma (ICP) were employed to characterize the aged Pt/AC catalyst and its chemically pretreated Pt/AC catalysts. The catalytic and adsorption activities of nano-structured heterogeneous Pt/AC catalyst were investigated on the basis of toluene oxidation and adsorption isotherm data. In addition, the adsorption isotherms of toluene were used to calculate the adsorption energy distribution functions for the parent catalyst and its pre-treated nano-structured Pt/AC catalysts. It was found that sulfuric acid aqueous treatment can enhance the catalytic performance of aged Pt/AC catalyst toward catalytic oxidation of toluene. It was also shown that a comparative analysis of the energy distribution functions for nano-structured Pt/AC catalysts as well as the pore size distribution provides valuable information about their structural and energetic heterogeneity.

  18. Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types

    Science.gov (United States)

    Al-Adawi, Kawther; Al-Nabhani, Abdurahman; Al-Kindi, Mohamed

    2017-01-01

    Breast cancer (BC) is the most common cause of cancer-related death worldwide. Although platinum-based drugs (PBDs) are effective anticancer agents, responsive patients eventually become resistant. While resistance of some cancers to PBDs has been explored, the cellular responses of BC cells are not studied yet. Therefore, we aim to assess the differential effects of PBDs on BC ultrastructure. Three representative cells were treated with different concentrations and timing of Cisplatin, Carboplatin, and Oxaliplatin. Changes on cell surface and ultrastructure were detected by scanning (SEM) and transmission electron microscope (TEM). In SEM, control cells were semiflattened containing microvilli with extending lamellipodia while treated ones were round with irregular surface and several pores, indicating drug entry. Prolonged treatment resembled distinct apoptotic features such as shrinkage, membrane blebs, and narrowing of lamellipodia with blunt microvilli. TEM detected PBDs' deposits that scattered among cellular organelles inducing structural distortion, lumen swelling, chromatin condensation, and nuclear fragmentation. Deposits were attracted to fat droplets, explained by drug hydrophobic properties, while later they were located close to cell membrane, suggesting drug efflux. Phagosomes with destructed organelles and deposits were detected as defending mechanism. Understanding BC cells response to PBDs might provide new insight for an effective treatment.

  19. Whole-tumour CT-perfusion of unresectable lung cancer for the monitoring of anti-angiogenetic chemotherapy effects.

    Science.gov (United States)

    Fraioli, F; Anzidei, M; Serra, G; Liberali, S; Fiorelli, A; Zaccagna, F; Longo, F; Anile, M; Catalano, C

    2013-09-01

    To determine whether CT-perfusion (CT-p) can be used to evaluate the effects of chemotherapy and anti-angiogenic treatment in patients with non-small-cell lung carcinoma (NSCLC) and whether CT-p and standard therapeutic response assessment (RECIST) data obtained before and after therapy correlate. 55 patients with unresectable NSCLC underwent CT-p before the beginning of therapy and 50 of them repeated CT-p 90 days after it. Therapeutic protocol included platinum-based doublets plus bevacizumab for non-squamous carcinoma and platinum-based doublets for squamous carcinoma. RECIST measurements and calculations of blood flow (BF), blood volume (BV), time to peak (TTP) and permeability surface (PS) were performed, and baseline and post-treatment measurements were tested for statistically significant differences. Baseline and follow-up perfusion parameters were also compared based on histopathological subclassification (2004 World Health Organization Classification of Tumours) and therapy response assessed by RECIST. Tumour histology was consistent with large cell carcinoma in 14/50 (28%) cases, adenocarcinoma in 22/50 (44%) cases and squamous cell carcinoma in the remaining 14/50 (28%) cases. BF and PS differences for all tumours between baseline and post-therapy measurements were significant (p=0.001); no significant changes were found for BV (p=0.3) and TTP (p=0.1). The highest increase of BV was demonstrated in adenocarcinoma (5.2±34.1%), whereas the highest increase of TTP was shown in large cell carcinoma (6.9±22.4%), and the highest decrease of PS was shown in squamous cell carcinoma (-21.5±18.5%). A significant difference between the three histological subtypes was demonstrated only for BV (p<0.007). On the basis of RECIST criteria, 8 (16%) patients were classified as partial response (PR), 2 (4%) as progressive disease (PD) and the remaining 40 (80%) as stable disease (SD). Among PR, a decrease of both BF (18±9.6%) and BV (12.6±9.2%) were observed; TTP

  20. Doublet-singlet model and unitarity

    Science.gov (United States)

    Cynolter, G.; Kovács, J.; Lendvai, E.

    2016-12-01

    We study the renormalizable singlet-doublet fermionic extension of the Standard Model (SM). In this model, the new vector-like fermions couple to the gauge bosons and to the Higgs via new Yukawa couplings that allow for nontrivial mixing in the new sector, providing a stable, neutral dark matter candidate. Approximate analytic formulae are given for the mass spectrum around the blind spots, where the dark matter candidate coupling to h or Z vanishes. We calculate the two particle scattering amplitudes in the model, impose the perturbative unitarity constraints and establish bounds on the Yukawa couplings.

  1. Doublet-singlet model and unitarity

    CERN Document Server

    Cynolter, G; Lendvai, E

    2016-01-01

    We study the renormalizable singlet-doublet fermionic extension of the Standard Model. In this model, the new vector-like fermions couple to the gauge bosons and to the Higgs via new Yukawa couplings, that allow for nontrivial mixing in the new sector, providing a stable, neutral dark matter candidate. Approximate analytic formulae are given for the mass spectrum around the blind spots, where the dark matter candidate coupling to $h$ or $Z$ vanishes. We calculate the two particle scattering amplitudes in the model, impose the perturbative unitarity constraints and establish bounds on the Yukawa couplings.

  2. Convection-enhancement delivery of platinum-based drugs and Lipoplatin™ to optimize the concomitant effect with radiotherapy in F98 glioma rat model

    OpenAIRE

    SHI, MINGHAN; Fortin, David; Sanche, Léon; Paquette, Benoit

    2015-01-01

    The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin™-liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by facto...

  3. Cancer Chemotherapy

    Science.gov (United States)

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  4. Yukawa textures or dark doublets from Two Higgs Doublet Models with $Z_3$ symmetry

    CERN Document Server

    Aranda, Alfredo; Noriega-Papaqui, Roberto; Vaquera-Araujo, Carlos A

    2014-01-01

    The effect of $Z_3$ symmetry on the general Two Higgs Doublet Model is explored. Of particular interest is the question of what can a $Z_3$ symmetry do beyond the usual case with $Z_2$. There are two independent scenarios that give some interesting results: first, by giving non-trivial charges to the Standard Model fermions, it is possible to use the $Z_3$ symmetry of the scalar potential to generate potentially useful Yukawa textures. This is not possible with $Z_2$. A series of possibilities is presented where their viability is addressed and a specific example in the quark sector is given for concreteness. The second venue of interest is in the area of inert doublets. It is shown that by considering the Standard Model plus two additional inert doublet scalars, i.e. a Dark Two Higgs Doublet Model, together with $Z_3$, a scenario can be obtained that differs from the $Z_2$ case. Some general comments are presented on the potentially interesting phenomenology of such model.

  5. Nano-structured Platinum-based Catalysts for the Complete Oxidation of Ethylene Glycol and Glycerol

    Science.gov (United States)

    Falase, Akinbayowa

    Direct alcohol fuel cells are a viable alternative to the traditional hydrogen PEM fuel cell. Fuel versatility, integration with existing distribution networks, and increased safety when handling these fuels increases their appeal for portable power applications. In order to maximize their utility, the liquid fuel must be fully oxidized to CO2 so as to harvest the full amount of energy. Methanol and ethanol are widely researched as potential fuels to power these devices, but methanol is a toxic substance, and ethanol has a much lower energy density than other liquids such as gasoline or glucose. Oxidation of complex fuels is difficult to realize, due to difficulty in breaking carbon-carbon bonding and poisoning of the catalysts by oxidative byproducts. In order to achieve the highest efficiency, an anode needs to be engineered in such a way as to maximize activity while minimizing poisoning effects of reaction byproducts. We have engineered an anode that uses platinum-based catalysts that is capable of completely oxidizing ethylene glycol and glycerol in neutral and alkaline media with little evidence of CO poisoning. We have constructed a hybrid anode consisting of a nano-structured PtRu electrocatayst with an NAD-dependent alcohol dehydrogenase for improved oxidation of complex molecules. A nano-structured PtRu catalyst was used to oxidize ethylene glycol and glycerol in neutral media. In situ infrared spectroscopy was used to verify complete oxidation via CO2 generation. There was no evidence of poisoning by CO species. A pH study was performed to determine the effect of pH on oxidative current. The peak currents did not trend at 60 mV/pH unit as would be expected from the Nernst equation, suggesting that adsorption of fuel to the surface of the electrode is not an electron-transfer step. We synthesized nano-structured PtRu, PtSn, and PtRuSn catalysts for oxidation of ethylene glycol and glycerol in alkaline media. The PtRu electrocatalyst the highest oxidative

  6. Neutrino signature of inert doublet dark matter

    Energy Technology Data Exchange (ETDEWEB)

    Andreas, Sarah [Technische Hochschule Aachen (Germany). Inst. fuer Theoretische Physik E; Univ. Libre de Bruxelles (Belgium). Service de Physique Theorique; Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2009-11-15

    In the framework of the Inert Doublet Model and extensions, the signature of neutrinos from dark matter annihilation in the Earth, the Sun and at the Galactic centre is presented. The model contains an extra Higgs doublet, a neutral component of which is chosen as dark matter candidate. There are three distinct mass ranges for which consistency both with WMAP abundance and direct searches can be obtained: a low (4-8 GeV), a middle (60-70 GeV) and a high (500-1500 GeV) WIMP mass range. The first case is of interest as we showed that the model can at the same time give the correct WMAP abundance and account for the positive DAMA results without contradicting other direct searches. We present how capture in the Sun can further constrain this scenario using Super-Kamiokande data. Indirect detection through neutrinos is challenging for the middle and high mass ranges. For the former, the presence of the so-called 'iron resonance' gives rise to larger neutrino fluxes for WIMP masses around 60-70 GeV since capture by the Earth is enhanced. The addition of light right-handed Majorana neutrinos to the particle content of the model further increases the signal since it opens a direct annihilation channel into mono-energetic neutrinos. Neutrinos from the Galactic centre might be detected for heavy WIMPs if the dark matter density at the Galactic centre is substantially boosted. (orig.)

  7. Tempered two-Higgs-doublet model

    Science.gov (United States)

    Grzadkowski, B.; Osland, P.

    2010-12-01

    We discuss the phenomenological consequences of requiring the cancellation of quadratic divergences up to the leading two-loop order within the two-Higgs-doublet model. Taking into account existing experimental constraints, allowed regions in the parameter space, permitting the cancellation, are determined. A degeneracy between masses of scalar bosons is observed for tan⁡β≳40. The possibility for CP violation in the scalar potential is discussed and regions of tan⁡β-MH± with a substantial amount of CP violation are determined. In order to provide a source for dark matter in a minimal manner, a scalar gauge singlet is introduced and discussed. The model allows to ameliorate the little hierarchy problem by lifting the minimal scalar Higgs-boson mass and by suppressing the quadratic corrections to scalar masses. The cutoff originating from the naturality arguments is therefore lifted from ˜0.6TeV in the standard model to ≳2.5TeV in two-Higgs-doublet model depending on the mass of the lightest scalar.

  8. Chiral doublet bands and energy-level crossing

    Institute of Scientific and Technical Information of China (English)

    QI Bin; MENG Jie; ZHANG Shuang-Quan; WANG Shou-Yu; PENG Jing

    2009-01-01

    Different definitions for chiral doublet bands based on excitation energies, B(E2) and B(M1) respectively are discussed in the triaxial particle rotor model. For the ideal chiral geometry, the selection rules of the electromagnetic transitions in different band definitions are illustrated. It is also shown that the energy-level crossings between chiral doublet bands may occur.

  9. The possible mass region for shears bands and chiral doublets

    Energy Technology Data Exchange (ETDEWEB)

    Meng, J. [Institute of Physical and Chemical Research, Wako, Saitama (Japan); Frauendorf, S.

    1998-03-01

    The Tilted Axis Cranking (TAC) theory is reviewed. The recent progress of TAC for triaxial deformed nuclei is reported. More emphasis has been paid to the new discovered phenomena - chiral doublets and their explanation. The possible mass region for the shears bands and chiral doublets and their experimental signature are discussed. (author)

  10. P11: 18FDG-PET/CT for early prediction of response to first line platinum chemotherapy in advanced thymic epithelial tumors

    Science.gov (United States)

    Palmieri, Giovannella; Ottaviano, Margaret; Del Vecchio, Silvana; Segreto, Sabrina; Tucci, Irene; Damiano, Vincenzo

    2015-01-01

    Background To investigate the value of the metabolic tumor response assessed with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiological markers, to predict the response disease to first line platinum based chemotherapy in advanced thymic epithelial tumors (TETs). Methods Twenty patients with diagnosis of TET and stage of disease III and IV sec, Masaoka-Koga, were retrospectively included in this monocentric study. Different pre-treatment clinical, biological and pathological parameters, including histotype sec, WHO 2004 and stage of disease sec, Masaoka-Koga were assessed. Tumor glucose metabolism at baseline and its change after the first line platinum based chemotherapy (from 4 to 6 cycles) were assessed using FDG-PET, moreover the response disease was assessed using total body CT scan for the evaluation of RECIST criteria 1.1. Results Twelve patients had an objective response to the first line platinum based chemotherapy according RECIST criteria 1.1 and all of them started with a SUVmax at baseline major than 5, indeed the other eight patients, non-responders to chemotherapy, had a SUVmax at baseline minor than 5. Conclusions It is important to define the chemosensitivity of advanced TETs early. Combining bio-pathological parameters with the metabolism at baseline assessed with FDG-PET can help the physician to early predict the probability of obtaining a disease response to first line platinum based chemotherapy. The SUVmax cut off of 5 at 18FDG-PET/CT performed at baseline treatment might be a new parameter for choosing the most powerful first line of chemotherapy. Given these results, further prospective studies are needed to establish a new first line therapy in advanced TETs with a low SUVmax at baseline, non-responders to conventional chemotherapy.

  11. Thrombocytosis and immunohistochemical expression of connexin 43 at diagnosis predict survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy.

    Science.gov (United States)

    Du, Gangjun; Yang, Yiming; Yang, Yingming; Zhang, Yaping; Sun, Ting; Liu, Weijie; Wang, Yingying; Li, Jiahuan; Zhang, Houyun

    2013-04-01

    Patients with advanced non-small-cell lung cancer (NSCLC) have poor survival, and platinum-based chemotherapy agents are the standard first-line chemotherapy agents for advanced NSCLC. This study aimed to identify predictive factors associated with the response to chemotherapy and survival in 258 patients with advanced NSCLC treated with platinum-based chemotherapy. Stage IIIA-IV NSCLC patients diagnosed in Kaifeng second people's hospital (Henan, China) between March 2002 and September 2011 were retrospectively reviewed. All of the patients had received platinum-based chemotherapy, and patients were followed up to date of death or last follow-up to obtain data of response to chemotherapy and survival. Potential prognostic factors such as gender, age, tumor size, tumor type, histologic stage, anemia, calcium levels, ECOG performance status (PS), thrombocytosis, TTF-1, p63, and connexin 43 were analyzed. Response to chemotherapy, overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan-Meier method and Cox regression model. A univariate analysis indicated that thrombocytosis and connexin 43 were found to be significant prognostic factors (p thrombocytosis was associated with increased mortality and resistance to chemotherapy in chemotherapy responders. In addition, all 21 patients of the 5-year OS were from chemotherapy responders with connexin 43 ≥ +2 or non-thrombocytosis. Thrombocytosis and connexin 43 absence may be reliable surrogate markers for the prediction of chemotherapy response and prognosis for patients with advanced NSCLC, and assessment of these factors may identify a population of patients with advanced NSCLC that is likely to have a prolonged life expectancy.

  12. Partially Natural Two Higgs Doublet Models

    CERN Document Server

    Draper, Patrick; Ruderman, Joshua T

    2016-01-01

    It is possible that the electroweak scale is low due to the fine-tuning of microscopic parameters, which can result from selection effects. The experimental discovery of new light fundamental scalars other than the Standard Model Higgs boson would seem to disfavor this possibility, since generically such states imply parametrically worse fine-tuning with no compelling connection to selection effects. We discuss counterexamples where the Higgs boson is light because of fine-tuning, and a second scalar doublet is light because a discrete symmetry relates its mass to the mass of the Standard Model Higgs boson. Our examples require new vectorlike fermions at the electroweak scale, and the models possess a rich electroweak vacuum structure. The mechanism that we discuss does not protect a small CP-odd Higgs mass in split or high-scale supersymmetry-breaking scenarios of the MSSM due to an incompatibility between the discrete symmetries and holomorphy.

  13. Partially composite two-Higgs doublet model

    Indian Academy of Sciences (India)

    Dong-Won Jung

    2007-11-01

    In the extra dimensional scenarios with gauge fields in the bulk, the Kaluza-Klein (KK) gauge bosons can induce Nambu-Jona-Lasinio (NJL) type attractive four-fermion interactions, which can break electroweak symmetry dynamically with accompanying composite Higgs fields. We consider a possibility that electroweak symmetry breaking (EWSB) is triggered by both a fundamental Higgs and a composite Higgs arising in a dynamical symmetry breaking mechanism induced by a new strong dynamics. The resulting Higgs sector is a partially composite two-Higgs doublet model with specific boundary conditions on the coupling and mass parameters originating at a compositeness scale . The phenomenology of this model is discussed including the collider phenomenology at LHC and ILC.

  14. Tuned Two-Higgs-Doublet Model

    CERN Document Server

    Grzadkowski, Bohdan

    2010-01-01

    We consider a Two-Higgs-Doublet Model (2HDM) constrained by the condition that assures cancellation of quadratic divergences up to the leading two-loop order. Regions in the parameter space consistent with existing experimental constraints and with the cancellation condition are determined. The possibility for CP violation in the scalar potential is discussed and regions of \\tan_\\beta-M_{H^\\pm} with substantial amount of CP violation are found. The model allows to ameliorate the little hierarchy problem by lifting the minimal scalar Higgs boson mass and by suppressing the quadratic corrections to scalar masses. The cutoff originating from the naturality arguments is therefore lifted from ~0.6 TeV in the Standard Model to ~2.5 TeV in the 2HDM, depending on the mass of the lightest scalar.

  15. Electromagnetic transitions in multiple chiral doublet bands

    CERN Document Server

    Jia, Hui; Wang, Shou-Yu; Wang, Shuo; Liu, Chen

    2016-01-01

    Multiple chiral doublet bands (M$\\chi$D) in the $80$, 130 and $190$ mass regions are studied by the model of $\\gamma$=90$^{\\circ}$ triaxial rotor coupled with identical symmetric proton-neutron configurations. By selecting the suitable basis, the calculated wave functions are explicitly exhibited to be symmetric under the operator $\\hat{A}$, which is defined as rotation by $90^{\\circ}$ about 3-axis with the exchange of valance proton and neutron. We found that both $M1$ and $E2$ transitions are allowed between the levels with different values of $A$, while are forbidden between the levels with same values of $A$. Such a selection rule holds true for M$\\chi$D in different mass regions.

  16. Platinum-based anticancer drugs in waste waters of a major UK hospital and predicted concentrations in recipient surface waters.

    OpenAIRE

    Vyas, N; Turner, A; Sewell, G.

    2014-01-01

    Concentrations of the cytotoxic platinum-based anticancer drugs, as total Pt, have been measured over a three week period in one of the main drains and in the effluent of the oncology ward of a major UK hospital (Derriford, Plymouth). Concentrations of Pt were highly variable in both discharges, and ranged from about 0.02 to 140 μg L(-1) in the oncology effluent and from about 0.03 to 100 μg L(-1) in the main drain. A comparison of drug administration figures over the study period with an est...

  17. Systemic chemotherapy for metastatic breast cancer

    Institute of Scientific and Technical Information of China (English)

    Yannan Zhao; Biyun Wang

    2015-01-01

    Breast cancer is the leading cause of cancer among women worldwide and the most common cancer in China. Many factors influence the treatment strategy for metastatic breast cancer (MBC). Chemotherapy should be administered to patients with hormone receptor-negative tumors, symptomatic visceral metastasis, and a short disease-free interval. Sequential single-agent chemotherapy has similar efficacy as combination agents in terms of overall survival and quality of life. Anthracyclines are the cornerstone of first-line treatment for MBC, and taxanes represent the second treatment option after resistance. When progression or intolerable toxicity occurs after optimal treatment, the alternative treatments include capecitabine, vinorel-bine, and gemcitabine. Ixabepilone and eribulin are relatively new effective single agents. A combination of cytotoxic agents for patients with rapid clinical progression can further improve the overall response rate and time to progression compared to single-agent treatment. For patients with MBC who were pretreated with anthracyclines in the neoadjuvant/adjuvant setting, a taxane-containing regimen such as docetaxel plus capecitabine or gemcitabine plus paclitaxel should be administered. Platinum-based therapies such as cisplatin or carboplatin have a role in the treatment of triple-negative breast cancer. Meanwhile, the efficacy of the addition of targeted drugs such as iniparib, bevacizumab, and cetuximab to chemotherapy remains unproven. Maintenance chemotherapy is routinely recommended in clinical practice at present. Patients who were previously treated with paclitaxel and gemcitabine have better progression-free and overall survival with maintenance chemotherapy according to a Korean phase Ⅲ clinical trial. Sequential maintenance treatment with capecitabine monotherapy after capecitabine-based combination chemotherapy (X-based X) appears favorable based on a series of domestic studies.

  18. Flow Injection Analysis with Electrochemical Detection for Rapid Identification of Platinum-Based Cytostatics and Platinum Chlorides in Water

    Directory of Open Access Journals (Sweden)

    Marketa Kominkova

    2014-02-01

    Full Text Available Platinum-based cytostatics, such as cisplatin, carboplatin or oxaliplatin are widely used agents in the treatment of various types of tumors. Large amounts of these drugs are excreted through the urine of patients into wastewaters in unmetabolised forms. This phenomenon leads to increased amounts of platinum ions in the water environment. The impacts of these pollutants on the water ecosystem are not sufficiently investigated as well as their content in water sources. In order to facilitate the detection of various types of platinum, we have developed a new, rapid, screening flow injection analysis method with electrochemical detection (FIA-ED. Our method, based on monitoring of the changes in electrochemical behavior of analytes, maintained by various pH buffers (Britton-Robinson and phosphate buffer and potential changes (1,000, 1,100 and 1,200 mV offers rapid and cheap selective determination of platinum-based cytostatics and platinum chlorides, which can also be present as contaminants in water environments.

  19. Flow injection analysis with electrochemical detection for rapid identification of platinum-based cytostatics and platinum chlorides in water.

    Science.gov (United States)

    Kominkova, Marketa; Heger, Zbynek; Zitka, Ondrej; Kynicky, Jindrich; Pohanka, Miroslav; Beklova, Miroslava; Adam, Vojtech; Kizek, Rene

    2014-02-04

    Platinum-based cytostatics, such as cisplatin, carboplatin or oxaliplatin are widely used agents in the treatment of various types of tumors. Large amounts of these drugs are excreted through the urine of patients into wastewaters in unmetabolised forms. This phenomenon leads to increased amounts of platinum ions in the water environment. The impacts of these pollutants on the water ecosystem are not sufficiently investigated as well as their content in water sources. In order to facilitate the detection of various types of platinum, we have developed a new, rapid, screening flow injection analysis method with electrochemical detection (FIA-ED). Our method, based on monitoring of the changes in electrochemical behavior of analytes, maintained by various pH buffers (Britton-Robinson and phosphate buffer) and potential changes (1,000, 1,100 and 1,200 mV) offers rapid and cheap selective determination of platinum-based cytostatics and platinum chlorides, which can also be present as contaminants in water environments.

  20. Ovarian cancer stem cell like side populations are enriched following chemotherapy and overexpress EZH2

    Science.gov (United States)

    Rizzo, Siân; Hersey, Jenny M.; Mellor, Paul; Dai, Wei; Santos-Silva, Alessandra; Liber, Daniel; Luk, Louisa; Titley, Ian; Carden, Craig P; Box, Garry; Hudson, David L.; Kaye, Stanley B.; Brown, Robert

    2010-01-01

    Platinum-based chemotherapy, with cytoreductive surgery, is the cornerstone of treatment of advanced ovarian cancer, however acquired drug resistance is a major clinical obstacle. It has been proposed that subpopulations of tumour cells with stem-cell like properties, such as so-called side populations (SP) which over-express ABC drug-transporters, can sustain the growth of drug resistant tumour cells, leading to tumour recurrence following chemotherapy. The histone methyltransferase EZH2 is a key component of the Polycomb Repressive Complex 2 (PRC2) required for maintenance of a stem cell state and overexpression has been implicated in drug resistance and shorter survival of ovarian cancer patients. We observe higher percentage SP in ascites from patients that have relapsed following chemotherapy compared to chemonaive patients, consistent with selection for this subpopulation during platinum-based chemotherapy. Furthermore, ABCB1 (P-glycoprotein) and EZH2 are consistently over-expressed in SP compared to non-SP from patients’ tumour cells. SiRNA knockdown of EZH2 leads to loss of SP in ovarian tumour models, reduced anchorage-independent growth and reduced tumour growth in vivo. Together these data support a key role for EZH2 in the maintenance of a drug-resistant tumour-sustaining subpopulation of cells in ovarian cancers undergoing chemotherapy. As such, EZH2 is an important target for anticancer drug development. PMID:21216927

  1. Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mathieu D. Saint-Pierre

    2015-01-01

    Full Text Available Introduction. Malignant pleural mesothelioma (MPM is associated with a poor prognosis. Palliative platinum-based chemotherapy may help to improve symptoms and prolong life. Since 2004, the platinum is commonly partnered with a folate antimetabolite. We performed a review investigating if survival had significantly changed before and after the arrival of folate antimetabolites in clinical practice. Methods. All MPM patients from January 1991 to June 2012 were identified. Data collected included age, gender, asbestos exposure, presenting signs/symptoms, performance status, histology, stage, bloodwork, treatment modalities including chemotherapy, and date of death or last follow-up. The primary endpoint was overall survival. Cox models were applied to determine variables associated with survival. Results. There were 245 patients identified. Median overall survival for all patients was 9.4 months. After multivariate analysis, performance status, stage, histology, leucocytosis, and thrombophilia remained independently associated with survival. Among all patients who received chemotherapy, there was no difference in overall survival between the periods before and after folate antimetabolite approval: 14.2 versus 13.2 months (P=0.35. Specifically receiving combined platinum-based/folate antimetabolite chemotherapy did not improve overall survival compared to all other chemotherapy regimens: 14.1 versus 13.6 months (P=0.97. Conclusions. In this review, we did not observe an incremental improvement in overall survival after folate antimetabolites became available.

  2. Low scale thermal leptogenesis in neutrinophilic Higgs doublet models

    CERN Document Server

    Haba, Naoyuki

    2011-01-01

    It is well-known that leptogenesis in low energy scale is difficult in the conventional Type-I seesaw mechanism with hierarchical right-handed neutrino masses. We show that in a class of two Higgs doublet model, where one Higgs doublet generates masses of quarks and charged leptons whereas the other Higgs doublet with a tiny vacuum expectation value generates neutrino Dirac masses, large Yukawa couplings lead to a large enough CP asymmetry of the right-handed neutrino decay. Thermal leptogenesis suitably works at low energy scale as keeping no enhancement of lepton number violating wash out effects. We will also point out that thermal leptogenesis works well without confronting gravitino problem in a supersymmetric neutrinophilic Higgs doublet model with gravity mediated supersymmetry breaking. Neutralino dark matter and baryon asymmetry generation by thermal leptogenesis are easily compatible in our setup.

  3. Inert Doublet Model with a 125 GeV Higgs

    CERN Document Server

    Krawczyk, Maria; Swiezewska, Bogumila

    2013-01-01

    A 125 GeV Higgs-like particle discovered at the LHC in 2012 has properties expected for it in the Standard Model (SM), with a possible enhancement in the two-photon channel. Such SM-like Higgs scenario can be realized within the Inert Doublet Model (IDM) - a version of the Two Higgs Doublet Model with an exact discrete D (Z_2-type) symmetry. In this model one SU(2) doublet plays the role of the SM Higgs doublet with one SM-like Higgs boson. The second doublet has no vacuum expectation value and does not interact with fermions. Among four scalars constituting this D-odd doublet the lightest one is stable, being if neutral a good DM candidate with the right relic density. In this paper an analysis of the two-photon Higgs decay rate in IDM, respecting theoretical and other experimental constraints, is presented. The enhancement in the two-photon channel is possible only if invisible channels are closed, with the enhancement R_{\\gamma \\gamma}>1.2 for masses of DM and charged scalars below 154 GeV. The temperature...

  4. G2HDM : Gauged Two Higgs Doublet Model

    CERN Document Server

    Huang, Wei-Chih; Yuan, Tzu-Chiang

    2015-01-01

    A novel model embedding the two Higgs doublets in the popular two Higgs doublet models into a doublet of a non-abelian gauge group $SU(2)_H$ is presented. The Standard Model $SU(2)_L$ right-handed fermion singlets are paired up with new heavy fermions to form $SU(2)_H$ doublets, while $SU(2)_L$ left-handed fermion doublets are singlets under $SU(2)_H$. Distinctive features of this anomaly-free model are: (1) Electroweak symmetry breaking is induced from spontaneous symmetry breaking of $SU(2)_H$ via its triplet vacuum expectation value; (2) One of the Higgs doublet can be inert, with its neutral component being a dark matter candidate as protected by the $SU(2)_H$ gauge symmetry instead of a discrete $Z_2$ symmetry in the usual case; (3) Unlike Left-Right Symmetric Models, the complex gauge fields $(W_1^{\\prime}\\mp i W_2^{\\prime})$ (along with other complex scalar fields) associated with the $SU(2)_H$ do not carry electric charges, while the third component $W^{\\prime}_3$ can mix with the hypercharge $U(1)_Y$...

  5. Doublets and other allied well patterns

    Energy Technology Data Exchange (ETDEWEB)

    Brigham, W.E.

    1997-06-01

    Whenever a liquid is injected into an infinite reservoir containing liquid with the same flow properties, the equations of flow are well known. The pressures in such a system vary over time and distance (radius) in ways that depend on the formation and liquid flow properties. Such equations are well known--they form the basis for the voluminous well-testing literature in petroleum engineering and ground water hydrology. Suppose there are two wells--one an injector and one a producer--with identical rates. The behavior of this system can be calculated using superposition; which merely means that the results can be added independently of each other. When this is done, the remarkable result is that after a period of time there is a region that approaches steady state flow. Thereafter, the pressures and flow velocities in this region stay constant. The size of this region increases with time. This ``steady state`` characteristic can be used to solve a number of interesting and useful problems, both in heat transfer and in fluid flow. The heat transfer problems can be addressed because the equations are identical in form. A number of such problems are solved herein for doublet systems. In addition, concepts are presented to help solve other cases that flow logically from the problems solved herein. It is not necessary that only two wells be involved. It turns out that any time the total injection and production are equal, the system approaches steady state. This idea is also addressed in these notes. A number of useful multiwell cases are addressed to present the flavor of such solutions.

  6. A first principles study of pristine and Al-doped boron nitride nanotubes interacting with platinum-based anticancer drugs

    Science.gov (United States)

    Shakerzadeh, Ehsan; Noorizadeh, Siamak

    2014-03-01

    Interaction of cis-platin and neda-platin, two conventional platinum-based anticancer drugs, with pristine [8,8] and Al-doped [8,0] boron nitride nanotubes (BNNTs) are investigated using the density functional theory (DFT) method. The obtained results indicate that cis-platin and neda-platin weakly interact with pristine zig zag or armchair BNNTs with a little dependency on the adsorbing positions; while both cis-platin and neda-platin are preferentially adsorbed onto the Al atom of the Al-doped BNNT with considerable adsorption energies. Therefore the Al-doped-BNNT might be an efficient carrier for delivery of these drugs in nanomedicine domain. The electronic structures of the stable configurations are also investigated through both DOS and PDOS spectra. The obtained results introduce the Al-doped-BNNT as an efficient carrier for delivery of cis-platin and neda-platin in nanomedicine domain.

  7. A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors

    Science.gov (United States)

    Wei, Yuming; Poon, Daniel C.; Fei, Rong; Lam, Amy S. M.; Au-Yeung, Steve C. F.; To, Kenneth K. W.

    2016-05-01

    Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted.

  8. A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors.

    Science.gov (United States)

    Wei, Yuming; Poon, Daniel C; Fei, Rong; Lam, Amy S M; Au-Yeung, Steve C F; To, Kenneth K W

    2016-05-06

    Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted.

  9. Evolving concepts in the management of drug resistant ovarian cancer: dose dense chemotherapy and the reversal of clinical platinum resistance.

    Science.gov (United States)

    Pinato, David J; Graham, Janet; Gabra, Hani; Sharma, Rohini

    2013-04-01

    Despite the initially high response rate to standard front-line debulking surgery followed by platinum-based chemotherapy, the relapse rate in ovarian cancer is high and many patients will recur within 6 months of completing platinum based treatment. These patients may still require further chemotherapy despite being considered "platinum resistant". In this setting, response rates to conventionally scheduled second line platinum and non-platinum agents is low, ranging between 5% and 15%. There is an emerging body of evidence that in this scenario, chemotherapeutic activity can be enhanced using unconventionally scheduled "dose-dense" platinum and non-platinum based regimens with improved response rates of up to 65%. Randomised studies to evaluate the impact of this approach on survival in recurrent, platinum resistant disease are urgently required to confirm the promising phase II findings if there is to be a change in the standard of care of patients with platinum resistant disease. In this review we discuss the evolving strategies to overcome resistance in patients with platinum resistant ovarian cancer with a particular focus on alterations in dose schedule as a means of reversing platinum resistance. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Singlet scalar Dark Matter in Dark Two Higgs Doublet Model

    CERN Document Server

    Gaitan, R; de Oca, J H Montes

    2014-01-01

    We consider the case of the Dark Two Higgs Doublet Model (D2HDM) where a $U(1)'$ symmetry group and an extra Higgs doublet are added to the Standard Model. This model leads to a gauge singlet particle as an interesting Dark Matter (DM) candidate. We obtain phenomenological constraints to the parameter space of the model considering the one necessary to produce the correct density of thermal relic dark matter $\\Omega h^2$. We find a relation between the masses of the DM matter candidate $m_S$ and $m_{Z'}$ that satisfy the relic density for given values of $\\tan\\beta$.

  11. Candidates for chiral doublet bands in 136Nd

    Science.gov (United States)

    Mergel, E.; Petrache, C. M.; Lo Bianco, G.; Hübel, H.; Domscheit, J.; Roßbach, D.; Schönwaßer, G.; Nenoff, N.; Neußer, A.; Görgen, A.; Becker, F.; Bouchez, E.; Houry, M.; Hürstel, A.; Le Coz, Y.; Lucas, R.; Theisen, Ch.; Korten, W.; Bracco, A.; Blasi, N.; Camera, F.; Leoni, S.; Hannachi, F.; Lopez-Martens, A.; Rejmund, M.; Gassmann, D.; Reiter, P.; Thirolf, P. G.; Astier, A.; Buforn, N.; Meyer, M.; Redon, N.; Stezowski, O.

    The even-even nucleus 136Nd was studied via in-beam γ-ray spectroscopy using the 16O + 125Te reaction at 100 MeV and the EUROBALL array. One new dipole band was observed. Together with a previously identified dipole band, whose position in the level scheme is revised, the new band forms a doublet structure similar to the recently observed chiral bands in the odd-odd neighboring nuclei. This would be the first case of a chiral doublet in an even-even nucleus.

  12. Towards systematic exploration of multi-Higgs-doublet models

    CERN Document Server

    Ivanov, I P

    2015-01-01

    Conservative bSM models with rich scalar sector, such as multi-Higgs-doublet models, can easily accommodate the SM-like properties of the 125 GeV scalar observed at the LHC. Possessing a variety of bSM signals, they are worth investigating in fuller detail. Systematic study of these models is hampered by the highly multi-dimensional parameter space and by mathematical challenges. I outline some directions along which multi-Higgs-doublet models in the vicinity of a large discrete symmetry can be systematically explored.

  13. Two Higgs doublet models with an $S_3$ symmetry

    CERN Document Server

    Cogollo, D

    2016-01-01

    We study all implementations of the $S_3$ symmetry in the two Higgs doublet model with quarks, consistent with non-zero quark masses and a Cabibbo-Kobayashi-Maskawa (CKM) matrix which is not block diagonal. We study the impact of the various soft-breaking terms and vacuum expectation values, and find an interesting relation between $\\alpha$ and $\\beta$. We also show that, in this minimal setting, only two types of assignments are possible: either all field sectors are in singlets or all field sectors have a doublet.

  14. Dense Matter and Neutron Stars in Parity Doublet Models

    CERN Document Server

    Schramm, S; Negreiros, R; Steinheimer, J

    2011-01-01

    We investigate the properties of dense matter and neutron stars. In particular we discuss model calculations based on the parity doublet picture of hadronic chiral symmetry. In this ansatz the onset of chiral symmetry restoration is reflected by the degeneracy of baryons and their parity partners. In this approach we also incorporate quarks as degrees of freedom to be able to study hybrid stars.

  15. Masses of a Fourth Generation with Two Higgs Doublets

    CERN Document Server

    Bellantoni, Leo; Heckman, Jonathan J; Ramirez-Homs, Enrique

    2012-01-01

    We use sampling techniques to find robust constraints on the masses of a possible fourth sequential fermion generation from electroweak oblique variables. We find that in the case of a light (115 GeV) Higgs from a single electroweak symmetry breaking doublet, inverted mass hierarchies are possible for both quarks and leptons, but a mass splitting more than M(W) in the quark sector is unlikely. We also find constraints in the case of a heavy (600 GeV) Higgs in a single doublet model. As recent data from the Large Hadron Collider hints at the existence of a resonance at 124.5 GeV and a single Higgs doublet at that mass is inconsistent with a fourth fermion generation, we examine a type II two Higgs doublet model. In this model, there are ranges of parameter space where the Higgs sector can potentially counteract the effects of the fourth generation. Even so, we find that such scenarios produce qualitatively similar fermion mass distribtions.

  16. s-particle doublets in certain light nuclei

    NARCIS (Netherlands)

    Bilaniuk, O.M.; French, J.B.

    1960-01-01

    The splitting of an s-particle doublet in B11 is examined to see what information it gives about the effective 1p-2s shell model interaction and it is concluded that the small splitting is explainable by an interaction whose spin dependence is primarily of s1 · s2t1 · t2 nature. Certain other s-doub

  17. The influence of reservoir heterogeneities on geothermal doublet performance

    NARCIS (Netherlands)

    Doddema, Leon

    2012-01-01

    SUMMARY The current main problem with deep geothermal energy in the Netherlands is the uncertainty in terms of attainable flow rate and life time. The goal of this research is therefore modeling a geothermal doublet in a heterogeneous reservoir, using a

  18. The influence of reservoir heterogeneities on geothermal doublet performance

    NARCIS (Netherlands)

    Doddema, Leon

    2012-01-01

    SUMMARY The current main problem with deep geothermal energy in the Netherlands is the uncertainty in terms of attainable flow rate and life time. The goal of this research is therefore modeling a geothermal doublet in a heterogeneous reservoir, using a

  19. Energy basis of recognition of base pair for platinum-based antitumour drug ZD0473 and cisplatin

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Platinum-based antitumour drug ZD0473 was designed to reduce the cisplatin resistance to the tumor cells. In this paper, the mixed method of molecular mechanics and quantum chemistry, HF/lanl2dz// MM/uff and B3LYP/lanl2dz//6-31G*, are used to investigate the differences between four types of GG, 3′AG5′, 3′GA5′, and AA complexes, which are formed from four discrete DNA fragments recognized by ZD0473 and cisplatin. The results show that the binding interaction of both ZD0473 and cisplatin drugs with the GG base pair is much stronger than with other base pairs, namely the recognition capability of such drugs to the GG base pair is more considerable. Moreover, the interaction of four complexes of ZD0473 with DNA fragments is stronger than that of cisplatin with corresponding DNA fragments, which indicates the stronger binding capability of ZD0473 with DNA fragments and high antitumour activity of ZD0473. The main reason for easier forming of 3′GA5′ complex than the 3′AG5′ one is that the drug molecule prefers to bind with a single G base to form a monoligand compound firstly; then the con- figuration transformation from such monoligand compound to the bi-ligand one is limited.

  20. Enersy basis of recognition of base pair for platinum-based antitumour drug ZD0473 and cisplatin

    Institute of Scientific and Technical Information of China (English)

    HAO Lan; LI XiChen; TAN HongWei; CHEN GuangJu; JIA MuXin

    2008-01-01

    Platinum-based antitumour drug ZD0473 was designed to reduce the cisplatin resistance to the tumor cells. In this paper, the mixed method of molecular mechanics and quantum chemistry, HF/lan12dz//MM/uff and B3LYP/lan12dz//6-31G*, are used to investigate the differences between four types of GG, 3'AG5', 3'GA5', and AA complexes, which are formed from four discrete DNA fragments recognized by ZD0473 and cisplatin. The results show that the binding interaction of both ZD0473 and cisplatin drugs with the GG base pair is much stronger than with other base pairs, namely the recognition capability of such drugs to the GG base pair is more considerable. Moreover, the interaction of four complexes of ZD0473 with DNA fragments is stronger than that of cisplatin with corresponding DNA fragments, which indicates the stronger binding capability of ZD0473 with DNA fragments and high antitumour activity of ZD0473. The main reason for easier forming of 3'GA5' complex than the 3'AG5' one is that the drug molecule prefers to bind with a single G base to form a monoligand compound firstly; then the con-figuration transformation from such monoligand compound to the bi-ligand one is limited.

  1. The pharmacogenomics of platinum chemotherapy in non-small cell lung cancer%非小细胞肺癌铂类化疗药物基因组学研究

    Institute of Scientific and Technical Information of China (English)

    崔佳佳; 尹继业

    2014-01-01

    Platinum-based chemotherapy is one of the major treatment methods for non-small-cell lung cancer (NSCLC), however, the therapeutic efficiency varies largely among different pa-tients.Genetic variation is one of the most important factors influencing NSCLC patients platinum-based chemotherapy, lots of gene mutations related to DNA damage and repair, drug metabolism and detoxification, cell cycle and apoptosis, drug transporter and membrane receptor were associated with response to platinum-based chemotherapy.In this review, the recent progress of pharmaco-genomics of platinum chemotherapy in NSCLC was systematically summarized, and also the possibility of establishing a pharmacogenomics model for accurately predicting platinum-based chemotherapy efficacy of NSCLC patients will be discussed.%基于铂类的联合化疗是当前非小细胞肺癌(non-small-cell lung cancer,NSCLC)治疗的主要途径之一,而不同患者的临床疗效差异较大。遗传因素是影响 NSCLC 铂类化疗疗效的重要因素之一,大量 DNA损伤与修复、药物代谢与解毒、细胞周期和凋亡、药物转运体与膜受体相关基因的变异都可以影响 NSCLC 铂类化疗药物化疗敏感性。本文将对上述内容进行系统全面的总结,并探讨建立准确预测 NSCLC 铂类化疗疗效的药物基因组学模型的可能性。

  2. Germline single nucleotide polymorphisms associated with response of urothelial carcinoma to platinum-based therapy: the role of the host.

    LENUS (Irish Health Repository)

    Gallagher, D J

    2013-09-01

    Variations in urothelial carcinoma (UC) response to platinum chemotherapy are common and frequently attributed to genetic and epigenetic variations of somatic DNA. We hypothesized that variations in germline DNA may contribute to UC chemosensitivity.

  3. Association of GWAS-identified lung cancer susceptibility loci with survival length in patients with small-cell lung cancer treated with platinum-based chemotherapy.

    Directory of Open Access Journals (Sweden)

    Dong Li

    Full Text Available Genetic variants have been shown to affect length of survival in cancer patients. This study explored the association between lung cancer susceptibility loci tagged by single-nucleotide polymorphisms (SNPs identified in the genome-wide association studies and length of survival in small-cell lung cancer (SCLC. Eighteen SNPs were genotyped among 874 SCLC patients and Cox proportional hazards regression was used to examine the effects of genotype on survival length under an additive model with age, sex, smoking status and clinical stage as covariates. We identified 3 loci, 20q13.2 (rs4809957G >A, 22q12.2 (rs36600C >T and 5p15.33 (rs401681C >T, significantly associated with the survival time of SCLC patients. The adjusted hazard ratio (HR for patients with the rs4809957 GA or AA genotype was 0.80 (95% CI, 0.66-0.96; P = 0.0187 and 0.73 (95% CI, 0.55-0.96; P = 0.0263 compared with the GG genotype. Using the dominant model, the adjusted HR for patients carrying at least one T allele at rs36600 or rs401681 was 0.78 (95% CI, 0.63-0.96; P = 0.0199 and 1.29 (95% CI, 1.08-1.55; P = 0.0047, respectively, compared with the CC genotype. Stratification analyses showed that the significant associations of these 3 loci were only seen in smokers and male patients. The rs4809957 SNP was only significantly associated with length of survival of patients with extensive-stage but not limited-stage tumor. These results suggest that some of the lung cancer susceptibility loci might also affect the prognosis of SCLC.

  4. Olaparib or Cediranib Maleate and Olaparib Compared With Standard Platinum-Based Chemotherapy in Treating Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    2017-04-05

    Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Endometrial Undifferentiated Carcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Tumor; Ovarian Seromucinous Carcinoma; Ovarian Serous Tumor; Ovarian Transitional Cell Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  5. SEM method for direct visual tracking of nanoscale morphological changes of platinum based electrocatalysts on fixed locations upon electrochemical or thermal treatments.

    Science.gov (United States)

    Zorko, Milena; Jozinović, Barbara; Bele, Marjan; Hodnik, Nejc; Gaberšček, Miran

    2014-05-01

    A general method for tracking morphological surface changes on a nanometer scale with scanning electron microscopy (SEM) is introduced. We exemplify the usefulness of the method by showing consecutive SEM images of an identical location before and after the electrochemical and thermal treatments of platinum-based nanoparticles deposited on a high surface area carbon. Observations reveal an insight into platinum based catalyst degradation occurring during potential cycling treatment. The presence of chloride clearly increases the rate of degradation. At these conditions the dominant degradation mechanism seems to be the platinum dissolution with some subsequent redeposition on the top of the catalyst film. By contrast, at the temperature of 60°C, under potentiostatic conditions some carbon corrosion and particle aggregation was observed. Temperature treatment simulating the annealing step of the synthesis reveals sintering of small platinum based composite aggregates into uniform spherical particles. The method provides a direct proof of induced surface phenomena occurring on a chosen location without the usual statistical uncertainty in usual, random SEM observations across relatively large surface areas.

  6. A multicenter study of recombinant human erythropoietin (epoetin alpha) in the management of anemia in cancer patients receiving chemotherapy.

    Science.gov (United States)

    Pawlicki, M; Jassem, J; Bösze, P; Lotan, C; Kurteva, G P; Siddiqui, M; Kosmidis, P A; Rigatos, G A; Kansu, E; Durkovic, P; Aziz, Z; Al Idrissi, H; Roth, A; Cozma, G

    1997-11-01

    Current evidence suggests that epoetin alpha administration is well tolerated and effective in the management of anemia of cancer and cancer chemotherapy. An open-label, multinational, non-comparative study was conducted in 215 cancer patients with anemia secondary to chemotherapy with platinum- or non-platinum-based combinations. Epoetin alpha was administered s.c. (150 IU/kg three times/week) for a planned period of 16 weeks. The response rate of epoetin alpha, defined as an increase in hemoglobin level of 2 g/dl or more from baseline, was 67%. The rate of response was not related to the chemotherapy regimen administered (platinum or non-platinum based). The percentage of patients transfused and the transfusion rate during epoetin alpha treatment were reduced. Transfusional need was eliminated in 64 (75%) of the 85 patients transfused before the study start, after 1 month of therapy. Quality of life, assessed using a visual analog scale, improved markedly in patients who experienced a hematological response. These patients also experienced a statistically significant (p performance score. These findings indicate that epoetin alpha is a well tolerated and effective agent which increases hemoglobin concentration and reduces transfusion requirements in anemic cancer patients receiving chemotherapy.

  7. Platinum-based anticancer drugs in waste waters of a major UK hospital and predicted concentrations in recipient surface waters.

    Science.gov (United States)

    Vyas, Nitin; Turner, Andrew; Sewell, Graham

    2014-09-15

    Concentrations of the cytotoxic platinum-based anticancer drugs, as total Pt, have been measured over a three week period in one of the main drains and in the effluent of the oncology ward of a major UK hospital (Derriford, Plymouth). Concentrations of Pt were highly variable in both discharges, and ranged from about 0.02 to 140 μg L(-1) in the oncology effluent and from about 0.03 to 100 μg L(-1) in the main drain. A comparison of drug administration figures over the study period with an estimate of the quantity of Pt discharged through the drains suggests that about 22% of total Pt is emitted to the environment from the hospital with the remainder being discharged by treated patients in the wider community. Administration figures for the three Pt-based drugs used in the hospital (cisplatin, carboplatin and oxaliplatin) coupled with published measurements on the removal of the drugs by conventional sewage treatment allowed the concentrations of Pt arising from each drug to be predicted in recipient surface waters as a function of water flow rate. For conditions representative of the region under study, concentrations of total Pt between a few tens and in excess of 100 pg L(-1) are predicted, with the principal form of the metal occurring as carboplatin and its metabolites. Although predicted concentrations are below EMEA guidelines warranting further risk assessment, the presence of substances in surface waters that are potentially carcinogenic, mutagenic and teratogenic and yet whose environmental effects are not understood is cause for concern. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Nanoengineering of Ruthenium and Platinum-based Nanocatalysts by Continuous-Flow Chemistry for Renewable Energy Applications

    KAUST Repository

    AlYami, Noktan Mohammed

    2017-04-15

    This thesis presents an integrated study of nanocatalysts for heterogenous catalytic and electrochemical processes using pure ruthenium (Ru) with mixed-phase and platinum-based nanomaterials synthesized by continuous-flow chemistry. There are three major challenges to the application of nanomaterials in heterogenous catalytic reactions and electrocatalytic processes in acidic solution. These challenges are the following: (i) controlling the size, shape and crystallography of nanoparticles to give the best catalytic properties, (ii) scaling these nanoparticles up to a commercial quantity (kg per day) and (iii) making stable nanoparticles that can be used catalytically without degrading in acidic electrolytes. Some crucial limitations of these nanostructured materials in energy conversion and storage applications were overcome by continuous-flow chemistry. By using a continuous-flow reactor, the creation of scalable nanoparticle systems was achieved and their functionality was modified to control the nanoparticles’ physical and chemical characteristics. The nanoparticles were also tested for long-term stability, to make sure these nanoparticles were feasible under realistic working conditions. These nanoparticles are (1) shape- and crystallography-controlled ruthenium (Ru) nanoparticles, (2) size-controlled platinum-metal (Pt-M= nickel (Ni) & copper (Cu)) nanooctahedra (while maintaining morphology) and (3) core-shell platinum@ruthenium (Pt@Ru) nanoparticles where an ultrathin ruthenium shell was templated onto the platinum core. Thus, a complete experimental validation of the formation of a scalable amount of these nanoparticles and their catalytic activity and stability towards the oxygen evolution reaction (OER) in acid medium, hydrolysis of ammonia borane (AB) along with plausible explanations were provided.

  9. Fat Branes, Orbifolds and Doublet-Triplet Splitting

    CERN Document Server

    Haba, N; Haba, Naoyuki; Maru, Nobuhito

    2003-01-01

    A simple higher dimensional mechanism of the doublet-triplet splitting is presented in a five dimensional supersymmetric SU(5) GUT on S^1/Z_2. The splitting of multiplets is realized by a VEV of the adjoint chiral superfield which breaks SU(5) gauge symmetry. Depending on the sign of the VEV, zero mode Higgs doublets and triplets are localized on the either side of the fixed points. The mass splitting is realized due to the difference of magnitudes of the overlap with a brane localized or a bulk singlet field. No unnatural fine-tuning of parameters is needed. The proton stability is ensured by locality {em without symmetries}. As well as a conventional mass splitting solution, it is shown that the weak scale Higgs triplet is consistent with the proton stability. This result might provide an alternative signature of GUT in future collider experiments.

  10. Discrete symmetries in the three-Higgs-doublet model

    CERN Document Server

    Ivanov, I P

    2012-01-01

    N-Higgs-doublet models (NHDM) are among the most popular examples of electroweak symmetry breaking mechanisms beyond the Standard Model. Discrete symmetries imposed on the NHDM scalar potential play a pivotal role in shaping the phenomenology of the model, and various symmetry groups have been studied so far. However, in spite of all efforts, the classification of finite Higgs-family symmetry groups realizable in NHDM for any N>2 is still missing. Here, we solve this problem for the three-Higgs-doublet model. Using recently found realizable abelian groups and applying Burnside's theorem and other group-theoretic tools, we find the full list of finite symmetry groups of Higgs-family transformations which are realizable in the scalar sector of 3HDM.

  11. A Three Higgs Doublet Model for Fermion Masses

    Science.gov (United States)

    Chao, Wei

    2016-09-01

    In this paper we propose a possible explanation to the Fermion mass hierarchy problem by fitting the type-II seesaw mechanism into the Higgs doublet sector, such that their vacuum expectation values are hierarchal. We extend the Standard Model with two extra Higgs doublets as well as a spontaneously broken UX (1) gauge symmetry. All the fermion Yukawa couplings except that of the top quark are of O}(10-2) in our model. Constraints on the parameter space of the model from low energy processes are studied. Besides, the lightest one of the neutral fermion fields, which is introduced to cancel the anomalies of the U(1)X gauge symmetry can be the cold dark matter candidate. We investigate its signature in the dark matter direct detection. Supported in part by the Wisconsin Alumni Research Foundation

  12. ATLAS diboson excesses from the stealth doublet model

    Directory of Open Access Journals (Sweden)

    Wei Chao

    2016-02-01

    Full Text Available The ATLAS Collaboration has reported excesses in diboson invariant mass searches of new resonances around 2 TeV, which might be a prediction of new physics around that mass range. We interpret these results in the context of a modified stealth doublet model where the extra Higgs doublet has a Yukawa interaction with the first generation quarks, and show that the heavy CP-even Higgs boson can naturally explain the excesses in the WW and ZZ channels with a small Yukawa coupling, ξ∼0.15, and a tiny mixing angle with the SM Higgs boson, α∼0.05. Furthermore, the model satisfies constraints from colliders and electroweak precision measurements.

  13. 3D-Simulation Studies of SNS Ring Doublet Magnets

    Energy Technology Data Exchange (ETDEWEB)

    Wang, J.G.; Tsoupas N.; Venturini, M.

    2005-05-05

    The accumulator ring of the Spallation Neutron Source (SNS) at ORNL employs in its straight sections closely packed quadrupole doublemagnets with large aperture of R=15.1 cm an relatively short iron-to-iron distance of 51.4 cm. These quads have much extended fringe field, and magnetic interferences among them in the doublet assemblies is not avoidable. Though each magnet in the assemblies has been individually mapped to high accuracy of lower than 0.01 percent level, the experimental data including the magnetic interference effect will not be available. We have performed 3D computing simulations on a quadrupole doublet model in order to assess the degree of the interference and to obtain relevant data for the SNS commissioning and operation.

  14. Automatic extraction of candidate nomenclature terms using the doublet method

    Directory of Open Access Journals (Sweden)

    Berman Jules J

    2005-10-01

    Full Text Available Abstract Background New terminology continuously enters the biomedical literature. How can curators identify new terms that can be added to existing nomenclatures? The most direct method, and one that has served well, involves reading the current literature. The scholarly curator adds new terms as they are encountered. Present-day scholars are severely challenged by the enormous volume of biomedical literature. Curators of medical nomenclatures need computational assistance if they hope to keep their terminologies current. The purpose of this paper is to describe a method of rapidly extracting new, candidate terms from huge volumes of biomedical text. The resulting lists of terms can be quickly reviewed by curators and added to nomenclatures, if appropriate. The candidate term extractor uses a variation of the previously described doublet coding method. The algorithm, which operates on virtually any nomenclature, derives from the observation that most terms within a knowledge domain are composed entirely of word combinations found in other terms from the same knowledge domain. Terms can be expressed as sequences of overlapping word doublets that have more specific meaning than the individual words that compose the term. The algorithm parses through text, finding contiguous sequences of word doublets that are known to occur somewhere in the reference nomenclature. When a sequence of matching word doublets is encountered, it is compared with whole terms already included in the nomenclature. If the doublet sequence is not already in the nomenclature, it is extracted as a candidate new term. Candidate new terms can be reviewed by a curator to determine if they should be added to the nomenclature. An implementation of the algorithm is demonstrated, using a corpus of published abstracts obtained through the National Library of Medicine's PubMed query service and using "The developmental lineage classification and taxonomy of neoplasms" as a reference

  15. A simple model for doublet bands in doubly odd nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Yoshinaga, N. [Saitama University, Department of Physics, Saitama City (Japan); Higashiyama, K. [Chiba Institute of Technology, Department of Physics, Narashino, Chiba (Japan); University of Tokyo, Department of Physics, Hongo, Tokyo (Japan)

    2006-11-15

    Nuclear structure of doublet bands in doubly odd nuclei with mass A {proportional_to} 130 is investigated within the framework of a simple model where the even-even core couples with a neutron and a proton in intruder orbitals through a quadrupole-quadrupole interaction. The model reproduces quite well the energy levels of doublet bands and electromagnetic transitions. The staggering of the ratios B(M1;I{yields}I-1)/B(E2;I{yields}I-2) of the yrast bands turns out to be described by the chopsticks-like motion of two angular momenta of the unpaired neutron and the unpaired proton when they are weakly coupled with the core. (orig.)

  16. A search for close-mass lepton doublet

    Energy Technology Data Exchange (ETDEWEB)

    Riles, J.K.

    1989-04-01

    Described is a search for a heavy charged lepton with an associated neutrino of nearly the same mass, together known as a close-mass lepton doublet. The search is conducted in e/sup +/e/sup/minus// annihilation data taken with the Mark II detector at a center-of-mass energy of 29 GeV. In order to suppress contamination from conventional two-photon reactions, the search applies a novel, radiative-tagging technique. Requiring the presence of an isolated, energetic photon allows exploration for lepton doublets with a mass splitting smaller than that previously accessible to experiment. No evidence for such a new lepton has been found, enabling limits to be placed on allowed mass combinations. Mass differences as low as 250-300 MeV are excluded for charged lepton masses up to 10 GeV. 78 refs., 64 figs., 8 tabs.

  17. Doublet vs. FODO structure: beam dynamics and layout

    CERN Document Server

    Eshraqi, M; CERN. Geneva. BE Department

    2010-01-01

    A FoDo (singlet) structure is designed for the CERN Superconducting Proton LINAC. This architecture is compared to the baseline (doublet) architecture of SPL on the basis of its beam dynamics performance and the required investment. The sensitivity of both layouts to quadrupole gradient errors and misalignment is checked and a correction scheme for beam steering is proposed. Finally a single quad beam dilution scheme is studied and designed for the pilot beam dump.

  18. Types of chemotherapy

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000910.htm Types of chemotherapy To use the sharing features on this page, ... or on cancer cells. How Doctors Choose Your Chemotherapy The type and dose of chemotherapy your doctor ...

  19. Chemotherapy for Thyroid Cancer

    Science.gov (United States)

    ... Type and Stage Thyroid Cancer Treating Thyroid Cancer Chemotherapy for Thyroid Cancer Chemotherapy (chemo) uses anti-cancer drugs that are injected ... vein or muscle, or are taken by mouth. Chemotherapy is systemic therapy, which means that the drug ...

  20. Chemotherapy for Testicular Cancer

    Science.gov (United States)

    ... Type and Stage Testicular Cancer Treating Testicular Cancer Chemotherapy for Testicular Cancer Chemotherapy (chemo) is the use of drugs to treat ... that is only in the testicle. Doctors give chemotherapy in cycles, with each period of treatment followed ...

  1. Side Effects of Chemotherapy

    Science.gov (United States)

    ... Jacket Fashion Show Contact Us Side Effects of Chemotherapy Each of the chemotherapy drugs available today works in a slightly different ... few rules of thumb when it comes to chemotherapy that should always be kept in mind. Ignore ...

  2. Chemotherapy and Your Mouth

    Science.gov (United States)

    ... Treatment and Oral Health > Chemotherapy and Your Mouth Chemotherapy and Your Mouth Main Content Are You Being ... Problems Too? Remember Are You Being Treated With Chemotherapy for Cancer? If so, this booklet can help ...

  3. A germline predictive signature of response to platinum chemotherapy in esophageal cancer.

    Science.gov (United States)

    Rumiato, Enrica; Boldrin, Elisa; Malacrida, Sandro; Battaglia, Giorgio; Bocus, Paolo; Castoro, Carlo; Cagol, Matteo; Chiarion-Sileni, Vanna; Ruol, Alberto; Amadori, Alberto; Saggioro, Daniela

    2016-05-01

    Platinum-based neoadjuvant therapy is the standard treatment for esophageal cancer (EC). At present, no reliable response markers exist, and patient therapeutic outcome is variable and very often unpredictable. The aim of this study was to understand the contribution of host constitutive DNA polymorphisms in discriminating between responder and nonresponder patients. DNA collected from 120 EC patients treated with platinum-based neoadjuvant chemotherapy was analyzed using drug metabolism enzymes and transporters (DMET) array platform that interrogates polymorphisms in 225 genes of drug metabolism and disposition. Four gene variants of DNA repair machinery, 2 in ERCC1 (rs11615; rs3212986), and 2 in XPD (rs1799793; rs13181) were also studied. Association analysis was performed with pTest software and corrected by permutation test. Predictive models of response were created using the receiver-operating characteristics curve approach and adjusted by the bootstrap procedure. Sixteen single nucleotide polymorphisms (SNPs) of the DMET array resulted significantly associated with either good or poor response; no association was found for the 4 variants mapping in DNA repair genes. The predictive power of 5 DMET SNPs mapping in ABCC2, ABCC3, CYP2A6, PPARG, and SLC7A8 genes was greater than that of clinical factors alone (area under the curve [AUC] = 0.74 vs 0.62). Interestingly, their combination with the clinical variables significantly increased the predictivity of the model (AUC = 0.78 vs 0.62, P = 0.0016). In conclusion, we identified a genetic signature of response to platinum-based neoadjuvant chemotherapy in EC patients. Our results also disclose the potential benefit of combining genetic and clinical variables for personalized EC management.

  4. SIRT1 expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC.

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    Full Text Available AIM: The role of Sirtuin 1 (SIRT 1 in carcinogenesis is controversial. This study was to explore the association between the SIRT1 expression and the clinical characteristics, the responsiveness to chemotherapy and prognosis in Non-small cell lung cancer (NSCLC. METHODS: We enrolled 295 patients with inoperable advanced stage of NSCLC, namely, stage III (A+B and IV NSCLC. All patients had received platinum-based chemotherapy after diagnosis and the chemotherapy response were evaluated. All patients were followed up for overall survival (OS and progression free survival (PFS. In vitro, H292 cells were tranfected with SIRT1 small interfering RNA (siRNA. The cell biological behaviors and chemosensitivity to cisplatin treatment were studied. The in vivo tumorgenesis and metastasis assays were performed in nude mice. RESULTS: We found that the SIRT1 expressions were significantly associated with the tumor stage, tumor size and differentiation status. Patients with high SIRT 1 expressions had a significantly higher chance to be resistant to chemotherapy than those with low SIRT 1 expression. Patients with high expression of SIRT1 had significantly shorter OS and DFS than those with low expression. Cox analyses confirmed that the SIRT 1 expression was a strong predictor for a poor OS and PFS in NSCLC patients underwent Platinum-based chemotherapy. In vitro studies revealed that the reduced expression SIRT 1 by siRNA technique significantly inhibited cell proliferation, migration and invasion. More importantly, SIRT1 si-RNA significantly enhanced the chemosensitivity of H292 cells to cisplatin treatment. The in vivo tumorgenesis and metastasis assays showed that SIRT1 knockdown dramatically reduced the tumor volume and the metastatic ability in nude mice. CONCLUSION: Collectively, our data suggest that the SIRT1 expression may be a molecular marker associated with the NSLCLC clinical features, treatment responsiveness and prognosis of advanced NSCLC.

  5. A new viable region of the inert doublet model

    CERN Document Server

    Lopez-Honorez, Laura

    2010-01-01

    The inert doublet model, a minimal extension of the Standard Model by a second Higgs doublet, is one of the simplest and most attractive scenarios that can explain the dark matter. In this paper, we demonstrate the existence of a new viable region of the inert doublet model featuring dark matter masses between Mw and about 160 GeV. Along this previously overlooked region of the parameter space, the correct relic density is obtained thanks to cancellations between different diagrams contributing to dark matter annihilation into gauge bosons (W+W- and ZZ). First, we explain how these cancellations come about and show several examples illustrating the effect of the parameters of the model on the cancellations themselves and on the predicted relic density. Then, we perform a full scan of the new viable region and analyze it in detail by projecting it onto several two-dimensional planes. Finally, the prospects for the direct and the indirect detection of inert Higgs dark matter within this new viable region are st...

  6. Singlet-Doublet model: dark matter searches and LHC constraints

    Energy Technology Data Exchange (ETDEWEB)

    Calibbi, Lorenzo [State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics,Chinese Academy of Sciences,Beijing 100190 (China); Service de Physique Théorique, Université Libre de Bruxelles,C.P. 225, B-1050, Brussels (Belgium); Mariotti, Alberto; Tziveloglou, Pantelis [Theoretische Natuurkunde and IIHE/ELEM, Vrije Universiteit Brussel,and International Solvay Institutes,Pleinlaan 2, B-1050 Brussels (Belgium)

    2015-10-19

    The Singlet-Doublet model of dark matter is a minimal extension of the Standard Model with dark matter that is a mixture of a singlet and a non-chiral pair of electroweak doublet fermions. The stability of dark matter is ensured by the typical parity symmetry, and, similar to a ‘Bino-Higgsino’ system, the extra matter content improves gauge coupling unification. We revisit the experimental constraints on the Singlet-Doublet dark matter model, combining the most relevant bounds from direct (spin independent and spin dependent) and indirect searches. We show that such comprehensive analysis sets strong constraints on a large part of the 4-dimensional parameter space, closing the notorious ‘blind-spots’ of spin independent direct searches. Our results emphasise the complementarity of direct and indirect searches in probing dark matter models in diverse mass scale regimes. We also discuss the LHC bounds on such scenario, which play a relevant role in the low mass region of the dark matter candidate.

  7. Singlet-Doublet Model: Dark matter searches and LHC constraints

    CERN Document Server

    Calibbi, Lorenzo; Tziveloglou, Pantelis

    2015-01-01

    The Singlet-Doublet model of dark matter is a minimal extension of the Standard Model with dark matter that is a mixture of a singlet and a non-chiral pair of electroweak doublet fermions. The stability of dark matter is ensured by the typical parity symmetry, and, similar to a "Bino-Higgsino" system, the extra matter content improves gauge coupling unification. We revisit the experimental constraints on the Singlet-Doublet dark matter model, combining the most relevant bounds from direct (spin independent and spin dependent) and indirect searches. We show that such comprehensive analysis sets strong constraints on a large part of the 4-dimensional parameter space, closing the notorious "blind-spots" of spin independent direct searches. Our results emphasise the complementarity of direct and indirect searches in probing dark matter models in diverse mass scale regimes. We also discuss the LHC bounds on such scenario, which play a relevant role in the low mass region of the dark matter candidate.

  8. Perturbative Unitarity Bounds in Composite 2-Higgs Doublet Models

    CERN Document Server

    De Curtis, Stefania; Yagyu, Kei; Yildirim, Emine

    2016-01-01

    We study bounds from perturbative unitarity in a Composite 2-Higgs Doublet Model (C2HDM) based on the spontaneous breakdown of a global symmetry $SO(6)\\to SO(4)\\times SO(2)$ at the compositeness scale $f$. The eight pseudo Nambu-Goldstone Bosons (pNGBs) emerging from such a dynamics are identified as two isospin doublet Higgs fields. We calculate the $S$-wave amplitude for all possible 2-to-2-body elastic (pseudo)scalar boson scatterings at energy scales $\\sqrt{s}$ reachable at the Large Hadron Collider (LHC) and beyond it, including the longitudinal components of weak gauge boson states as the corresponding pNGB states. In our calculation, the Higgs potential is assumed to have the same form as that in the Elementary 2-Higgs Doublet Model (E2HDM) with a discrete $Z_2$ symmetry, which is expected to be generated at the one-loop level via the Coleman-Weinberg (CW) mechanism. We find that the $S$-wave amplitude matrix can be block-diagonalized with maximally $2\\times 2$ submatrices in a way similar to the E2HDM...

  9. chemotherapy patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  10. chemotherapy patients

    Directory of Open Access Journals (Sweden)

    Katarzyna Augustyniuk

    2016-02-01

    Full Text Available Background . Complementary and alternative medicine (CAM practices for cancer have become popular among oncology patients. An increasing interest in alternative medicine can be explained by the inefficiency of conventional treatment, dissatisfaction with treating patients like objects, and the will to use all available treatment methods. Objectives . The authors assessed how often patients use CAM methods, and which of them are most popular. Material and methods . The study was conducted in Military Hospital no. 109 and the Independent Public Clinical Hospital no. 1 in Szczecin among 100 chemotherapy patients. This survey-based study was performed using an original questionnaire. Results. Most respondents (68% did not use alternative methods to fight the disease. The most popular treatment methods were: herbal medicine (50%, alternative medicine preparations (38% and diet (25%, and the least common: hypnosis (3% and aromatherapy (3%. Analyzed sociodemographic factors had no effects on a choice of a CAM method. Patients obtained information about CAM methods mainly from the Internet (40%, medical staff (37% and literature (31%. Conclusions . 1. Using CAM by patients receiving chemotherapy for neoplasms is quite a common phenomenon. 2. CAM were more often chosen by women. Neither the duration of the disease nor sociodemographic data had effects on making the decision to use CAM methods. 3. The most popular CAM were: herbal medicine, alternative medicine preparations, and diet. 4. Cancer patients should receive special support from nurses and doctors as well as other members of the therapeutic team. Oncology patients should never be left on their own so that they were forced to seek help and support in therapies unconfirmed by scientific investigation.

  11. Phenomenology of the Inert (2+1) and (4+2) Higgs Doublet Models

    CERN Document Server

    Keus, Venus; Moretti, Stefano

    2014-01-01

    We make a phenomenological study of a model with two inert doublets plus one Higgs doublet (I(2+1)HDM) which is symmetric under a Z$_2$ group, preserved after Electro-Weak Symmetry Breaking (EWSB) by the vacuum alignment $(0,0,v)$. This model may be regarded as an extension to the model with one inert doublet plus one Higgs doublet (I(1+1)HDM), by the addition of an extra inert scalar doublet. The neutral fields from the two inert doublets provide a viable Dark Matter (DM) candidate which is stabilised by the conserved $Z_2$ symmetry. We study the new Higgs decay channels offered by the scalar fields from the extra doublets and their effect on the Standard Model (SM) Higgs couplings, including a new decay channel into photon(s) plus missing energy, which distinguishes the I(2+1)HDM from the I(1+1)HDM. Motivated by Supersymmetry, which requires an even number of doublets, we then extend this model into a model with four inert doublets plus two Higgs doublets (I(4+2)HDM) and study the phenomenology of the model...

  12. Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas

    Directory of Open Access Journals (Sweden)

    Walsh Tom

    2009-07-01

    Full Text Available Abstract Background DNA repair genes critically regulate the cellular response to chemotherapy and epigenetic regulation of these genes may be influenced by chemotherapy exposure. Restoration of BRCA1 and BRCA2 mediates resistance to platinum chemotherapy in recurrent BRCA1 and BRCA2 mutated hereditary ovarian carcinomas. We evaluated BRCA1, BRCA2, and MLH1 protein expression in 115 sporadic primary ovarian carcinomas, of which 31 had paired recurrent neoplasms collected after chemotherapy. Additionally, we assessed whether promoter methylation of BRCA1, MLH1 or FANCF influenced response to chemotherapy or explained alterations in protein expression after chemotherapy exposure. Results Of 115 primary sporadic ovarian carcinomas, 39 (34% had low BRCA1 protein and 49 (42% had low BRCA2 expression. BRCA1 and BRCA2 protein expression were highly concordant (p Conclusion Low BRCA1 expression in primary sporadic ovarian carcinoma is associated with prolonged survival. Recurrent ovarian carcinomas commonly have increased BRCA1 and/or BRCA2 protein expression post chemotherapy exposure which could mediate resistance to platinum based therapies. However, alterations in expression of these proteins after chemotherapy are not commonly mediated by promoter methylation, and other regulatory mechanisms are likely to contribute to these alterations.

  13. Class III β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2011-01-01

    Platinum-based doublets are the cornerstone of treatment in advanced non-small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III ß-tubulin (TUBB3...

  14. Class III β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2011-01-01

    Platinum-based doublets are the cornerstone of treatment in advanced non-small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III β-tubulin (TUBB3...

  15. Gauged Two Higgs Doublet Model confronts the LHC 750 GeV diphoton anomaly

    Science.gov (United States)

    Huang, Wei-Chih; Tsai, Yue-Lin Sming; Yuan, Tzu-Chiang

    2016-08-01

    In light of the recent 750 GeV diphoton anomaly observed at the LHC, we study the possibility of accommodating the deviation from the standard model prediction based on the recently proposed Gauged Two Higgs Doublet Model. The model embeds two Higgs doublets into a doublet of a non-abelian gauge group SU(2)H, while the standard model SU(2)L right-handed fermion singlets are paired up with new heavy fermions to form SU(2)H doublets, and SU(2)L left-handed fermion doublets are singlets under SU(2)H. An SU(2)H scalar doublet, which provides masses to the new heavy fermions as well as the SU(2)H gauge bosons, can be produced via gluon fusion and subsequently decays into two photons with the new fermions circulating the triangle loops to account for the deviation from the standard model prediction.

  16. Gauged Two Higgs Doublet Model confronts the LHC 750 GeV diphoton anomaly

    Directory of Open Access Journals (Sweden)

    Wei-Chih Huang

    2016-08-01

    Full Text Available In light of the recent 750 GeV diphoton anomaly observed at the LHC, we study the possibility of accommodating the deviation from the standard model prediction based on the recently proposed Gauged Two Higgs Doublet Model. The model embeds two Higgs doublets into a doublet of a non-abelian gauge group SU(2H, while the standard model SU(2L right-handed fermion singlets are paired up with new heavy fermions to form SU(2H doublets, and SU(2L left-handed fermion doublets are singlets under SU(2H. An SU(2H scalar doublet, which provides masses to the new heavy fermions as well as the SU(2H gauge bosons, can be produced via gluon fusion and subsequently decays into two photons with the new fermions circulating the triangle loops to account for the deviation from the standard model prediction.

  17. Gauged Two Higgs Doublet Model confronts the LHC 750 GeV di-photon anomaly

    CERN Document Server

    Huang, Wei-Chih; Yuan, Tzu-Chiang

    2015-01-01

    In light of the recent 750 GeV di-photon anomaly observed at the LHC, we check the possibility of accommodating the deviation from the Standard Model~(SM) prediction based on the Gauged Two Higgs Doublet Model, which has been proposed lately. The model embeds two Higgs doublets into a doublet of a non-abelian gauge group $SU(2)_H$, while the SM $SU(2)_L$ right-handed fermion singlets are paired up with new heavy fermions to form $SU(2)_H$ doublets, and $SU(2)_L$ left-handed fermion doublets are singlets under $SU(2)_H$. An $SU(2)_H$ scalar doublet, which provides a mass to the new heavy fermions as well as the $SU(2)_H$ gauge bosons, can be produced via gluon fusion and subsequently decays into two photons with the help of the new fermions to account for the deviation from the SM prediction.

  18. Abelian symmetries in multi-Higgs-doublet models

    CERN Document Server

    Ivanov, Igor P; Vdovin, Evgeny

    2012-01-01

    Classifying symmetry groups which can be implemented in the scalar sector of a model with $N$ Higgs doublets is a difficult and an unsolved task for $N>2$. Here, we make the first step towards this goal by classifying the Abelian symmetry groups. We describe a strategy that identifies all Abelian groups which can be realized as symmetry groups of the NHDM scalar potential. We give examples of the use of this strategy in 3HDM and 4HDM and prove several statements for arbitrary $N$.

  19. Competing Kondo Effects in Non-Kramers Doublet Systems

    OpenAIRE

    Kusunose, Hiroaki

    2016-01-01

    In non-Kramers Kondo systems with a quadrupolar degrees of freedom, an ordinary magnetic Kondo effect can compete with the quadrupolar Kondo effect. We discuss such competition keeping Pr$T_{2}$Zn$_{20}$ ($T$=Ir, Rh) and Pr$T_{2}$Al$_{20}$ ($T$=V, Ti) in mind, where the $\\Gamma_{3}$ non-Kramers crystalline-electric-field (CEF) doublet ground state is realized in Pr$^{3+}$ ion with $(4f)^{2}$ configuration under cubic symmetry. The quadrupolar Kondo effect can be described by the two-channel K...

  20. (1)-covariant gauge for the two-Higgs doublet model

    Indian Academy of Sciences (India)

    C G Honorato; J J Toscano

    2009-12-01

    A (1)-covariant gauge for the two-Higgs doublet model based on BRST (Becchi–Rouet–Stora–Tyutin) symmetry is introduced. This gauge allows one to remove a significant number of nonphysical vertices appearing in conventional linear gauges, which greatly simplifies the loop calculations, since the resultant theory satisfies QED-like Ward identities. The presence of four ghost interactions in these types of gauges and their connection with the BRST symmetry are stressed. The Feynman rules for those new vertices that arise in this gauge, as well as for those couplings already present in the linear gauge but that are modified by this gauge-fixing procedure, are presented.

  1. Wafer-level fabrication of arrays of glass lens doublets

    Science.gov (United States)

    Passilly, Nicolas; Perrin, Stéphane; Albero, Jorge; Krauter, Johann; Gaiffe, Olivier; Gauthier-Manuel, Ludovic; Froehly, Luc; Lullin, Justine; Bargiel, Sylwester; Osten, Wolfgang; Gorecki, Christophe

    2016-04-01

    Systems for imaging require to employ high quality optical components in order to dispose of optical aberrations and thus reach sufficient resolution. However, well-known methods to get rid of optical aberrations, such as aspherical profiles or diffractive corrections are not easy to apply to micro-optics. In particular, some of these methods rely on polymers which cannot be associated when such lenses are to be used in integrated devices requiring high temperature process for their further assembly and separation. Among the different approaches, the most common is the lens splitting that consists in dividing the focusing power between two or more optical components. In here, we propose to take advantage of a wafer-level technique, devoted to the generation of glass lenses, which involves thermal reflow in silicon cavities to generate lens doublets. After the convex lens sides are generated, grinding and polishing of both stack sides allow, on the first hand, to form the planar lens backside and, on the other hand, to open the silicon cavity. Nevertheless, silicon frames are then kept and thinned down to form well-controlled and auto-aligned spacers between the lenses. Subsequent accurate vertical assembly of the glass lens arrays is performed by anodic bonding. The latter ensures a high level of alignment both laterally and axially since no additional material is required. Thanks to polishing, the generated lens doublets are then as thin as several hundreds of microns and compatible with micro-opto-electro-systems (MOEMS) technologies since they are only made of glass and silicon. The generated optical module is then robust and provide improved optical performances. Indeed, theoretically, two stacked lenses with similar features and spherical profiles can be almost diffraction limited whereas a single lens characterized by the same numerical aperture than the doublet presents five times higher wavefront error. To demonstrate such assumption, we fabricated glass

  2. Neutron electric dipole momento in two-Higgs-doublet model

    CERN Document Server

    Hayashi, T; Matsuda, M; Tanimoto, M; Hayashi, T; Koide, Y; Matsuda, M; Tanimoto, M

    1994-01-01

    The effect of the "chromo-electric" dipole moment on the electric dipole moment(EDM) of the neutron is studied in the two-Higgs-doublet model. The Weinberg's operator O_{3g}=GG\\t G and the operator O_{qg}=\\bar q\\sigma\\t Gq are both investigated in the cases of \\tan\\b\\gg 1, \\tan\\b\\ll 1 and \\tan\\b\\simeq 1. The neutron EDM is considerably reduced due to the destructive contribution with two light Higgs scalars exchanges.

  3. Biochemical characterization of tektins from sperm flagellar doublet microtubules

    OpenAIRE

    1987-01-01

    Tektins, protein components of stable protofilaments from sea urchin sperm flagellar outer doublet microtubules (Linck, R. W., and G. L. Langevin, 1982, J. Cell Sci., 58:1-22), are separable by preparative SDS PAGE into 47-, 51-, and 55-kD equimolar components. High resolution two-dimensional tryptic peptide mapping reveals 63-67% coincidence among peptides of the 51-kD tektin chain and its 47- and 55-kD counterparts, greater than 70% coincidence between the 47- and 55-kD tektins, but little ...

  4. Molecular architecture of axonemal microtubule doublets revealedby cryo-electron tomography

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Haixin; Downing, Kenneth H.

    2006-05-22

    The axoneme, which forms the core of eukaryotic flagella and cilia, is one of the largest macromolecular machines with a structure that is largely conserved from protists to mammals. Microtubule doublets are structural components of axonemes containing a number of proteins besides tubulin, and are usually found in arrays of nine doublets arranged around two singlet microtubules. Coordinated sliding of adjacent doublets, which involves a host of other proteins in the axoneme, produces periodic beating movements of the axoneme. We have obtained a 3D density map of intact microtubule doublets using cryo-electron tomography and image averaging. Our map, with a resolution of about 3 nm, provides insights into locations of particular proteins within the doublets and the structural features of the doublets that define their mechanical properties. We identify likely candidates for several of these non-tubulin components of the doublets. This work offers novel insight on how tubulin protofilaments and accessory proteins attach together to form the doublets and provides a structural basis for understanding doublet function in axonemes.

  5. Light charged Higgs boson scenario in 3-Higgs doublet models

    CERN Document Server

    Akeroyd, A G; Yagyu, Kei; Yildirim, Emine

    2016-01-01

    The constraints from the measurements of the $B\\to X_s\\gamma$ decay rate on the parameter space of 3-Higgs Doublet Models (3HDMs), where all the doublets have non-zero vacuum expectation values, are studied at the next-to-leading order in QCD. In order to naturally avoid the presence of flavour changing neutral currents at the tree level, we impose two softly-broken discrete $Z_2$ symmetries. This gives rise to five independent types of 3HDMs that differ in their Yukawa couplings. We show that in all these 3HDMs (including the case of type-II-like Yukawa interactions) both masses of the two charged Higgs bosons $m_{H_1^\\pm}$ and $m_{H_2^\\pm}$ can be smaller than the top mass $m_t$ while complying with the constraints from $B\\to X_s\\gamma$. As an interesting phenomenological consequence, the branching ratios of the charged Higgs bosons decay into the $cb$ final states can be as large as $80\\%$ when their masses are taken to be below $m_t$ in two of the five 3HDMs (named as Type-Y and Type-Z). This light charge...

  6. Collisional broadening of alkali doublets by helium perturbers

    CERN Document Server

    Mullamphy, D F T; Peach, G; Venturi, V; Whittingham, I B

    2006-01-01

    We report results for the Lorentzian profiles of the Li I, Na I and K I doublets and the Na I subordinate doublet broadened by helium perturbers for temperatures up to 3000 K They have been obtained from a fully quantum-mechanical close-coupling description of the colliding atoms, the Baranger theory of line shapes and new ab initio potentials for the alkali-helium interaction. For all lines except the 769.9 nm K I line, the temperature dependence of the widths over the range 70 < T < 3000 K is accurately represented by the power law form w=aT^b with 0.37 < b < 0.43. The 769.9 K I line has this form for 500 < T < 3000 K with b = 0.49. Although the shifts have a more complex temperature dependence, they all have the general feature of increasing with temperature above T=500 K apart from the 769.9 K I line whose shift decreases with temperature.

  7. Classical scale invariance in the inert doublet model

    CERN Document Server

    Plascencia, Alexis D

    2015-01-01

    The inert doublet model (IDM) is a minimal extension of the Standard Model (SM) that can account for the dark matter in the universe. Naturalness arguments motivate us to study whether the model can be embedded into a theory with dynamically generated scales. In this work we study a classically scale invariant version of the IDM with a minimal hidden sector, which has a $U(1)_{\\text{CW}}$ gauge symmetry and a complex scalar $\\Phi$. The mass scale is generated in the hidden sector via the Coleman-Weinberg (CW) mechanism and communicated to the two Higgs doublets via portal couplings. Since the CW scalar remains light, acquires a vacuum expectation value and mixes with the SM Higgs boson, the phenomenology of this construction can be modified with respect to the traditional IDM. We analyze the impact of adding this CW scalar and the $Z'$ gauge boson on the calculation of the dark matter relic density and on the spin-independent nucleon cross section for direct detection experiments. Finally, by studying the RG ...

  8. Spinning Janus doublets driven in uniform ac electric fields

    Science.gov (United States)

    Boymelgreen, Alicia; Yossifon, Gilad; Park, Sinwook; Miloh, Touvia

    2014-01-01

    We provide an experimental proof of concept for a robust, continuously rotating microstructure—consisting of two metallodielectric (gold-polystyrene) Janus particles rigidly attached to each other—which is driven in uniform ac fields by asymmetric induced-charge electro-osmosis. The pairs (doublets) are stabilized on the substrate surface which is parallel to the plane of view and normal to the direction of the applied electric field. We find that the radius of orbit and angular velocity of the pair are predominantly dependent on the relative orientations of the interfaces between the metallic and dielectric hemispheres and that the electrohydrodynamic particle-particle interactions are small. Additionally, we verify that both the angular and linear velocities of the pair are proportional to the square of the applied field which is consistent with the theory for nonlinear electrokinetics. A simple kinematic rigid body model is used to predict the paths and doublet velocities (angular and linear) based on their relative orientations with good agreement.

  9. Vacuum Topology of the Two Higgs Doublet Model

    CERN Document Server

    Battye, Richard A; Pilaftsis, Apostolos

    2011-01-01

    We perform a systematic study of generic accidental Higgs-family and CP symmetries that could occur in the two-Higgs-doublet-model potential, based on a Majorana scalar-field formalism which realizes a subgroup of GL(8,C). We derive the general conditions of convexity and stability of the scalar potential and present analytical solutions for two non-zero neutral vacuum expectation values of the Higgs doublets for a typical set of six symmetries, in terms of the gauge-invariant parameters of the theory. By means of a homotopy-group analysis, we identify the topological defects associated with the spontaneous symmetry breaking of each symmetry, as well as the massless Goldstone bosons emerging from the breaking of the continuous symmetries. We find the existence of domain walls from the breaking of Z_2, CP1 and CP2 discrete symmetries, vortices in models with broken U(1)_PQ and CP3 symmetries and a global monopole in the SO(3)_HF-broken model. The spatial profile of the topological defect solutions is studied i...

  10. LHC Phenomenology of Composite 2-Higgs Doublet Models

    CERN Document Server

    De Curtis, Stefania; Yagyu, Kei; Yildirim, Emine

    2016-01-01

    We investigate the phenomenology of Composite 2-Higgs Doublet Models (C2HDMs) of various Yukawa types based on the global symmetry breaking $SO(6)\\to SO(4)\\times SO(2)$. The kinetic term and the Yukawa Lagrangian are constructed in terms of the pseudo Nambu-Goldstone Boson (pNGB) matrix and a 6-plet of fermions under $SO(6)$. The scalar potential is assumed to be the same as that of the Elementary 2-Higgs Doublet Model (E2HDM) with a softly-broken discrete $Z_2$ symmetry. We then discuss the phenomenological differences between the E2HDM and C2HDM by focusing on the deviations from Standard Model (SM) couplings of the discovered Higgs state ($h$) as well as on the production cross sections and Branching Ratios (BRs) at the Large Hadron Collider (LHC) of extra Higgs bosons. We find that, even if the same deviation in the $hVV$ ($V=W,Z$) coupling is assumed in both scenarios, there appear significant differences between E2HDM and C2HDM from the structure of the Yukawa couplings, so that production and decay fea...

  11. Fitting the Two-Higgs-Doublet model of type II

    CERN Document Server

    Eberhardt, Otto

    2014-01-01

    We present the current status of the Two-Higgs-Doublet model of type II. Taking into account all available relevant information, we exclude at $95$% CL sizeable deviations of the so-called alignment limit, in which all couplings of the light CP-even Higgs boson $h$ are Standard-Model-like. While we can set a lower limit of $240$ GeV on the mass of the pseudoscalar Higgs boson at $95$% CL, the mass of the heavy CP-even Higgs boson $H$ can be even lighter than $200$ GeV. The strong constraints on the model parameters also set limits on the triple Higgs couplings: the $hhh$ coupling in the Two-Higgs-Doublet model of type II cannot be larger than in the Standard Model, while the $hhH$ coupling can maximally be $2.5$ times the size of the Standard Model $hhh$ coupling, assuming an $H$ mass below $1$ TeV. The selection of benchmark scenarios which maximize specific effects within the allowed regions for further collider studies is illustrated for the $H$ branching fraction to fermions and gauge bosons. As an exampl...

  12. RAGE genetic polymorphisms are associated with risk, chemotherapy response and prognosis in patients with advanced NSCLC.

    Directory of Open Access Journals (Sweden)

    Xiang Wang

    Full Text Available AIM: To explore the association between genetic polymorphisms of the receptor for advanced glycation end-products (RAGE and susceptibility, chemotherapy response rate and prognosis of non-small cell lung cancer (NSCLC. METHOD: This is a prospective study in which 562 patients with NSCLC and 764 healthy controls were enrolled. Three RAGE genetic polymorphisms, namely, -429T/C, -374T/A and 82G/S were genotyped. Platinum-based chemotherapy was given to 432 subjects with advanced inoperable NSCLC and their responses to chemotherapy were evaluated. RESULTS: All the polymorphic genotypes of RAGE polymorphisms were associated with susceptibility for NSCLC. Only the 82G/S polymorphisms denoted a significant difference between responders and non-responders to chemotherapy. The 82SS genotype and 82S allele distribution not only increased the NSCLC risk, but also was associated with a lower chemotherapy response rate and poor prognosis, indicated by overall survival and progression free survival. CONCLUSION: The 82G/S genetic polymorphism of RAGE gene might be used as a genetic marker to screen for patients sensitive to thermotherapy and to predict the prognosis of NSCLC.

  13. Multiple chiral doublet candidate nucleus $^{105}$Rh in a relativistic mean-field approach

    CERN Document Server

    Li, Jian; Meng, J; 10.1103/PhysRevC.83.037301

    2011-01-01

    Following the reports of two pairs of chiral doublet bands observed in $^{105}$Rh, the adiabatic and configuration-fixed constrained triaxial relativistic mean-field (RMF) calculations are performed to investigate their triaxial deformations with the corresponding configuration and the possible multiple chiral doublet (M$\\chi$D) phenomenon. The existence of M$\\chi$D phenomenon in $^{105}$Rh is highly expected.

  14. New final doublets and power densities for the international linear collider small crossing angle layout

    Indian Academy of Sciences (India)

    R Appleby; P Bambade

    2007-12-01

    In this paper we use current and proposed final doublet magnet technologies to reoptimise the interaction region of the international linear collider and reduce the power losses. The result is a set of three new final doublet layouts with improved beam transport properties. The effect of localised power deposition and it's reduction using tungsten liners are considered.

  15. Doublet Production in the Development of Medieval and Modern Spanish: New Approaches to Phonolexical Duplication

    Science.gov (United States)

    Haney, Darren W.

    2011-01-01

    This dissertation offers new approaches to an old and well-known problem in the study of the development of Romance varieties: duplicate lexis or doublets. Traditional analyses of duplication are narrow in scope both in what qualifies as a doublet (the popular/learned opposition has dominated, to the exclusion of other pairs) and in channels of…

  16. Doublet Production in the Development of Medieval and Modern Spanish: New Approaches to Phonolexical Duplication

    Science.gov (United States)

    Haney, Darren W.

    2011-01-01

    This dissertation offers new approaches to an old and well-known problem in the study of the development of Romance varieties: duplicate lexis or doublets. Traditional analyses of duplication are narrow in scope both in what qualifies as a doublet (the popular/learned opposition has dominated, to the exclusion of other pairs) and in channels of…

  17. Chemotherapy (For Parents)

    Science.gov (United States)

    ... Getting Involved Teaching Kids to Be Smart About Social Media Chemotherapy KidsHealth ... and Where Chemo Is Given Common Side Effects of Chemotherapy Common Side Effects (continued) Common Side ...

  18. Chemotherapy | Smokefree.gov

    Science.gov (United States)

    Chemotherapy works by killing cancer cells, but healthy cells get attacked too. Damage to healthy cells can cause uncomfortable side effects. Use this action deck to get information on common chemotherapy side effects and learn how to manage them.

  19. Three-Higgs-doublet models: symmetries, potentials and Higgs boson masses

    Energy Technology Data Exchange (ETDEWEB)

    Keus, Venus [School of Physics and Astronomy, University of Southampton,Southampton, SO17 1BJ (United Kingdom); Department of Physics, Royal Holloway, University of London,Egham Hill, Egham TW20 0EX (United Kingdom); Particle Physics Department, Rutherford Appleton Laboratory,Chilton, Didcot, Oxon OX11 0QX (United Kingdom); King, Stephen F. [School of Physics and Astronomy, University of Southampton,Southampton, SO17 1BJ (United Kingdom); Moretti, Stefano [School of Physics and Astronomy, University of Southampton,Southampton, SO17 1BJ (United Kingdom); Particle Physics Department, Rutherford Appleton Laboratory,Chilton, Didcot, Oxon OX11 0QX (United Kingdom)

    2014-01-13

    We catalogue and study three-Higgs-doublet models in terms of all possible allowed symmetries (continuous and discrete, Abelian and non-Abelian), where such symmetries may be identified as flavour symmetries of quarks and leptons. We analyse the potential in each case, and derive the conditions under which the vacuum alignments (0,0,v), (0,v,v) and (v,v,v) are minima of the potential. For the alignment (0,0,v), relevant for dark matter models, we calculate the corresponding physical Higgs boson mass spectrum. Motivated by supersymmetry, we extend the analysis to the case of three up-type Higgs doublets and three down-type Higgs doublets (six doublets in total). Many of the results are also applicable to flavon models where the three Higgs doublets are replaced by three electroweak singlets.

  20. Uterine/Endometrial Cancer: Chemotherapy

    Science.gov (United States)

    ... Types of Gynecologic Cancers Uterine/Endometrial Cancer Chemotherapy Chemotherapy Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy for endometrial cancer is usually given intravenously (injected ...

  1. Two Higgs doublet models augmented by a scalar colour octet

    Science.gov (United States)

    Cheng, Li; Valencia, German

    2016-09-01

    The LHC is now studying in detail the couplings of the Higgs boson in order to determine if there is new physics. Many recent studies have examined the available fits to Higgs couplings from the perspective of constraining two Higgs doublet models (2HDM). In this paper we extend those studies to include constraints on the one loop couplings of the Higgs to gluons and photons. These couplings are particularly sensitive to the existence of new coloured particles that are hard to detect otherwise and we use them to constrain a 2HDM augmented with a colour-octet scalar, a possibility motivated by minimal flavour violation. We first study theoretical constraints on this model and then compare them with LHC measurements.

  2. Leptonic Precision Test of Leptophilic Two-Higgs-Doublet Model

    CERN Document Server

    Chun, Eung Jin

    2016-01-01

    The type X (lepton-specific) two-Higgs-doublet model at large $\\tan\\beta$ becomes leptophilic and thus allows a light pseudoscalar $A$ accommodating the observed muon g-2 deviation without conflicting with various hadronic constraints. On the other hand, it is strongly constrained by leptonic precision observables such as lepton universality test in the neutral and charged currents. Treating all the lepton universality data in a consistent way, we show how the current data constrain the parameter space of $m_A$ and $\\tan\\beta$ for given degenerate masses of heavy Higgs bosons $H$ and $H^\\pm$. While no overlapping region is found at $1\\sigma$, a sizable region is still viable at $2\\sigma$ for $H/H^\\pm$ masses at around 200$\\sim$400 GeV.

  3. Abelian symmetries in multi-Higgs-doublet models

    CERN Document Server

    Ivanov, Igor P; Vdovin, Evgeny

    2011-01-01

    N-Higgs-doublet models (NHDM) are a popular framework to construct electroweak symmetry breaking mechanisms beyond the Standard model. Usually, one builds an NHDM scalar sector which is invariant under a certain symmetry group. Although several such groups have been used, no general analysis of symmetries possible in the NHDM scalar sector exists. Here, we describe a strategy that identifies all abelian groups which are realizable as symmetry groups of the NHDM Higgs potential. We consider both the groups of Higgs-family transformations only and the groups which also contain generalized CP transformations. We illustrate this strategy with the examples of 3HDM and 4HDM and prove several statements for arbitrary N.

  4. Controlled flavour changing neutral couplings in two Higgs Doublet models

    Science.gov (United States)

    Alves, Joao M.; Botella, Francisco J.; Branco, Gustavo C.; Cornet-Gomez, Fernando; Nebot, Miguel

    2017-09-01

    We propose a class of two Higgs doublet models where there are flavour changing neutral currents (FCNC) at tree level, but under control due to the introduction of a discrete symmetry in the full Lagrangian. It is shown that in this class of models, one can have simultaneously FCNC in the up and down sectors, in contrast to the situation encountered in the renormalisable and minimal flavour violating 2HDM models put forward by Branco et al. (Phys Lett B 380:119, 1996). The intensity of FCNC is analysed and it is shown that in this class of models one can respect all the strong constraints from experiment without unnatural fine-tuning. It is pointed out that the additional sources of flavour and CP violation are such that they can enhance significantly the generation of the Bbaryon asymmetry of the Universe, with respect to the standard model.

  5. Top-bottom doublet in the sphaleron background

    CERN Document Server

    Moreno, J M; Quirós, Mariano

    1995-01-01

    We consider the top-bottom doublet in the background of the sphaleron for the realistic case of large non-degeneracy of fermion masses, in particular m_b=5 GeV and m_t=175 GeV. We propose an axially symmetric (r,\\theta)-dependent ansatz for fermion fields and investigate the effects of the non-degeneracy on them. The exact solution is described, with an error less than 0.01\\%, by a set of ten radial functions. We also propose an approximate solution, in the m_b/m_t\\rightarrow 0 limit, with an error {\\cal O}(m_b/m_t). We have found that the effects of non-degeneracy provide a \\theta-dependence typically \\sim 10\\%.

  6. Emulsion sheet doublets as interface trackers for the OPERA experiment

    CERN Document Server

    Anokhina, A.; Ariga, A.; Arrabito, L.; Autiero, D.; Badertscher, A.; Bay, F.; Greggio, F.Bersani; Bertolin, A.; Besnier, M.; Bick, D.; Bozza, C.; Brugiere, T.; Brugnera, R.; Brunetti, G.; Buontempo, S.; Carrara, E.; Cazes, A.; Chaussard, L.; Chernyavsky, M.; Chiarella, V.; Chon-Sen, N.; Chukanov, A.; Consiglio, L.; Cozzi, M.; Cuha, V.; Dal Corso, F.; D'Amato, G.; D'Ambrosio, N.; De Lellis, G.; Declais, Y.; De Serio, M.; Di Capua, F.; Di Ferdinando, D.; Di Giovanni, A.; Di Marco, N.; Di Troia, C.; Dmitrievski, S.; Dominjon, A.; Dracos, Marcos; Duchesneau, D.; Dusini, S.; Ebert, J.; Egorov, O.; Enikeev, R.; Ereditato, Antonio; Esposito, L.S.; Favier, J.; Felici, G.; Ferber, T.; Fini, R.; Frekers, D.; Fukuda, T.; Galkin, V.I.; Galkin, V.A.; Garfagnini, A.; Giacomelli, G.; Giorgini, M.; Goellnitz, C.; Goldberg, J.; Golubkov, D.; Gornushkin, Y.; Grella, G.; Grianti, F.; Guler, M.; Gusev, G.; Gustavino, C.; Hagner, Caren; Hara, T.; Hierholzer, M.; Hiramatsu, S.; Hoshino, Kaoru; Ieva, M.; Jakovcic, K.; Janicsko Csathy, J.; Janutta, B.; Jollet, C.; Juget, F.; Kawai, T.; Kazuyama, M.; Kim, S.H.; Knuesel, J.; Kodama, K.; Komatsu, M.; Kose, U.; Kreslo, I.; Laktineh, I.; Lazzaro, C.; Lenkeit, J.; Ljubicic, A.; Longhin, Andrea; Lutter, G.; Manai, K.; Mandrioli, G.; Marotta, A.; Marteau, J.; Matsuo, T.; Matsuoka, H.; Mauri, N.; Meisel, F.; Meregaglia, A.; Messina, M.; Migliozzi, P.; Mikado, S.; Miyamoto, S.; Monacelli, Piero; Morishima, Kunihiro; Moser, U.; Muciaccia, Maria Teresa; Naganawa, N.; Naka, T.; Nakamura, M.; Nakamura, T.; Nakano, T.; Nikitina, V.; Niwa, K.; Nonoyama, Y.; Ogawa, S.; Osedlo, V.; Ossetski, D.; Paoloni, A.; Park, B.D.; Park, I.G.; Pastore, A.; Patrizii, L.; Pennacchio, E.; Pessard, H.; Pilipenko, V.; Pistillo, C.; Polukhina, N.; Pozzato, M.; Pretzl, Klaus P.; Publichenko, P.; Pupilli, F.; Roganova, T.; Rosa, G.; Rostovtseva, I.; Rubbia, A.; Russo, A.; Ryazhskaya, O.; Ryzhikov, D.; Sato, O.; Sato, Y.; Saveliev, V.; Sazhina, G.; Schembri, A.; Scotto Lavina, L.; Shibuya, H.; Simone, S.; Sioli, Max; Sirignano, C.; Sirri, G.; Song, J.S.; Spinetti, M.; Stanco, L.; Starkov, N.; Stipcevic, M.; Strauss, T.; Strolin, Paolo Emilio; Sugonyaev, V.; Taira, Y.; Takahashi, S.; Tenti, M.; Terranova, F.; Tezuka, I.; Tioukov, V.; Tolun, P.; Tsarev, V.; Tufanli, S.; Ushida, N.; Vilain, P.; Vladimirov, M.; Votano, L.; Vuilleumier, J.L.; Wilquet, G.; Wonsak, B.; Wurtz, J.; Yoon, C.S.; Yoshida, J.; Zaitsev, Y.; Zemskova, S.; Zghiche, Amina; Zimmermann, R.

    2008-01-01

    New methods for efficient and unambiguous interconnection between electronic counters and target units based on nuclear photographic emulsion films have been developed. The application to the OPERA experiment, that aims at detecting oscillations between mu neutrino and tau neutrino in the CNGS neutrino beam, is reported in this paper. In order to reduce background due to latent tracks collected before installation in the detector, on-site large-scale treatments of the emulsions ("refreshing") have been applied. Changeable Sheet (CSd) packages, each made of a doublet of emulsion films, have been designed, assembled and coupled to the OPERA target units ("ECC bricks"). A device has been built to print X-ray spots for accurate interconnection both within the CSd and between the CSd and the related ECC brick. Sample emulsion films have been extensively scanned with state-of-the-art automated optical microscopes. Efficient track-matching and powerful background rejection have been achieved in tests with electronic...

  7. Two Higgs doublet models augmented by a scalar color octet

    CERN Document Server

    Cheng, Li

    2016-01-01

    The LHC is now studying in detail the couplings of the Higgs boson in order to determine if there is new physics. Many recent studies have examined the available fits to Higgs couplings from the perspective of constraining two Higgs doublet models (2HDM). In this paper we extend those studies to include constraints on the one loop couplings of the Higgs to gluons and photons. These couplings are particularly sensitive to the existence of new colored particles that are hard to detect otherwise and we use them to constrain a 2HDM augmented with a color-octet scalar, a possibility motivated by minimal flavor violation. We first study theoretical constraints on this model and then compare them with LHC measurements.

  8. Parity-doublet representation of Majorana fermions and neutron oscillation

    CERN Document Server

    Fujikawa, Kazuo

    2016-01-01

    We present a parity-doublet theorem for the representation of the intrinsic parity of Majorana fermions, which is expected to be useful also in condensed matter physics, and it is illustrated to provide a criterion of neutron-antineutron oscillation in a BCS-like effective theory with $\\Delta B=2$ baryon number violating terms. The CP violation in the present effective theory causes no direct CP violating effects in the oscillation itself, which is demonstrated by the exact solution, although it influences the neutron electric dipole moment in the leading order of small $\\Delta B=2$ parameters. An analogue of Bogoliubov transformation, which preserves P and CP, is crucial in the analysis.

  9. Spinning Janus doublets driven in uniform AC electric fields

    CERN Document Server

    Boymelgreen, Alicia; Park, Sinwook; Miloh, Touvia

    2013-01-01

    We provide an experimental proof-of-concept for a robust, continuously rotating microstructure - consisting of two metallodielectric (gold-polystyrene)Janus particles rigidly attached to each other - which is driven in uniform ac fields by asymmetric induced-charge electroosmosis. The pairs (doublets) are stabilized on the substrate surface which is parallel to the plane of view and normal to the direction of the applied electric field. We find that the radius of orbit and angular velocity of the pair are predominantly dependent on the relative orientations of the interfaces between the metallic and dielectric hemispheres and that the electrohydrodynamic particle-particle interactions are small. Additionally, we verify that both the angular and linear velocities of the pair are proportional to the square of the applied field which is consistent with the theory for non-linear electrokinetics. A simple kinematic rigid body model is used to predict the paths and double velocities (angular and linear) based on th...

  10. A two-Higgs-doublet model facing experimental hints

    Directory of Open Access Journals (Sweden)

    Crivellin Andreas

    2016-01-01

    Full Text Available Physics beyond the Standard Model has so far eluded our experimental probes. Nevertheless, a number of interesting anomalies have accumulated that can be taken as hints towards new physics: BaBar, Belle, and LHCb have found deviations of approximately 3:8σ in B → Dτν and B → D*τν; the anomalous magnetic moment of the muon differs by about 3σ from the theoretic prediction; the branching ratio for τ → μνν is about 2σ above the Standard Model expectation; and CMS and ATLAS found hints for a non-zero decay rate of h → μτ at 2.6σ. Here we consider these processes within a lepton-specific two-Higgs doublet model with additional non-standard Yukawa couplings and show how (and which of these excesses can be accommodated.

  11. Scalar sector of two-Higgs-doublet models: A minireview

    Indian Academy of Sciences (India)

    GAUTAM BHATTACHARYYA; DIPANKAR DAS

    2016-09-01

    A vast literature on the theory and phenomenology of two-Higgs-doublet models (2HDM) exists since long. However, the present situation demands a revisit of some 2HDM properties. Now that a 125 GeV scalar resonance has been discovered at the LHC, with its couplings to other particles showing increasing affinity to the Standard Model Higgs-like behaviour, the 2HDM parameter space is more squeezed than ever. We briefly review the different parametrizations of the 2HDM potential and discuss the constraints on the parameter spacearising from the unitarity and stability of the potential together with constraints from the oblique electroweak $T$ -parameter. We also differentiate the consequences of imposing a global continuous $U(1)$ symmetry on thepotential from a discrete $Z_2$ symmetry.

  12. Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Khaleel R Fareed; Irshad N Soomro; Khalid Hameed; Arvind Arora; Dileep N Lobo; Simon L Parsons; Srinivasan Madhusudan

    2012-01-01

    AIM:To examine cytokeratin-18 (CK-18) and caspasecleaved CK-18 expression in tumouts and correlate with clinicopathological outcomes including tumour regression grade (TRG) response.METHODS:Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays.The first set consisted of 122 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 97 gastric/gastrooesophageal cancer cases exposed to pre-operative platinum-based chemotherapy.Expression of CK-18 and caspase-cleaved CK-18 was investigated using immunohistochemistry.RESULTS:CK18 was commonly expressed in gastrooesophageal tumours (92.6%).Fifty-six point seven percent of tumours previously exposed to neoadjuvant chemotherapy were positive for caspase-cleaved CK-18 expression compared to only 24.6% of tumours not previously exposed to neoadjuvant chemotherapy (P =0.009).In patients who received neoadjuvant chemotherapy,caspase-cleaved cytokeratin-18 expression correlated with favourable TRG response (TRG 1,2 or 3,P =0.043).CONCLUSION:This is the largest study to date of CK-18 and caspase-cleaved CK-18 expression in gastrooesophageal tumours.We provide the first evidence that caspase-cleaved CK-18 predicts tumour regression with neoadjuvant chemotherapy.

  13. [History of cancer and chemotherapy before chemotherapy].

    Science.gov (United States)

    Bonnichon, Philippe; Berger, J P; Bonni, N; Fontaine, M; Pion-Graff, J

    2014-01-01

    Chemotherapy stands today for cancer. In 1909, Paul Ehrlich (1854-1915) advocates the use of arsphenamine by infusion. So, he is considered as the father of chemotherapy. In fact, the first to have thought through chemotherapy was Sir Christopher Wren (1632-1723). In 1676, ideas and experiments on animals had sufficiently progressed to allow Michel Ettmuller (1644-1683) to publish the first edition of his book and several others were printed until 1753. In this book, he describes the first intravenous treatment, it sets the first indications, dosages and different products which can be used. However this method has been forgotten until the late 19th century.

  14. Altered Brain Functional Connectivity in Small-Cell Lung Cancer Patients after Chemotherapy Treatment: A Resting-State fMRI Study

    Directory of Open Access Journals (Sweden)

    Konstantinos Bromis

    2017-01-01

    Full Text Available Previous studies in small-cell lung cancer (SCLC patients have mainly focused on exploring neurocognitive deficits associated with prophylactic cranial irradiation (PCI. Little is known about functional brain alterations that might occur due to chemotherapy treatment in this population before PCI is administered. For this reason, we used resting-state functional Magnetic Resonance Imaging (fMRI to examine potential functional connectivity disruptions in brain networks, including the Default Mode Network (DMN, the Sensorimotor Network, and the Task-Positive Network (TPN. Nineteen SCLC patients after platinum-based chemotherapy treatment and thirteen controls were recruited in the current study. ROI-to-ROI and Seed-to-Voxel analyses were carried out and revealed functional connectivity deficits in patients within all the networks investigated demonstrating the possible negative effect of chemotherapy in cognitive functions in SCLC populations.

  15. Concomitant Radiotherapy and Chemotherapy for High-Risk Nonmelanoma Skin Carcinomas of the Head and Neck

    Directory of Open Access Journals (Sweden)

    Smith Apisarnthanarax

    2011-01-01

    Full Text Available Background. To report on the use and feasibility of a multimodality approach using concomitant radiotherapy and chemotherapy in patients with high-risk nonmelanoma skin carcinoma (NMSC of the head and neck. Methods. Records of patients with NMSC of the head and neck who received concomitant CRT at the University of North Carolina between 2001 and 2007 were reviewed. Results. Fifteen identified patients had at least one of the following high-risk factors: T4 disease (93%, unresectability (60%, regional nodal involvement (40%, and/or recurrence (47%. Ten patients were treated in the definitive setting and five in the postoperative setting. Platinum based chemotherapy was given in 14 (93% patients. Ten of fifteen (67% patients completed all planned chemotherapy treatments, and thirteen patients (87% completed at least 80% of planned chemotherapy. Mild radiation dermatitis occurred in all patients and reached grade 3 in 13% of patients. No patients experienced grade 4 or 5 toxicity. With a median followup of 31 months in surviving patients, the 2-year actuarial locoregional control and relapse-free survival were 79% and 49%, respectively. Conclusions. Definitive or postoperative chemoradiotherapy for patients with locally advanced or regionally metastasized NMSC of the head and neck appears feasible with acceptable toxicities and favorable locoregional control.

  16. Third-Line Chemotherapy for Metastatic Urothelial Cancer: A Retrospective Observational Study.

    Science.gov (United States)

    Di Lorenzo, Giuseppe; Buonerba, Carlo; Bellelli, Teresa; Romano, Concetta; Montanaro, Vittorino; Ferro, Matteo; Benincasa, Alfonso; Ribera, Dario; Lucarelli, Giuseppe; De Cobelli, Ottavio; Sonpavde, Guru; De Placido, Sabino

    2015-12-01

    The prognosis of locally advanced (T3/T4 or N1) and metastatic disease urothelial carcinoma is poor. In this retrospective study, we reviewed data about patients receiving third-line chemotherapy for metastatic disease, in view of the lack of data in this setting.We retrospectively analyzed medical records of patients with a pathologic diagnosis of urothelial carcinoma treated with systemic chemotherapy for metastatic disease at 4 participating Institutions between January, 2010, and January, 2015. Cox proportional hazards regression was used to evaluate the association of the chemotherapy agent used versus others with overall survival, adjusted for 5 externally validated prognostic factors in advanced urothelial carcinoma.Of 182 patients that received first-line chemotherapy/adjuvant chemotherapy as defined above, 116 patients (63.73%) received second-line salvage treatment. Fifty-two patients were finally included in this analysis, whereas 9 were excluded due to missing data. Third-line chemotherapy was based on cyclophosphamide, platinum, vinflunine, taxanes, and gemcitabine in 16, 12, 11, 10, and 3 patients, respectively. Median PFS (progression-free survival) and OS (overall survival) of the population were 13 (10-17) and 31 (28-36) weeks. Single-agent cyclophosphamide was associated with a PFS of 18 (13-22) and an OS of 38 (33-41) weeks, whereas platinum-based combinations were associated with a PFS of 5 weeks and an OS of 8 weeks. Multivariate analysis showed improved survival in patients treated with cyclophosphamide (hazard ratio (HR) = 0.42; 95% CI: 0.20-0.89; P = 0.025) and a worse survival in those treated with platinum-based regimens (HR: 4.37; 95% CI = 1.95-9.77; P < 0.01).We observed a significantly longer overall survival in patients receiving single-agent cyclophosphamide, with few grade 3 to 4 toxicities. Further studies should assess the efficacy of metronomic single-agent cyclophosphamide in advanced lines of treatment, as it may

  17. Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer

    Directory of Open Access Journals (Sweden)

    Uribe Jesus

    2005-09-01

    Full Text Available Abstract Background Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection. Methods Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method. Results Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration. Conclusion Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed.

  18. Improved final doublet designs for the ILC baseline small crossing angle scheme

    CERN Document Server

    Appleby, R

    2006-01-01

    The ILC baseline consists of two interaction regions, one with a 20mrad crossing angle and the other with a 2mrad crossing angle. It is known that the outgoing beam losses in the final doublet and subsequent extraction line are larger in the 2mrad than in the 20mrad layout. In this work, we exploit NbTi and Nb$_3$Sn superconducting magnet technologies to redesign and optimise the final doublet, with the aim of providing satisfactory outgoing disrupted beam power losses in this region. We present three new final doublet layouts, specifically optimised for the 500 GeV and the 1 TeV machines.

  19. Ramucirumab plus docetaxel versus placebo plus docetaxel in patients with locally advanced or metastatic urothelial carcinoma after platinum-based therapy (RANGE): a randomised, double-blind, phase 3 trial.

    Science.gov (United States)

    Petrylak, Daniel P; de Wit, Ronald; Chi, Kim N; Drakaki, Alexandra; Sternberg, Cora N; Nishiyama, Hiroyuki; Castellano, Daniel; Hussain, Syed; Fléchon, Aude; Bamias, Aristotelis; Yu, Evan Y; van der Heijden, Michiel S; Matsubara, Nobuaki; Alekseev, Boris; Necchi, Andrea; Géczi, Lajos; Ou, Yen-Chuan; Coskun, Hasan Senol; Su, Wen-Pin; Hegemann, Miriam; Percent, Ivor J; Lee, Jae-Lyun; Tucci, Marcello; Semenov, Andrey; Laestadius, Fredrik; Peer, Avivit; Tortora, Giampaolo; Safina, Sufia; Del Muro, Xavier Garcia; Rodriguez-Vida, Alejo; Cicin, Irfan; Harputluoglu, Hakan; Widau, Ryan C; Liepa, Astra M; Walgren, Richard A; Hamid, Oday; Zimmermann, Annamaria H; Bell-McGuinn, Katherine M; Powles, Thomas

    2017-09-12

    Few treatments with a distinct mechanism of action are available for patients with platinum-refractory advanced or metastatic urothelial carcinoma. We assessed the efficacy and safety of treatment with docetaxel plus either ramucirumab-a human IgG1 VEGFR-2 antagonist-or placebo in this patient population. We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 sites in 23 countries. Previous treatment with one immune-checkpoint inhibitor was permitted. Patients were randomised (1:1) using an interactive web response system to receive intravenous docetaxel 75 mg/m(2) plus either intravenous ramucirumab 10 mg/kg or matching placebo on day 1 of repeating 21-day cycles, until disease progression or other discontinuation criteria were met. The primary endpoint was investigator-assessed progression-free survival, analysed by intention-to-treat in the first 437 randomised patients. This study is registered with ClinicalTrials.gov, number NCT02426125. Between July, 2015, and April, 2017, 530 patients were randomly allocated either ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267). Progression-free survival was prolonged significantly in patients allocated ramucirumab plus docetaxel versus placebo plus docetaxel (median 4·07 months [95% CI 2·96-4·47] vs 2·76 months [2·60-2·96]; hazard ratio [HR] 0·757, 95% CI 0·607-0·943; p=0·0118). A blinded independent central analysis was consistent with these results. An objective response was achieved by 53 (24·5%, 95% CI 18·8-30·3) of 216 patients allocated ramucirumab and 31 (14·0%, 9·4-18·6) of 221 assigned placebo. The most frequently reported treatment-emergent adverse events, regardless of causality, in either treatment group (any grade) were fatigue, alopecia, diarrhoea, decreased appetite, and nausea. These events occurred predominantly at grade 1

  20. On the scalar potential of two-Higgs doublet models

    CERN Document Server

    Chakraborty, Indrani

    2015-01-01

    We perform a detailed analysis of the Two-Higgs Doublet Model (2HDM) potential. At the tree-level, the potential may accommodate more than one minima, one of them being the electroweak (EW) minimum where the universe lives. The parameter space allowed after the data from the Large Hadron Collider (LHC) came in almost excludes those cases where the EW vacuum is shallower than the second minimum. We extend the analysis by including terms in the 2HDM potential that break the $Z_2$ symmetry of the potential by dimension-4 operators and show that the conclusions remain unchanged. Furthermore, a one-loop analysis of the potential is performed for both cases, namely, where the $Z_2$ symmetry of the potential is broken by dimension-2 or dimension-4 operators. For quantitative analysis, we show our results for the Type-II 2HDM, qualitative results remaining the same for other 2HDMs. We find that the nature of the vacua from the tree-level analysis does not change; the EW vacuum still remains deeper.

  1. Higgcision in the Two-Higgs Doublet Models

    CERN Document Server

    Cheung, Kingman; Tseng, Po-Yan

    2013-01-01

    We perform global fits to general two-Higgs doublet models (2HDMs) with generalized couplings using the most updated data from ATLAS, CMS, and Tevatron. We include both scenarios with CP-conserving and CP-violating couplings. By relaxing the requirement on the discrete symmetries that are often imposed on the Yukawa couplings, we try to see which of the 2HDMs is preferred. We found that (i) Higgcision in 2HDMs can be performed efficiently by using only 4 parameters including the charged Higgs contributions to the Higgs couplings to two photons, (ii) the differences among various types of 2HDMs are very small with respect to the chi-square fits, (iii) $\\tan\\beta$ is constrained to be small, (iv) the $p$-values for various fits in 2HDMs are worse than that of the standard model. Finally, we put emphasis on our findings that future precision measurements of the Higgs coupling to the scalar top-quark bilinear ($C_u^S$) and $\\tan\\beta$ may endow us with the discriminating power among various types of 2HDMs especia...

  2. Invariants and flavour in the general Two Higgs Doublet Model

    Energy Technology Data Exchange (ETDEWEB)

    Botella, F.J., E-mail: fbotella@uv.es [Departament de Física Teòrica and IFIC, Universitat de València-CSIC, E-46100, Burjassot (Spain); Branco, G.C., E-mail: gustavo.branco@cern.ch [Departamento de Física and Centro de Física Teórica de Partículas (CFTP), Instituto Superior Técnico, Av. Rovisco Pais, P-1049-001 Lisboa (Portugal); Rebelo, M.N., E-mail: margarida.rebelo@cern.ch [Universidade Técnica de Lisboa, Centro de Física Teórica de Partículas (CFTP), Instituto Superior Técnico, Av. Rovisco Pais, P-1049-001 Lisboa (Portugal)

    2013-05-13

    The flavour structure of the general Two Higgs Doublet Model (2HDM) is analysed and a detailed study of the parameter space is presented, showing that flavour mixing in the 2HDM can be parametrized by various unitary matrices which arise from the misalignment in flavour space between pairs of various Hermitian flavour matrices which can be constructed within the model. This is entirely analogous to the generation of the CKM matrix in the Standard Model (SM). We construct weak basis invariants which can give insight into the physical implications of any flavour model, written in an arbitrary weak basis (WB) in the context of 2HDM. We apply this technique to two special cases, models with MFV and models with NNI structures. In both cases non-trivial CP-odd WB invariants arise in a mass power order much smaller than what one encounters in the SM, which can have important implications for baryogenesis in the framework of the general 2HDM.

  3. Exploring collider signatures of the inert Higgs doublet model

    Science.gov (United States)

    Datta, Amitava; Ganguly, Nabanita; Khan, Najimuddin; Rakshit, Subhendu

    2017-01-01

    We revisit the multilepton (m l )+ ET+X signatures of the inert doublet model (IDM) of dark matter in future LHC experiments for m =3 , 4 and simulate, for the first time, the m =5 case. Here X stands for any number of jets. We illustrate these signals with benchmark points consistent with the usual constraints like unitarity, perturbativity, the precision electroweak data, the observed dark matter relic density of the Universe and, most importantly, the stringent LHC constraints from the post-Higgs (h ) discovery era like the measured Mh and the upper bound on the invisible width of h decay, which were not included in earlier analyses of multilepton signatures. We find that if the IDM is embedded in a grand desert scenario so that the unitarity constraint holds up to a very high scale, the whole of the highly restricted parameter space allowed by the above constraints can be probed at the LHC via the 3 l signal for an integrated luminosity ˜3000 fb-1 . On the other hand, if any new physics shows up at a scale ˜10 TeV , only a part of the enlarged allowed parameter space can be probed. The 4 l and 5 l signals can help to discriminate among different IDM scenarios as and when sufficient integrated luminosity accumulates.

  4. Higgs doublet decay as the origin of the baryon asymmetry

    CERN Document Server

    Hambye, Thomas

    2016-01-01

    We consider a question which curiously had not been properly considered so far: in the standard seesaw model what is the minimum value the mass of a right-handed (RH) neutrino must have for allowing successful leptogenesis via CP-violating decays? To answer this question requires to take into account a number of thermal effects. We show that, for low RH neutrino masses and thanks to these effects, leptogenesis turns out to proceed efficiently from the decay of the Standard Model (SM) scalar doublet components into a RH neutrino and a lepton. Such decays produce the asymmetry at low temperatures, slightly before sphaleron decoupling. If the RH neutrino has thermalized prior from producing the asymmetry, this mechanism turns out to lead to the bound $m_N>2$ GeV. If, instead, the RH neutrinos have not thermalized, leptogenesis from these decays is enhanced further and can be easily successful, even at lower scales. This Higgs-decay leptogenesis new mechanism works without requiring an interplay of flavor effects...

  5. Dark matter physics in neutrino specific two Higgs doublet model

    CERN Document Server

    Baek, Seungwon

    2016-01-01

    Although the seesaw mechanism is a natural explanation for the small neutrino masses, there are cases when the Majorana mass terms for the right-handed neutrinos are not allowed due to symmetry. In that case, if neutrino-specific Higgs doublet is introduced, neutrinos become Dirac particles and their small masses can be explained by its small VEV. We show that the same symmetry, which we assume a global $U(1)_X$, can also be used to explain the stability of dark matter. In our model, a new singlet scalar breaks the global symmetry spontaneously down to a discrete $Z_2$ symmetry. The dark matter particle, lightest $Z_2$-odd fermion, is stabilized. We discuss the phenomenology of dark matter: relic density, direct detection, and indirect detection. We find that the relic density can be explained by a novel Goldstone boson channel or by resonance channel. In the most region of parameter space considered, the direct detections is suppressed well below the current experimental bound. Our model can be further teste...

  6. Diverse rupture processes in the 2015 Peru deep earthquake doublet.

    Science.gov (United States)

    Ye, Lingling; Lay, Thorne; Kanamori, Hiroo; Zhan, Zhongwen; Duputel, Zacharie

    2016-06-01

    Earthquakes in deeply subducted oceanic lithosphere can involve either brittle or dissipative ruptures. On 24 November 2015, two deep (606 and 622 km) magnitude 7.5 and 7.6 earthquakes occurred 316 s and 55 km apart. The first event (E1) was a brittle rupture with a sequence of comparable-size subevents extending unilaterally ~50 km southward with a rupture speed of ~4.5 km/s. This earthquake triggered several aftershocks to the north along with the other major event (E2), which had 40% larger seismic moment and the same duration (~20 s), but much smaller rupture area and lower rupture speed than E1, indicating a more dissipative rupture. A minor energy release ~12 s after E1 near the E2 hypocenter, possibly initiated by the S wave from E1, and a clear aftershock ~165 s after E1 also near the E2 hypocenter, suggest that E2 was likely dynamically triggered. Differences in deep earthquake rupture behavior are commonly attributed to variations in thermal state between subduction zones. However, the marked difference in rupture behavior of the nearby Peru doublet events suggests that local variations of stress state and material properties significantly contribute to diverse behavior of deep earthquakes.

  7. Neutron Electric Dipole Moment in Two Higgs Doublet Model

    CERN Document Server

    Hayashi, T; Matsuda, M; Tanimoto, M; Hayashi, Tkemi; Koide, Yoshio; Matsuda, Masahisa; Tanimoto, Morimitsu

    1994-01-01

    We study the effect of the "chromo-electric" dipole moment on the electric dipole moment(EDM) of the neutron in the two Higgs doublet model. We systematically investigate the Weinberg's operator $O_{3g}=GG\\t G$ and the operator $O_{qg}=\\bar q\\sigma\\t Gq$, in the cases of $\\tan\\b\\gg 1$, $\\tan\\b\\ll 1$ and $\\tan\\b\\simeq 1$. It is shown that $O_{sg}$ gives the main contribution to the neutron EDM compared to the other operators, and also that the contributions of $O_{ug}$ and $O_{3g}$ cancel out each other. It is pointed out that the inclusion of second lightest neutral Higgs scalar adding to the lightest one is of essential importance to estimate the neutron EDM. The neutron EDM is considerably reduced due to the destructive contribution with each other if the mass difference of the two Higgs scalars is of the order $O(50\\G)$.

  8. Exploring collider signatures of the inert Higgs doublet model

    CERN Document Server

    Datta, Amitava; Khan, Najimuddin; Rakshit, Subhendu

    2016-01-01

    We revisit the multilepton ($ml$) + ${E\\!\\!\\!\\!/_T}$ signatures of the Inert Doublet Model of dark matter in future LHC experiments for m = 3,4 and simulate, for the first time, the m = 5 case. In addition to the usual constraints like unitarity, perturbativity, the precision electroweak data, the observed dark matter relic density of the universe, we take into account the stringent constraints from the post Higgs ($h$) discovery era like the measured $m_h$ and the upper bound on the width of $h$ decay which were not included in the earlier analyses. We find that the IDM model embedded in a grand dessert scenario so that the unitarity constraint holds up to a very high scale, the entire parameter space allowed by the above constraints can be probed by the LHC via the $3l$ for an integrated luminosity $\\sim 3000$ fb$^{-1}$. On the other hand if any new physics shows up at a scale $\\sim$ 10 TeV only a part of the enlarged allowed parameter space can be probed. The $4l$ and $5l$ signals can help to discriminate ...

  9. Muon $g-2$ in the Aligned Two Higgs Doublet Model

    CERN Document Server

    Han, Tao; Sayre, Joshua

    2015-01-01

    We study the Two-Higgs-Doublet Model with the aligned Yukawa sector (A2HDM) in light of the observed excess measured in the muon anomalous magnetic moment. We take into account the existing theoretical and experimental constraints with up-to-date values and demonstrate that a phenomenologically interesting region of parameter space exists. With a detailed parameter scan, we show a much larger region of viable parameter space in this model beyond the limiting case Type X 2HDM as obtained before. It features the existence of light scalar states with masses $3$ GeV $\\lesssim m_H^{} \\lesssim 50$ GeV, or $\\ 10$ GeV $\\lesssim m_A^{} \\lesssim 130$ GeV, with enhanced couplings to tau leptons. The charged Higgs boson is typically heavier, with $200$ GeV $ \\lesssim m^{}_{H^+} \\lesssim 630$ GeV. The surviving parameter space is forced into the CP-conserving limit by EDM constraints. Some Standard Model observables may be significantly modified, including a possible new decay mode of the SM-like Higgs boson to four taus....

  10. Microtubule doublets are double-track railways for intraflagellar transport trains.

    Science.gov (United States)

    Stepanek, Ludek; Pigino, Gaia

    2016-05-06

    The cilium is a large macromolecular machine that is vital for motility, signaling, and sensing in most eukaryotic cells. Its conserved core structure, the axoneme, contains nine microtubule doublets, each comprising a full A-microtubule and an incomplete B-microtubule. However, thus far, the function of this doublet geometry has not been understood. We developed a time-resolved correlative fluorescence and three-dimensional electron microscopy approach to investigate the dynamics of intraflagellar transport (IFT) trains, which carry ciliary building blocks along microtubules during the assembly and disassembly of the cilium. Using this method, we showed that each microtubule doublet is used as a bidirectional double-track railway: Anterograde IFT trains move along B-microtubules, and retrograde trains move along A-microtubules. Thus, the microtubule doublet geometry provides direction-specific rails to coordinate bidirectional transport of ciliary components.

  11. Derivative interactions and perturbative UV contributions in N Higgs doublet models

    Energy Technology Data Exchange (ETDEWEB)

    Kikuta, Yohei [KEK Theory Center, KEK, Tsukuba (Japan); The Graduate University for Advanced Studies, Department of Particle and Nuclear Physics, Tsukuba (Japan); Yamamoto, Yasuhiro [Universidad de Granada, Deportamento de Fisica Teorica y del Cosmos, Facultad de Ciencias and CAFPE, Granada (Spain)

    2016-05-15

    We study the Higgs derivative interactions on models including arbitrary number of the Higgs doublets. These interactions are generated by two ways. One is higher order corrections of composite Higgs models, and the other is integration of heavy scalars and vectors. In the latter case, three point couplings between the Higgs doublets and these heavy states are the sources of the derivative interactions. Their representations are constrained to couple with the doublets. We explicitly calculate all derivative interactions generated by integrating out. Their degrees of freedom and conditions to impose the custodial symmetry are discussed. We also study the vector boson scattering processes with a couple of two Higgs doublet models to see experimental signals of the derivative interactions. They are differently affected by each heavy field. (orig.)

  12. Product lambda-doublet ratios for the O(3P) + D2 reaction: A mechanistic imprint

    CERN Document Server

    Jambrina, P G; Aldegunde, J; Brouard, M; Aoiz, F J

    2016-01-01

    In the last decade, the development of theoretical methods have allowed chemists to reproduce and explain almost all of the experimental data associated with elementary atom plus diatom collisions. However, there are still a few examples where theory cannot account yet for experimental results. This is the case for the preferential population of one of the $\\Lambda$-doublet states produced by chemical reactions. In particular, recent measurements of the OD($^2\\Pi$) product of the O($^3$P) + D$_2$ reaction have shown a clear preference for the $\\Pi(A')$ $\\Lambda$-doublet states, in apparent contradiction with {\\em ab initio} calculations, which predict a larger reactivity on the $A"$ potential energy surface. Here we present a method to calculate the $\\Lambda$-doublet ratio when concurrent potential energy surfaces participate in the reaction. It accounts for the experimental $\\Lambda$-doublet populations via explicit consideration of the stereodynamics of the process. Furthermore, our results demonstrate that...

  13. Radiative neutrino masses in the singlet-doublet fermion dark matter model with scalar singlets

    CERN Document Server

    Restrepo, Diego; Sánchez-Peláez, Marta; Zapata, Oscar; Tangarife, Walter

    2015-01-01

    When the singlet-doublet fermion dark matter model is extended with additional $Z_2$--odd real singlet scalars, neutrino masses and mixings can be generated at one-loop level. In this work, we discuss the salient features arising from the combination of the two resulting simplified dark matter models. When the $Z_2$-lightest odd particle is a scalar singlet, $\\operatorname{Br}(\\mu\\to e \\gamma)$ could be measurable provided that the singlet-doublet fermion mixing is small enough. In this scenario, also the new decay channels of vector-like fermions into scalars can generate interesting leptonic plus missing transverse energy signals at the LHC. On the other hand, in the case of doublet-like fermion dark matter, scalar coannihilations lead to an increase in the relic density which allow to lower the bound of doublet-like fermion dark matter.

  14. The Lee-Wick Extension of the Two-Higgs Doublet Model

    CERN Document Server

    Johansen, Aria R; Thrasher, Keith

    2015-01-01

    The Lee-Wick Standard Model is a highly constrained model which solves the gauge hierarchy problem at the expense of including fields with negative norm. It appears to be macroscopically causal and consistent. This model is extended by considering the two-Higgs doublet extension of the Lee-Wick model. Rewriting the Lagrangian using auxiliary fields introduces two additional doublets of Lee-Wick partners. The model is highly constrained, with only one or two additional parameters beyond that of the usual two-Higgs doublet model, and yet there are four doublets. Mass relations are established by diagonalizing the mass matrices and further constraints are established by studying results from B --> tau nu, neutral B-meson mixing, and B --> X_s gamma. The prospects of detecting evidence for this model at the LHC are discussed.

  15. Localized temporal variation of Earth's inner-core boundary from high-quality waveform doublets

    Science.gov (United States)

    Xin, Danhua

    2016-04-01

    The accurate determination of the topography of an Earth's internal boundary is difficult because of the possible trade-off with the velocity of the media above it. Here we use waveform-doublet method to map the ICB topography. A waveform doublet is a pair of earthquakes occurring at essentially the same spatial position and received by the same station with high similarity in their waveforms (Poupinet et al. 1984), which make the exact detection of the ICB topography possible. In this study, we used this method to detect temporal change of the ICB using doublets from the Western Pacific (WP) area to increase global coverage of the ICB. Compared with previous study using doublets from South Sandwich Islands (SSI) (Song and Dai, 2008), the new samples showed negligible temporal change of the ICB.

  16. On the connectivity anisotropy in fluvial Hot Sedimentary Aquifers and its influence on geothermal doublet performance

    DEFF Research Database (Denmark)

    Willems, Cees J.L.; Nick, Hamid; Donselaar, Marinus E.

    2017-01-01

    This study finds that the geothermal doublet layout with respect to the paleo flow direction in fluvial sedimentary reservoirs could significantly affect pump energy losses. These losses can be reduced by up to 10% if a doublet well pair is oriented parallel to the paleo flow trend compared...... Cretaceous Nieuwerkerk Formation in the West Netherlands Basin. Finally, this study emphasizes the importance of detailed facies architecture modelling for the assessment of both risks and production strategies in Hot Sedimentary Aquifers....

  17. Flavour constraints on the Aligned Two-Higgs-Doublet Model and CP violation

    CERN Document Server

    Tuzón, Paula

    2010-01-01

    The Aligned Two-Higgs-Doublet Model (A2HDM) describes a particular way of enlarging the scalar sector of the Standard Model, with a second Higgs doublet which is aligned to first the one in flavour space. This implies the absence of flavour-changing neutral currents at tree level and the presence of three complex parameters. Within this general approach, we analyze the charged Higgs phenomenology, including CP asymmetries in the K and B systems.

  18. Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Dimitra T Stefanou

    Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780 and one resistant (A2780/C30 to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs from OC patients, sensitive (n = 7 or resistant (n = 4 to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9 were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05. Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03. Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05. We conclude

  19. Passive athermalization of doublets in 8-13 micron waveband

    Science.gov (United States)

    Schuster, Norbert

    2014-10-01

    Passive athermalization of lenses has become a key-technology for automotive and other outdoor applications using modern uncooled 25, 17 and 12 micron pixel pitch bolometer arrays. Typical pixel counts for thermal imaging are 384x288 (qVGA), 640x480 (VGA), and 1024x768 (XGA). Two lens arrangements (called Doublets) represent a cost effective way to satisfy resolution requirements of these detectors with F-numbers 1.4 or faster. Thermal drift of index of refraction and the geometrical changes (in lenses and housing) versus temperature defocus the initial image plane from the detector plane. The passive athermalization restricts this drop of spatial resolution in a wide temperature range (typically -40°C…+80°C) to an acceptable value without any additional external refocus. In particular, lenses with long focal lengths and high apertures claim athermalization. A careful choice of lens and housing materials and a sophistical dimensioning lead to three different principles of passivation: The Passive Mechanical Athermalization (PMA) shifts the complete lens cell, the Passive Optical and Mechanical Athermalization (POMA) shifts only one lens inside the housing, the Passive Optical Athermalization (POA) works without any mechanism. All three principles will be demonstrated for a typical narrow-field lens (HFOV about 12°) with high aperture (aperture based F-number 1.3) for the actual uncooled reference detector (17micron VGA). Six design examples using different combinations of lens materials show the impact on spatial lens resolution, on overall length, and on weight. First order relations are discussed. They give some hints for optimization solutions. Pros and cons of different passive athermalization principles are evaluated in regards of housing design, availability of materials and costing. Examples with a convergent GASIR®1-lens in front distinguish by best resolution, short overall length, and lowest weight.

  20. Competing Kondo Effects in Non-Kramers Doublet Systems

    Science.gov (United States)

    Kusunose, Hiroaki

    2016-06-01

    In non-Kramers Kondo systems with quadrupolar degrees of freedom, an ordinary magnetic Kondo effect can compete with the quadrupolar Kondo effect. We discuss such competition keeping PrT2Zn20 (T = Ir, Rh) and PrT2Al20 (T = V, Ti) in mind, where the Γ3 non-Kramers crystalline-electric-field (CEF) doublet ground state is realized in a Pr3+ ion with a (4f)2 configuration under cubic symmetry. The quadrupolar Kondo effect can be described by the two-channel Kondo model, which leads to the local non-Fermi-liquid (NFL) ground state, while the magnetic Kondo effect favors the ordinary local Fermi-liquid (FL) ground state. On the basis of the minimal extended two-channel Kondo model including the magnetic Kondo coupling as well, we investigate the competition and resulting thermodynamics, and orbital/magnetic and single-particle excitation spectra by Wilson's numerical renormalization group (NRG) method. There is a first-order transition between the NFL and FL ground states. In addition to these two states, the alternative FL state accompanied by a free magnetic spin appears in the intermediate temperature range, which eventually reaches the true NFL ground state, as a consequence of the stronger competition between the magnetic and quadrupolar Kondo effects. In this peculiar state, the magnetic susceptibility shows a Curie-like behavior, while the orbital fluctuation exhibits the FL behavior. Moreover, the single-particle spectra yield a more singular behavior. Implications to the Pr 1-2-20 systems are briefly discussed.

  1. Biochemical characterization of tektins from sperm flagellar doublet microtubules.

    Science.gov (United States)

    Linck, R W; Stephens, R E

    1987-04-01

    Tektins, protein components of stable protofilaments from sea urchin sperm flagellar outer doublet microtubules (Linck, R. W., and G. L. Langevin, 1982, J. Cell Sci., 58:1-22), are separable by preparative SDS PAGE into 47-, 51-, and 55-kD equimolar components. High resolution two-dimensional tryptic peptide mapping reveals 63-67% coincidence among peptides of the 51-kD tektin chain and its 47- and 55-kD counterparts, greater than 70% coincidence between the 47- and 55-kD tektins, but little obvious similarity to either alpha- or beta-tubulin. With reverse-phase HPLC on a C18 column, using 6 M guanidine-HCl solubilization and a 0.1% trifluoroacetic acid/CH3CN gradient system (Stephens, R. E., 1984, J. Cell Biol. 90:37a [Abstr.]), the relatively less hydrophobic 51-kD tektin elutes at greater than 45% CH3CN, immediately followed by the 55-kD chain. The 47-kD tektin is substantially more hydrophobic, eluting between the two tubulins. The amino acid compositions of the tektins are very similar to each other but totally distinct from tubulin chains, being characterized by a greater than 50% higher arginine plus lysine content (in good agreement with the number of tryptic peptides) and about half the content of glycine, histidine, proline, and tyrosine. The proline content correlates well with the fact that tektin filaments have twice as much alpha-helical content as tubulin. Total hydrophobic amino acid content correlates with HPLC elution times for the tektins but not tubulins. The average amino acid composition of the tektins indicates that they resemble intermediate filament proteins, as originally postulated from structural, solubility, and electrophoretic properties. Tektins have higher cysteine and tryptophan contents than desmin and vimentin, which characteristically have only one residue of each, more closely resembling certain keratins in these amino acids.

  2. Extravasation of chemotherapy

    DEFF Research Database (Denmark)

    Langer, Seppo W

    2010-01-01

    Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led...

  3. Chemotherapy for Soft Tissue Sarcomas

    Science.gov (United States)

    ... Stage Soft Tissue Sarcoma Treating Soft Tissue Sarcomas Chemotherapy for Soft Tissue Sarcomas Chemotherapy (chemo) is the use of drugs given into ... Depending on the type and stage of sarcoma, chemotherapy may be given as the main treatment or ...

  4. Partial Response in an RRx-001-Primed Patient with Refractory Small-Cell Lung Cancer after a Third Introduction of Platinum Doublets

    Directory of Open Access Journals (Sweden)

    Corey A. Carter

    2016-05-01

    Full Text Available Small-cell lung cancer (SCLC, initially exquisitely sensitive to first-line cisplatin/etoposide, invariably relapses and acquires a multidrug chemoresistant phenotype that generally renders retreatment with first-line therapy both futile and counterproductive. This report presents the case of a 77-year-old Caucasian male with extensive-stage refractory SCLC who was restarted on platinum doublets as part of a clinical trial called TRIPLE THREAT (NCT02489903 involving pretreatment with the epi-immunotherapeutic agent RRx-001, and who achieved a partial response after only 4 cycles. The patient had received a platinum drug twice before, in 2009 for a diagnosis of non-small-cell lung cancer (squamous cell carcinoma and in 2015 for SCLC, suggesting that RRx-001 pretreatment may sensitize or resensitize refractory SCLC patients to first-line chemotherapy.

  5. Description of Chiral Doublets in $A\\sim130$ Nuclei and the Possible Chiral Doublets in $A\\sim100$ Nuclei

    CERN Document Server

    Peng, J; Zhang, S Q

    2003-01-01

    The chiral doublets for nuclei in $A\\sim100$ and $A\\sim130$ regions have been studied with the particle-rotor model. The experimental spectra of chiral partners bands for four N=75 isotones in $A\\sim130$ region have been well reproduced by the calculation with the configuration $\\pi h_{11/2}\\otimes\

  6. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment

    Science.gov (United States)

    Martinez-Trufero, J; Isla, D; Adansa, J C; Irigoyen, A; Hitt, R; Gil-Arnaiz, I; Lambea, J; Lecumberri, M J; Cruz, J J

    2010-01-01

    Background: Platinum-based therapy (PBT) is the standard therapy for recurrent and/or metastatic head and neck cancer (HNC), but the incidence of recurrence remains high. This study evaluates the efficacy and tolerability of capecitabine as palliative monotherapy for recurrent HNC previously treated with PBT. Methods: Patients aged 18–75 years, with Eastern Cooperative Oncology Group performance status 0–2, squamous HNC with locoregional and/or metastatic recurrence previously treated with PBT and adequate organ functions, were included. Capecitabine (1.250 mg m−2 BID) was administered on days 1–14 every 21 days for at least two cycles. Results: A total of 40 male patients with a median age of 58 years were analysed. All patients received a median number of four cycles of capecitabine (range: 1–9) and the median relative dose intensity was 91%. Seven patients were not evaluable for response. Overall response rate was 24.2%. Median time to progression and overall survival were 4.8 and 7.3 months, respectively. Haematological adverse events (AEs) grade 3/4 were reported in six patients. Most common grade 3/4 non-haematological AEs were asthenia (12.5%), palmar-plantar eritrodisestesia (10%), mucositis (10%), dysphagia (10%) and diarrhoea (7.5%). Conclusions: Capecitabine seems to be an active, feasible and well-tolerated mode of palliative treatment for advanced HNC patients who have previously received PBT schedules. PMID:20485287

  7. The Doublet Extension of Tensor Gauge Potentials and a Reassessment of the Non-Abelian Topological Mass Mechanism

    CERN Document Server

    Cantcheff, M Botta

    2011-01-01

    A well-defined local gauge structure for non-Abelian two-form gauge fields was introduced some years ago. This was achieved by introducing doublet group representations and doublet-assembled connections. We provide a summarized version of this formalism, in order to recall its features and applications. We also build up doublet-extended gauge-invariant actions for bosonic and fermionic matter, and discuss the appearance of novel topological quantities in these doublet-type gauge models. A partner action for higher spin fields appears in the doublet version of the fermionic matter sector. As an application of the formalism, a Chern-Simons and an Yang-Mills action in four dimensions may both be rigorously defined. We carry out this task and show that, in this doublet framework, their combination constitutes a consistent (power-counting renormalizable and unitary) non-Abelian generalization of the Cremmer-Scherk-Kalb-Ramond theory with topological mass.

  8. Toxicity and prognosis in overweight and obese women with lung cancer receiving carboplatin-paclitaxel doublet chemotherapy.

    Science.gov (United States)

    Kashiwabara, Kosuke; Yamane, Hiromi; Tanaka, Hideyuki

    2013-05-01

    We retrospectively analyzed overdosing-related toxicity and prognosis in 127 women with lung cancer receiving carboplatin (6AUC) estimated by the Cockcroft-Gault formula using actual body weight and paclitaxel (200 mg/m(2)). Between the body mass index (BMI) > 25 group (n = 42) and the BMI ≤ 25 group (n = 85), there was no difference in dose intensity of carboplatin (122 mg/m(2)/week vs. 124 mg/m(2)/week, p = .323), median overall survival (285 days vs. 282 days, p = .820), and toxicity, except Grade 4 neutropenia in the second cycle. Women with BMI > 25 did not have an increased risk of toxicity because of an appropriate dose reduction.

  9. Outcomes of Induction Chemotherapy for Head and Neck Cancer Patients: A Combined Study of Two National Cohorts in Taiwan.

    Science.gov (United States)

    Chen, Jin-Hua; Yen, Yu-Chun; Liu, Shing-Hwa; Yuan, Sheng-Po; Wu, Li-Li; Lee, Fei-Peng; Lin, Kuan-Chou; Lai, Ming-Tang; Wu, Chia-Che; Chen, Tsung-Ming; Chang, Chia-Lun; Chow, Jyh-Ming; Ding, Yi-Fang; Lin, Ming-Chin; Wu, Szu-Yuan

    2016-02-01

    The use of induction chemotherapy (CT) is controversial. We compared the survival of head and neck cancer patients receiving docetaxel- or platinum-based induction CT before concomitant chemoradiotherapy (CCRT) with the survival of those receiving upfront CCRT alone. Data from the National Health Insurance and cancer registry databases in Taiwan were linked and analyzed. We enrolled patients who had head and neck cancer between January 1, 2002 and December 31, 2011. Follow-up was from the index date to December 31, 2013. We included head and neck patients diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 140.0-148.9 who were aged >20 years, at American Joint Committee on Cancer clinical cancer stage III or IV, and receiving induction CT or platinum-based CCRT. The exclusion criteria were a cancer history before head and neck cancer diagnosis, distant metastasis, AJCC clinical cancer stage I or II, receipt of platinum and docetaxel before radiotherapy, an age induction CT for >8 weeks before RT, induction CT alone before RT, cetuximab use, adjuvant CT within 90 days after RT completion, an RT dose cancer surgery before RT, nasopharyngeal cancer, in situ carcinoma, sarcoma, and head and neck cancer recurrence. We enrolled 10,721 stage III-IV head and neck cancer patients, with a median follow-up of 4.18 years (interquartile range, 3.25 years). The CCRT (arm 1), docetaxel-based induction CT (arm 2), and platinum-based CCRT (arm 3; control arm) groups comprised 7968, 503, and 2232 patients, respectively. Arm 3 was used to investigate mortality risk after induction CT. After adjustment for age, sex, clinical stage, and comorbidities, the adjusted hazard ratios (aHRs) (95% confidence interval [CI]) for overall death were 1.37 (1.22-1.53) and 1.44 (1.36-1.52) in arms 2 and 3, respectively. In a disease-specific survival rate analysis, aHRs (95% CI) of head and neck cancer-related death were 1.29 (1

  10. Renal Medullary Carcinoma: Case Report of an Aggressive Malignancy with Near-Complete Response to Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin Chemotherapy

    Directory of Open Access Journals (Sweden)

    Ali Imran Amjad

    2014-01-01

    Full Text Available Renal medullary carcinoma (RMC is a rare but aggressive malignancy affecting young individuals with sickle cell trait. Renal medullary carcinoma commonly presents with advanced or metastatic disease and is associated with a rapidly progressive clinical course and an extremely short overall survival measured in weeks to few months. Due to the rarity of RMC, there is no proven effective therapy and patients are often treated with platinum-based chemotherapy. We report near-complete radiological and pathological response in a patient treated with dose-dense MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy. The patient underwent consolidation nephrectomy and retroperitoneal lymph node dissection and had a 16-month progression-free survival, one of the longest reported in patients with RMC.

  11. Critical Assessment of TD-DFT for Excited States of Open-Shell Systems: I. Doublet-Doublet Transitions.

    Science.gov (United States)

    Li, Zhendong; Liu, Wenjian

    2016-01-12

    A benchmark set of 11 small radicals is set up to assess the performance of time-dependent density functional theory (TD-DFT) for the excited states of open-shell systems. Both the unrestricted (U-TD-DFT) and spin-adapted (X-TD-DFT) formulations of TD-DFT are considered. For comparison, the well-established EOM-CCSD (equation-of-motion coupled-cluster with singles and doubles) is also used. In total, 111 low-lying singly excited doublet states are accessed by all the three approaches. Taking the MRCISD+Q (multireference configuration interaction with singles and doubles plus the Davidson correction) results as the benchmark, it is found that both U-TD-DFT and EOM-CCSD perform well for those states dominated by singlet-coupled single excitations (SCSE) from closed-shell to open-shell, open-shell to vacant-shell, or closed-shell to vacant-shell orbitals. However, for those states dominated by triplet-coupled single excitations (TCSE) from closed-shell to vacant-shell orbitals, both U-TD-DFT and EOM-CCSD fail miserably due to severe spin contaminations. In contrast, X-TD-DFT provides balanced descriptions of both SCSE and TCSE. As far as the functional dependence is concerned, it is found that, when the Hartree-Fock ground state does not suffer from the instability problem, both global hybrid (GH) and range-separated hybrid (RSH) functionals perform grossly better than pure density functionals, especially for Rydberg and charge-transfer excitations. However, if the Hartree-Fock ground state is instable or nearly instable, GH and RSH tend to underestimate severely the excitation energies. The SAOP (statistically averaging of model orbital potentials) performs more uniformly than any other density functionals, although it generally overestimates the excitation energies of valence excitations. Not surprisingly, both EOM-CCSD and adiabatic TD-DFT are incapable of describing excited states with substantial double excitation characters.

  12. Adjuvant chemotherapy for advanced endometrial cancer.

    Science.gov (United States)

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    .Overall survival (OS) and progression-free survival (PFS) was longer with adjuvant chemotherapy compared with adjuvant radiotherapy (OS: hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.57 to 0.99, I² = 22%; and PFS: HR 0.74, 95% CI 0.59 to 0.92, I² = 0%). Sensitivity analysis using adjusted and unadjusted OS data, gave similar results. In subgroup analyses, the effects on survival in favour of chemotherapy were not different for stage III and IV, or stage IIIA and IIIC (tests for subgroup differences were not significant and I² = 0%). This evidence was of moderate quality. Data from one trial showed that women receiving adjuvant chemotherapy were more likely to experience haematological and neurological adverse events and alopecia, and more likely to discontinue treatment (33/194 versus 6/202; RR 5.73, 95% CI 2.45 to 13.36), than those receiving adjuvant radiotherapy. There was no statistically significant difference in treatment-related deaths between the chemotherapy and radiotherapy treatment arms (8/309 versus 5/311; Risk Ratio (RR) 1.67, 95% CI 0.55 to 5.00).There was no clear difference in PFS between intervention groups in the one trial that compared CDP versus CD (552 women; HR 0.90, 95% CI 0.69 to 1.17). We considered this evidence to be of moderate quality. Mature OS data from this trial were not yet available. Severe haematological and neurological adverse events occurred more frequently with CDP than CD.We found no trials to include of adjuvant chemotherapy versus chemoradiation in advanced endometrial cancer; however we identified one ongoing trial of this comparison. There is moderate quality evidence that chemotherapy increases survival time after primary surgery by approximately 25% relative to radiotherapy in stage III and IV endometrial cancer. There is limited evidence that it is associated with more adverse effects. There is some uncertainty as to whether triplet regimens offer similar survival benefits over doublet regimens in the long-term. Further

  13. Neurotoxicity of cancer chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Miyoung Yang; Changjong Moon

    2013-01-01

    There is accumulating clinical evidence that chemotherapeutic agents induce neurological side effects, including memory deficits and mood disorders, in cancer patients who have undergone chemotherapeutic treatments. This review focuses on chemotherapy-induced neurodegeneration and hippocampal dysfunctions and related mechanisms as measured by in vivo and in vitro approaches. These investigations are helpful in determining how best to further explore the causal mechanisms of chemotherapy-induced neurological side effects and in providing direction for the future development of novel optimized chemotherapeutic agents.

  14. Chemotherapy beyond first-line in stage IV metastatic non-small cell lung cancer Quimioterapia em câncer de pulmão não pequenas células metastático estádio IV: além da primeira linha

    Directory of Open Access Journals (Sweden)

    Riad Naim Younes

    2011-12-01

    Full Text Available OBJECTIVE: Platinum-based doublet chemotherapy is considered the standard of care for advanced non-small cell lung cancer (NSCLC. However, prognosis after recurrent or progressive disease following first-line chemotherapy is usually poor. Maintenance chemotherapy, second line treatment and even third line chemotherapy are available for patients with advanced NSCLC. Unfortunately, few patients are candidates for chemotherapy beyond first line. The present study evaluated characteristics of patients with NSCLC and outcomes of the treatment of their metastatic disease, with emphasis on second and third-line chemotherapy. METHODS: This was a retrospective observational study of 2,673 patients with metastatic, stage IV, non-small cell lung cancer admitted for treatment in two São Paulo institutions. First-line chemotherapy was defined as the first chemotherapeutic approach administered to the patient. Second and third-line chemotherapy were defined as the systemic treatment administered after discontinuing first-line chemotherapy, either for intolerance or for progressive or recurrent disease. RESULTS: Most patients (57.9% received first-line chemotherapy, and approximately 23.4% received second-line and 8% third-line regimens. Only 2.5% received fourth-line chemotherapy. Median overall survival (OS was 8 months (95% CI: 8-9 months. At univariate analyses, gender (p OBJETIVO: A quimioterapia dupla com base em platina consiste no tratamento padrão para o câncer de pulmão não pequenas células (CPNPC avançado. Contudo, o prognóstico dos pacientes com doença recorrente ou em progressão após a quimioterapia de primeira linha é ruim. Quimioterapia de manutenção, de segunda linha e até de terceira linha são tratamentos válidos para pacientes com CPNPC de estádio avançado. Infelizmente, poucos pacientes são candidatos para o tratamento quimioterápico além daquele de primeira linha. O presente estudo avalia as características de

  15. Chemotherapy for Melanoma.

    Science.gov (United States)

    Wilson, Melissa A; Schuchter, Lynn M

    2016-01-01

    Prior to the recent therapeutic advances, chemotherapy was the mainstay of treatment options for advanced-stage melanoma. A number of studies have investigated various chemotherapy combinations in order to expand on the clinical responses achieved with single-agent dacarbazine, but these have not demonstrated an improvement in overall survival. Similar objective responses were observed with the combination of carboplatin and paclitaxel as were seen with single-agent dacarbazine. The combination of chemotherapy and immunotherapy, known as biochemo-therapy, has shown high clinical responses; however, biochemo-therapy has not been shown to improve overall survival and resulted in increased toxicities. In contrast, palliation and long-term responses have been observed with localized treatment with isolated limb perfusion or infusion in limb-isolated disease. Although new, improved therapeutic options exist for first-line management of advanced-stage melanoma, chemotherapy may still be important in the palliative treatment of refractory, progressive, and relapsed melanoma. We review the various chemotherapy options available for use in the treatment and palliation of advanced-stage melanoma, discuss the important clinical trials supporting the treatment recommendations, and focus on the clinical circumstances in which treatment with chemotherapy is useful.

  16. Classification of finite reparametrization symmetry groups in the three-Higgs-doublet model

    CERN Document Server

    Ivanov, I P

    2012-01-01

    Symmetries play a crucial role in electroweak symmetry breaking models with non-minimal Higgs content. Within each class of these models, it is desirable to know which symmetry groups can be implemented via the scalar sector. In N-Higgs-doublet models, this classification problem was solved only for N=2 doublets. Very recently, we suggested a method to classify all realizable finite symmetry groups of Higgs-family transformations in the three-Higgs-doublet model (3HDM). Here, we present this classification in all detail together with an introduction to the theory of solvable groups, which play the key role in our derivation. We also consider generalized-CP symmetries, and discuss the interplay between Higgs-family symmetries and CP-conservation. In particular, we prove that presence of the $Z_4$ symmetry guarantees the explicit CP-conservation of the potential. This work completes classification of finite reparametrization symmetry groups in 3HDM.

  17. Classification of finite reparametrization symmetry groups in the three-Higgs-doublet model

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, Igor P. [Universite de Liege, IFPA, Liege (Belgium); Sobolev Institute of Mathematics, Novosibirsk (Russian Federation); Vdovin, E. [Sobolev Institute of Mathematics, Novosibirsk (Russian Federation)

    2013-02-15

    Symmetries play a crucial role in electroweak symmetry breaking models with non-minimal Higgs content. Within each class of these models, it is desirable to know which symmetry groups can be implemented via the scalar sector. In N-Higgs-doublet models, this classification problem was solved only for N=2 doublets. Very recently, we suggested a method to classify all realizable finite symmetry groups of Higgs-family transformations in the three-Higgs-doublet model (3HDM). Here, we present this classification in all detail together with an introduction to the theory of solvable groups, which play the key role in our derivation. We also consider generalized-CP symmetries, and discuss the interplay between Higgs-family symmetries and CP-conservation. In particular, we prove that presence of the Z{sub 4} symmetry guarantees the explicit CP-conservation of the potential. This work completes classification of finite reparametrization symmetry groups in 3HDM. (orig.)

  18. Classification of finite reparametrization symmetry groups in the three-Higgs-doublet model

    Science.gov (United States)

    Ivanov, Igor P.; Vdovin, E.

    2013-02-01

    Symmetries play a crucial role in electroweak symmetry breaking models with non-minimal Higgs content. Within each class of these models, it is desirable to know which symmetry groups can be implemented via the scalar sector. In N-Higgs-doublet models, this classification problem was solved only for N=2 doublets. Very recently, we suggested a method to classify all realizable finite symmetry groups of Higgs-family transformations in the three-Higgs-doublet model (3HDM). Here, we present this classification in all detail together with an introduction to the theory of solvable groups, which play the key role in our derivation. We also consider generalized- CP symmetries, and discuss the interplay between Higgs-family symmetries and CP-conservation. In particular, we prove that presence of the ℤ4 symmetry guarantees the explicit CP-conservation of the potential. This work completes classification of finite reparametrization symmetry groups in 3HDM.

  19. Higgs boson couplings in multi-doublet models with natural flavour conservation

    Science.gov (United States)

    Yagyu, Kei

    2016-12-01

    We investigate the deviation in the couplings of the standard model (SM) like Higgs boson (h) with a mass of 125 GeV from the prediction of the SM in multi-doublet models within the framework where flavour changing neutral currents at the tree level are naturally forbidden. After we present the general expressions for the modified gauge and Yukawa couplings for h, we show the correlation between the deviation in the Yukawa coupling for the tau lepton hτ+τ- and that for the bottom quark hb b bar under the assumption of a non-zero deviation in the hVV (V = W , Z) couplings in two Higgs doublet models (2HDMs) and three Higgs doublet models (3HDMs) as simple examples. We clarify the possible allowed prediction of the deviations in the 3HDMs which cannot be explained in the 2HDMs even taking into account the one-loop electroweak corrections to the Yukawa coupling.

  20. Design and construction of an electrostatic quadrupole doublet lens for nuclear microprobe application

    Science.gov (United States)

    Manuel, Jack E.; Szilasi, Szabolcs Z.; Phillips, Dustin; Dymnikov, Alexander D.; Reinert, Tilo; Rout, Bibhudutta; Glass, Gary A.

    2017-08-01

    An electrostatic quadrupole doublet lens system has been designed and constructed to provide strong, mass-independent focusing of 1-3 MeV ions to a 1 μm2 spot size. The electrostatic doublet consists of four sets of gold electrodes deposited on quartz rods that are positioned in a precision machined rigid frame. The 38 mm electrodes are fixed in a quadrupole doublet arrangement having a bore diameter of 6.35 mm. The coating process allows uniform, 360° coverage with minimal edge defects. Determined via optical interferometry, typical surface roughness is 6 nm peak to valley. Radial and coaxial alignment of the electrodes within the frame is accomplished by using a combination of rigid and adjustable mechanical supports. Axial alignment along the ion beam is accomplished via external manipulators. COMSOL Multiphysics® v5.2 and Propagate Rays and Aberrations by Matrices (PRAM) were used to simulate ion trajectories through the system.

  1. The influence of facies heterogeneity on the doublet performance in low-enthalpy geothermal sedimentary reservoirs

    DEFF Research Database (Denmark)

    Crooijmans, R. A.; Willems, C. J L; Nick, Hamid

    2016-01-01

    A three-dimensional model is used to study the influence of facies heterogeneity on energy production under different operational conditions of low-enthalpy geothermal doublet systems. Process-based facies modelling is utilised for the Nieuwerkerk sedimentary formation in the West Netherlands Basin...... and the energy recovery rate for different discharge rates and the production temperature (Tmin) above which the doublet is working. With respect to the results, we propose a design model to estimate the life time and energy recovery rate of the geothermal doublet. The life time is estimated as a function of N....../G, Tmin and discharge rate, while the design model for the energy recovery rate is only a function of N/G and Tmin. Both life time and recovery show a positive relation with an increasing N/G. Further our results suggest that neglecting details of process-based facies modelling may lead to significant...

  2. Physiological consequences of doublet discharges on motoneuronal firing and motor unit force

    Directory of Open Access Journals (Sweden)

    Włodzimierz eMrówczyński

    2015-03-01

    Full Text Available The double discharges are observed at the onset of contractions of mammalian motor units (MUs, especially during their recruitment to strong or fast movements. Doublets lead to MU force increase and improve ability of muscles to maintain high force during prolonged contractions. In this review we discuss an ability to produce doublets by fast and slow motoneurons (MNs, their influence on the course of action potential afterhyperpolarization as well as its role in modulation of the initial stage of the firing pattern of MNs. In conclusion, a generation of doublets is an important strategy of motor control, responsible for fitting the motoneuronal firing rate to the optimal for MUs at the start of their contraction, necessary for increment of muscle force.

  3. Structural, elastic, electronic and optical properties of platinum-based superconductor SrPt3P under pressure: a first-principles study

    Science.gov (United States)

    Zhang, Xiu-Qing; Li, Guo-Jun; Cheng, Yan; Ji, Guang-Fu

    2016-02-01

    The structural, elastic, electronic and optical properties of the platinum-based superconductor SrPt3P under pressure are investigated by the generalized gradient approximation with the Perdew-Burke-Ernzerhof exchange-correlation functional in the framework of density-functional theory. The calculated structural parameters (a, c) and the primitive cell volume V of SrPt3P at the ground state are in good agreement with the available experimental data and seem to be better than other calculated results. The pressure dependences of the elastic constants Cnolimitsij, bulk modulus B, shear modulus G, Young's modulus E and Poisson's ratio σ of SrPt3P are also obtained successfully. The computed elastic constants indicate that SrPt3P is mechanically stable up to 100 GPa. The obtained B/G is 2.56 at the ground state, indicating that SrPt3P behaves in a ductile manner. The ratio B/G also increases with growing pressures, indicating that the structure becomes more and more ductile. Even though SrPt3P is an ionic-covalent crystal, the obtained density of states shows that it has metallic characteristic. These conclusions can be further demonstrated by analysing the charge and Mulliken population. In addition, we have investigated the dielectric function and the loss function. It is found that the dielectric function in (E||x, E||y) is isotropic, whereas the directions (E||x, E||z) are anisotropic; the effect of pressure on the loss function of the deep ultraviolet region gradually increases as the pressure increases.

  4. Efficient Synthesis of a Maghemite/Gold Hybrid Nanoparticle System as a Magnetic Carrier for the Transport of Platinum-Based Metallotherapeutics

    Directory of Open Access Journals (Sweden)

    Pavel Štarha

    2015-01-01

    Full Text Available The preparation and thorough characterization of a hybrid magnetic carrier system for the possible transport of activated platinum-based anticancer drugs, as demonstrated for cisplatin (cis-[Pt(NH32Cl2], CDDP, are described. The final functionalized mag/Au–LA–CDDP* system consists of maghemite/gold nanoparticles (mag/Au coated by lipoic acid (HLA; LA stands for deprotonated form of lipoic acid and functionalized by activated cisplatin in the form of cis-[Pt(NH32(H2O2]2+ (CDDP*. The relevant techniques (XPS, EDS, ICP-MS proved the incorporation of the platinum-containing species on the surface of the studied hybrid system. HRTEM, TEM and SEM images showed the nanoparticles as spherical with an average size of 12 nm, while their superparamagnetic feature was proven by 57Fe Mössbauer spectroscopy. In the case of mag/Au, mag/Au–HLA and mag/Au–LA–CDDP*, weaker magnetic interactions among the Fe3+ centers of maghemite, as compared to maghemite nanoparticles (mag, were detected, which can be associated with the non-covalent coating of the maghemite surface by gold. The pH and time-dependent stability of the mag/Au–LA–CDDP* system in different media, represented by acetate (pH 5.0, phosphate (pH 7.0 and carbonate (pH 9.0 buffers and connected with the release of the platinum-containing species, showed the ability of CDDP* to be released from the functionalized nanosystem.

  5. Microscopic study of doublet bands in odd–odd A∼100 nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Dar, W.A. [Department of Physics, University of Kashmir, Srinagar, 190 006 (India); Sheikh, J.A. [Department of Physics, University of Kashmir, Srinagar, 190 006 (India); Department of Physics and Astronomy, University of Tennessee, Knoxville, TN 37996 (United States); Bhat, G.H., E-mail: gwhr.bhat@gmail.com [Department of Physics, University of Kashmir, Srinagar, 190 006 (India); Palit, R. [Department of Nuclear and Atomic Physics, Tata Institute of Fundamental Research, Colaba, Mumbai, 400 005 (India); Ali, R.N. [Department of Physics, University of Kashmir, Srinagar, 190 006 (India); Frauendorf, S. [Department of Physics, University of Notre Dame, Notre Dame (United States)

    2015-01-15

    A systematic study of the doublet bands observed in odd–odd mass ∼100 is performed using the microscopic triaxial projected shell model approach. This mass region has depicted some novel features which are not observed in other mass regions, for instance, it has been observed that doublet bands cross diabatically in {sup 106}Ag. It is demonstrated that this unique feature is due to crossing of the two 2-quasiparticle configurations having different intrinsic structures. Further, we provide a complete set of transition probabilities for all the six-isotopes studied in this work and it is shown that the predicted transitions are in good agreement with the available experimental data.

  6. Higgs doublet as a Goldstone boson in perturbative extensions of the Standard Model

    CERN Document Server

    Bellazzini, Brando; Rychkov, Vyacheslav S; Varagnolo, Alvise

    2008-01-01

    We investigate the idea of the Higgs doublet as a pseudo-Goldstone boson in perturbative extensions of the Standard Model, motivated by the desire to ameliorate its hierarchy problem without conflict with the electroweak precision data. Two realistic supersymmetric models with global SU(3) symmetry are proposed, one for large and another for small values of tan\\beta. The two models demonstrate two different mechanisms for EWSB and the Higgs mass generation. Their experimental signatures are quite different. Our constructions show that a pseudo-Goldstone Higgs doublet in perturbative extensions is just as plausible as in non-perturbative ones.

  7. Spatial Distribution of Ground water Level Changes Induced by the 2006 Hengchun Earthquake Doublet

    OpenAIRE

    Yeeping Chia; Jessie J. Chiu; Po-Yu Chung; Ya-Lan Chang; Wen-Chi Lai; Yen-Chun Kuan

    2009-01-01

    Water-level changes were ob served in 107 wells at 67 monitoring stations in the southern coastal plain of Tai wan during the 2006 Mw 7.1 Hengchun earthquake doublet. Two consecutive coseismic changes induced by the earth quake doublet can be observed from high-frequency data. Obervations from multiple-well stations indicate that the magnitude and direction of coseismic change may vary in wells of different depths. Coseismic rises were dominant on the south east side of the costal plain; wher...

  8. Characterization of Wave Dispersion in Viscoelastic Cellular Assemblies by Doublet Mechanics

    Institute of Scientific and Technical Information of China (English)

    JIN Yan-Fang; XIONG Chun-Yang; FANG Jing; FERRARI Mauro

    2009-01-01

    Using the Voigt model, we analyze wave propagation in viscoelastic granular media with a monatomic lattice, planar simple cubic package and cubical-tetrahedral assembly within the context of doublet mechanics. Microstrains of elongation between the doublet particles are considered in the models. Wave dispersive relations are derived from dynamic equations of the particles involved in the media, and phase velocities and attenuations of the dispersive waves are obtained for the different assemblies. Variations in these dispersion characteristics are analyzed with the changes of cell interval, modulus, and wave frequency. The relations between micro-constants and macro-parameters are presented under the condition of non-scale continuity of the media.

  9. Measurements of Narrow Mg II Associated Absorption Doublets with Two Observations

    Indian Academy of Sciences (India)

    Zhi-Fu Chen; Cai-Juan Pan; Guo-Qiang Li; Wei-Rong Huang; Mu-Sheng Li

    2013-12-01

    The measurement of the variations of absorption lines over time is a good method to study the physical conditions of absorbers. In this paper, we measure the variations of the line strength of 36 narrow Mg II2796, 2803 associated absorption doublets, which are imprinted on 31 quasar spectra with two observations of the Sloan Digital Sky Survey (SDSS). The timescales of these quasar span 1.1–5.5 years at the quasar rest-frame. On these timescales, we find that these narrow Mg II associated absorption doublets are stable, with no one 2796 line showing strength variation beyond 2 times error (2).

  10. Search for a lighter Higgs boson in Two Higgs Doublet Models

    Energy Technology Data Exchange (ETDEWEB)

    Cacciapaglia, Giacomo; Deandrea, Aldo; Gascon-Shotkin, Suzanne; Corre, Solène Le; Lethuillier, Morgan [University Lyon, Université Claude Bernard Lyon 1, CNRS/IN2P3, UMR5822 IPNL,4, rue E. Fermi, Villeurbanne, F-69622 (France); Tao, Junquan [Institute High Energy Physics, Chinese Academy of Sciences,P.O. Box 918, Beijing, 100049 (China)

    2016-12-15

    We consider present constraints on Two Higgs Doublet Models, both from the LHC at Run 1 and from other sources in order to explore the possibility of constraining a neutral scalar or pseudo-scalar particle lighter than the 125 GeV Higgs boson. Such a lighter particle is not yet completely excluded by present data. We show with a simplified analysis that some new constraints could be obtained at the LHC if such a search is performed by the experimental collaborations, which we therefore encourage to continue carrying out light diphoton resonance searches at √s=13 TeV in the context of Two Higgs Doublet Models.

  11. Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    ZHUO Ming-lei; DUAN Jian-chun; WANG Yu-yan; GUO Qing-zhi; LIU Xu-yi; LIU Ning-hong; WANG Jie; WU Mei-na; ZHAO Jun; Sonya Wei Song; BAI Hua; WANG Shu-hang; YANG Lu; AN Tong-tong; WANG Xin

    2011-01-01

    Background The genotype of epidermal growth factor receptor (EGFR) is associated with tyrosine kinase inhibitor and effectiveness of therapy,but its role in cytotoxic chemotherapy is still unknown.Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy.Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer (NSCLC).In this study,we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis.Methods We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department.We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes.Results There were 54 patients with known EGFR mutations and 91 cases of wild types.No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients (37.0% vs.31.9%).The median survival time and 1-,2-year survival rates were higher in mutation carriers than wild-types (24months vs.18 months,85.7% vs.65.7% and 43.7% vs.25.9%,P=0.047).Clinical stage (IV vs.Ⅲb),response to the first-line chemotherapy (partial vs.no) and EGFR genotype were independent prognostic factors.Conclusion Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy,but an independent prognostic factor indicating longer survival.

  12. The role of neoadjuvant chemotherapy in the management of locally advanced cervix cancer: a systematic review

    Directory of Open Access Journals (Sweden)

    Mohammed Osman

    2014-09-01

    Full Text Available Cervical cancer is the second most common cancer in women. Neoadjuvant chemotherapy for patients with locally advanced cervix cancer has comparable benefits to concurrent chemoradiotherapy (CCRT, but with fewer side effects. This systematic review aims to provide a comprehensive summary of the benefits of neoadjuvant chemotherapy for the management of locally advanced cervix cancer from stage IB2 (tumor >4.0 cm to IIIB (tumor extending to the pelvic wall and/or hydronephrosis. Our primary objective was to assess benefits in terms of survival. The data source included the USA national library of medicine, Medline search, and the National Cancer Institute PDQ Clinical Protocols. Inclusion criteria for consideration in the current systematic review included studies published between January 1997 and December 2012. In terms of histology, they had to be focused on squamous cell carcinoma, adenosquamous carcinoma, and/or adenocarcinoma. Patients should be either chemotherapy naïve or cervix cancer chemotherapy naïve, and have a performance status ≤2. The search in the above-mentioned scientific websites led to identify 49 publications, 19 of which were excluded, as they did not meet the inclusion criteria of this systematic review. Therefore only 30 studies were deemed eligible. Data was collected from 1760 patients enrolled in the current systematic review study. The mean age was 45.2 years. The mean tumor size was 4.7 cm. The most commonly used chemotherapies were cisplatin doublets. Paclitaxel was the most commonly used chemotherapeutic agent in the doublets. The mean chemotherapy cycles were 2.7. After chemotherapy, patients underwent surgery after a mean time of 2.5 weeks. The standard operation was radical hysterectomy with pelvic lymphadenectomy. Chemotherapy achieved an objective response rate of 84%. The 5-year progression-free survival and overall survival were 61.9% and 72.8% respectively. The treatment protocol was associated

  13. Combination Chemotherapy for Influenza

    Directory of Open Access Journals (Sweden)

    Robert G. Webster

    2010-07-01

    Full Text Available The emergence of pandemic H1N1 influenza viruses in April 2009 and the continuous evolution of highly pathogenic H5N1 influenza viruses underscore the urgency of novel approaches to chemotherapy for human influenza infection. Anti-influenza drugs are currently limited to the neuraminidase inhibitors (oseltamivir and zanamivir and to M2 ion channel blockers (amantadine and rimantadine, although resistance to the latter class develops rapidly. Potential targets for the development of new anti-influenza agents include the viral polymerase (and endonuclease, the hemagglutinin, and the non-structural protein NS1. The limitations of monotherapy and the emergence of drug-resistant variants make combination chemotherapy the logical therapeutic option. Here we review the experimental data on combination chemotherapy with currently available agents and the development of new agents and therapy targets.

  14. Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

    Science.gov (United States)

    Kerckhove, Nicolas; Collin, Aurore; Condé, Sakahlé; Chaleteix, Carine; Pezet, Denis; Balayssac, David

    2017-01-01

    Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a “stocking and glove” distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in

  15. Cisplatin-based chemotherapy followed by focal, reduced-dose irradiation for pediatric primary central nervous system germinomas.

    Science.gov (United States)

    Douglas, James G; Rockhill, Jason K; Olson, James M; Ellenbogen, Richard G; Geyer, J Russell

    2006-01-01

    The objective of this study was to evaluate retrospectively one institution's experience treating pediatric central nervous system (CNS) pure germinomas with platinum-based chemotherapy followed by focal, reduced-dose irradiation. Eight patients were identified with localized, pure CNS germinomas from 1993 to 2004 at the authors' institution. The median age at diagnosis was 13 years (range 7-19). The median follow-up was 40 months (range 8-141). The tumor location was suprasellar in four, the pineal region in three, and the third ventricle in one. Irradiation was started a median of 20 weeks (range 17-22) from diagnosis and consisted of conformal fields to the primary site as determined by the initial diagnostic MR plus a 1.5- to 2-cm margin. Six of the eight patients received a dose of 3,060 cGy; two patients received 3,600 cGy. The 5-year actuarial event free survival was 71% (56-86%, 95% CI). Two patients suffered marginal (at field edge) failures and both were salvaged using reinduction platinum-based chemotherapy followed by cranial spinal irradiation and a boost to the primary tumor. The 5-year actuarial overall survival was 100%. There were no spinal failures. These data suggest that a reduction in both volume and dose (30.6-36 Gy) retains the excellent survival rates for patients with localized, pure germinomas of the CNS. A higher rate of ventricular relapse rate is observed, although salvage of those patients is feasible.

  16. Vacuum stability and supersymmetry at high scales with two Higgs doublets

    Energy Technology Data Exchange (ETDEWEB)

    Bagnaschi, E.; Buchmueller, W.; Voigt, A.; Weiglein, G. [DESY Hamburg (Germany); Bruemmer, F. [Montpellier Univ. (France). Lab. Univers et Particules de Montpellier

    2016-02-15

    We investigate the stability of the electroweak vacuum for two-Higgs doublet models with a supersymmetric UV completion. The supersymmetry breaking scale is taken to be of the order of the grand unification scale. We first study the case where all superpartners decouple at this scale. We show that contrary to the Standard Model with one Higgs doublet, matching to the supersymmetric UV completion is possible if the low-scale model contains two Higgs doublets. In this case vacuum stability and experimental constraints point towards low values of tanβdoublets), the model cannot be matched to supersymmetry at very high scales when requiring a 125 GeV Higgs. Light neutral and charged higgsinos therefore emerge as a promising signature of a supersymmetric UV completion of the Standard Model at the grand unification scale.

  17. The Permian Rotliegend reservoir architecture of the Dutch Koekoekspolder geothermal doublet

    NARCIS (Netherlands)

    Mijnlieff, H.F.; Bloemsma, M.R.; Donselaar, M.E.; Henares, S.; Redjosentono, A.E.; Veldkamp, J.G.; Weltje, G.J.

    2014-01-01

    The Dutch Koekoekspolder geothermal doublet was drilled in 2011 targeting the Permian Rotliegendreservoir. The encountered reservoir properties were less favorable than expected pre-drill. Post-drill integrated evaluation of vintage data and the new data from the geothermal wells resulted in a refin

  18. Symmetry enriched U(1) topological orders for dipole-octupole doublets on a pyrochlore lattice

    Science.gov (United States)

    Li, Yao-Dong; Chen, Gang

    2017-01-01

    Symmetry plays a fundamental role in our understanding of both conventional symmetry breaking phases and the more exotic quantum and topological phases of matter. We explore the experimental signatures of symmetry enriched U(1) quantum spin liquids (QSLs) on the pyrochlore lattice. We point out that the Ce local moment of the newly discovered pyrochlore QSL candidate Ce2Sn2O7 , is a dipole-octupole doublet. The generic model for these unusual doublets supports two distinct symmetry enriched U(1) QSL ground states in the corresponding quantum spin ice regimes. These two U(1) QSLs are dubbed dipolar U(1) QSL and octupolar U(1) QSL. While the dipolar U(1) QSL has been discussed in many contexts, the octupolar U(1) QSL is rather unique. Based on the symmetry properties of the dipole-octupole doublets, we predict the peculiar physical properties of the octupolar U(1) QSL, elucidating the unique spectroscopic properties in the external magnetic fields. We further predict the Anderson-Higgs transition from the octupolar U(1) QSL driven by the external magnetic fields. We identify the experimental relevance with the candidate material Ce2Sn2O7 and other dipole-octupole doublet systems.

  19. Description of the Chiral Doublet Bands in 135Nd and 136Nd

    Institute of Scientific and Technical Information of China (English)

    ZHANG Da-Li; DING Bin-Gang

    2011-01-01

    The chiral doublet bands in 135 Nd and 136Nd are investigated systematically within the supersymmetry scheme including many-body interactions and possessing the SO(5)(or SU(5)) symmetry on the rotational symmetry.Quantitatively good results of the energy spectra, the energy staggering parameter as a function of the spin and the spin assignment are obtained. The calculation shows that the stronger competition between the pairing and anti-pairing effects exists in these chiral doublet bands and the SU(3) symmetry breaking more seriously exists in the stable chiral structure.%@@ The chiral doublet bands in 135 Nd and 136Nd are investigated systematically within the supersymmetry scheme including many-body interactions and possessing the SO(5)(or SU(5)) symmetry on the rotational symmetry.Quantitatively good results of the energy spectra,the energy staggering parameter as a function of the spin and the spin assignment are obtained.The calculation shows that the stronger competition between the pairing and anti-pairing effects exists in these chiral doublet bands and the SU(3) symmetry breaking more seriously exists in the stable chiral structure.

  20. Constraints on the septet-doublet mixing models from oblique parameters

    CERN Document Server

    Geng, Chao-Qiang; Yu, Yao

    2014-01-01

    The limitations of the doublet-septet mixing models by electroweak oblique parameters of $S$ and $T$ are studied. In the minimal model, the mixture of the septet and the scalar doublet in the standard model (SM) is driven by a non-Hermitian dimension-7 operator. For a smaller bare mass of the septet, $\\Delta S$ gives a stringent constraint on $\\sin\\beta$, for example, $\\sin\\beta\\lesssim 0.22$ for $M_\\eta=300\\,{\\rm GeV}$. In general, increasing $M_\\eta$ will enhance the deviation of $T$ from the SM, whereas it decreases the magnitude of $\\Delta S$ for a larger bare mass within the range $M_\\eta\\lesssim 400\\,{\\rm GeV}$. We also examine two expended models from the ordinary doublet-septet mixture pattern. One of them is based on a inert doublet-septet mixing pattern, in which there is no vacuum expectation value for the neutral component of $\\eta$, and a stable dark matter could naturally exist. For a benchmark point with $M_\\chi=250{\\rm}$ and $M_\\eta=400\\,{\\rm GeV}$ in this model, the mixing coefficient is foun...

  1. Product lambda-doublet ratios as an imprint of chemical reaction mechanism

    Science.gov (United States)

    Jambrina, P. G.; Zanchet, A.; Aldegunde, J.; Brouard, M.; Aoiz, F. J.

    2016-11-01

    In the last decade, the development of theoretical methods has allowed chemists to reproduce and explain almost all of the experimental data associated with elementary atom plus diatom collisions. However, there are still a few examples where theory cannot account yet for experimental results. This is the case for the preferential population of one of the Λ-doublet states produced by chemical reactions. In particular, recent measurements of the OD(2Π) product of the O(3P)+D2 reaction have shown a clear preference for the Π(A') Λ-doublet states, in apparent contradiction with ab initio calculations, which predict a larger reactivity on the A'' potential energy surface. Here we present a method to calculate the Λ-doublet ratio when concurrent potential energy surfaces participate in the reaction. It accounts for the experimental Λ-doublet populations via explicit consideration of the stereodynamics of the process. Furthermore, our results demonstrate that the propensity of the Π(A') state is a consequence of the different mechanisms of the reaction on the two concurrent potential energy surfaces

  2. Limit on Br(b --> sg) in two Higgs doublet models

    CERN Document Server

    Geng, C Q; Hou Wei Shu; Chao-Qiang Geng; Paul Turcotte; Wei-Shu Hou

    1994-01-01

    Using the recent CLEO measurement of Br(b\\to s \\gamma), we find that the branching ratio of b\\to s g cannot be larger than 10\\% in two Higgs doublet models. The small experimental value of Br(b\\to e\\bar{\

  3. Advances in the Design of the SuperB Final Doublet

    Energy Technology Data Exchange (ETDEWEB)

    Paoloni, E.; Carmignani, N.; Pilo, F.; /Pisa U. /INFN, Pisa; Bettoni, S.; /CERN; Fabbricatore, P.; Farinon, S.; Musenich, R.; /INFN, Genoa; Bosi, F.; /INFN, Pisa; Biagini, M.E.; Raimondi, P.; /Frascati; Sullivan, M.; /SLAC

    2012-04-26

    SuperB is an asymmetric energy e{sup +}e{sup -} collider operating at the {Upsilon}(4S) peak with a design peak luminosity of 10{sup 36} Hz/cm{sup 2} to be built in Italy in the very near future. The design luminosity is almost a factor hundred higher than that of the present generation comparable facilities. To get the design luminosity a novel collision scheme, the so called 'large Piwinski angle with crab waist', has been designed. The scheme requires a short focus final doublet to reduce the vertical beta function down to {beta}*{sub y} = 0.2mm at the interaction point (IP). The final doublet will be composed by a set of permanent and superconducting (SC) quadrupoles. The SC quadrupole doublets QD0/QF1 will be placed as close to the IP as possible. This layout is critical because the space available for the doublets is very small. An advanced design of the quadrupole has been developed, based on the so-called helical coil concept. The paper discusses the design concept, the construction and the results of test of a model of the superconducting quadrupole based on NbTi technology. Future developments are also presented.

  4. Spin-slip structure and central peak phenomena in singlet-doublet system: Praseodymium

    DEFF Research Database (Denmark)

    Lindgård, Per-Anker

    1997-01-01

    A theory is given for the central peaks observed in praseodymium, which is an effective singlet-doublet System of localized spins. The dominant peak is due to induced longitudinal magnetic ordering, which can be accounted for by mode-mode coupling theory. The second, broader peak is due to an ind...

  5. Correlated four-component EPR g-tensors for doublet molecules

    DEFF Research Database (Denmark)

    Vad, M.S.; Pedersen, M.N.; Nørager, A.

    2013-01-01

    The first correlated ab initio four-component calculations of electron paramagnetic resonance (EPR) g-tensors for doublet radicals are reported. We have implemented a first-order degenerate perturbation theory approach based on the four-component Dirac-Coulomb Hamiltonian and fully relativistic c...

  6. Deformed pseudospin doublets as a fingerprint of a relativistic supersymmetry in nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Leviatan, A, E-mail: ami@phys.huji.ac.il [Racah Institute of Physics, The Hebrew University, Jerusalem 91904 (Israel)

    2011-01-01

    The single-particle spectrum of deformed shell-model states in nuclei, is shown to exhibit a supersymmetric pattern. The latter involves deformed pseudospin doublets and intruder levels. The underlying supersymmetry is associated with the relativistic pseudospin symmetry of the nuclear mean-field Dirac Hamiltonian with scalar and vector potentials.

  7. Deformed Pseudospin Doublets as a Fingerprint of a Relativistic Supersymmetry in Nuclei

    CERN Document Server

    Leviatan, A

    2010-01-01

    The single-particle spectrum of deformed shell-model states in nuclei, is shown to exhibit a supersymmetric pattern. The latter involves deformed pseudospin doublets and intruder levels. The underlying supersymmetry is associated with the relativistic pseudospin symmetry of the nuclear mean-field Dirac Hamiltonian with scalar and vector potentials.

  8. Nonclassical Effects of a Four-Level Excited-Doublet Atom Model

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jian-Song; XU Jing-Bo

    2006-01-01

    We adopt a dynamical algebraic method to study a four-level excited-doublet atom model and obtain the explicit expressions of the time-evolution operator and the density operator for the system. The nonclassical effects of the system, such as collapses and revivals of the atomic inversion and squeezing of the radiation field, are also discussed.

  9. Separation of the 1+/1− parity doublet in 20Ne

    Directory of Open Access Journals (Sweden)

    J. Beller

    2015-02-01

    Full Text Available The (J,T=(1,1 parity doublet in 20Ne at 11.26 MeV is a good candidate to study parity violation in nuclei. However, its energy splitting is known with insufficient accuracy for quantitative estimates of parity violating effects. To improve on this unsatisfactory situation, nuclear resonance fluorescence experiments using linearly and circularly polarized γ-ray beams were used to determine the energy difference of the parity doublet ΔE=E(1−−E(1+=−3.2(±0.7stat(−1.2+0.6sys keV and the ratio of their integrated cross sections Is,0(+/Is,0(−=29(±3stat(−7+14sys. Shell-model calculations predict a parity-violating matrix element having a value in the range 0.46–0.83 eV for the parity doublet. The small energy difference of the parity doublet makes 20Ne an excellent candidate to study parity violation in nuclear excitations.

  10. Experimental comparative study of doublet and triplet impinging atomization of gelled fuel based on PIV

    Science.gov (United States)

    Yang, Jian-lu; Li, Ning; Weng, Chun-sheng

    2016-10-01

    Gelled propellant is promising for future aerospace application because of its combination of the advantages of solid propellants and liquid propellants. An effort was made to reveal the atomization properties of gelled fuel by particle image velocimetry (PIV) system. The gelled fuel which was formed by gasoline and Nano-silica was atomized using a like-doublet impingement injector and an axisymmetric like-triplet impingement injector. The orifice diameter and length of the nozzle used in this work were of 0.8mm, 4.8mm, respectively. In the impinging spray process, the impingement angles were set at 90° and 120°, and the injection pressures were of 0.50MPa and 1.00MPa. The distance from the exit of the orifice to the impingement point was fixed at 9.6mm. In this study, high-speed visualization and temporal resolution particle image velocimetry techniques were employed to investigate the impingement atomization characteristics. The experimental investigation demonstrated that a long narrow high speed droplets belt formed around the axis of symmetry in the like-doublet impinging atomization area. However, there was no obvious high-speed belt with impingement angle 2θ = 90° and two high-speed belts appeared with impingement angle 2θ = 120° in the like-doublet impingement spray field. The high droplet velocity zone of the like-doublet impingement atomization symmetrically distributed around the central axis, and that of the like-triplet impingement spray deflected to the left of the central axis - opposite of injector. Although the droplets velocity distribution was asymmetry of like-triplet impingement atomization, the injectors were arranged like axisymmetric conical shape, and the cross section of spray area was similar to a circle rather than a narrow rectangle like the like-doublet impingement atomization.

  11. Premenopausal hormone-responsive breast cancer with extensive axillary nodes involvement: total estrogen blockade and chemotherapy.

    Science.gov (United States)

    Recchia, Francesco; Candeloro, Giampiero; Necozione, Stefano; Desideri, Giovambattista; Recchia, Cornelia Ortensia Carla; Piazze, Juan; Rea, Silvio

    2011-02-01

    Poor prognosis is associated with estrogen- and/or progesterone receptor-positive (ER(+), PGR(+)) premenopausal breast cancer (PM-BC) with high Ki-67 labeling index and extensive axillary lymph node involvement. The role of adjuvant chemotherapy (CT) and hormonal therapy have not yet been established in these patients. Twenty-five PM-BC patients received, in sequence, leuprorelin, taxane-anthracycline induction chemotherapy, radiation therapy, a platinum-based intensification high-dose CT, followed by leuprorelin and anastrazole for five years. Vascular endothelial growth factor (VEGF) levels were measured as the primary end-point; secondary end-points were 10-year relapse-free survival (RFS) and overall survival (OS) rates. The median patient age was 44 years, and the mean number of positive axillary nodes was 14. All patients were ER(+) and/or PGR(+), with a median Ki-67 index of 33%. Five patients were Cerb-B2 positive. Grade 4 hematologic toxicity was observed in all patients, no patient showed a decrease of cardiac ejection fraction and hot flashes and arthralgias were of moderate intensity. After a median follow-up of 70 months, VEGF levels significantly decreased (p<0.001); 10-year RFS and OS were 76% and 78%, respectively. Total estrogen blockade and high-dose CT in PM-BC patients is feasible, has moderate toxicity, significantly reduces VEGF levels, and seems to improve the expected RFS and OS.

  12. Chemotherapy for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Javier Sastre; Jose Angel García-Saenz; Eduardo Díaz-Rubio

    2006-01-01

    Metastatic gastric cancer remains a non-curative disease.Palliative chemotherapy has been demonstrated to prolong survival without quality of life compromise. Many single-agents and combinations have been confirmed to be active in the treatment of metastatic disease. Objective response rates ranged from 10-30% for single-agent therapy and 30-60% for polychemotherapy. Results of phase Ⅱ and Ⅲ studies are reviewed in this paper as well as the potential efficacy of new drugs. For patients with localized disease, the role of adjuvant and neoadjuvant chemotherapy and radiation therapy is discussed.Most studies on adjuvant chemotherapy failed to demonstrate a survival advantage, and therefore, it is not considered as standard treatment in most centres. Adjuvant immunochemotherapy has been developed fundamentally in Korea and Japan. A meta-analysis of phase Ⅲ trials with OK-432 suggested that immunochemotherapy may improve survival of patients with curatively resected gastric cancer. Based on the results of US Intergroup 0116study, postoperative chemoradiation has been Accepted as standard care in patients with resected gastric cancer in North America. However, the results are somewhat confounded by the fact that patients underwent less than a recommended D1 lymph node dissection and the pattern of recurrence suggested a positive effect derived from local radiotherapy without any effect on micrometastatic disease.Neoadjuvant chemotherapy or chemoradiation therapy remains experimental, but several phase Ⅱstudies are showing promising results. Phase Ⅲ trials are needed.

  13. Chemotherapy of herpesvirus infections.

    Science.gov (United States)

    Jawetz, E

    1975-07-01

    Herpesviruses commonly produce lesions that come to the attention of physicians. Many different chemicals are known to suppress the growth of herpesviruses in vitro, but only a few of these have found application in clinical practice. A critical assessment of the place of some of these forms of chemotherapy was briefly presented.

  14. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC. A phase III randomised controlled trial by the Norwegian Lung Cancer Study Group

    DEFF Research Database (Denmark)

    Fløtten, Ø; Grønberg, B H; Bremnes, R;

    2012-01-01

    BACKGROUND: Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare...... of radiotherapy did not differ significantly between the treatment groups. CONCLUSION: The two regimens yielded similar overall survival. The VG combination had only a slightly better toxicity profile....

  15. Doublet discharge stimulation increases sarcoplasmic reticulum Ca2+ release and improves performance during fatiguing contractions in mouse muscle fibres.

    Science.gov (United States)

    Cheng, Arthur J; Place, Nicolas; Bruton, Joseph D; Holmberg, Hans-Christer; Westerblad, Håkan

    2013-08-01

    Double discharges (doublets) of motor neurones at the onset of contractions increase both force and rate of force development during voluntary submaximal contractions. The purpose of this study was to examine the role of doublet discharges on force and myoplasmic free [Ca(2+)] ([Ca(2+)]i) during repeated fatiguing contractions, using a stimulation protocol mimicking the in vivo activation pattern during running. Individual intact fibres from the flexor digitorum brevis muscle of mice were stimulated at 33°C to undergo 150 constant-frequency (five pulses at 70 Hz) or doublet (an initial, extra pulse at 200 Hz) contractions at 300 ms intervals. In the unfatigued state, doublet stimulation resulted in a transient (∼10 ms) approximate doubling of [Ca(2+)]i, which was accompanied by a greater force-time integral (∼70%) and peak force (∼40%) compared to constant frequency contractions. Moreover, doublets markedly increased force-time integral and peak force during the first 25 contractions of the fatiguing stimulation. In later stages of fatigue, addition of doublets increased force production but the increase in force production corresponded to only a minor portion of the fatigue-induced reduction in force. In conclusion, double discharges at the onset of contractions effectively increase force production, especially in early stages of fatigue. This beneficial effect occurs without additional force loss in later stages of fatigue, indicating that the additional energy cost induced by doublet discharges to skeletal muscle is limited.

  16. Wave equations, dispersion relations, and van Hove singularities for applications of doublet mechanics to ultrasound propagation in bio- and nanomaterials

    Science.gov (United States)

    Wu, Junru; Layman, Christopher; Liu, Jun

    2004-02-01

    A fundamental mathematical framework for applications of Doublet Mechanics to ultrasound propagation in a discrete material is introduced. A multiscale wave equation, dispersion relation for longitudinal waves, and shear waves are derived. The van Hove singularities and corresponding highest frequency limits for the Mth-order wave equations of longitudinal and shear waves are determined for a widely used microbundle structure. Doublet Mechanics is applied to soft tissue and low-density polyethylene. The experimental dispersion data for soft tissue and low-density polyethylene are compared with results predicted by Doublet Mechanics and an attenuation model based on a Kramers-Kronig relation in classical continuum mechanics.

  17. Overexpression of eIF3a in Squamous Cell Carcinoma of the Oral Cavity and Its Putative Relation to Chemotherapy Response

    Directory of Open Access Journals (Sweden)

    Rita Spilka

    2012-01-01

    Full Text Available The eukaryotic translation initiation factor eIF3a is one of the core subunits of the translation initiation complex eIF3, responsible for ribosomal subunit joining and mRNA recruitment to the ribosome. It is known to play an important role in general translation initiation as well as in the specific translational regulation of various gene products, among which many influence tumour development, progression, and the therapeutically important pathways of DNA damage repair. Therefore, beyond its role in protein synthesis, eIF3a is emerging as regulator in tumour pathogenesis and therapy response and, therefore, a potential tumor marker. By means of a tissue microarray (TMA for histopathological and statistical assessment, we here show eIF3a expression in 103 cases of squamous cell carcinoma of the oral cavity (OSCC, representing tissues from 103 independent patients. A subset of the study cohort was treated with platinum based therapy. Our results show that the 170 kDa protein is upregulated in OSCC and correlates with good overall survival. Overexpressing tumors respond better to platinum-based chemotherapy, suggesting eIF3a as a putative predictive as well as prognostic tumor marker in OSCC.

  18. Prevent Infections During Chemotherapy

    Centers for Disease Control (CDC) Podcasts

    2011-10-24

    This podcast discusses the importance of preventing infections in cancer patients who are undergoing chemotherapy. Dr. Lisa Richardson, CDC oncologist, talks about a new Web site for cancer patients and their caregivers.  Created: 10/24/2011 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 10/24/2011.

  19. Chemotherapy of Leishmaniasis.

    Science.gov (United States)

    1978-12-01

    NOTES 1S. KEY WORDS (Continue on reverse side linscoeawy and identiIIy by block number) LEISHMANIA LEISHMANIASIS CHEMOTHERAPY ANTILEISHMANIAL PENTOSTAM...number of compounds was supplied by WRAIR for testing on four strains of Leishmania in December 1977. Preliminary data were supplied to WRAIR by the...j_ = L. tropica major (Strain LV39 from USSR) and the New World cutaneous leishmaniasis by L. mexicana amazonensis (Strain LV78 from Brazil). The test

  20. High-scale validity of a two Higgs doublet scenario: metastability included

    CERN Document Server

    Chakrabarty, Nabarun

    2016-01-01

    We make an attempt to identify regions in a Type II Two-Higgs Doublet Model, which correspond to a metastable electroweak vacuum with lifetime larger than the age of the universe. We analyse scenarios which retain perturbative unitarity up to Grand unification and Planck scales. Each point in the parameter space is restricted using Data from the Large Hadron Collider (LHC) as well as flavor and precision electroweak constraints. We find that substantial regions of the parameter space are thus identified as corresponding to metastability, which compliment the allowed regions for absolute stability, for top quark mass at the high as well as low end of its currently allowed range. Thus, a two-Higgs doublet scenario with the electroweak vacuum, either stable or metastable, can sail through all the way up to the Planck scale without facing any contradictions.

  1. The Mg 280-nm doublet as a monitor of changes in solar ultraviolet irradiance

    Science.gov (United States)

    Heath, D. F.; Schlesinger, B. M.

    1986-01-01

    Solar irradiance data gathered with the Nimbus 7 spacecraft from 1978-1985 are compared with atmospheric MG 289-nm doublet emission line data to evaluate the possibility of using the rotational line data to calculate the total solar UV input. The satellite instrumentation is described, including the calibration equipment and procedures. The spacecraft records solar irradiance once per day and the remainder of the time records irradiance scattered by the atmosphere. The measured irradiances are converted to equivalent brightness temperatures, which can be interpolated for specific layers of the atmosphere. Sample daily data are provided to illustrate the correlation between variations in the Mg-II core radiation and the soalr UV irradiance. Techniques are defined for correcting for periodic variations in instrument performance to quantify long-term solar UV radiance variations. Using the atmospheric Mg-II doublet radiation for measuring soalr UV irradiance is concluded of value for characterizing the effects of solar radiation on the atmosphere.

  2. A rotated transmission grating spectrometer for detecting spectral separation of doublet Na

    Energy Technology Data Exchange (ETDEWEB)

    Santosa, Ignatius Edi [Department of Physics Education, Sanata Dharma University, Paingan Maguwohardjo Depok Sleman, Yogyakarta 55281, Indonesia edi@usd.ac.id (Indonesia)

    2015-04-16

    Transmission gratings are usually used in a spectrometer for measuring the wavelength of light. In the common design, the position of the grating is perpendicular to the incident light. In order to increase the angular dispersion, in contrary to the common design, in this experiment the transmission grating was rotated. Due to the non-zero incident angle, the diffracted light was shifted. This rotated transmission grating spectrometer has been used to determine the separation of doublet Na. In this experiment, the diffraction angle was measured at various incident angles. The spectral separation of doublet Na was identified from the difference in the diffraction angle of two spectral lines. This spectral separation depends on the incident angle, the grating constant and the order of diffraction. As the effect of increasing the incident angle, a significant increase of the spectral separation can be achieved up to three fold.

  3. Energy splitting of the ground-state doublet in the nucleus 229Th.

    Science.gov (United States)

    Beck, B R; Becker, J A; Beiersdorfer, P; Brown, G V; Moody, K J; Wilhelmy, J B; Porter, F S; Kilbourne, C A; Kelley, R L

    2007-04-01

    The energy splitting of the 229Th ground-state doublet is measured to be 7.6+/-0.5 eV, significantly greater than earlier measurements. Gamma rays produced following the alpha decay of 233U (105 muCi) were counted in the NASA/electron beam ion trap x-ray microcalorimeter spectrometer with an experimental energy resolution of 26 eV (FWHM). A difference technique was applied to the gamma-ray decay of the 71.82 keV level that populates both members of the doublet. A positive correction amounting to 0.6 eV was made for the unobserved interband decay of the 29.19 keV state (29.19-->0 keV).

  4. Energy Splitting of the Ground-State Doublet in the Nucleus Th229

    Science.gov (United States)

    Beck, B. R.; Becker, J. A.; Beiersdorfer, P.; Brown, G. V.; Moody, K. J.; Wilhelmy, J. B.; Porter, F. S.; Kilbourne, C. A.; Kelley, R. L.

    2007-04-01

    The energy splitting of the Th229 ground-state doublet is measured to be 7.6±0.5eV, significantly greater than earlier measurements. Gamma rays produced following the alpha decay of U233 (105μCi) were counted in the NASA/electron beam ion trap x-ray microcalorimeter spectrometer with an experimental energy resolution of 26 eV (FWHM). A difference technique was applied to the gamma-ray decay of the 71.82 keV level that populates both members of the doublet. A positive correction amounting to 0.6 eV was made for the unobserved interband decay of the 29.19 keV state (29.19→0keV).

  5. Ultrasound Attenuation in Biological Tissue Predicted by the Modified Doublet Mechanics Model

    Institute of Scientific and Technical Information of China (English)

    JIANG Xin; LIU Xiao-Zhou; WU Jun-Ru

    2009-01-01

    Experimental results have shown that in the megahertz frequency range the relationship between the acoustic attenuation coefficient in soft tissues and frequency is nearly linear. The classical continuum mechanics (CCM),which assumes that the material is uniform and continuous, fails to explain this relationship particularly in the high megahertz range. Doublet mechanics (DM) is a new elastic theory which takes the discrete nature of material into account. The current DM theory however does not consider the loss. We revise the doublet mechanics (DM)theory by including the loss term, and calculate the attenuation of a soft tissue as a function of frequency using the modified the DM theory (MDM). The MDM can now well explain the nearly linear relationship between the acoustic attenuation coefficient in soft tissues and frequency.

  6. Photochemistry of atomic oxygen green and red-doublet emissions in comets at larger heliocentric distances

    Science.gov (United States)

    Raghuram, Susarla; Bhardwaj, Anil

    2014-06-01

    Context. In comets, the atomic oxygen green (5577 Å) to red-doublet (6300, 6364 Å) emission intensity ratio (G/R ratio) of 0.1 has been used to confirm H2O as the parent species producing forbidden oxygen emission lines. The larger (>0.1) value of G/R ratio observed in a few comets is ascribed to the presence of higher CO2 and CO relative abundances in the cometary coma. Aims: We aim to study the effect of CO2 and CO relative abundances on the observed G/R ratio in comets observed at large (>2 au) heliocentric distances by accounting for important production and loss processes of O(1S) and O(1D) atoms in the cometary coma. Methods: Recently we have developed a coupled chemistry-emission model to study photochemistry of O(1S) and O(1D) atoms and the production of green and red-doublet emissions in comets Hyakutake and Hale-Bopp. In the present work we applied the model to six comets where green and red-doublet emissions are observed when they are beyond 2 au from the Sun. Results: The collisional quenching of O(1S) and O(1D) can alter the G/R ratio more significantly than that due to change in the relative abundances of CO2 and CO. In a water-dominated cometary coma and with significant (>10%) CO2 relative abundance, photodissociation of H2O mainly governs the red-doublet emission, whereas CO2 controls the green line emission. If a comet has equal composition of CO2 and H2O, then ~50% of red-doublet emission intensity is controlled by the photodissociation of CO2. The role of CO photodissociation is insignificant in producing both green and red-doublet emission lines and consequently in determining the G/R ratio. Involvement of multiple production sources in the O(1S) formation may be the reason for the observed higher green line width than that of red lines. The G/R ratio values and green and red-doublet line widths calculated by the model are consistent with the observation. Conclusions: Our model calculations suggest that in low gas production rate comets the G

  7. The dispersive properties of an excited-doublet four-level atomic system

    Institute of Scientific and Technical Information of China (English)

    Hu Zheng-Feng; Deng Jian-Liao; Wang Yu-Zhu

    2008-01-01

    We have investigated the dispersive properties of excited-doublet four-level atoms interacting with a weak probe field and an intense coupling laser field.We have derived an analytical expression of the dispersion relation for a general excited-doublet four-level atomic system sunject to a one-photon detuning.The numerical results demonstrate that for a typical rubidium D1 line configuration,due to the unequal dipole moments for the transitions of each ground state to double excited states,generally there exists no exact dark state in the system.Close to the two-photon resonance,the probe light can be absorbed or gained and propagate in the so-called superluminal form.This system may be used as an optical switch.

  8. CP violating Two-Higgs-Doublet Model: constraints and LHC predictions

    Energy Technology Data Exchange (ETDEWEB)

    Keus, Venus [Department of Physics and Helsinki Institute of Physics,University of Helsinki, Gustaf Hallstromin katu 2, FIN-00014 (Finland); School of Physics and Astronomy, University of Southampton,Southampton, SO17 1BJ (United Kingdom); King, Stephen F. [School of Physics and Astronomy, University of Southampton,Southampton, SO17 1BJ (United Kingdom); Moretti, Stefano [School of Physics and Astronomy, University of Southampton,Southampton, SO17 1BJ (United Kingdom); Particle Physics Department, Rutherford Appleton Laboratory,Chilton, Didcot, Oxon OX11 0QX (United Kingdom); Yagyu, Kei [School of Physics and Astronomy, University of Southampton,Southampton, SO17 1BJ (United Kingdom)

    2016-04-08

    Two-Higgs-Doublet Models (2HDMs) are amongst the simplest extensions of the Standard Model. Such models allow for tree-level CP Violation (CPV) in the Higgs sector. We analyse a class of CPV 2HDM (of Type-I) in which only one of the two Higgs doublets couples to quarks and leptons, avoiding dangerous Flavour Changing Neutral Currents. We provide an up to date and comprehensive analysis of the constraints and Large Hadron Collider (LHC) predictions of such a model. Of immediate interest to the LHC Run 2 is the golden channel where all three neutral Higgs bosons are observed to decay into gauge boson pairs, WW and ZZ, providing a smoking gun signature of the CPV 2HDM.

  9. Enhanced coherence of a quantum doublet coupled to Tomonaga-Luttinger liquid leads

    Energy Technology Data Exchange (ETDEWEB)

    Cirillo, Antonio, E-mail: antonio.cirillo@fisica.unipg.it [Dipartimento di Fisica, Universita di Perugia, Via A. Pascoli, I-06123, Perugia (Italy); I.N.F.N., Sezione di Perugia, Via A. Pascoli, I-06123, Perugia (Italy); Mancini, Matteo, E-mail: matteo.mancini@fisica.unipg.it [Dipartimento di Fisica, Universita di Perugia, Via A. Pascoli, I-06123, Perugia (Italy); I.N.F.N., Sezione di Perugia, Via A. Pascoli, I-06123, Perugia (Italy); Giuliano, Domenico, E-mail: domenico.giuliano@fis.unical.it [Dipartimento di Fisica, Universita della Calabria, Arcavacata di Rende I-87036, Cosenza (Italy); I.N.F.N., Gruppo Collegato di Cosenza, Arcavacata di Rende I-87036, Cosenza (Italy); Sodano, Pasquale, E-mail: pasquale.sodano@pg.infn.it [Perimeter Institute for Theoretical Physics, 31 Caroline St. N, Waterloo ON, N2L 2Y5 (Canada); Dipartimento di Fisica, Universita di Perugia, Via A. Pascoli, I-06123, Perugia (Italy); I.N.F.N., Sezione di Perugia, Via A. Pascoli, I-06123, Perugia (Italy)

    2011-11-01

    We use boundary field theory to describe the phases accessible to a tetrahedral qubit coupled to Josephson junction chains acting as Tomonaga-Luttinger liquid leads. We prove that, in a pertinent range of the fabrication and control parameters, an attractive finite coupling fixed point emerges due to the geometry of the composite Josephson junction network. We show that this new stable phase is characterized by the emergence of a quantum doublet which is robust not only against the noise in the external control parameters (magnetic flux, gate voltage) but also against the decoherence induced by the coupling of the tetrahedral qubit with the superconducting leads. We provide protocols allowing to read and to manipulate the state of the emerging quantum doublet and argue that a tetrahedral Josephson junction network operating near the new finite coupling fixed point may be fabricated with today's technologies.

  10. High-scale validity of a two-Higgs-doublet scenario: metastability included

    Energy Technology Data Exchange (ETDEWEB)

    Chakrabarty, Nabarun; Mukhopadhyaya, Biswarup [Harish-Chandra Research Institute, Regional Centre for Accelerator-based Particle Physics, Allahabad (India)

    2017-03-15

    We identify regions in a Type-II two-Higgs-doublet model which correspond to a metastable electroweak vacuum with lifetime larger than the age of the universe. We analyse scenarios which retain perturbative unitarity up to grand unification and Planck scales. Each point in the parameter space is restricted using data from the Large Hadron Collider (LHC) as well as flavour and precision electroweak constraints. We find that substantial regions of the parameter space are thus identified as corresponding to metastability, which complement the allowed regions for absolute stability, for top quark mass at the high as well as low end of its currently allowed range. Thus, a two-Higgs-doublet scenario with the electroweak vacuum, either stable or metastable, can sail through all the way up to the Planck scale without facing any contradiction. (orig.)

  11. Mu to e gamma in the 2 Higgs Doublet Model: an exercise in EFT

    CERN Document Server

    Davidson, Sacha

    2016-01-01

    The 2 Higgs Doublet Model (2HDM) of type III has renormalisable Lepton Flavour-Violating couplings, and its one and two-loop ("Barr-Zee") contributions to $\\mu \\to e \\gamma$ are known. In the decoupling limit, where the mass scale M of the second doublet is much greater than the electroweak scale, the model can be parametrised with an Effective Field Theory(EFT) containing dimension six operators. The $1/M^2$ terms of the exact calculation are reproduced in the EFT, provided that the four-fermion operator basis below the weak scale is enlarged with respect to the SU(2)-invariant Buchmuller-Wyler list. The two-loop "Barr-Zee" contributions are located in the EFT, showing that two-loop matching and running would be required to obtain the most important contributions, and that dimension eight operators can be numerically relevant.

  12. CP Violating Two-Higgs-Doublet Model: Constraints and LHC Predictions

    CERN Document Server

    Keus, Venus; Moretti, Stefano; Yagyu, Kei

    2015-01-01

    Two-Higgs-Doublet Models (2HDMs) are amongst the simplest extensions of the Standard Model. Such models allow for tree-level CP Violation (CPV) in the Higgs sector. We analyse a class of CPV 2HDM (of Type-I) in which only one of the two Higgs doublets couples to quarks and leptons, avoiding dangerous Flavour Changing Neutral Currents. We provide an up to date and comprehensive analysis of the constraints and Large Hadron Collider (LHC) predictions of such a model. Of immediate interest to the LHC Run 2 is the golden channel where all three neutral Higgs bosons are observed to decay into gauge boson pairs, $WW$ and $ZZ$, providing a smoking gun signature of the CPV 2HDM.

  13. Baryogenesis in the two doublet and inert singlet extension of the Standard Model

    DEFF Research Database (Denmark)

    Alanne, Tommi; Kainulainen, Kimmo; Tuominen, Kimmo

    2016-01-01

    We investigate an extension of the Standard Model containing two Higgs doublets and a singlet scalar field (2HDSM). We show that the model can have a strongly first-order phase transition and give rise to the observed baryon asymmetry of the Universe, consistent with all experimental constraints....... In particular, the constraints from the electron and neutron electric dipole moments are less constraining here than in pure two-Higgs-doublet model (2HDM). The two-step, first-order transition in 2HDSM, induced by the singlet field, may lead to strong supercooling and low nucleation temperatures in comparison...... with the critical temperature, Tn Tc, which can significantly alter the usual phase-transition pattern in 2HD models with Tn ≈ Tc. Furthermore, the singlet field can be the dark matter particle. However, in models with a strong first-order transition its abundance is typically but a thousandth of the observed dark...

  14. Cold Baryogenesis from first principles in the Two-Higgs Doublet model with Fermions

    CERN Document Server

    Mou, Zong-Gang; Tranberg, Anders

    2015-01-01

    We present a first-principles numerical computation of the baryon asymmetry in electroweak-scale baryogenesis. For the scenario of Cold Baryogenesis, we consider a one fermion-family reduced CP-violating two Higgs-doublet model, including a classical SU(2)-gauge/two-Higgs sector coupled to one quantum left-handed fermion doublet and two right-handed singlets. Separately, the C(CP) breaking of the two-Higgs potential and the C and P breaking of the gauge-fermion interactions do not provide a baryon asymmetry. Only when combined does baryogenesis occur. Through large-scale computer simulations, we compute the asymmetry for one particularly favourable scalar potential. The numerical signal is at the boundary of what is numerically discernible with the available computer resources, but we tentatively find an asymmetry of $|\\eta|\\leq 3.5\\times 10^{-7}$.

  15. New decay modes of heavy Higgs bosons in a two Higgs doublet model with vectorlike leptons

    CERN Document Server

    Dermisek, Radovan; Shin, Seodong

    2015-01-01

    In models with extended Higgs sector and additional matter fields, the decay modes of heavy Higgs bosons can be dominated by cascade decays through the new fermions rendering present search strategies ineffective. We investigate new decay topologies of heavy neutral Higgses in two Higgs doublet model with vectorlike leptons. We also discuss constraints from existing searches and discovery prospects. Among the most interesting signatures are monojet, mono Z, mono Higgs, and Z and Higgs bosons produced with a pair of charged leptons.

  16. Implications of b{yields}s{gamma} in the Weinberg three-Higgs-doublet models

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Darwin; Chen, Chuan-Hung; Geng, Chao-Qiang [National Tsing Hua Univ., Hsinchu, TW (China). Dept. of Physics

    1996-06-01

    Using recent experimental measurements on Br(b{yields}s{gamma}) from CLEO, we study the constraints on the charged Higgs sector in various three-Higgs-doublet models. Some phenomenological implications in these models with emphasis on CP violation are presented. In particular, in some of these models, the CP violating muon polarization in K{sub {mu}3} can be detected using the current KEK experiment E246. (author)

  17. Exploring the Origin of Nearly Degenerate Doublet Bands in Ag106

    Science.gov (United States)

    Rather, N.; Datta, P.; Chattopadhyay, S.; Rajbanshi, S.; Goswami, A.; Bhat, G. H.; Sheikh, J. A.; Roy, S.; Palit, R.; Pal, S.; Saha, S.; Sethi, J.; Biswas, S.; Singh, P.; Jain, H. C.

    2014-05-01

    The lifetimes of the excited levels for the two nearly degenerate bands of Ag106 have been measured using the Doppler-shift attenuation method. The deduced B(E2) and B(M1) rates in the two bands are found to be similar, except around the band crossing spin, while their moments of inertia are quite different. This is a novel observation for a nearly degenerate doublet band.

  18. Pseudo-Goldstone Higgs Doublets from Non-Vectorlike Grand Unified Higgs Sector

    CERN Document Server

    Hernández, A E Cárcamo

    2016-01-01

    We present a novel way of realizing the pseudo-Nambu-Goldstone boson mechanism for the doublet-triplet splitting in supersymmetric grand unified theories. The global symmetries of the Higgs sector are attributed to a non-vectorlike Higgs content, which is consistent with unbroken supersymmetry in a scenario with flat extra dimensions and branes. We also show how in such a model one can naturally obtain a realistic pattern for the Standard Model fermion masses and mixings.

  19. Higgs-Mediated e -> mu transitions in II Higgs doublet Model and Supersymmetry

    CERN Document Server

    Paradisi, P

    2006-01-01

    We study the phenomenology of the e-mu lepton flavour violation (LFV) in a general two Higgs Doublet Model (2HDM) including the supersymmetric case. We compute the decay rate expressions of mu -> e gamma, mu -> eee, and mu -> e conversion in nuclei at two loop level. In particular, it is shown that mu -> e gamma is generally the most sensitive channels to probe Higgs-mediated LFV. The correlations among the decay rates of the above processes are also discussed.

  20. Searching the charged Higgs boson of the type III two Higss doublet model

    CERN Document Server

    Cardenas, H

    2008-01-01

    In the framework of the Two Higgs Doublet Model (2HDM) type III appears two charged Higgs boson and recently there are experimental reports from D0 and CDF collaborations searching a particular signature of new physics. We present a review of the analisys done in the region $M_{H^+}>m_t$ by D0 collaboration and we use the ratio $R_\\sigma$ for the region $M_{H^+} < m_t$ in different scenarios of space parameter of this model.

  1. FCNI suppression and CP violation in a two-Higgs-doublet model

    Energy Technology Data Exchange (ETDEWEB)

    Epele, L.; Fanchiotti, H.; Canal, C.G.; Dumm, D.G. (La Plata Univ. Nacional (Argentina). Dept. de Fisica)

    1994-08-01

    A two-Higgs-doublet model including a tree-level suppression mechanism for flavour-changing neutral interactions is analysed. In this framework, explicit CT violation is considered. One finds the model capable of saturating the neutron EDM experimental bound while simultaneously preserving the correct low-energy predictions of the standard model. A compatibility check with the observed CP violation phenomena in kaon physics is also presented. (Author).

  2. The two Suvasvesi impact structures, Finland: Argon isotopic evidence for a "false" impact crater doublet

    Science.gov (United States)

    Schmieder, Martin; Schwarz, Winfried H.; Trieloff, Mario; Buchner, Elmar; Hopp, Jens; Tohver, Eric; Pesonen, Lauri J.; Lehtinen, Martti; Moilanen, Jarmo; Werner, Stephanie C.; Öhman, Teemu

    2016-05-01

    The two neighboring Suvasvesi North and South impact structures in central-east Finland have been discussed as a possible impact crater doublet produced by the impact of a binary asteroid. This study presents 40Ar/39Ar geochronologic data for impact melt rocks recovered from the drilling into the center of the Suvasvesi North impact structure and melt rock from glacially transported boulders linked to Suvasvesi South. 40Ar/39Ar step-heating analysis yielded two essentially flat age spectra indicating a Late Cretaceous age of ~85 Ma for the Suvasvesi North melt rock, whereas the Suvasvesi South melt sample gave a Neoproterozoic minimum (alteration) age of ~710 Ma. Although the statistical likelihood for two independent meteorite strikes in close proximity to each other is rather low, the remarkable difference in 40Ar/39Ar ages of >600 Myr for the two Suvasvesi impact melt samples is interpreted as evidence for two temporally separate, but geographically closely spaced, impacts into the Fennoscandian Shield. The Suvasvesi North and South impact structures are, thus, interpreted as a "false" crater doublet, similar to the larger East and West Clearwater Lake impact structures in Québec, Canada, recently shown to be unrelated. Our findings have implications for the reliable recognition of impact crater doublets and the apparent rate of binary asteroid impacts on Earth and other planetary bodies in the inner solar system.

  3. Chiral heavy fermions in a two Higgs doublet model: 750 GeV resonance or not

    CERN Document Server

    Bar-Shalom, Shaouly

    2016-01-01

    We revisit models where a heavy chiral 4th generation doublet of fermions is embedded in a class of two Higgs doublets models (2HDM) with a discrete $Z_2$ symmetry, which couples the "heavy" scalar doublet only to the 4th generation fermions and the "light" one to the Standard Model (SM) fermions - the so-called 4G2HDM introduced by us several years ago. We study the constraints imposed on the 4G2HDM from direct searches of heavy fermions, from precision electroweak data (PEWD) and from the measured production and decay signals of the 125 GeV scalar, which in the 4G2HDM corresponds to the lightest CP-even scalar h. We then show that the recently reported excess in the $\\gamma\\gamma$ spectrum around 750 GeV can be accommodated by the heavy CP-even scalar of the 4G2HDM, H, resulting in a unique choice of parameter space: negligible mixing (sin\\alpha ~ O(0.001)) between the two CP-even scalars h,H and heavy 4th generation quark and lepton masses m_t',m_b' 900 GeV, respectively. Whether or not the 750 GeV \\gamma...

  4. Higgs boson couplings in multi-doublet models with natural flavour conservation

    Directory of Open Access Journals (Sweden)

    Kei Yagyu

    2016-12-01

    Full Text Available We investigate the deviation in the couplings of the standard model (SM like Higgs boson (h with a mass of 125 GeV from the prediction of the SM in multi-doublet models within the framework where flavour changing neutral currents at the tree level are naturally forbidden. After we present the general expressions for the modified gauge and Yukawa couplings for h, we show the correlation between the deviation in the Yukawa coupling for the tau lepton hτ+τ− and that for the bottom quark hbb¯ under the assumption of a non-zero deviation in the hVV (V=W,Z couplings in two Higgs doublet models (2HDMs and three Higgs doublet models (3HDMs as simple examples. We clarify the possible allowed prediction of the deviations in the 3HDMs which cannot be explained in the 2HDMs even taking into account the one-loop electroweak corrections to the Yukawa coupling.

  5. Photochemistry of atomic oxygen green and red-doublet emissions in comets at larger heliocentric distances

    CERN Document Server

    Raghuram, Susarla

    2014-01-01

    In comets the atomic oxygen green to red-doublet emission intensity ratio (G/R ratio) of 0.1 has been used to confirm H$_2$O as the parent species producing oxygen emission lines. The larger ($>$0.1) value of G/R ratio observed in a few comets is ascribed to the presence of higher CO$_2$ and CO relative abundances in the cometary coma. We aim to study the effect of CO$_2$ and CO relative abundances on the observed G/R ratio in comets observed at large ($>$2 au) heliocentric distances by accounting for important production and loss processes of O($^1$S) and O($^1$D) in the cometary coma. Recently we have developed a coupled chemistry-emission model to study photochemistry of O($^1$S) and O($^1$D) atoms and the production of green and red-doublet emissions in comets Hyakutake and Hale-Bopp. In the present work we applied the model to six comets where green and red-doublet emissions are observed when they are beyond 2 au from the Sun. In a water-dominated cometary coma and with significant ($>$10%) CO$_2$ relati...

  6. Calculation of Doublet Capture Rate for Muon Capture in Deuterium within Chiral Effective Field Theory

    CERN Document Server

    Adam, J; Tater, M; Truhlik, E; Epelbaum, E; Machleidt, R; Ricci, P

    2011-01-01

    The doublet capture rate of the negative muon capture in deuterium is calculated employing the nuclear wave functions generated from accurate nucleon-nucleon potentials constructed at next-to-next-to-next-to-leading order of heavy-baryon chiral perturbation theory and the weak meson exchange current operator derived within the same formalism. All but one of the low-energy constants that enter the calculation were fixed from pion-nucleon and nucleon-nucleon scattering data. The low-energy constant d^R (c_D), which cannot be determined from the purely two-nucleon data, was extracted recently from the triton beta-decay and the binding energies of the three-nucleon systems. The calculated values of the doublet capture rates show a rather large spread for the used values of the d^R. Precise measurement of the doublet capture rate in the future will not only help to constrain the value of d^R, but also provide a highly nontrivial test of the nuclear chiral EFT framework. Besides, the precise knowledge of the consta...

  7. The 125 GeV Higgs in the context of four generations with 2 Higgs doublets

    CERN Document Server

    Geller, Michael; Eilam, Gad; Soni, Amarjit

    2012-01-01

    We interpret the recent discovery of a 125 GeV Higgs-like state in the context of a two Higgs doublets model with a heavy 4th sequential generation of fermions, in which one Higgs doublet couples only to the 4th generation fermions, while the second doublet couples to the lighter fermions of the 1st-3rd families. This model is designed to accommodate the apparent heaviness of the 4th generation fermions and to effectively address the low-energy phenomenology of a dynamical electroweak symmetry breaking scenario. The physical Higgs states of the model are, therefore, viewed as composites primarily of the 4th generation fermions. We find that the lightest Higgs, h, is a good candidate for the recently discovered 125 GeV spin-zero particle, when tan\\beta ~ O(1), for typical 4th generation fermion masses of M_{4G} = 400 -600 GeV, and with a large t - t' mixing in the right-handed quarks sector. This, in turn, leads to BR(t' -> t h) ~ O(1), which drastically changes the t' decay pattern. We also find that, based o...

  8. Doublet III limiter performance and implications for mechanical design and material selection for future limiters

    Energy Technology Data Exchange (ETDEWEB)

    Sabado, M.M.; Marcus, F.B.; Trester, P.W.; Wesley, J.C.

    1979-10-01

    The plasma limiter system for Doublet III is described. Initially, high-Z materials, Ta-10W for the primary limiter and Mo for the backup limiters, were selected as the most attractive metallic candidates from the standpoint of thermal and structural properties. For the purpose of evaluating the effect of material Z on plasma performance, the nonmagnetic, Ni-base alloy Inconel X-750 was selected for a medium-Z limiter material. Graphite, a low-Z material, will likely be the next limiter material for evaluation. Design and material selection criteria for the different Z ranges are presented. The performance of the high-Z limiters in Doublet III is reviewed for an operation period that included approximately 5000 plasma shots. Changes in surface appearance and metallurgical changes are characterized. Discussion is presented on how and to what extent the high-Z elements affected the performance of the plasma based on theory and measurements in Doublet III. The fabrication processes for the Inconel X-750 limiters are summarized, and, last, observations on early performance of the Inconel limiters are described. (MOW)

  9. Two Higgs Doublet Type III Seesaw with mu-tau symmetry at LHC

    CERN Document Server

    Bandyopadhyay, Priyotosh; Mitra, Manimala

    2009-01-01

    We propose a two Higgs doublet Type III seesaw model with $\\mu$-$\\tau$ flavor symmetry. We add an additional SU(2) Higgs doublet and three SU(2) fermion triplets in our model. The presence of two Higgs doublets allows for natural explanation of small neutrino masses with triplet fermions in the 100 GeV mass range, without fine tuning of the Yukawa couplings to extremely small values. The triplet fermions couple to the gauge bosons and can be thus produced at the LHC. We study in detail the effective cross-sections for the production and subsequent decays of these heavy exotic fermions. We show for the first time that the $\\mu$-$\\tau$ flavor symmetry in the low energy neutrino mass matrix results in mixing matrices for the neutral and charged heavy fermions that are not unity and which carry the flavor symmetry pattern. This flavor structure can be observed in the decays of the heavy fermions at LHC. The large Yukawa couplings in our model result in the decay of the heavy fermions into lighter leptons and Higg...

  10. Measuring galaxy [OII] emission line doublet with future ground-based wide-field spectroscopic surveys

    CERN Document Server

    Comparat, Johan; Bacon, Roland; Mostek, Nick J; Newman, Jeffrey A; Schlegel, David J; Yèche, Christophe

    2013-01-01

    The next generation of wide-field spectroscopic redshift surveys will map the large-scale galaxy distribution in the redshift range 0.7< z<2 to measure baryonic acoustic oscillations (BAO). The primary optical signature used in this redshift range comes from the [OII] emission line doublet, which provides a unique redshift identification that can minimize confusion with other single emission lines. To derive the required spectrograph resolution for these redshift surveys, we simulate observations of the [OII] (3727,3729) doublet for various instrument resolutions, and line velocities. We foresee two strategies about the choice of the resolution for future spectrographs for BAO surveys. For bright [OII] emitter surveys ([OII] flux ~30.10^{-17} erg /cm2/s like SDSS-IV/eBOSS), a resolution of R~3300 allows the separation of 90 percent of the doublets. The impact of the sky lines on the completeness in redshift is less than 6 percent. For faint [OII] emitter surveys ([OII] flux ~10.10^{-17} erg /cm2/s like ...

  11. Higgs boson couplings in multi-doublet models with natural flavour conservation

    CERN Document Server

    Yagyu, Kei

    2016-01-01

    We investigate the deviation in couplings of the standard model (SM) like Higgs boson ($h$) with the mass of 125 GeV from the prediction of the SM in multi-doublet models within the framework where flavour changing neutral currents at the tree level are naturally forbidden. After we present the general expressions for the modified gauge and Yukawa couplings for $h$, we show the correlation between the deviation in the Yukawa coupling for the tau lepton $h\\tau^+\\tau^-$ and that for the bottom quark $hb\\bar{b}$ under the assumption of a non-zero deviation in the $hVV$ $(V=W,Z)$ couplings in two Higgs doublet models (2HDMs) and three Higgs doublet models (3HDMs) as the simple examples. We clarify the possible allowed prediction of the deviations in the 3HDMs which cannot be explained in the 2HDMs even taking into account the one-loop electroweak corrections to the Yukawa coupling.

  12. Epidemiology of doublet/multiplet mutations in lung cancers: evidence that a subset arises by chronocoordinate events.

    Directory of Open Access Journals (Sweden)

    Zhenbin Chen

    Full Text Available BACKGROUND: Evidence strongly suggests that spontaneous doublet mutations in normal mouse tissues generally arise from chronocoordinate events. These chronocoordinate mutations sometimes reflect "mutation showers", which are multiple chronocoordinate mutations spanning many kilobases. However, little is known about mutagenesis of doublet and multiplet mutations (domuplets in human cancer. Lung cancer accounts for about 25% of all cancer deaths. Herein, we analyze the epidemiology of domuplets in the EGFR and TP53 genes in lung cancer. The EGFR gene is an oncogene in which doublets are generally driver plus driver mutations, while the TP53 gene is a tumor suppressor gene with a more typical situation in which doublets derive from a driver and passenger mutation. METHODOLOGY/PRINCIPAL FINDINGS: EGFR mutations identified by sequencing were collected from 66 published papers and our updated EGFR mutation database (www.egfr.org. TP53 mutations were collected from IARC version 12 (www-p53.iarc.fr. For EGFR and TP53 doublets, no clearly significant differences in race, ethnicity, gender and smoking status were observed. Doublets in the EGFR and TP53 genes in human lung cancer are elevated about eight- and three-fold, respectively, relative to spontaneous doublets in mouse (6% and 2.3% versus 0.7%. CONCLUSIONS/SIGNIFICANCE: Although no one characteristic is definitive, the aggregate properties of doublet and multiplet mutations in lung cancer are consistent with a subset derived from chronocoordinate events in the EGFR gene: i the eight frameshift doublets (present in 0.5% of all patients with EGFR mutations are clustered and produce a net in-frame change; ii about 32% of doublets are very closely spaced (< or =30 nt; and iii multiplets contain two or more closely spaced mutations. TP53 mutations in lung cancer are very closely spaced (< or =30 nt in 33% of doublets, and multiplets generally contain two or more very closely spaced mutations. Work in

  13. Photonic generation of ultrawideband monocycle and doublet pulses by using a semiconductor-optical-amplifier-based wavelength converter

    DEFF Research Database (Denmark)

    Zhou, Enbo; Yu, Xianbin; Zhang, Xinliang;

    2009-01-01

    Photonic generation of ultrawideband (UWB) monocycle and doublet pulses is experimentally demonstrated using a cascaded electroabsorption modulator (EAM) and semiconductor optical amplifier by exploiting a combination of cross-absorption modulation and cross-gain modulation. The polarities...... and shapes of UWB monocycle and doublet pulses can be simply controlled using an optical time-delay controller and the reverse voltage applied to the EAM. The corresponding measured rf spectra meet the UWB criteria....

  14. Wide-scale detection of earthquake waveform doublets and further evidence for inner core super-rotation

    Science.gov (United States)

    Zhang, Jian; Richards, Paul G.; Schaff, David P.

    2008-09-01

    We report on more than 100 earthquake waveform doublets in five subduction zones, including an earthquake nest in Bucaramanga, Colombia. Each doublet is presumed to be a pair of earthquakes that repeat at essentially the same location. These doublets are important for studying earthquake physics, as well as temporal changes of the inner core. Particularly, our observation from one South Sandwich Islands (SSI) doublet recorded at station INK in Canada shows an inner core traveltime change of ~0.1 s over ~6 yr, confirming the inner-core differential motion occurring beneath Central America. Observations from one Aleutian Islands doublet, recorded at station BOSA in South Africa, and from one Kuril Islands doublet, recorded at station BDFB in Brazil, show an apparent inner core traveltime change of ~0.1 s over ~7 yr and ~6 yr, respectively, providing evidence for the temporal change of inner core properties beneath Central Asia and Canada, respectively. On the other hand, observations from one Tonga-Fiji-Solomon Islands doublet, recorded at station PTGA in Brazil, and from one Bucaramanga doublet, recorded at station WRAB in Australia and station CHTO in Thailand, show no/little temporal change (no more than 0.005 s yr-1, if any) of inner core traveltimes for the three corresponding ray paths for which the path in the inner core is nearly parallel to the equatorial plane. Such a pattern of observations showing both presence and possible absence of inner-core traveltime change can be explained by the geometry and relative directions of ray path, lateral velocity gradient and inner-core particle motion due to an eastward super-rotation of a few tenths of a degree per year.

  15. Why chemotherapy can fail?

    Science.gov (United States)

    Król, M; Pawłowski, K M; Majchrzak, K; Szyszko, K; Motyl, T

    2010-01-01

    There are many reasons that lead to failure of cancer chemotherapy. Cancer has the ability to become resistant to many different types of drugs. Increased efflux of drug, enhanced repair/increased tolerance to DNA damage, high antiapoptotic potential, decreased permeability and enzymatic deactivation allow cancer cell survive the chemotherapy. Treatment can lead to the death of most tumor cells (drug-sensitive), but some of them (drug-resistant) survive and grow again. These tumor cells may arise from stem cells. There are many studies describing human experiments with multidrug resistance, especially in breast cancer. Unfortunately, studies of canine or feline ABC super family members are not as extensive as in human or mice and they are limited to several papers describing PGP in mammary cancer, cutaneous mast cell tumors and lymphoma. Multidrug resistance is one of the most significant problems in oncology today. The involvement of many different, not fully recognized, mechanisms in multidrug resistance of cancer cells makes the development of effective methods of therapy very difficult. Understanding the mechanisms of drug resistance in cancer cells may improve the results of treatment. This review article provides a synopsis of all aspects that refer to cancer cell resistance to antitumor drugs.

  16. Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

    Science.gov (United States)

    Franco, Pierfrancesco; Rampino, Monica; Ostellino, Oliviero; Schena, Marina; Pecorari, Giancarlo; Garzino Demo, Paolo; Fasolis, Massimo; Arcadipane, Francesca; Martini, Stefania; Cavallin, Chiara; Airoldi, Mario; Ricardi, Umberto

    2017-02-01

    Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

  17. Palliative chemotherapy: oxymoron or misunderstanding?

    Science.gov (United States)

    Roeland, E J; LeBlanc, T W

    2016-03-21

    Oncologists routinely prescribe chemotherapy for patients with advanced cancer. This practice is sometimes misunderstood by palliative care clinicians, yet data clearly show that chemotherapy can be a powerful palliative intervention when applied appropriately. Clarity regarding the term "palliative chemotherapy" is needed: it is chemotherapy given in the non-curative setting to optimize symptom control, improve quality of life, and sometimes to improve survival. Unfortunately, oncologists lack adequate tools to predict which patients will benefit. In a study recently published in BMC Palliative Care, Creutzfeldt et al. presented an innovative approach to advancing the science in this area: using patient reported outcomes to predict responses to palliative chemotherapy. With further research, investigators may be able to develop predictive models for use at the bedside to inform clinical decision-making about the risks and benefits of treatment. In the meantime, oncologists and palliative care clinicians must work together to reduce the use of "end-of-life chemotherapy"-chemotherapy given close to death, which does not improve longevity or symptom control-while optimizing the use of chemotherapy that has true palliative benefits for patients.

  18. Chemotherapy for children with medulloblastoma

    NARCIS (Netherlands)

    Michiels, E.M.; Schouten-van Meeteren, A.Y.; Doz, F.; Janssens, G.O.R.J.; Dalen, E.C. van

    2015-01-01

    BACKGROUND: Post-surgical radiotherapy (RT) in combination with chemotherapy is considered as standard of care for medulloblastoma in children. Chemotherapy has been introduced to improve survival and to reduce RT-induced adverse effects. Reduction of RT-induced adverse effects was achieved by delet

  19. A multicenter retrospective study of chemotherapy for recurrent intracranial ependymal tumors in adults by the Gruppo Italiano Cooperativo di Neuro-Oncologia.

    Science.gov (United States)

    Brandes, Alba A; Cavallo, Giovanna; Reni, Michele; Tosoni, Alicia; Nicolardi, Linda; Scopece, Luciano; Franceschi, Enrico; Sotti, Guido; Talacchi, Andrea; Turazzi, Sergio; Ermani, Mario

    2005-07-01

    No data on the role of chemotherapy in recurrent ependymal tumors are available in adults. The aim of the current study was to investigate outcomes after salvage chemotherapy in this setting. A retrospective review was made of the charts of 28 adults (> or = 18 years) with progressive or recurrent ependymal tumors after surgery and radiotherapy, who received chemotherapy between 1993 and 2003 in 3 institutions of the Gruppo Italiano Cooperativo di Neuro-Oncologia network. Thirteen patients (46.3%) received cisplatin-based chemotherapy (Group A) and 15 (53.7%) received regimens without cisplatin (Group B). Platinum-based chemotherapy yielded 2 complete responses (CR) (15.4%) and 2 (15.4%) partial responses (PR), whereas 7 patients (53.8%) remained stable (SD). After regimens without cisplatin, there were no CR, 2 PR (13.3%), and 11 SD (73.3%). The overall median time to progression was 9.9 months (95% confidence interval [95% CI], 7.5-21.7 months), 9.9 months (5.2-not reached) for Group A and 10.9 months (95% CI, 7.17-23.9 months) for Group B. The overall median survival (OS) was 40.7 months (95% CI, 16-not reached), 31 months (21-not reached) for Group A and 40.7 months (13.4-not reached) for Group B. Cisplatin-based chemotherapy achieved a higher response rate, but did not prolong disease progression-free survival or OS. More active regimens for the salvage treatment of ependymal tumors have yet to be found.

  20. A history of cancer chemotherapy.

    Science.gov (United States)

    DeVita, Vincent T; Chu, Edward

    2008-11-01

    The use of chemotherapy to treat cancer began at the start of the 20th century with attempts to narrow the universe of chemicals that might affect the disease by developing methods to screen chemicals using transplantable tumors in rodents. It was, however, four World War II-related programs, and the effects of drugs that evolved from them, that provided the impetus to establish in 1955 the national drug development effort known as the Cancer Chemotherapy National Service Center. The ability of combination chemotherapy to cure acute childhood leukemia and advanced Hodgkin's disease in the 1960s and early 1970s overcame the prevailing pessimism about the ability of drugs to cure advanced cancers, facilitated the study of adjuvant chemotherapy, and helped foster the national cancer program. Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.

  1. Interstitial pneumonitis following intrapleural chemotherapy

    Directory of Open Access Journals (Sweden)

    Humphries Gary N

    2009-02-01

    Full Text Available Abstract Background Mucinous neoplasms within the abdomen may disseminate by direct extension through the diaphragm to involve the pleural space. Treatment of this condition is by parietal and visceral pleurectomy followed by hyperthermic intrapleural chemotherapy. Case presentation In this case report a patient developed persistent right upper lobe interstitial pneumonitis and progressive parenchymal fibrosis following intrapleural chemotherapy treatment with mitomycin C and doxrubicin. The condition persisted until death 28 months later. Death was from progressive intraabdominal disease with intestinal obstruction and sepsis associated with progressive pulmonary parenchymal disease. The right pleural space disease did not recur. Conclusion This manuscript is the first case report describing interstitial pneumonitis and lung fibrosis following intrapleural chemotherapy. Since pulmonary toxicity from chemotherapy is a dose-dependent phenomenon, dose reduction of intrapleural as compared to intraperitoneal hyperthermic chemotherapy may be necessary.

  2. Doublet potentiation in the triceps surae is limited by series compliance and dynamic fascicle behavior.

    Science.gov (United States)

    Mayfield, Dean L; Lichtwark, Glen A; Cronin, Neil J; Avela, Janne; Cresswell, Andrew G

    2015-10-01

    Activation of skeletal muscle twice in quick succession results in nonlinear force summation (i.e., doublet potentiation). The force contributed by a second activation is typically of augmented amplitude, longer in duration, and generated at a greater rate. The purpose of this study was to examine force summation in a muscle attached to a compliant tendon, where considerable internal shortening occurs during a fixed-end contraction. The triceps surae of 21 (Experiment 1) and 9 (Experiment 2) young adults were maximally activated with doublet stimulation of different interstimulus intervals (ISIs) (5-100 ms) at several muscle lengths. Ultrasound images acquired from lateral gastrocnemius and soleus muscles allowed quantification of dynamic fascicle behavior. Force summation was muscle length dependent. Force augmentation was limited to a short muscle length. Lateral gastrocnemius and soleus fascicles underwent large amounts of active shortening and achieved high velocities in response to doublet stimulation, dynamics unfavorable for force production. Summation amplitude and the sensitivity of summation to ISI were dramatically depressed in the triceps surae after comparison to muscles with less fixed-end compliance. We propose that the internal shortening permitted by high series compliance limited force augmentation by offsetting and/or interfering with activation and cross-bridge processes driving augmentation. High series compliance may also reduce the sensitivity of the summated response to ISI, an assertion supported by predictions from a Hill-type muscle model. These muscles may exhibit greater force augmentation during more accustomed stretch-shorten tasks (i.e., hopping), where the compliance of the Achilles tendon actually enables near-isometric fascicle behavior.

  3. Higgs dark matter from a warped extra dimension — the truncated-inert-doublet model

    Science.gov (United States)

    Ahmed, Aqeel; Grzadkowski, Bohdan; Gunion, John F.; Jiang, Yun

    2015-10-01

    We construct a 5D {{Z}}_2 -symmetric model with three D3-branes: two IR ones with negative tension located at the ends of an extra-dimensional interval and a UV-brane with positive tension placed in the middle of the interval — IR-UV-IR model. The background solutions for this geometric setup are found without and with taking into account the backreaction of the matter fields. A 5D SU(2) Higgs doublet is employed as the Goldberger-Wise stabilizing field in this geometry and solutions of the 5D coupled scalar-gravity equations are found by using the superpotential method. Within this setup we investigate the low-energy (zero-mode) effective theory for the bulk Standard Model (SM) bosonic sector. The {{Z}}_2 -even zero-modes correspond to known standard degrees of freedom, whereas the {{Z}}_2 -odd zero modes might serve as a dark sector. The effective low-energy scalar sector contains a scalar which mimics the SM Higgs boson and a second stable scalar particle (dark-Higgs) is a dark matter candidate; the latter is a component of the zero-mode of the {{Z}}_2 -odd Higgs doublet. The model that results from the {{Z}}_2 -symmetric background geometry resembles the Inert Two Higgs Doublet Model. The effective theory turns out to have an extra residual SU(2) × U(1) global symmetry that is reminiscent of an underlying 5D gauge transformation for the odd degrees of freedom. At tree level the SM Higgs and the dark-Higgs have the same mass; however, when leading radiative corrections are taken into account the dark-Higgs turns out to be heavier than the SM Higgs. Implications for dark matter are discussed; it is found that the dark-Higgs can provide only a small fraction of the observed dark matter abundance.

  4. Causal hydrodynamics from kinetic theory by doublet scheme in renormalization-group method

    Science.gov (United States)

    Tsumura, Kyosuke; Kikuchi, Yuta; Kunihiro, Teiji

    2016-12-01

    We develop a general framework in the renormalization-group (RG) method for extracting a mesoscopic dynamics from an evolution equation by incorporating some excited (fast) modes as additional components to the invariant manifold spanned by zero modes. We call this framework the doublet scheme. The validity of the doublet scheme is first tested and demonstrated by taking the Lorenz model as a simple three-dimensional dynamical system; it is shown that the two-dimensional reduced dynamics on the attractive manifold composed of the would-be zero and a fast modes are successfully obtained in a natural way. We then apply the doublet scheme to construct causal hydrodynamics as a mesoscopic dynamics of kinetic theory, i.e., the Boltzmann equation, in a systematic manner with no ad-hoc assumption. It is found that our equation has the same form as Grad's thirteen-moment causal hydrodynamic equation, but the microscopic formulae of the transport coefficients and relaxation times are different. In fact, in contrast to the Grad equation, our equation leads to the same expressions for the transport coefficients as given by the Chapman-Enskog expansion method and suggests novel formulae of the relaxation times expressed in terms of relaxation functions which allow a natural physical interpretation of the relaxation times. Furthermore, our theory nicely gives the explicit forms of the distribution function and the thirteen hydrodynamic variables in terms of the linearized collision operator, which in turn clearly suggest the proper ansatz forms of them to be adopted in the method of moments.

  5. SINGLE AGENT DOCETAXEL AS SECOND- LINE CHEMOTHERAPY FOR PRETREATED PATIENTS WITH RECURRENT NON- SMALL CELL LUNG CANCER

    Directory of Open Access Journals (Sweden)

    Deyan N. Davidov

    2013-04-01

    Full Text Available Objective: Single agent Docetaxel is a standard therapy for patients with non- small cell lung cancer after the failure of platinum- containing regimens. The aim of this study was to explore the efficacy and safety of Docetaxel monotherapy as second- line chemotherapy in pretreated patient with inoperable non- small cell lung cancer. Methods: From January 2005 to May 2008 thirty- six consecutive patients with locally advanced or metastatic morphologically proven stage IIIB/ IV non- small cell lung cancer entered the study after failure of previous platinum- based regimens. Treatment schedule consist of Docetaxel 75 mg/m2 administered every three weeks with repetition after 21 days with Dexamethasone premedication. Results: Overall response rate, median time to progression and median survival was 16,6 %, 4,5 months and 5,6 months respectively. The main hematological toxicity was neutropenia. Conclusions: That data suggest that single agent Docetaxel remain reasonable choices for the chemotherapy in pretreated patients with non- small cell lung cancer.

  6. Model-independent determination of doublet and quartet cross sections in Nd fusion

    CERN Document Server

    Ramachandran, G

    2001-01-01

    A model-independent theoretical formalism is outlined to describe Nd fusion in terms of irreducible tensor amplitudes labelled by the initial channel spins s=((1)/(2)),((3)/(2)). A comprehensive form for the initial spin density matrix rho is given in the channel spin representation, when both the beam and target are polarized. It is then suggested that an incisive study of Nd fusion may be carried out employing a polarized beam on a polarized target, leading to the determination of the differential cross sections for the doublet and quartet states individually.

  7. Spontaneous symmetry breaking in three-Higgs-doublet S 3-symmetric models

    Science.gov (United States)

    Emmanuel-Costa, D.; Ogreid, O. M.; Osland, P.; Rebelo, M. N.

    2017-07-01

    The talk summarises work done by the authors consisting of a detailed study of the possible vacua in models with three Higgs doublets with S 3 symmetry and without explicit CP violation. Different vacua require special regions of the parameter space which were analysed in our work. We establish the possibility of spontaneous CP violation in this framework and we also show which complex vacua conserve CP. In our work we discussed constraints from vacuum stability. The results presented here are relevant for model building.

  8. Quantum correction to tiny vacuum expectation value in two Higgs doublet model for Dirac neutrino mass

    CERN Document Server

    Morozumi, Takuya; Tamai, Kotaro

    2011-01-01

    We study a Dirac neutrino mass model of Davidson and Logan. In the model, the smallness of the neutrino mass is originated from the small vacuum expectation value of the second Higgs of two Higgs doublets. We study the one loop effective potential of the Higgs sector and examine how the small vacuum expectation is stable under the radiative correction. By deriving formulae of the radiative correction, we numerically study how large the one loop correction is and show how it depends on the quadratic mass terms and quartic couplings of the Higgs potential. The correction changes depending on the various scenarios for extra Higgs mass spectrum.

  9. LHC phenomenology of a two-Higgs-doublet neutrino mass model

    OpenAIRE

    Davidson, Shainen M.; Logan, Heather E.

    2010-01-01

    We study the LHC search prospects for a model in which the neutrinos obtain Dirac masses from couplings to a second Higgs doublet with tiny vacuum expectation value. The model contains a charged Higgs boson that decays to l nu with branching fractions controlled by the neutrino masses and mixing angles as measured in neutrino oscillation experiments. The most promising signal is electroweak production of H+ H- pairs with decays to l l' pTmiss, where l l' = e+ e-, mu+ mu-, and e+- mu-+. We fin...

  10. Effects of Two Inert Scalar Doublets on Higgs Interactions and Electroweak Phase Transition

    CERN Document Server

    Ahriche, Amine; Ho, Shu-Yu; Nasri, Salah; Tandean, Jusak

    2015-01-01

    We study some implications of the presence of two inert scalar doublets which are charged under a dark Abelian gauge symmetry. Specifically, we investigate the effects of the new scalars on oblique electroweak parameters and on the interactions of the 125 GeV Higgs boson, especially its decay modes $h\\to\\gamma\\gamma,\\gamma Z$, and trilinear coupling, all of which will be probed with improved precision in future Higgs measurements. Moreover, we explore how the inert scalars may give rise to strongly first-order electroweak phase transition and also show its correlation with sizable modifications to the Higgs trilinear coupling.

  11. Lightest Higgs boson production at photon colliders in the two Higgs doublet model type III

    CERN Document Server

    Martínez, R; Rodríguez, José Alberto; 10.1103/PhysRevD.72.035017

    2005-01-01

    The branching ratios of the lightest CP-even Higgs boson h/sup 0/ are calculated in the framework of the general two higgs doublet model. Different scenarios are presented taking into account constraints on the flavor changing neutral currents factors obtained in previous works. Plausible scenarios where appear flavor changing processes at tree level like bs and tc are analyzed for relevant parameters. The loop-induced Higgs couplings to photon pairs can be tested with a photon collider. The number of events of h/sup 0/ as a resonance in photon colliders are calculated taking into account its corresponding background signal at TESLA, CLIC, and NLC.

  12. A Second Higgs Doublet in the Early Universe: Baryogenesis and Gravitational Waves

    CERN Document Server

    Dorsch, G C; Konstandin, T; No, J M

    2016-01-01

    We show that simple Two Higgs Doublet models still provide a viable explanation for the matter-antimatter asymmetry of the Universe via electroweak baryogenesis, even after taking into account the recent order-of-magnitude improvement on the electron-EDM experimental bound by the ACME Collaboration. Moreover we show that, in the region of parameter space where baryogenesis is possible, the gravitational wave spectrum generated at the end of the electroweak phase transition is within the sensitivity reach of the future space-based interferometer LISA.

  13. Scalar sector properties of two-Higgs-doublet models with a global U(1) symmetry

    CERN Document Server

    Bhattacharyya, Gautam; Pal, Palash B; Rebelo, M N

    2013-01-01

    We analyze the scalar sector properties of a general class of two-Higgs-doublet models which has a global U(1) symmetry in the quartic terms. We find constraints on the parameters of the potential from the considerations of unitarity of scattering amplitudes, the global stability of the potential and the $\\rho$-parameter. We concentrate on the spectrum of the non-standard scalar masses in the decoupling limit which is preferred by the Higgs data at the LHC. We exhibit charged-Higgs induced contributions to the diphoton decay width of the 125\\,GeV Higgs boson and its correlation with the corresponding $Z\\gamma$ width.

  14. Scalar sector properties of two-Higgs-doublet models with a global U(1) symmetry

    OpenAIRE

    Bhattacharyya, Gautam; Das, Dipankar; Pal, Palash B.; Rebelo, M. N.

    2013-01-01

    We analyze the scalar sector properties of a general class of two-Higgs-doublet models which has a global U(1) symmetry in the quartic terms. We find constraints on the parameters of the potential from the considerations of unitarity of scattering amplitudes, the global stability of the potential and the $\\rho$-parameter. We concentrate on the spectrum of the non-standard scalar masses in the decoupling limit which is preferred by the Higgs data at the LHC. We exhibit charged-Higgs induced co...

  15. Tree-level metastability bounds for the most general two Higgs doublet model

    CERN Document Server

    Ivanov, I P

    2015-01-01

    Within two Higgs doublet models, it is possible that the current vacuum is not the global minimum, in which case it could possibly decay at a later stage. We discuss the tree-level conditions which must be obeyed by the most general scalar potential in order to preclude that possibility. We propose a new procedure which is not only more general but also easier to implement than the previously published one, including CP conserving as well as CP violating scalar sectors. We illustrate these conditions within the context of the Z2 model, softly broken by a complex, CP violating parameter.

  16. Dilepton constraints in the Inert Doublet Model from Run 1 of the LHC

    CERN Document Server

    Belanger, G; Goudelis, A; Herrmann, B; Kraml, S; Sengupta, D

    2015-01-01

    Searches in final states with two leptons plus missing transverse energy, targeting supersymmetric particles or invisible decays of the Higgs boson, were performed during Run 1 of the LHC. Recasting the results of these analyses in the context of the Inert Doublet Model (IDM) using MadAnalysis 5, we show that they provide constraints on inert scalars that significantly extend previous limits from LEP. Moreover, these LHC constraints allow to test the IDM in the limit of very small Higgs-inert scalar coupling, where the constraints from direct detection of dark matter and the invisible Higgs width vanish.

  17. The right top coupling in the aligned two-Higgs-doublet model

    CERN Document Server

    Ayala, Cesar; Martinez, R; Vidal, Jordi

    2016-01-01

    We compute the right top quark coupling in the aligned two-Higgs-doublet model. In the Standard Model the real part of this coupling is dominated by QCD-gluon-exchange diagram, but the imaginary part, instead, is purely electroweak at one loop. Within this model we show that values for the imaginary part of the coupling up to one order of magnitude larger than the electroweak prediction can be obtained. For the real part of the electroweak contribution we find that it can be up to three orders of magnitude larger than the standard model one. We also present detailed results of the one loop analytical computation.

  18. The Electron/Muon Specific Two Higgs Doublet Model at e+ e- Colliders

    OpenAIRE

    Johansen, Aria R.; Sher, Marc

    2015-01-01

    Recently, Kajiyama, Okada and Yagyu (KOY) proposed an electron/muon specific two Higgs doublet model. In this model, an S3 symmetry suppresses flavor changing neutral currents instead of a Z2 symmetry. In the "Type I" version of the model, the heavy Higgs bosons have a greatly enhanced coupling to electrons and muons. KOY studied the phenomenology of the heavy Higgs bosons at the LHC. In this paper, the phenomenology at electron-positron colliders is studied. For the heavy Higgs mass range be...

  19. Orbifold Grand Unification: A Solution to the Doublet-Triplet Problem

    CERN Document Server

    Jia, Bei

    2014-01-01

    To solve the doublet-triplet splitting problem in SU(5) grand unified theories, we propose a four dimensional orbifold grand unified theory by acting Z2 on the SU(5) gauge group. Without an adjoint Higgs, the orbifold procedure breaks the SU(5) gauge symmetry down to the standard model gauge group, and removes the triplet component of the fundamental SU(5) Higgs. In the supersymmetric framework, we show that the orbifold procedure removes two triplet superfields of the Higgs multiplets and leaves us with the minimal supersymmetric standard model, which also solves the hierarchy problem and realizes gauge coupling unification. We also discuss possible UV completions of the orbifold theories.

  20. Phase shift experiments identifying Kramers doublets in a chaotic superconducting microwave billiard of threefold symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Dembowski, C.; Dietz, B.; Graef, H.D.; Heine, A.; Leyvraz, F.; Miski-Oglu, M.; Richter, A.; Seligman, T.H.

    2002-11-01

    The spectral properties of a two-dimensional microwave billiard showing threefold symmetry have been studied with a new experimental technique. This method is based on the behavior of the eigenmodes under variation of a phase shift between two input channels, which strongly depends on the symmetries of the eigenfunctions. Thereby a complete set of 108 Kramers doublets has been identified by a simple and purely experimental method. This set clearly shows Gaussian unitary ensemble statistics, although the system is time-reversal invariant. (orig.)

  1. The vacuum structure of the Higgs complex singlet-doublet model

    CERN Document Server

    Ferreira, P M

    2016-01-01

    The complex singlet-doublet model is a popular theory to account for dark matter and electroweak baryogenesis, wherein the Standard Model particle content is supplemented by a complex scalar gauge singlet, with certain discrete symmetries imposed. The scalar potential which results thereof can have seven different types of minima at tree-level, which may coexist for specific choices of parameters. There is therefore the possibility that a given minimum is not global but rather a local one, and may tunnel to a deeper extremum, thus causing vacuum instability. This rich vacuum structure is explained and discussed in detail.

  2. Higgs boson pair production at the Photon Linear Collider in the two Higgs doublet model

    CERN Document Server

    Asakawa, Eri; Kanemura, Shinya; Okada, Yasuhiro; Tsumura, Koji

    2009-01-01

    We calculate the cross section of the lightest Higgs boson pair production at the Photon Linear Collider in the two Higgs doublet model. We focus on the scenario in which the lightest Higgs boson has the standard model like couplings to gauge bosons. We take into account the one-loop correction to the $hhh$ coupling as well as additional one-loop diagrams due to charged bosons to the $\\gamma\\gamma \\to hh$ helicity amplitudes. We discuss the impact of these corrections on the $hhh$ coupling measurement at the Photon Linear Collider.

  3. The Half-composite Two Higgs Doublet Model and the Relaxion

    CERN Document Server

    Antipin, Oleg

    2015-01-01

    We study a new confining gauge theory with fermions in a vectorial representation under the SM gauge group that allows for Yukawa interactions with the Higgs. If the fermion masses are smaller than the confinement scale this realizes a type I two Higgs doublet model where a composite Higgs mixes with the elementary Higgs. This class of models interpolates between an elementary and a composite Higgs and has interesting phenomenology with potentially observables effects in collider physics, EDMs and SM couplings but very weak bounds from indirect searches. The very same framework can be used to realize the cosmological relaxation of the electro-weak scale recently discussed in the literature.

  4. The half-composite two Higgs doublet model and the relaxion

    Science.gov (United States)

    Antipin, Oleg; Redi, Michele

    2015-12-01

    We study a new confining gauge theory with fermions in a vectorial representation under the SM gauge group that allows for Yukawa interactions with the Higgs. If the fermion masses are smaller than the confinement scale this realizes a type I two Higgs doublet model where a composite Higgs mixes with the elementary Higgs. This class of models interpolates between an elementary and a composite Higgs and has interesting phenomenology with potentially observable effects in collider physics, EDMs and SM couplings but very weak bounds from indirect searches. The very same framework can be used to realize the cosmological relaxation of the electro-weak scale recently discussed in the literature.

  5. Doublet stimulation increases Ca(2+) binding to troponin C to ensure rapid force development in skeletal muscle.

    Science.gov (United States)

    Bakker, Anthony J; Cully, Tanya R; Wingate, Catherine D; Barclay, Christopher J; Launikonis, Bradley S

    2017-03-06

    Fast-twitch skeletal muscle fibers are often exposed to motor neuron double discharges (≥200 Hz), which markedly increase both the rate of contraction and the magnitude of the resulting force responses. However, the mechanism responsible for these effects is poorly understood, likely because of technical limitations in previous studies. In this study, we measured cytosolic Ca(2+) during doublet activation using the low-affinity indicator Mag-Fluo-4 at high temporal resolution and modeled the effects of doublet stimulation on sarcoplasmic reticulum (SR) Ca(2+) release, binding of Ca(2+) to cytosolic buffers, and force enhancement in fast-twitch fibers. Single isolated fibers respond to doublet pulses with two clear Ca(2+) spikes, at doublet frequencies up to 1 KHz. A 200-Hz doublet at the start of a tetanic stimulation train (70 Hz) decreases the drop in free Ca(2+) between the first three Ca(2+) spikes of the transient, maintaining a higher overall free Ca(2+) level during first 20-30 ms of the response. Doublet stimulation also increased the rate of force development in isolated fast-twitch muscles. We also modeled SR Ca(2+) release rates during doublet stimulation and showed that Ca(2+)-dependent inactivation of ryanodine receptor activity is rapid, occurring ≤1ms after initial release. Furthermore, we modeled Ca(2+) binding to the main intracellular Ca(2+) buffers of troponin C (TnC), parvalbumin, and the SR Ca(2+) pump during Ca(2+) release and found that the main effect of the second response in the doublet is to more rapidly increase the occupation of the second Ca(2+)-binding site on TnC (TnC2), resulting in earlier activation of force. We conclude that doublet stimulation maintains high cytosolic Ca(2+) levels for longer in the early phase of the Ca(2+) response, resulting in faster saturation of TnC2 with Ca(2+), faster initiation of cross-bridge cycling, and more rapid force development.

  6. Breakdown of doublet recirculation and direct line drives by far-field flow in reservoirs: implications for geothermal and hydrocarbon well placement

    Science.gov (United States)

    Weijermars, R.; van Harmelen, A.

    2016-07-01

    An important real world application of doublet flow occurs in well design of both geothermal and hydrocarbon reservoirs. A guiding principle for fluid management of injection and extraction wells is that mass balance is commonly assumed between the injected and produced fluid. Because the doublets are considered closed loops, the injection fluid is assumed to eventually reach the producer well and all the produced fluid ideally comes from stream tubes connected to the injector of the well pair making up the doublet. We show that when an aquifer background flow occurs, doublets will rarely retain closed loops of fluid recirculation. When the far-field flow rate increases relative to the doublet's strength, the area occupied by the doublet will diminish and eventually vanishes. Alternatively, rather than using a single injector (source) and single producer (sink), a linear array of multiple injectors separated by some distance from a parallel array of producers can be used in geothermal energy projects as well as in waterflooding of hydrocarbon reservoirs. Fluid flow in such an arrangement of parallel source-sink arrays is shown to be macroscopically equivalent to that of a line doublet. Again, any far-field flow that is strong enough will breach through the line doublet, which then splits into two vortices. Apart from fundamental insight into elementary flow dynamics, our new results provide practical clues that may contribute to improve the planning and design of doublets and direct line drives commonly used for flow management of groundwater, geothermal and hydrocarbon reservoirs.

  7. Therapeutic pathomorphosis of advanced NSCLC as a criteria for effectiveness of induction chemotherapy.

    Directory of Open Access Journals (Sweden)

    Kosse V.A.

    2007-01-01

    Full Text Available The aim of the study was the investigation of therapeutic pathomorphosis (ThP of non-small cell lung cancer (NSCLC and definition of its role as a criteria for effectiveness of induction chemotherapy (ICT. In the context of investigation there were 152 patients with IIIA st. NSCLC, being treated with ICT (102 pts and without it (50 pts. The analysis of qualitative and quantitative pathomorphological changes in tumors after platinum-based ICT was performed. Patients’ operability in the group with ICT was significantly higher than in control group (72.6% versus 56.0% that proves the effectiveness of ICT as a method of induction influence. The ICT estimation has to be complex, that means – the clinical effect should be verified by pathomorphological studies. Under the influence of ICT in NSCLC noticed the different ThP: 1 st. – 51%, 2-3 st. – 48%, 4 st. – 1% with better response rate in low-differentiation tumor. Being influenced by ICT, the part of viable tumors’ paren-chyma and its proliferating activity has significantly decreased, that is the essential component of further prognosis. The tu-mors’ resectability correlated with the level of its ThP, which serves the basis for necessity of reaching the maximal clinical effect of ICT.

  8. Targeting Nuclear Factor-kappa B to overcome resistance to chemotherapy.

    Directory of Open Access Journals (Sweden)

    Peter eGodwin

    2013-05-01

    Full Text Available Intrinsic or acquired resistance to chemotherapeutic agents is a common phenomenon and a major challenge to the treatment of cancer patients, especially those with progressive disease. Chemoresistance is defined by a complex network of factors including multi-drug resistance proteins, reduced cellular uptake of the drug, enhanced DNA repair, intracellular drug inactivation and evasion of apoptosis. Preclinical models have demonstrated activation of the NF-κB pathway by several chemotherapy drugs, including platinum based agents, anthracyclines and taxanes. NF-κB is a key transcription factor, playing a role in the development and progression of cancer as well as chemoresistance through the activation of anti-apoptotic genes. Consequently, NF-κB has emerged as a promising anticancer target. Here, we describe the role of NF-κB in the cancer cell and in resistance to chemotherapeutic agents, particularly cisplatin. Additionally, the potential benefits and disadvantages of targeting NF-κB signalling by pharmacological intervention will be addressed.

  9. Flavor violating Higgs signals in the Texturized Two-Higgs Doublet Model (THDM-Tx)

    Science.gov (United States)

    Arroyo-Ureña, M. A.; Diaz-Cruz, J. Lorenzo; Díaz, Enrique; Orduz-Ducuara, Javier A.

    2016-12-01

    Flavor violating Higgs signals, such as the top FCNC decay t→ch0 and the LFV Higgs decay h0→τμ, have been studied at the LHC. These signals can arise within the general Two-Higgs Doublet Model (THDM), where each Higgs doublet couples to all fermion types through Yukawa matrices and . The Yukawa matrices can be assumed to have the same form or they could have different structures. In this paper we study the case when both and have completely different forms, but in such a way that they complement to produce a specific hermitian mass matrix. We find that for specific four-zero textures, the flavor violating Higgs couplings depend only on the free parameters tanβ, γf and the fermion masses. We use the current bounds on the low energy processes to derive constraints on the heavy Higgs boson mass, tanβ and γf. Then, we use these constraints to evaluate the LFV Higgs decays, which reach branching ratios that could be tested at the LHC.

  10. Effects of Constant and Doublet Frequency Electrical Stimulation Patterns on Force Production of Knee Extensor Muscles.

    Science.gov (United States)

    Cometti, Carole; Babault, Nicolas; Deley, Gaëlle

    2016-01-01

    This study compared knee extensors' neuromuscular fatigue in response to two 30-minute stimulation patterns: constant frequency train (CFT) and doublet frequency train (DFT). Fifteen men underwent two separate sessions corresponding to each pattern. Measurements included torque evoked by each contraction and maximal voluntary contractions (MVC) measured before and immediately after the stimulation sessions. In addition, activation level and torque evoked during doublets (Pd) and tetanic contractions at 80-Hz (P80) and 20-Hz (P20) were determined in six subjects. Results indicated greater mean torque during the DFT stimulation session as compared with CFT. But, no difference was obtained between the two stimulation patterns for MVC and evoked torque decreases. Measurements conducted in the subgroup depicted a significant reduction of Pd, P20 and P80. Statistical analyses also revealed bigger P20 immediate reductions after CFT than after DFT. We concluded that DFT could be a useful stimulation pattern to produce and maintain greater force with quite similar fatigue than CFT.

  11. Effects of Constant and Doublet Frequency Electrical Stimulation Patterns on Force Production of Knee Extensor Muscles.

    Directory of Open Access Journals (Sweden)

    Carole Cometti

    Full Text Available This study compared knee extensors' neuromuscular fatigue in response to two 30-minute stimulation patterns: constant frequency train (CFT and doublet frequency train (DFT. Fifteen men underwent two separate sessions corresponding to each pattern. Measurements included torque evoked by each contraction and maximal voluntary contractions (MVC measured before and immediately after the stimulation sessions. In addition, activation level and torque evoked during doublets (Pd and tetanic contractions at 80-Hz (P80 and 20-Hz (P20 were determined in six subjects. Results indicated greater mean torque during the DFT stimulation session as compared with CFT. But, no difference was obtained between the two stimulation patterns for MVC and evoked torque decreases. Measurements conducted in the subgroup depicted a significant reduction of Pd, P20 and P80. Statistical analyses also revealed bigger P20 immediate reductions after CFT than after DFT. We concluded that DFT could be a useful stimulation pattern to produce and maintain greater force with quite similar fatigue than CFT.

  12. Scrutinizing h(125) in Two Higgs Doublet Models at the LHC, ILC, and Muon Collider

    CERN Document Server

    Barger, Vernon; Logan, Heather E; Shaughnessy, Gabe

    2013-01-01

    The discovery at the LHC of a scalar particle with properties that are so far consistent with the SM Higgs boson is one of the most important advances in the history of particle physics. The challenge of future collider experiments is to determine whether its couplings will show deviations from the SM Higgs, as this would indicate new physics at the TeV scale, and also to probe the flavor structure of the Yukawa couplings. As a benchmark alternative to the SM Higgs, we consider a generic two Higgs doublet model (2HDM) and analyze the precision to which the LHC14, an ILC250, 500, 1000 GeV and a 125 GeV Muon Collider (MC) can determine the gauge and Yukawa couplings. We allow for correlations among the couplings. We include the impact of a Higgs total width measurement, indirectly at the LHC and ILC and by a direct scan at the MC. We also discuss pattern relations among the couplings that can test for singlet or doublet Higgs extensions of 2HDMs.

  13. Two Higgs bi-doublet left-right model with spontaneous P and CP violation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A left-right symmetric model with two Higgs bi-doublet is shown to be a consistent model for both spontaneous P and CP violation. The flavor changing neutral cur- rents can be suppressed by the mechanism of approximate global U(1) family symmetry. The constraints from neural K meson mass difference ΔmK are calcu- lated and it is demonstrated that a right-handed gauge boson W2 contribution in box-diagrams with mass well below 1 TeV is allowed due to a cancelation caused by a light-charged Higgs boson with a mass range of 150-300 GeV. The W2 con- tribution to εK can be suppressed from an appropriate choice of additional CP phases appearing in the right-handed Cabbibo-Kobayashi-Maskawa matrix. The model is also found to be fully consistent with B0 mass difference ΔmB and the mixing induced CP violation sin2βJ/ψ , which is usually difficult for the model with only one Higgs bi-doublet. The new physics beyond the standard model can be directly searched at the colliders LHC and ILC.

  14. Two Higgs bi-doublet left-right model with spontaneous P and CP violation

    Institute of Scientific and Technical Information of China (English)

    WU YueLiang; ZHOU YuFeng

    2008-01-01

    A left-right symmetric model with two Higgs bi-doublet is shown to be a consistent model for both spontaneous P and CP violation.The flavor changing neutral cur-rents can be suppressed by the mechanism of approximate global U(1) family symmetry.The constraints from neural K meson mass difference △mK are calcu-lated and it is demonstrated that a right-handed gauge boson W2 contribution in box-diagrams with mass well below 1 TeV is allowed due to a cancelation caused by a light-charged Higgs boson with a mass range of 150-300 GeV.The W2 contribution to εK can be suppressed from an appropriate choice of additional CP phases appearing in the right-handed Cabbibo-Kobayashi-Maskawa matrix.The model is also found to be fully consistent with B0 mass difference △mB and the mixing induced CP violation sin2βJ/ψ,which is usually difficult for the model with only one Higgs bi-doublet.The new physics beyond the standard model can be directly searched at the colliders LHC and ILC.

  15. Implications of the LHC two-photon signal for two-Higgs-doublet models

    Energy Technology Data Exchange (ETDEWEB)

    P. M. Ferreira, Rui Santos, Marc Sher, Joao P. Silva

    2012-04-01

    We study the implications for Two Higgs Doublet Models of the recent announcement at the LHC giving a tantalizing hint for a Higgs boson of mass 125 GeV decaying into two photons. We require that the experimental result be within a factor of two of the theoretical Standard Model prediction, and analyze the type I and type II models as well as the lepton-specific and flipped models, subject to this requirement. It is assumed that there is no new physics other than two Higgs doublets. In all of the models, we display the allowed region of parameter space taking the recent LHC announcement at face value, and we analyze the W{sup +}W{sup -}, ZZ, {bar b}b and {tau}{sup +}{tau}{sup -} expectations in these allowed regions. Throughout the entire range of parameter space allowed by the {gamma}{gamma} constraint, the number of events for Higgs decays into WW, ZZ and b{bar b} are not changed from the Standard Model by more than a factor of two. In contrast, in the Lepton Specific model, decays to {tau}{sup +}{tau}{sup -} are very sensitive across the entire {gamma}{gamma}-allowed region.

  16. Collider and dark matter searches in the inert doublet model from Peccei-Quinn symmetry

    Science.gov (United States)

    Alves, Alexandre; Camargo, Daniel A.; Dias, Alex G.; Longas, Robinson; Nishi, Celso C.; Queiroz, Farinaldo S.

    2016-10-01

    Weakly Interacting Massive Particles (WIMPs) and axions are arguably the most compelling dark matter candidates in the literature. Could they coexist as dark matter particles? More importantly, can they be incorporated in a well motivated framework in agreement with experimental data? In this work, we show that this two component dark matter can be realized in the Inert Doublet Model in an elegant and natural manner by virtue of the spontaneous breaking of a Peccei-Quinn U(1) P Q symmetry into a residual {Z}_2 symmetry. The WIMP stability is guaranteed by the {Z}_2 symmetry and a new dark matter component, the axion, arises. There are two interesting outcomes: (i) vector-like quarks needed to implement the Peccei-Quinn symmetry in the model may act as a portal between the dark sector and the SM fields with a supersymmetry-type phenomenology at colliders; (ii) two-component Inert Doublet Model re-opens the phenomenologically interesting 100-500 GeV mass region. We show that the model can successfully realize a two component dark matter framework and at the same time avoid low and high energy physics constraints such as monojet and dijet plus missing energy, as well as indirect and direct dark matter detection bounds.

  17. Spatial Distribution of Ground water Level Changes Induced by the 2006 Hengchun Earthquake Doublet

    Directory of Open Access Journals (Sweden)

    Yeeping Chia

    2009-01-01

    Full Text Available Water-level changes were ob served in 107 wells at 67 monitoring stations in the southern coastal plain of Tai wan during the 2006 Mw 7.1 Hengchun earthquake doublet. Two consecutive coseismic changes induced by the earth quake doublet can be observed from high-frequency data. Obervations from multiple-well stations indicate that the magnitude and direction of coseismic change may vary in wells of different depths. Coseismic rises were dominant on the south east side of the costal plain; whereas, coseismic falls prevailed on the north west side. In the transition zone, rises appeared in shallow wells whilst falls were evident in deep wells. As coseismic ground water level changes can reflect the tectonic strain field, tectonic extension likely dominates the deep subsurface in the transition area, and possibly in the en tire southern coastal plain. The coseismic rises in water level showed a tendency to de crease with distance from the hypocenter, but no clear trend was found for the coseismic falls.

  18. Doublets, triplets, or quadruplets of novel agents in newly diagnosed myeloma?

    Science.gov (United States)

    Rajkumar, S Vincent

    2012-01-01

    The treatment of multiple myeloma is evolving rapidly. A plethora of doublet, triplet, and quadruplet combinations have been studied for the treatment of newly diagnosed myeloma. Although randomized trials have been conducted comparing older regimens such as melphalan-prednisone with newer regimens containing drugs such as thalidomide, lenalidomide, or bortezomib, there are few if any randomized trials that have compared modern combinations with each other. Even in the few trials that have done so, definitive overall survival or patient-reported quality-of-life differences have not been demonstrated. Therefore, there is marked heterogeneity in how newly diagnosed patients with myeloma are treated around the world. The choice of initial therapy is often dictated by availability of drugs, age and comorbidities of the patient, and assessment of prognosis and disease aggressiveness. This chapter reviews the current data on the most commonly used and tested doublet, triplet, and quadruplet combinations for the treatment of newly diagnosed myeloma and provides guidance on choosing the optimal initial treatment regimen.

  19. Numerical Analysis of Doublet Wells for Cold Energy Storage on Heat Damage Treatment in Deep Mines

    Institute of Scientific and Technical Information of China (English)

    HE Man-chao; ZHANG Yi; GUO Dong-ming; QIAN Zeng-zhen

    2006-01-01

    Deep mining is an inevitable tendency in the development of coal industry. There are many heat damage problems with the increase of mining depth. The technology of using doublet wells, together with Heat Exchange Machine Systems (HEMSs), to store cold energy is a key to solve the heat damage problems in deep mines. Based on the geological conditions, thermodynamic and hydraulic parameters of Jiahe Mine, the isotherms in the period of cold energy storage and refrigeration and the volumes of cold water within different temperature ranges of the cold energy storage well were numerically analyzed. The results show that 1) with the same pumped and injected water volumes, the lower the temperature of injected water is, the larger the volume of cold water in the cold energy storage well is. With the larger volume, the effect of cold energy storage is better. 2) the larger the volumes of pumped and reinjected water are, the larger the volume of cold water from the cold energy storage well is. With the larger volume, the effect of refrigeration is better. And 3) without disturbance, the volume and temperature of cold water in the cold energy storage well can keep unchanged or have only a little change for a long time. Therefore the technology of doublet wells for cold energy storage is feasible and the cold energy storage aquifers can meet the requirement of the technology.

  20. A search for neutral Higgs bosons in the MSSM and models with two scalar field doublets

    CERN Document Server

    Ackerstaff, K.; Allison, John; Altekamp, N.; Anderson, K.J.; Anderson, S.; Arcelli, S.; Asai, S.; Ashby, S.F.; Axen, D.; Azuelos, G.; Ball, A.H.; Barberio, E.; Barlow, Roger J.; Bartoldus, R.; Batley, J.R.; Baumann, S.; Bechtluft, J.; Behnke, T.; Bell, Kenneth Watson; Bella, G.; Bentvelsen, S.; Bethke, S.; Betts, S.; Biebel, O.; Biguzzi, A.; Bird, S.D.; Blobel, V.; Bloodworth, I.J.; Bobinski, M.; Bock, P.; Bonacorsi, D.; Boutemeur, M.; Braibant, S.; Brigliadori, L.; Brown, Robert M.; Burckhart, H.J.; Burgard, C.; Burgin, R.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, David G.; Chrisman, D.; Clarke, P.E.L.; Cohen, I.; Conboy, J.E.; Cooke, O.C.; Couyoumtzelis, C.; Coxe, R.L.; Cuffiani, M.; Dado, S.; Dallapiccola, C.; Dallavalle, G.Marco; Davis, R.; De Jong, S.; del Pozo, L.A.; de Roeck, A.; Desch, K.; Dienes, B.; Dixit, M.S.; Doucet, M.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Eatough, D.; Estabrooks, P.G.; Etzion, E.; Evans, H.G.; Evans, M.; Fabbri, F.; Fanfani, A.; Fanti, M.; Faust, A.A.; Feld, L.; Fiedler, F.; Fierro, M.; Fischer, H.M.; Fleck, I.; Folman, R.; Fong, D.G.; Foucher, M.; Furtjes, A.; Futyan, D.I.; Gagnon, P.; Gary, J.W.; Gascon, J.; Gascon-Shotkin, S.M.; Geddes, N.I.; Geich-Gimbel, C.; Geralis, T.; Giacomelli, G.; Giacomelli, P.; Giacomelli, R.; Gibson, V.; Gibson, W.R.; Gingrich, D.M.; Glenzinski, D.; Goldberg, J.; Goodrick, M.J.; Gorn, W.; Grandi, C.; Gross, E.; Grunhaus, J.; Gruwe, M.; Hajdu, C.; Hanson, G.G.; Hansroul, M.; Hapke, M.; Hargrove, C.K.; Hart, P.A.; Hartmann, C.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herndon, M.; Herten, G.; Heuer, R.D.; Hildreth, M.D.; Hill, J.C.; Hillier, S.J.; Hobson, P.R.; Hocker, James Andrew; Homer, R.J.; Honma, A.K.; Horvath, D.; Hossain, K.R.; Howard, R.; Huntemeyer, P.; Hutchcroft, D.E.; Igo-Kemenes, P.; Imrie, D.C.; Ishii, K.; Jawahery, A.; Jeffreys, P.W.; Jeremie, H.; Jimack, M.; Joly, A.; Jones, C.R.; Jones, M.; Jost, U.; Jovanovic, P.; Junk, T.R.; Kanzaki, J.; Karlen, D.; Kartvelishvili, V.; Kawagoe, K.; Kawamoto, T.; Kayal, P.I.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kirk, J.; Klier, A.; Kluth, S.; Kobayashi, T.; Kobel, M.; Koetke, D.S.; Kokott, T.P.; Kolrep, M.; Komamiya, S.; Kowalewski, Robert V.; Kress, T.; Krieger, P.; von Krogh, J.; Kyberd, P.; Lafferty, G.D.; Lahmann, R.; Lai, W.P.; Lanske, D.; Lauber, J.; Lautenschlager, S.R.; Lawson, I.; Layter, J.G.; Lazic, D.; Lee, A.M.; Lefebvre, E.; Lellouch, D.; Letts, J.; Levinson, L.; List, B.; Lloyd, S.L.; Loebinger, F.K.; Long, G.D.; Losty, M.J.; Ludwig, J.; Lui, D.; Macchiolo, A.; Macpherson, A.; Mannelli, M.; Marcellini, S.; Markopoulos, C.; Markus, C.; Martin, A.J.; Martin, J.P.; Martinez, G.; Mashimo, T.; Mattig, Peter; McDonald, W.John; McKenna, J.; Mckigney, E.A.; McMahon, T.J.; McPherson, R.A.; Meijers, F.; Menke, S.; Merritt, F.S.; Mes, H.; Meyer, J.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mincer, A.; Mir, R.; Mohr, W.; Montanari, A.; Mori, T.; Nagai, K.; Nakamura, I.; Neal, H.A.; Nellen, B.; Nisius, R.; O'Neale, S.W.; Oakham, F.G.; Odorici, F.; Ogren, H.O.; Oh, A.; Oldershaw, N.J.; Oreglia, M.J.; Orito, S.; Palinkas, J.; Pasztor, G.; Pater, J.R.; Patrick, G.N.; Patt, J.; Perez-Ochoa, R.; Petzold, S.; Pfeifenschneider, P.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poffenberger, P.; Poli, B.; Posthaus, A.; Rembser, C.; Robertson, S.; Robins, S.A.; Rodning, N.; Roney, J.M.; Rooke, A.; Rossi, A.M.; Routenburg, P.; Rozen, Y.; Runge, K.; Runolfsson, O.; Ruppel, U.; Rust, D.R.; Sachs, K.; Saeki, T.; Sahr, O.; Sang, W.M.; Sarkisian, E.K.G.; Sbarra, C.; Schaile, A.D.; Schaile, O.; Scharf, F.; Scharff-Hansen, P.; Schieck, J.; Schleper, P.; Schmitt, B.; Schmitt, S.; Schoning, A.; Schroder, Matthias; Schumacher, M.; Schwick, C.; Scott, W.G.; Shears, T.G.; Shen, B.C.; Shepherd-Themistocleous, C.H.; Sherwood, P.; Siroli, G.P.; Sittler, A.; Skillman, A.; Skuja, A.; Smith, A.M.; Snow, G.A.; Sobie, R.; Soldner-Rembold, S.; Springer, Robert Wayne; Sproston, M.; Stephens, K.; Steuerer, J.; Stockhausen, B.; Stoll, K.; Strom, David M.; Strohmer, R.; Szymanski, P.; Tafirout, R.; Talbot, S.D.; Taras, P.; Tarem, S.; Teuscher, R.; Thiergen, M.; Thomson, M.A.; von Torne, E.; Torrence, E.; Towers, S.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turcot, A.S.; Turner-Watson, M.F.; Ueda, I.; Utzat, P.; Van Kooten, Rick J.; Vannerem, P.; Verzocchi, M.; Vikas, P.; Vokurka, E.H.; Voss, H.; Wackerle, F.; Wagner, A.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wermes, N.; White, J.S.; Wilson, G.W.; Wilson, J.A.; Wyatt, T.R.; Yamashita, S.; Yekutieli, G.; Zacek, V.; Zer-Zion, D.

    1998-01-01

    A search is described for the neutral Higgs bosons h^0 and A^0 predicted by models with two scalar field doublets and, in particular, the Minimal Supersymmetric Standard Model (MSSM). The search in the Z^0 h^0 and h^0 A^0 production channels is based on data corresponding to an integrated luminosity of 25 pb^{-1} from e^+e^- collisions at centre-of-mass energies between 130 and 172GeV collected with the OPAL detector at LEP. The observation of a number of candidates consistent with Standard Model background expectations is used in combination with earlier results from data collected at the Z^0 resonance to set limits on m_h and m_A in general models with two scalar field doublets and in the MSSM. For example, in the MSSM, for tan(beta) > 1, minimal and maximal scalar top quark mixing and soft SUSY-breaking masses of 1 TeV, the 95% confidence level limits m_h > 59.0 GeV and m_A > 59.5 GeV are obtained. For the first time, the MSSM parameter space is explored in a detailed scan.

  1. Status of the Charged Higgs Boson in Two Higgs Doublet Models arXiv

    CERN Document Server

    Arbey, A.; Stal, O.; Stefaniak, T.

    The existence of charged Higgs boson(s) is inevitable in models with two (or more) Higgs doublets. Hence, their discovery would constitute unambiguous evidence for new physics beyond the Standard Model (SM). Taking into account all relevant results from direct charged and neutral Higgs boson searches at LEP and the LHC, as well as the most recent constraints from flavour physics, we present a detailed analysis of the current phenomenological status of the charged Higgs sector in a variety of well-motivated Two Higgs Doublet Models (2HDMs). We find that charged Higgs bosons as light as 75 GeV can still be compatible with the combined data, although this implies severely suppressed charged Higgs couplings to all fermions. In more popular models, e.g. the 2HDM of Type II, we find that flavour physics observables impose a combined lower limit on the charged Higgs mass of M_H+ > 600 GeV - independent of tan(beta) - which increases to M_H+ > 650 GeV for tan(beta) < 1. We furthermore find that in certain scenario...

  2. Baryogenesis in the two doublet and inert singlet extension of the Standard Model

    Energy Technology Data Exchange (ETDEWEB)

    Alanne, Tommi [CP" 3-Origins, University of Southern Denmark,Campusvej 55, DK-5230 Odense M (Denmark); Kainulainen, Kimmo [Department of Physics, University of Jyväskylä,P.O. Box 35 (YFL), FI-40014 Jyväskylä (Finland); Helsinki Institute of Physics, University of Helsinki,P.O. Box 64, FI-00014 Helsinki (Finland); Tuominen, Kimmo [Department of Physics, University of Helsinki,P.O. Box 64, FI-00014 Helsinki (Finland); Helsinki Institute of Physics, University of Helsinki,P.O. Box 64, FI-00014 Helsinki (Finland); Vaskonen, Ville [Department of Physics, University of Jyväskylä,P.O. Box 35 (YFL), FI-40014 Jyväskylä (Finland); Helsinki Institute of Physics, University of Helsinki,P.O. Box 64, FI-00014 Helsinki (Finland)

    2016-08-25

    We investigate an extension of the Standard Model containing two Higgs doublets and a singlet scalar field (2HDSM). We show that the model can have a strongly first-order phase transition and give rise to the observed baryon asymmetry of the Universe, consistent with all experimental constraints. In particular, the constraints from the electron and neutron electric dipole moments are less constraining here than in pure two-Higgs-doublet model (2HDM). The two-step, first-order transition in 2HDSM, induced by the singlet field, may lead to strong supercooling and low nucleation temperatures in comparison with the critical temperature, T{sub n}≪T{sub c}, which can significantly alter the usual phase-transition pattern in 2HD models with T{sub n}≈T{sub c}. Furthermore, the singlet field can be the dark matter particle. However, in models with a strong first-order transition its abundance is typically but a thousandth of the observed dark matter abundance.

  3. Baryogenesis in the two doublet and inert singlet extension of the Standard Model

    CERN Document Server

    Alanne, Tommi; Tuominen, Kimmo; Vaskonen, Ville

    2016-01-01

    We investigate an extension of the Standard Model containing two Higgs doublets and a singlet scalar field (2HDSM). We show that the model can have a strongly first-order phase transition and give rise to the observed baryon asymmetry of the Universe, consistent with all experimental constraints. In particular, the constraints from the electron and neutron electric dipole moments are less constraining here than in pure two-Higgs-doublet model (2HDM). The two-step, first-order transition in 2HDSM, induced by the singlet field, may lead to strong supercooling and low nucleation temperatures in comparison with the critical temperature, $T_n \\ll T_c$, which can significantly alter the usual phase-transition pattern in 2HD models with $T_n \\approx T_c$. Furthermore, the singlet field can be the dark matter particle. However, in models with a strong first-order transition its abundance is typically but a thousandth of the observed dark matter abundance.

  4. The relative line strength and intensity of the N II 2143 doublet

    Science.gov (United States)

    Bucsela, Eric J.; Sharp, William E.

    1989-01-01

    The doublet emission from N II at 2139.7 A and 2143.6 A was observed by a 1.4-m scanning spectrometer with 3.1 A resolution in the daytime, high-altitude thermosphere during moderate levels of solar activity. The spectrometer viewed the earth's limb 5 deg below the local horizontal to give a nominal tangent height of 152 km. Both sub band heads of the nitric oxide gamma band system were resolved in the data at the resolution used. The emission features from N II are clearly evident on the short wavelength shoulder of the (1, 0) band. Synthetic profiles of the (1, 0) gamma band and the (0, 3) delta band of nitric oxide were fitted to the data using a chi-square analysis. These contributions were removed from the data leaving a residual emission, considered to be the N II doublet. A chi-square minimization of the data relative to a synthetic intensity profile was done. The minimum was for a line strength ratio between the 2139 A and 2143 A lines of 0.58 + or - 0.08. The mean solar EUV flux deduced from the intensity of the N II emission in this experiment is lower than other reported observations, consistent with a lower solar activity level.

  5. Phenomenology of the Basis-Independent CP-Violating Two-Higgs Doublet Model [Dissertation

    CERN Document Server

    O'Neil, Deva

    2009-01-01

    The Two-Higgs Doublet Model (2HDM) is a model of low-energy particle interactions that is identical to the Standard Model except for the addition of an extra Higgs doublet. This extended Higgs sector would appear in experiments as the presence of multiple Higgs particles, both neutral and charged. The neutral states may either be eigenstates of CP (in the CP-conserving 2HDM), or be mixtures of CP eigenstates (in the CP-violating 2HDM). In order to understand how to measure the couplings of these new particles, this document presents the theory of the CP-violating 2HDM in a basis-independent formalism and explicitly identifies the physical parameters of the model, including a discussion of tan(beta)-like parameters. The CP-conserving limit, decoupling limit, and the custodial limit of the model are presented. In addition, phenomenological constraints from the oblique parameters (S, T, and U) are discussed. A survey of the parameter space of this model shows that the 2HDM is consistent with a large range of pos...

  6. Low energy gamma ray excess confronting a singlet scalar extended inert doublet dark matter model

    Directory of Open Access Journals (Sweden)

    Amit Dutta Banik

    2015-04-01

    Full Text Available Recent study of gamma rays originating from the region of galactic centre has confirmed an anomalous γ-ray excess within the energy range 1–3 GeV. This can be explained as the consequence of pair annihilation of a 31–40 GeV dark matter into bb¯ with thermal annihilation cross-section σv∼1.4–2.0×10−26 cm3/s. In this work we revisit the Inert Doublet Model (IDM in order to explain this gamma ray excess. Taking the lightest inert particle (LIP as a stable DM candidate we show that a 31–40 GeV dark matter derived from IDM will fail to satisfy experimental limits on dark matter direct detection cross-section obtained from ongoing direct detection experiments and is also inconsistent with LHC findings. We show that a singlet extended inert doublet model can easily explain the reported γ-ray excess which is as well in agreement with Higgs search results at LHC and other observed results like DM relic density and direct detection constraints.

  7. Fermion number conservation and two Higgs doublet models without tree level flavour changing neutral currents

    CERN Document Server

    Joshipura, Anjan S

    2010-01-01

    The charged fermion mass matrices are always invariant under $U(1)^3$ symmetry linked to the fermion number transformation. A class of two Higgs doublet models (2HDM) can be identified by requiring that the definition of this symmetry in an arbitrary weak basis be independent of Higgs parameters such as the ratio of the Higgs vacuum expectation values. The tree level flavour changing neutral currents normally present in 2HDM are absent in this class of models but unlike the type I or type II Higgs doublet models, the charged Higgs couplings in these models contain additional flavour dependent CP violating phases. These phases can account for the recent hints of the beyond standard model CP violation in the $B_d$ and $B_s$ mixing. In particular, there is a range of parameters in which new phases do not contribute to the $K$ meson CP violation but give identical new physics contribution to the $B_d$ and $B_s$ meson mixing. Specific model realizations of the above scenario are briefly discussed.

  8. Variety of SO(10) GUTs with Natural Doublet-Triplet Splitting via the Missing Partner Mechanism

    CERN Document Server

    Babu, K S; Nath, Pran; Syed, Raza M

    2011-01-01

    We present a new class of unified SO(10) models where the GUT symmetry breaking down to the standard model gauge group involves just one scale, in contrast to the conventional SO(10) models which require two scales. Further, the models we discuss possess a natural doublet-triplet splitting via the missing partner mechanism without fine tuning. Such models involve $560+\\ov{560}$ pair of heavy Higgs fields along with a set of light fields. The $560+\\ov{560}$ are the simplest representations of SO(10) besides the $126+\\ov{126}$ which contain an excess of color triplets over $SU(2)_L$ doublets. We discuss several possibilities for realizing the missing partner mechanism within these schemes. With the $126+\\ov{126}$ multiplets, three viable models are found with additional fields belonging to ${210 + 2 \\times 10 + 120}$, ${45 + 10 + 120}$, or ${210 + 16 + \\ov{16} + 10 + 120}$. With the $560+\\ov{560}$, a unique possibility arises for the missing partner mechanism, with additional ${2\\times 10+ 320}$ fields. These m...

  9. Collider and dark matter searches in the inert doublet model from Peccei-Quinn symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Alexandre [Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo,Diadema-SP, 09972-270 (Brazil); Camargo, Daniel A.; Dias, Alex G. [Universidade Federal do ABC, Centro de Ciências Naturais e Humanas,09210-580, Santo André-SP (Brazil); Longas, Robinson [Instituto de Física, Universidad de Antioquia,Calle 70 No. 52-21, Medellín (Colombia); Nishi, Celso C. [Universidade Federal do ABC, Centro de Matemática, Computação e Cognição Naturais,09210-580, Santo André-SP (Brazil); Queiroz, Farinaldo S. [Max-Planck-Institut fur Kernphysik,Saupfercheckweg 1, 69117 Heidelberg (Germany)

    2016-10-04

    Weakly Interacting Massive Particles (WIMPs) and axions are arguably the most compelling dark matter candidates in the literature. Could they coexist as dark matter particles? More importantly, can they be incorporated in a well motivated framework in agreement with experimental data? In this work, we show that this two component dark matter can be realized in the Inert Doublet Model in an elegant and natural manner by virtue of the spontaneous breaking of a Peccei-Quinn U(1){sub PQ} symmetry into a residual ℤ{sub 2} symmetry. The WIMP stability is guaranteed by the ℤ{sub 2} symmetry and a new dark matter component, the axion, arises. There are two interesting outcomes: (i) vector-like quarks needed to implement the Peccei-Quinn symmetry in the model may act as a portal between the dark sector and the SM fields with a supersymmetry-type phenomenology at colliders; (ii) two-component Inert Doublet Model re-opens the phenomenologically interesting 100–500 GeV mass region. We show that the model can successfully realize a two component dark matter framework and at the same time avoid low and high energy physics constraints such as monojet and dijet plus missing energy, as well as indirect and direct dark matter detection bounds.

  10. Natural quasi-alignment with two Higgs doublets and RGE stability

    Energy Technology Data Exchange (ETDEWEB)

    Botella, F.J. [Universitat de Valencia-CSIC, Departament de Fisica Teorica y IFIC, Burjassot (Spain); Branco, G.C. [Universidade de Lisboa, Centro de Fisica Teorica de Particulas (CFTP), Instituto Superior Tecnico (IST), Lisbon (Portugal); Universidade de Lisboa, Departamento de Fisica, Instituto Superior Tecnico (IST), Lisbon (Portugal); CERN, Theory Group, Physics Department, Geneva (Switzerland); Coutinho, Antonio M.; Rebelo, M.N.; Silva-Marcos, J.I. [Universidade de Lisboa, Centro de Fisica Teorica de Particulas (CFTP), Instituto Superior Tecnico (IST), Lisbon (Portugal)

    2015-06-15

    In the context of two Higgs doublet models, we study the conditions required in order to have stable quasi-alignment in flavour space. We show that stability under the renormalisation group equations imposes strong constraints on the flavour structure of the Yukawa couplings associated to each one of the Higgs doublets. In particular, we find a novel solution, where all Yukawa couplings are proportional to the so-called democratic matrix. This solution is rather unique, since it is the only stable solution which is a good starting point for reproducing the observed pattern of quark masses and mixing. We also show that this stable solution can be obtained by imposing on the Lagrangian a Z{sub 3} x Z{sub 3}{sup '} flavour symmetry. Quark masses of the lighter quark generations are generated through the breaking of this discrete symmetry, and, at this stage, scalar-mediated flavour-changing neutral-currents arise, but they are naturally suppressed by the smallness of the light quark masses. In this way, we relate Higgs alignment to the hierarchy of the quark masses through a discrete family symmetry. (orig.)

  11. Feynman Rules in the Type III Natural Flavour-Conserving Two-Higgs Doublet Model

    CERN Document Server

    Lin, C; Yang, Y W; Lin, Chilong; Lee, Chien-er; Yang, Yeou-Wei

    1994-01-01

    We consider a two Higgs-doublet model with $S_3$ symmetry, which implies a $\\pi \\over 2$ rather than 0 relative phase between the vacuum expectation values $$ and $$. The corresponding Feynman rules are derived accordingly and the transformation of the Higgs fields from the weak to the mass eigenstates includes not only an angle rotation but also a phase transformation. In this model, both doublets couple to the same type of fermions and the flavour-changing neutral currents are naturally suppressed. We also demonstrate that the Type III natural flavour-conserving model is valid at tree-level even when an explicit $S_3$ symmetry breaking perturbation is introduced to get a reasonable CKM matrix. In the special case $\\beta = \\alpha$, as the ratio $\\tan\\beta = {v_2 \\over v_1}$ runs from 0 to $\\infty$, the dominant Yukawa coupling will change from the first two generations to the third generation. In the Feynman rules, we also find that the charged Higgs currents are explicitly left-right asymmetric. The ratios ...

  12. Extending two Higgs doublet models for two-loop neutrino mass generation and one-loop neutrinoless double beta decay

    CERN Document Server

    Liu, Zhen

    2016-01-01

    We extend some two Higgs doublet models, where the Yukawa couplings for the charged fermion mass generation only involve one Higgs doublet, by two singlet scalars respectively carrying a singly electric charge and a doubly electric charge. The doublet and singlet scalars together can mediate a two-loop diagram to generate a tiny Majorana mass matrix of the standard model neutrinos. Remarkably, the structure of the neutrino mass matrix is fully determined by the symmetric Yukawa couplings of the doubly charged scalar to the right-handed leptons. Meanwhile, a one-loop induced neutrinoless double beta decay can arrive at a testable level even if the electron neutrino has an extremely small Majorana mass. We also study other experimental constraints and implications including some rare processes and Higgs phenomenology.

  13. Extending two Higgs doublet models for two-loop neutrino mass generation and one-loop neutrinoless double beta decay

    Directory of Open Access Journals (Sweden)

    Zhen Liu

    2017-02-01

    Full Text Available We extend some two Higgs doublet models, where the Yukawa couplings for the charged fermion mass generation only involve one Higgs doublet, by two singlet scalars respectively carrying a singly electric charge and a doubly electric charge. The doublet and singlet scalars together can mediate a two-loop diagram to generate a tiny Majorana mass matrix of the standard model neutrinos. Remarkably, the structure of the neutrino mass matrix is fully determined by the symmetric Yukawa couplings of the doubly charged scalar to the right-handed leptons. Meanwhile, a one-loop induced neutrinoless double beta decay can arrive at a testable level even if the electron neutrino has an extremely small Majorana mass. We also study other experimental constraints and implications including some rare processes and Higgs phenomenology.

  14. Search for alpha variation in UVES spectra: Analysis of C IV and Si IV doublets towards QSO 1101-264

    Science.gov (United States)

    Martínez Fiorenzano, A. F.; Vladilo, G.; Bonifacio, P.

    Motivated by previous studies of QSO spectra that reported a variation of the fine structure constant alpha , a search for C IV and Si IV doublets was conducted in the absorption spectrum toward QSO 1101-264, obtained by VLT-UVES during the Science Verification. Seven C IV and two Si IV systems were identified and accurate measurements of wavelengths over the redshift range 1.1862 < z < 1.8377 were performed. After a careful selection of pairs of lines, the ``Alkali Doublet" method with a derived analitical expression for the error analysis was applied to compute the alpha variation. The result according in magnitud order with previous doublets measurements, corresponds to one Si IV system: Delta alpha /alpha = (- 3.09 +/- 8.46) x 10-5. Data from UVES-VLT.

  15. Search for alpha variation in UVES spectra: Analysis of C IV and Si IV doublets towards QSO 1101-264

    CERN Document Server

    Fiorenzano, A F M; Bonifacio, P

    2003-01-01

    Motivated by previous studies of QSO spectra that reported a variation of the fine structure constant alpha, a search for C IV and Si IV doublets was conducted in the absorption spectrum towardS QSO 1101-264, obtained by VLT-UVES during the Science Verification. Seven C IV and two Si IV systems were identified and accurate measurements of wavelengths over the redshift range 1.1862 < z < 1.8377 were performed. After a careful selection of pairs of lines, the "Alkali Doublet" method with a derived analitical expression for the error analysis was applied to compute the alpha variation. The result according in magnitud order with previous doublets measurements, corresponds to one Si IV system: Delta alpha/alpha = (- 3.09 +/- 8.46) x 10^(-5).

  16. Extending two Higgs doublet models for two-loop neutrino mass generation and one-loop neutrinoless double beta decay

    Science.gov (United States)

    Liu, Zhen; Gu, Pei-Hong

    2017-02-01

    We extend some two Higgs doublet models, where the Yukawa couplings for the charged fermion mass generation only involve one Higgs doublet, by two singlet scalars respectively carrying a singly electric charge and a doubly electric charge. The doublet and singlet scalars together can mediate a two-loop diagram to generate a tiny Majorana mass matrix of the standard model neutrinos. Remarkably, the structure of the neutrino mass matrix is fully determined by the symmetric Yukawa couplings of the doubly charged scalar to the right-handed leptons. Meanwhile, a one-loop induced neutrinoless double beta decay can arrive at a testable level even if the electron neutrino has an extremely small Majorana mass. We also study other experimental constraints and implications including some rare processes and Higgs phenomenology.

  17. Sizable NSI from the $SU(2)_L$ scalar doublet-singlet mixing and the implications in DUNE

    CERN Document Server

    Forero, David V

    2016-01-01

    We propose a novel and simple mechanism where sizable effects of non-standard interactions (NSI) in neutrino propagation are induced from the mixing between an electrophilic second Higgs doublet and a charged singlet. The mixing arises from a dimensionful coupling of the scalar doublet and singlet to the standard model Higgs boson. In light of the small mass, the light mass eigenstate from the doublet-singlet mixing can generate much larger NSI than those from the heavy eigenstate. We show that a sizable NSI $\\varepsilon_{e\\tau}$ ($\\sim 0.3$) can be attained without being excluded by a variety of experimental constraints. Furthermore, we demonstrate that NSI can mimic effects of the Dirac CP phase in the neutrino mixing matrix but they can potentially be disentangled by future long-baseline neutrino experiments, such as the Deep Underground Neutrino Experiment (DUNE).

  18. Comparison of acute toxicities of two chemotherapy schedules for head and neck cancers

    Directory of Open Access Journals (Sweden)

    Geeta S

    2006-01-01

    Full Text Available Background: Chemo-radiotherapy has become the standard of care for loco-regionally advanced head and neck cancers. Platinum based regimens are the most effective. Although benefits are proven with chemo-radiation, acute toxicities are markedly increased. The dose and delivery schedules of Cisplatin have ranged from intermittent higher dose [100 mg/m2] every 3 weeks to low dose [6 mg/m2] daily administration. At present there is no data indicating which regimen is superior. Purpose: To compare acute toxicities of two chemotherapy schedules for head and neck cancers. Materials and Methods: A total of 83 head and neck cancer patients treated with two schedules of concurrent chemo RT were analyzed, retrospectively, for treatment toxicity. In group A [51 patients], chemotherapy [CT] was administered on week 1, 4 and 7 [cisplatin 100 mg/m2] over a period of 2-3 days. In group B [32 patients], CT was delivered weekly [cisplatin 40 mg/m2]. Radiotherapy dose was 7000 cGy in 35 fractions for definitive concurrent chemo-radiation and 6600 cGy in 33 fractions for adjuvant treatment. Results: Group B patients had increased grade III skin and hematological toxicity, where as patients in group A had more pharyngeal toxicity. Treatment interruptions and percentage of weight loss were higher in group B. Weekly CT schedule had higher rate of severe mucositis, which was statistically significant on both univariate [ P =0.005] and multivariate [ P =0.007] analysis. Conclusions: Three weekly CT is less toxic than weekly. Weekly CT can be made more acceptable by reducing the dose and using feeding tubes for nutrition.

  19. Quark horizontal flavor symmetry and two-Higgs doublet in (7+1)-dimensional extended spin space

    CERN Document Server

    Romero, R

    2016-01-01

    An extended spin-space model in $7+1$ dimensions is presented that describes the standard-model electroweak quark sector. Up to four generations of massless and massive quarks and two-Higgs doublets derive from the associated representation space, in addition to the W- and Z-vector bosons. Other mass operators are obtained that put restrictions on additional non-Higgs scalars and their vacuum expectation value. After symmetry breaking, the scalar components give rise to a hierarchy effect vertically (within doublets) associated to the Higgs fields, and horizontally (within generations) associated to the non-Higgs elements.

  20. Metronomic chemotherapy regimens in oncology

    Directory of Open Access Journals (Sweden)

    M. Yu. Fedyanin

    2016-01-01

    Full Text Available Metronomic chemotherapy implies the regular use of cytotoxic agents in doses much smaller than the maximum tolerable doses for a long time. Preclinical experiments show that this treatment option has a many-sided (antiangiogenic, immunostimulating, and direct cytotoxic effect on tumor. Moreover, this approach has gained the widest acceptance in treating patients with metastatic breast cancer in clinical practice. By taking into account the high activity of angiogenesis in colon cancer progression, it is interesting to study the impact of metronomic chemotherapy regimens for this nosological entity as well. This literature review considers not only the history of metronomic chemotherapy, the mechanisms of action, and a range of drugs having an antitumor effect in the metronomic regimens, but also analyzes clinical trials of metronomic chemotherapy regimens in patients with metastatic colon cancer.

  1. Acute emesis: moderately emetogenic chemotherapy

    DEFF Research Database (Denmark)

    Herrstedt, Jørn; Rapoport, Bernardo; Warr, David

    2011-01-01

    This paper is a review of the recommendations for the prophylaxis of acute emesis induced by moderately emetogenic chemotherapy as concluded at the third Perugia Consensus Conference, which took place in June 2009. The review will focus on new studies appearing since the Second consensus conference...... receiving multiple cycles of moderately emetogenic chemotherapy will be reviewed. Consensus statements are given, including optimal dose and schedule of serotonin(3) receptor antagonists, dexamethasone, and neurokinin(1) receptor antagonists. The most significant recommendations (and changes since the 2004...... version of the guidelines) are as follows: the best prophylaxis in patients receiving moderately emetogenic chemotherapy (not including a combination of an anthracycline plus cyclophosphamide) is the combination of palonosetron and dexamethasone on the day of chemotherapy, followed by dexamethasone...

  2. Managing Chemotherapy Side Effects: Constipation

    Science.gov (United States)

    N ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods such as: ● ● Whole-grain breads and cereals ● ● Fruits and vegetables ● ● Nuts and seeds ...

  3. Detecting acute neurotoxicity during platinum chemotherapy by neurophysiological assessment of motor nerve hyperexcitability

    Directory of Open Access Journals (Sweden)

    Hill Andrew

    2010-08-01

    Full Text Available Abstract Background Platinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised. Use was made of nerve conduction studies and needle electromyography (EMG to assess motor nerve excitability in cancer patients during their first treatment cycle with platinum-based chemotherapy in this study. Methods Twenty-nine adult cancer patients had a neurophysiological assessment either before oxaliplatin plus capecitabine, on days 2 to 4 or 14 to 20 after oxaliplatin plus capecitabine, or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin, undertaken by a neurophysiologist who was blinded to patient and treatment details. Patients completed a symptom questionnaire at the end of the treatment cycle. Results Abnormal spontaneous high frequency motor fibre action potentials were detected in 100% of patients (n = 6 and 72% of muscles (n = 22 on days 2 to 4 post-oxaliplatin, and in 25% of patients (n = 8 and 13% of muscles (n = 32 on days 14 to 20 post-oxaliplatin, but in none of the patients (n = 14 or muscles (n = 56 tested prior to oxaliplatin or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin. Repetitive compound motor action potentials were less sensitive and less specific than spontaneous high frequency motor fibre action potentials for detection of acute oxaliplatin-induced motor nerve hyperexcitability but were present in 71% of patients (n = 7 and 32% of muscles (n = 32 on days 2 to 4 after oxaliplatin treatment. Acute neurotoxicity symptoms, most commonly cold-induced paraesthesiae and jaw or throat tightness, were reported by all patients treated with oxaliplatin (n = 22 and none of those treated with carboplatin plus paclitaxel or cisplatin (n = 6. Conclusions Abnormal spontaneous high frequency motor fibre activity is a sensitive and specific endpoint of acute oxaliplatin-induced motor nerve

  4. Is there a role for postoperative treatment in patients with stage Ib2-IIb cervical cancer treated with neo-adjuvant chemotherapy and radical surgery? An Italian multicenter retrospective study.

    Science.gov (United States)

    Landoni, F; Sartori, E; Maggino, T; Zola, P; Zanagnolo, V; Cosio, S; Ferrari, F; Piovano, E; Gadducci, A

    2014-03-01

    Neoadjuvant chemotherapy [NACT] followed by radical hysterectomy is an alternative therapeutic option to concurrent chemotherapy-radiotherapy for locally advanced cervical cancer. However there are very few data about the effectiveness of any post-operative treatment in this clinical setting. The purpose of this study was to correlate the patterns of recurrence and the clinical outcomes of cervical cancer patients who received NACT, with postoperative adjuvant treatment. This retrospective multicenter study included 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent platinum-based NACT followed by radical surgery. Pathological responses were retrospectively assessed as complete; optimal partial; and suboptimal response. Overall optimal response rate was the sum of complete and optimal partial response rates. On the whole series, recurrence-free survival was significantly longer in patients who achieved an overall optimal response than in those who did not (ptreatment for FIGO stage Ib2-IIb cervical cancer do not need any further treatment. Additional cycles of chemotherapy could be of benefit for patients with suboptimal response and intra-cervical residual disease. Both adjuvant chemotherapy and adjuvant radiation treatments do not seem to improve the clinical outcome of patients with extra-cervical residual disease compared to no further treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Chiral heavy fermions in a two Higgs doublet model: 750 GeV resonance or not

    Science.gov (United States)

    Bar-Shalom, Shaouly; Soni, Amarjit

    2017-03-01

    We revisit models where a heavy chiral 4th generation doublet of fermions is embedded in a class of two Higgs doublets models (2HDM) with a discrete Z2 symmetry, which couples the ;heavy; scalar doublet only to the 4th generation fermions and the ;light; one to the Standard Model (SM) fermions - the so-called 4G2HDM introduced by us several years ago. We study the constraints imposed on the 4G2HDM from direct searches of heavy fermions, from precision electroweak data (PEWD) and from the measured production and decay signals of the 125 GeV scalar, which in the 4G2HDM corresponds to the lightest CP-even scalar h. We then show that the recently reported excess in the γγ spectrum around 750 GeV can be accommodated by the heavy CP-even scalar of the 4G2HDM, H, resulting in a unique choice of parameter space: negligible mixing (sin ⁡ α ≲ O (10-3)) between the two CP-even scalars h , H and heavy 4th generation quark and lepton masses mt‧ ,mb‧ ≲ 400 GeV and mν‧ ,mτ‧ ≳ 900 GeV, respectively. Whether or not the 750 GeV γγ resonance is confirmed, interesting phenomenology emerges in q‧ - Higgs systems (q‧ =t‧ ,b‧), that can be searched for at the LHC. For example, the heavy scalar states of the model, S = H , A ,H+, may have BR (S →qbar‧q‧) ∼ O (1), giving rise to observable qbar‧q‧ signals on resonance, followed by the flavor changing q‧ decays t‧ → uh (u = u , c) and/or b‧ → dh (d = d , s , b). This leads to rather distinct signatures, with or without charged leptons, of the form qbar‧q‧ →(nj + mb + ℓW) S (j and b being light and b-quark jets, respectively), with n + m + ℓ = 6- 8 and unique kinematic features. These high jet-multiplicity signals appear to be very challenging and may need new search strategies for detection of such heavy chiral quarks. It is also shown that the flavor structure of the 4G2HDM can easily accommodate the interesting recent indications of a percent-level branching ratio in the

  6. Risk of Misinterpreting Nearly Degenerate Doublet Bands as Chiral Partners in Odd-even 103,105,107Ag and Odd-odd 106Ag

    Institute of Scientific and Technical Information of China (English)

    MA; Hai-liang; YAO; Shun-he; DONG; Bao-guo; WU; Xiao-guang; ZHANG; Huan-qiao; ZHANG; Xi-zhen

    2013-01-01

    The chiral doublet bands were claimed to be found in several silver isotopes.In the present study of negative parity bands of the odd-even 103,105,107Ag,by using the principal cranking Nilsson-Strutinsky approach it is demonstrated from the point view of spectroscopy that the nearly degenerateΔI=1 doublet

  7. The prognostic and predictive value of excision repair cross-complementation group 1 (ERCC1) protein in 1288 patients with head and neck squamous cell carcinoma treated with platinum-based therapy: a meta-analysis.

    Science.gov (United States)

    Bišof, Vesna; Zajc Petranović, Matea; Rakušić, Zoran; Samardžić, Kristina Ruža; Juretić, Antonio

    2016-09-01

    Excision repair cross-complementation group 1 (ERCC1) protein has been extensively investigated as a prognostic and predictive factor for platinum-based treatment in head and neck squamous cell carcinoma (HNSCC) but with inconsistent results. We performed the present meta-analysis to better elucidate this issue in advanced HNSCC. A literature search was conducted using the PubMed and Web of Science databases. The inclusion criteria were head and neck cancer patients with platinum-based treatment and evaluation of the correlation between ERCC1 expression and clinical outcomes [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), both unadjusted and adjusted estimates]. In high vs. low pooled analyses, high ERCC1 expression was associated with unfavorable OS [hazard ratio (HR) = 1.95, 95 % confidence interval (CI) 1.18-3.21, p = 0.009], PFS (HR = 2.39, 95 % CI 1.74-3.28, p = 0.000) and ORR (odds ratio = 0.48, 95 % CI 0.23-0.98, p = 0.044). In the subgroup analysis of adjusted OS estimates, ERCC1 was a predictor of shorter survival in Asians (HR = 3.13, 95 % CI 2.09-4.70, p = 0.000) and Caucasians (HR = 2.02, 95 % CI 1.32-3.07, p = 0.001) but of longer survival in South Americans (HR = 0.17, 95 % CI 0.07-0.40, p = 0.000). Immunohistochemistry proved to be of predictive value irrespective of used antibody (p = 0.009). In the stratified analysis according to the tumor site, ERCC1 expression was associated with OS in nasopharyngeal cancer (HR = 2.72, 95 % CI 1.79-4.13, p = 0.000). ERCC1 has a potential to become predictive and prognostic factor enabling treatment tailoring in HNSCC patients.

  8. On the doublet/triplet splitting and intermediate mass scales in locally supersymmetric SO(10)

    Science.gov (United States)

    Pulido, João

    1985-01-01

    In the light of the doublet/triplet splitting, the possibilities for an intermediate mass scale in locally supersymmetric SO(10) are analysed. It is found that the subgroup SU(4)c × SU(2)L × SU(2)R and more generally left-right symmetric models are unlikely to survive as intermediate symmetries since they imply too large values of the weak mixing angle. An alternative model using the subgroup SU(3)c × U(1)L × U(1)R is discussed. Requirements from global SUSY preservation impose an extra constraint and predictions for the grand unification and the intermediate masses are obtained at MX ~ 6 × 1015 GeV and MI ~ 1012 GeV. Address after March 1984: Centro de Fisica da Materia Condensada, Av. Prof. Gama Pinto, 2, 1699 Lisbon Codex, Portugal.

  9. The general Two-Higgs doublet eXtensions of the SM: a saucerful of secrets

    CERN Document Server

    Diaz-Cruz, J L; Y., J H Montes de Oca

    2010-01-01

    We discuss the most general formulation of the Two-Higgs doublet model, which incorporates flavor changing neutral scalar interactions (FCNSI) and CP violation (CPV) from several sources. CP violation can arise either from Yukawa terms or from the Higgs potential, be it explicit or spontaneous. We show how the model, which is denoted as 2HDM-X, reduces to some versions known in the literature (2HDM-I,II,III), as well as some of their variants (top, lepton, dark) denoted here as 2HDM-IV. We also discuss another limit that includes CPV and Yukawa four textures to control FCNSI, which we denote as 2HDM-V. We evaluate the CPV asymmetry for the decay $h\\to bcW$, which may allow to test the patterns of FCNSI and CPV, that arises in these models.

  10. tbW anomalous couplings in the Two Higgs Doublet Model

    Science.gov (United States)

    Arhrib, Abdesslam; Jueid, Adil

    2016-08-01

    We make a complete one loop calculation of the tbW couplings in the Two Higgs Doublet Model. We evaluate both the anomalous couplings g L and g R as well as left handed and right handed component of tbW . The computation is done in the Feynman gauge using the on-shell scheme renormalization for the Standard Model wave functions and parameters. We first show that the relative corrections to these anomalous couplings are rather small in most regions of the parameter space. We then analyze the effects of these anomalous couplings on certain observables such as top quark polarization in single top production through t-channel as well as W ± boson helicity fractions in top decay.

  11. Isospin-violating dark-matter-nucleon scattering via two-Higgs-doublet-model portals

    Science.gov (United States)

    Drozd, Aleksandra; Grzadkowski, Bohdan; Gunion, John F.; Jiang, Yun

    2016-10-01

    We show that in a multi-Higgs model in which one Higgs fits the LHC 125 GeV state, one or more of the other Higgs bosons can mediate DM-nucleon interactions with maximal DM isospin violation being possible for appropriate Higgs-quark couplings, independent of the nature of DM. We then consider the explicit example of a Type II two-Higgs-doublet model, identifying the h or H as the 125 GeV state while the H or h, respectively, mediates DM-nucleon interactions. Finally, we show that if a stable scalar, S, is added then it can be a viable light DM candidate with correct relic density while obeying all direct and indirect detection limits.

  12. Doublet N-Terminal Oriented Proteomics for N-Terminomics and Proteolytic Processing Identification.

    Science.gov (United States)

    Westermann, Benoit; Jacome, Alvaro Sebastian Vaca; Rompais, Magali; Carapito, Christine; Schaeffer-Reiss, Christine

    2017-01-01

    The study of the N-terminome and the precise identification of proteolytic processing events are key in biology. Dedicated methodologies have been developed as the comprehensive characterization of the N-terminome can hardly be achieved by standard proteomics methods. In this context, we have set up a trimethoxyphenyl phosphonium (TMPP) labeling approach that allows the characterization of both N-terminal and internal digestion peptides in a single experiment. This latter point is a major advantage of our strategy as most N-terminomics methods rely on the enrichment of N-terminal peptides and thus exclude internal peptides.We have implemented a double heavy/light TMPP labeling and an automated data validation workflow that make our doublet N-terminal oriented proteomics (dN-TOP) strategy efficient for high-throughput N-terminome analysis.

  13. Doublet Pulse Coherent Laser Radar for Tracking of Resident Space Objects

    Science.gov (United States)

    Prasad, Narasimha S.; Rudd, Van; Shald, Scott; Sandford, Stephen; Dimarcantonio, Albert

    2014-01-01

    In this paper, the development of a long range ladar system known as ExoSPEAR at NASA Langley Research Center for tracking rapidly moving resident space objects is discussed. Based on 100 W, nanosecond class, near-IR laser, this ladar system with coherent detection technique is currently being investigated for short dwell time measurements of resident space objects (RSOs) in LEO and beyond for space surveillance applications. This unique ladar architecture is configured using a continuously agile doublet-pulse waveform scheme coupled to a closed-loop tracking and control loop approach to simultaneously achieve mm class range precision and mm/s velocity precision and hence obtain unprecedented track accuracies. Salient features of the design architecture followed by performance modeling and engagement simulations illustrating the dependence of range and velocity precision in LEO orbits on ladar parameters are presented. Estimated limits on detectable optical cross sections of RSOs in LEO orbits are discussed.

  14. Isospin-violating dark-matter-nucleon scattering via 2-Higgs-doublet-model portals

    CERN Document Server

    Drozd, Aleksandra; Gunion, John F; Jiang, Yun

    2015-01-01

    We show that in a multi-Higgs model in which one Higgs fits the LHC 125 GeV state, one or more of the other Higgs bosons can mediate DM-nucleon interactions with maximal DM isospin violation being possible for appropriate Higgs-quark couplings, independent of the nature of DM. We then consider the explicit example of a Type II two-Higgs-doublet model, identifying the h or H as the 125 GeV state while the H or h, respectively, mediates DM-nucleon interactions. Finally, we show that if a stable scalar, S, is added then it can be a viable light DM candidate with correct relic density while obeying all direct and indirect detection limits.

  15. Dobletes etimológicos en fraseología / Etymological doublets in phraseology

    Directory of Open Access Journals (Sweden)

    Oksana Gorelova

    2010-07-01

    Full Text Available RESUMEN: El artículo analiza un grupo de frases proverbiales españolas que proceden de un mismo étimo latino pero que entraron en la lengua española por dos vías diferentes: la escrita y la hablada, lo que permite llegar a la conclusión de que en el sistema fraseológico español existen dobletes etimológicos.ABSTRACT: The article analyses a group of Spanish proverbial sayings that originate in the same Latin etymon but entered the Spanish language though two two different routes - the written one and the spoken one. This allows us draw conclusions about the existence of etymological doublets in the Spanish phraseological system.

  16. Effect of CP violation in the singlet-doublet dark matter model

    Directory of Open Access Journals (Sweden)

    Tomohiro Abe

    2017-08-01

    Full Text Available We revisit the singlet-doublet dark matter model with a special emphasis on the effect of CP violation on the dark matter phenomenology. The CP violation in the dark sector induces a pseudoscalar interaction of a fermionic dark matter candidate with the SM Higgs boson. The pseudoscalar interaction helps the dark matter candidate evade the strong constraints from the dark matter direct detection experiments. We show that the model can explain the measured value of the dark matter density even if dark matter direct detection experiments do not observe any signal. We also show that the electron electric dipole moment is an important complement to the direct detection for testing this model. Its value is smaller than the current upper bound but within the reach of future experiments.

  17. Isospin-violating dark-matter-nucleon scattering via two-Higgs-doublet-model portals

    Energy Technology Data Exchange (ETDEWEB)

    Drozd, Aleksandra [Theoretical Particle Physics and Cosmology Group, Physics Department, King’s College London,London WC2R 2LS (United Kingdom); Grzadkowski, Bohdan [Faculty of Physics, University of Warsaw,Pasteura 5, 02-093 Warsaw (Poland); Gunion, John F. [Department of Physics, University of California,Davis, CA 95616 (United States); Jiang, Yun [Department of Physics, University of California,Davis, CA 95616 (United States); NBIA and Discovery Center, Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, DK-2100, Copenhagen (Denmark)

    2016-10-24

    We show that in a multi-Higgs model in which one Higgs fits the LHC 125 GeV state, one or more of the other Higgs bosons can mediate DM-nucleon interactions with maximal DM isospin violation being possible for appropriate Higgs-quark couplings, independent of the nature of DM. We then consider the explicit example of a Type II two-Higgs-doublet model, identifying the h or H as the 125 GeV state while the H or h, respectively, mediates DM-nucleon interactions. Finally, we show that if a stable scalar, S, is added then it can be a viable light DM candidate with correct relic density while obeying all direct and indirect detection limits.

  18. Novel gamma-ray spectral features in the inert doublet model

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Cely, Camilo; Ibarra, Alejandro, E-mail: camilo.garcia@tum.de, E-mail: alejandro.ibarra@ph.tum.de [Physik-Department T30d, Technische Universität München, James-Franck-Straße, 85748 Garching (Germany)

    2013-09-01

    The inert doublet model contains a neutral stable particle which is an excellent dark matter candidate. We discuss in this paper the indirect signatures of this model in gamma-rays when the dark matter mass is larger than the W boson mass. We show that, in addition to the featureless gamma-ray spectrum produced in the annihilations into two weak gauge bosons, the model generically predicts a distinctive spectral feature from the internal bremsstrahlung process H{sup 0}H{sup 0}→W{sup +}W{sup −}γ. We discuss under which conditions the spectral feature is generated and we construct a number of benchmark points, compatible with the observed relic density and all other direct and indirect detection experiments, which lead to a sharp gamma-ray feature from internal bremsstrahlung.

  19. Associated production of Higgs at linear collider in the inert Higgs Doublet Model

    Energy Technology Data Exchange (ETDEWEB)

    Arhrib, Abdesslam [Universite Abdelmalek Essaadi, Departement de Mathematique, Faculte des Sciences et Techniques, B. 416, Tangier (Morocco); Institute of Physics, Academia Sinica, Nankang, Taipei (China); Benbrik, Rachid [Faculte Polydisciplinaire de Safi, MSISM team, Departement de Physique, Sidi Bouzid, B.P. 4162, Safi (Morocco); Instituto de Fisica de Cantabria (CSIC-UC), Santander (Spain); Cadi Ayyad University, LPHEA, FSSM, B.P. 2390, Marrakech (Morocco); Yuan, Tzu-Chiang [Institute of Physics, Academia Sinica, Nankang, Taipei (China)

    2014-05-15

    We study the correlation between the Standard Model Higgs decay h → γγ and h → Zγ in the Inert Higgs Doublet Model. It is found that these two one-loop-induced decays are positively correlated, with the latter channel having slightly smaller branching ratio than the former one. At the Linear Collider, we study the interplay of the off-shell extension of these two amplitudes that contributed significantly to the associated production of the Higgs boson with a photon in the process e{sup +}e{sup -} → γh and with an electron in the process e{sup -}γ → e{sup -}h in the s and t channels, respectively, via both γ and Z exchange for each process. (orig.)

  20. Autler-Townes doublet in novel sub-Doppler spectra with caesium vapour cell

    Institute of Scientific and Technical Information of China (English)

    Wang Yan-Hua; Yang Jai-Jing; Du Zhi-Jing; Zhang Tian-Cai; Wang Jun-Min

    2006-01-01

    With a coupling laser locked to caesium 6S1/2 Fg=4-6P3/2Fe=5 cycling transition and a co-propagating probe laser scanned across 6S1/2Fg=4-6P3/2Fe=3, 4 and 5 transitions, a novel scheme for sub-Doppler spectra in Doppler-broadened V-type three-level system is demonstrated by detecting the transmission of the coupling laser through a caesium vapour cell. The Autler-Townes doublet in the sub-Doppler spectra of the coupling laser is clearly observed. The effects of coupling laser intensity on the splitting and linewidth of the Autleraking the multiple hyperfine levels of caesium atom into account, a brief analysis is presented.

  1. Radiative generation of quark masses and mixing angles in the two Higgs doublet model

    Energy Technology Data Exchange (ETDEWEB)

    Ibarra, Alejandro [Physik-Department T30d, Technische Universität München, James-Franck-Straße, 85748 Garching (Germany); Solaguren-Beascoa, Ana [Physik-Department T30d, Technische Universität München, James-Franck-Straße, 85748 Garching (Germany); Max-Planck-Institut für Physik (Werner-Heisenberg-Institut), Föhringer Ring 6, 80805 München (Germany)

    2014-09-07

    We present a framework to generate the quark mass hierarchies and mixing angles by extending the Standard Model with one extra Higgs doublet. The charm and strange quark masses are generated by small quantum effects, thus explaining the hierarchy between the second and third generation quark masses. All the mixing angles are also generated by small quantum effects: the Cabibbo angle is generated at zeroth order in perturbation theory, while the remaining off-diagonal entries of the Cabibbo–Kobayashi–Maskawa matrix are generated at first order, hence explaining the observed hierarchy |V{sub ub}|,|V{sub cb}|≪|V{sub us}|. The values of the radiatively generated parameters depend only logarithmically on the heavy Higgs mass, therefore this framework can be reconciled with the stringent limits on flavor violation by postulating a sufficiently large new physics scale.

  2. Status of the Inert Doublet Model of dark matter after Run-1 of the LHC

    CERN Document Server

    Goudelis, Andreas

    2015-01-01

    The Inert Doublet Model (IDM) is one of the simplest extensions of the Standard Model that can provide a viable dark matter (DM) candidate. Despite its simplicity, it predicts a versatile phenomenology both for cosmology and for the Large Hadron Collider. We briefly summarize the status of searches for IDM dark matter in direct DM detection experiments and the LHC, focusing on the impact of the latter on the model parameter space. In particular, we discuss the consequences of the Higgs boson discovery as well as those of searches for dileptons accompanied by missing transverse energy during the first LHC Run and comment on the prospects of probing some of the hardest to test regions of the IDM parameter space during the 13 TeV Run.

  3. Neutrino masses in RPV models with two pairs of Higgs doublets

    Energy Technology Data Exchange (ETDEWEB)

    Grossman, Yuval [Laboratory for Elementary-Particle Physics, Cornell University,Ithaca, N.Y. (United States); Peset, Clara [Institut de Fisica d’Altes Energies (IFAE), Universitat Autònoma de Barcelona,08193 Bellaterra, Barcelona (Spain)

    2014-04-07

    We study the generation of neutrino masses and mixing in supersymmetric R-parity violating models containing two pairs of Higgs doublets. In these models, new RPV terms H^{sub D{sub 1}}H^{sub D{sub 2}}E^ arise in the superpotential, as well as new soft terms. Such terms give new contributions to neutrino masses. We identify the different parameters and suppression/enhancement factors that control each of these contributions. At tree level, just like in the MSSM, only one neutrino acquires a mass due to neutrino-neutralino mixing. There are no new one loop effects. We study the two loop contributions and find the conditions under which they can be important.

  4. Analysis of the Lepton Mixing Matrix in the Two Higgs Doublet Model

    CERN Document Server

    Barradas-Guevara, E; Gonzalez-Canales, F; Rodríguez-Jáuregui, E; Zeleny-Mora, M

    2016-01-01

    In the theoretical framework of Two Higgs Doublet Model (2HDM) plus three right-handed neutrinos we consider a universal treatment for the mass matrices, aside from that the active neutrinos acquire their small mass through the type-I seesaw mechanism. Then, as long as a matrix with four-zero texture is used to represent the right-handed neutrinos and Yukawa matrices, we obtain a unified treatment where all fermion mass matrices have four-zero texture. We obtain analytical and explicit expressions for the lepton flavour mixing matrix PMNS in terms of fermion masses and parameters associated with the 2HDM-III. Further, we compare these expressions of the PMNS matrix with the most up to date values of masses and mixing in the lepton sector, via a likelihood test $\\chi^{2}$. We find that the analytical expressions that we derived reproduce remarkably well the most recent experimental data of neutrino oscillations.

  5. Almost-Commutative Geometries Beyond the Standard Model III: Vector Doublets

    CERN Document Server

    Squellari, Romain

    2007-01-01

    We will present a new extension of the standard model of particle physics in its almostcommutative formulation. This extension has as its basis the algebra of the standard model with four summands [11], and enlarges only the particle content by an arbitrary number of generations of left-right symmetric doublets which couple vectorially to the U(1)_YxSU(2)_w subgroup of the standard model. As in the model presented in [8], which introduced particles with a new colour, grand unification is no longer required by the spectral action. The new model may also possess a candidate for dark matter in the hundred TeV mass range with neutrino-like cross section.

  6. New LHC Benchmarks for the CP-conserving Two-Higgs-Doublet Model

    CERN Document Server

    Haber, Howard E

    2015-01-01

    We introduce a strategy to study the parameter space of the general, CP-conserving, two-Higgs-doublet Model (2HDM) with a softly broken Z_2-symmetry by means of a new "hybrid" basis. In this basis the input parameters are the measured values of the mass of the observed Standard Model (SM)-like Higgs boson and its coupling strength to vector boson pairs, the mass of the second CP-even Higgs boson, the ratio of neutral Higgs vacuum expectation values, and three additional dimensionless parameters. Using the hybrid basis, we present numerical scans of the 2HDM parameter space where we survey available parameter regions and analyze model constraints. From these results, we define a number of benchmark scenarios that capture different aspects of non-standard Higgs phenomenology that are of interest for future LHC Higgs searches.

  7. Inflation Model (with doublet scalar field) consistent with Lambda CDM and WMAP cosmological observations

    CERN Document Server

    Amruth, B R; R., Amruth B.; Patwardhan, Ajay

    2006-01-01

    Cosmological inflation models with modifications to include recent cosmological observations has been an active area of research after WMAP 3 results, which have given us information about the composition of dark matter, normal matter and dark energy and the anisotropy at the 300,000 years horizon with high precision. We work on inflation models of Guth and Linde and modify them by introducing a doublet scalar field to give normal matter particles and their supersymmetric partners which result in normal and dark matter of our universe. We include the cosmological constant term as the vaccuum expectation value of the stress energy tensor, as the dark energy. We callibrate the parameters of our model using recent observations of density fluctuations. We develop a model which consistently fits with the recent observations.

  8. The Electron/Muon Specific Two Higgs Doublet Model at e+ e- Colliders

    CERN Document Server

    Johansen, Aria R

    2015-01-01

    Recently, Kajiyama, Okada and Yagyu (KOY) proposed an electron/muon specific two Higgs doublet model. In this model, an S3 symmetry suppresses flavor changing neutral currents instead of a Z2 symmetry. In the "Type I" version of the model, the heavy Higgs bosons have a greatly enhanced coupling to electrons and muons. KOY studied the phenomenology of the heavy Higgs bosons at the LHC. In this paper, the phenomenology at electron-positron colliders is studied. For the heavy Higgs mass range between 150 and 210 GeV, bounds from LEP-200 are stronger than those from the LHC. The model allows for the interesting possibility that muon pair production at the ILC can be mediated by s-channel Higgs exchange. This requires an energy scan. The scanning rate and necessary resolution are discussed.

  9. $tbW$ Anomalous Couplings in the Two Higgs Doublet Model

    CERN Document Server

    Arhrib, Abdesslam

    2016-01-01

    We make a complete one loop calculation of the $tbW$ couplings in the Two Higgs Doublet Model. We evaluate both the anomalous couplings $g_L$ and $g_R$ as well as left handed and right handed component of $tbW$. The computation is done in the Feynman gauge using the on-shell scheme renormalization for the Standard Model wave functions and parameters. We first show that the relative corrections to these anomalous couplings are rather small in most regions of the parameter space. We then analyze the effects of these anomalous couplings on certain observables such as top quark polarization in single top production through $t-$channel as well as $W^\\pm$ boson helicity fractions in top decay.

  10. The Higgs Pair Productions in The CP-violating Two-Higgs-Doublet Model

    CERN Document Server

    Bian, Ligong

    2016-01-01

    In this work, we study the SM-like Higgs pair productions in the framework of the general CP-violating two-Higgs-doublet model. Several constraints are imposed to the model sequentially, including the SM-like Higgs boson signal fits, the precise measurements of the electric dipole moments, the perturbative unitarity and stability bounds to the Higgs potential, and the most recent LHC searches for the heavy Higgs bosons. We show how are the CP-violating mixing angles related to the Higgs cubic self couplings in this setup. Afterwards, we estimate the cross sections of the future LHC/SppC searches for the Higgs pair productions, as well as other possible decay modes for the heavy Higgs bosons.

  11. Gamma Vibrational Bands and Chiral Doublet Bands in A≈100 Neutron-rich Nuclei

    Institute of Scientific and Technical Information of China (English)

    ZHU Sheng-jiang; DING Huai-bo; J.H.Hamilton; A.V.Ramayya; CHE Xing-lai; J.K.Hwang; Y.X.Luo; J.O.Rasmussen; K.Li; WANG Jian-guo; XU Qiang; GU Long; YANG Yun-yi; S.Frauendorf; V.Dimitrov

    2009-01-01

    The level structures of neutron-rich ~(105)Mo,~(106)Mo,~(108)Mo and 110Ru nuclei in A≈100 region have been carefully investigated by coincidence measurements of the prompt γ-rays populated in the spontaneous fission of ~(252)Cf with the Gammasphere detector array.In 105Mo,one-phonon K =9/2 and two-phonon K=13/2 γ-vibrational bands have been identified.In ~(108)Mo,one-phonon γ-vibrational band is expanded and two-phonon γ-vibrational band has been identified.Two similar sets of bands in ~(106)Mo and ~(110)Ru are observed to high spins,which have been proposed as the soft chiral γ-vibrational bands.The characteristics for these γ-vibrational bands and chiral doublet bands have been discussed.

  12. Neutrino masses in RPV models with two pairs of Higgs doublets

    CERN Document Server

    Grossman, Yuval

    2014-01-01

    We study the generation of neutrino masses and mixing in supersymmetric R-parity violating models containing two pairs of Higgs doublets. In these models, new RPV terms $\\hat H_{D_1} \\hat H_{D_2} \\hat E$ arise in the superpotential, as well as new soft terms. Such terms give new contributions to neutrino masses. We identify the different parameters and suppression/enhancement factors that control each of these contributions. At tree level, just like in the MSSM, only one neutrino acquires a mass due to neutrino-neutralino mixing. There are no new one loop effects. We study the two loop contributions and find the conditions under which they can be important.

  13. Search for Charged Higgs Bosons at LEP in General Two Higgs Doublet Models

    CERN Document Server

    Abdallah, J; Adam, W; Adzic, P; Albrecht, T; Alderweireld, T; Alemany-Fernandez, R; Allmendinger, T; Allport, P P; Amaldi, Ugo; Amapane, N; Amato, S; Anashkin, E; Andreazza, A; Andringa, S; Anjos, N; Antilogus, P; Apel, W D; Arnoud, Y; Ask, S; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Ballestrero, A; Bambade, P; Barbier, R; Bardin, Dimitri Yuri; Barker, G; Baroncelli, A; Battaglia, Marco; Baubillier, M; Becks, K H; Begalli, M; Behrmann, A; Ben-Haim, E; Benekos, N C; Benvenuti, Alberto C; Bérat, C; Berggren, M; Berntzon, L; Bertrand, D; Besançon, M; Besson, N; Bloch, D; Blom, M; Bluj, M; Bonesini, M; Boonekamp, M; Booth, P S L; Borisov, G; Botner, O; Bouquet, B; Bowcock, T J V; Boyko, I; Bracko, M; Brenner, R; Brodet, E; Brückman, P; Brunet, J M; Bugge, L; Buschmann, P; Calvi, M; Camporesi, T; Canale, V; Carena, F; Castro, N; Cavallo, F R; Chapkin, M M; Charpentier, P; Checchia, P; Chierici, R; Shlyapnikov, P; Chudoba, J; Chung, S U; Cieslik, K; Collins, P; Contri, R; Cosme, G; Cossutti, F; Costa, M J; Crennell, D J; Cuevas-Maestro, J; D'Hondt, J; Dalmau, J; Da Silva, T; Da Silva, W; Della Ricca, G; De Angelis, A; de Boer, Wim; De Clercq, C; De Lotto, B; De Maria, N; De Min, A; De Paula, L S; Di Ciaccio, L; Di Simone, A; Doroba, K; Drees, J; Dris, M; Eigen, G; Ekelöf, T J C; Ellert, M; Elsing, M; Espirito-Santo, M C; Fanourakis, G K; Fassouliotis, D; Feindt, M; Fernández, J; Ferrer, A; Ferro, F; Flagmeyer, U; Föth, H; Fokitis, E; Fulda-Quenzer, F; Fuster, J A; Gandelman, M; García, C; Gavillet, P; Gazis, E N; Gokieli, R; Golob, B; Gómez-Ceballos, G; Gonçalves, P; Graziani, E; Grosdidier, G; Grzelak, K; Guy, J; Haag, C; Hallgren, A; Hamacher, K; Hamilton, K; Haug, S; Hauler, F; Hedberg, V; Hennecke, M; Herr, H; Hoffman, J; Holmgren, S O; Holt, P J; Houlden, M A; Hultqvist, K; Jackson, J N; Jarlskog, G; Jarry, P; Jeans, D; Johansson, E K; Johansson, P D; Jonsson, P; Joram, C; Jungermann, L; Kapusta, F; Katsanevas, S; Katsoufis, E C; Kernel, G; Kersevan, Borut P; Kerzel, U; Kiiskinen, A P; King, B T; Kjaer, N J; Kluit, P; Kokkinias, P; Kourkoumelis, C; Kuznetsov, O; Krumshtein, Z; Kucharczyk, M; Lamsa, J; Leder, G; Ledroit, F; Leinonen, L; Leitner, R; Lemonne, J; Lepeltier, V; Lesiak, T; Liebig, W; Liko, D; Lipniacka, A; Lopes, J H; López, J M; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J; Malek, A; Maltezos, S; Mandl, F; Marco, J; Marco, R; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Masik, J; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Mazzucato, F; Mazzucato, M; McNulty, R; Meroni, C; Migliore, E; Mitaroff, W A; Mjörnmark, U; Moa, T; Moch, M; Mönig, K; Monge, R; Montenegro, J; Moraes, D; Moreno, S; Morettini, P; Müller, U; Münich, K; Mulders, M; Mundim, L M; Murray, W; Muryn, B; Myatt, G; Myklebust, T; Nassiakou, M; Navarria, Francesco Luigi; Nawrocki, K; Nicolaidou, R; Nikolenko, M; Oblakowska-Mucha, A; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, R; Österberg, K; Ouraou, A; Oyanguren, A; Paganoni, M; Paiano, S; Palacios, J P; Palka, H; Papadopoulou, T D; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Peralta, L; Perepelitsa, V F; Perrotta, A; Petrolini, A; Piedra, J; Pieri, L; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Poireau, V; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Pukhaeva, N; Pullia, Antonio; Rames, J; Ramler, L; Read, A; Rebecchi, P; Rehn, J; Reid, D; Reinhardt, R; Renton, P B; Richard, F; Rídky, J; Rivero, M; Rodríguez, D; Romero, A; Ronchese, P; Roudeau, Patrick; Rovelli, T; Ruhlmann-Kleider, V; Ryabtchikov, D; Sadovskii, A; Salmi, L; Salt, J; Savoy-Navarro, A; Schwickerath, U; Segar, A; Sekulin, R L; Siebel, M; Sissakian, A N; Smadja, G; Smirnova, O G; Sokolov, A; Sopczak, A; Sosnowski, R; Spassoff, Tz; Stanitzki, M; Stocchi, A; Strauss, J; Stugu, B; Szczekowski, M; Szeptycka, M; Szumlak, T; Tabarelli de Fatis, T; Taffard, A C; Tegenfeldt, F; Timmermans, J; Tkatchev, L G; Tobin, M; Todorovova, S; Tomé, B; Tonazzo, A; Tortosa, P; Travnicek, P; Treille, D; Tristram, G; Trochimczuk, M; Troncon, C; Turluer, M L; Tyapkin, I A; Tyapkin, P; Tzamarias, S; Uvarov, V; Valenti, G; van Dam, P; Van Eldik, J; Van Lysebetten, A; Van Remortel, N; Van Vulpen, I; Vegni, G; Veloso, F; Venus, W A; Verdier, P; Verzi, V; Vilanova, D; Vitale, L; Vrba, V; Wahlen, H; Washbrook, A J; Weiser, C; Wicke, D; Wickens, J H; Wilkinson, G; Winter, M; Witek, M; Yushchenko, O P; Zalewska-Bak, A; Zalewski, P; Zavrtanik, D; Zhuravlov, V; Zimin, N I; Zintchenko, A; Zupan, M

    2004-01-01

    A search for pair-produced charged Higgs bosons was performed in the data collected by the DELPHI detector at LEP II at centre-of-mass energies from 189 GeV to 209 GeV. Five different final states, tau+ nu_tau tau- anti-nu_tau, c sbar cbar s, c sbar tau- anti-nu_tau, W* A W* A and W* A tau- anti-nu_tau were considered, accounting for the major expected decays in type I and type II Two Higgs Doublet Models. No significant excess of data compared to the expected Standard Model processes was observed. The existence of a charged Higgs boson with mass lower than 76.7 GeV/c^2 (type I) or 74.4 GeV/c^2 (type II) is excluded at the 95% confidence level, for a wide range of the model parameters. Model independent cross-section limits have also been calculated.

  14. Radiative Decay Bc → Ds*γ in the Technicolor with a Massless Scalar Doublet Model

    Institute of Scientific and Technical Information of China (English)

    CAO Yi-Gang; JIAO Zheng-Kuan

    2002-01-01

    Applying perturbative QCD, we study the process Bc → Dsγ in the technicolor with a massless scalar doublet model (TCMLSM). There are mainly two mechanisms contributing to the Bc → D*sγ process. One proceeds through the short distance b → sγ transition and the other through weak annihilation accompanied by a photon emission.We find that, compared with the standard model, the modification of Bc → D*sγ from πρ (the physical pions in the TCMLSM) is so small that can be neglected for the allowed mass ofπρ. The weak-annihilation contribution is found to be about one order larger than that of the electromagnetic penguin diagrams.

  15. Tuning The Cells Of The Accelerating Structure With Rf-quadrupole Doublets

    CERN Document Server

    Bomko, V A; Dyachenko, A F; Kobets, A F; Marynina, E D; Ptukhina, Z E; Tishkin, S S; Zajtsev, B V

    2004-01-01

    The versions of the high frequency quadrupole doublets (RFQD) in heavy ion linear accelerators are discussed. Advantages of focusing of this type over magnetic quadrupoles lie in the simplicity of the structure, and high efficiency and reliability of focusing. In the multi-gap structures, focusing periods contain a sequence of focusing and accelerating cells. The elaborated technique of the local cell adjustment provides the high acceleration rate. Various RFQD versions for the specific peculiarities of accelerating interdigital H-structures are dicussed. Application of the RFQD will allow to increase the efficiency of ion beam focusing and to expand the energy range of the ion being accelerated over 10 MeV/u.

  16. tbW anomalous couplings in the Two Higgs Doublet Model

    Energy Technology Data Exchange (ETDEWEB)

    Arhrib, Abdesslam; Jueid, Adil [Département de Mathématiques, Faculté des Sciences et Techniques,Université Abdelmalek Essaadi,B. 416, Tangier (Morocco)

    2016-08-11

    We make a complete one loop calculation of the tbW couplings in the Two Higgs Doublet Model. We evaluate both the anomalous couplings g{sub L} and g{sub R} as well as left handed and right handed component of tbW. The computation is done in the Feynman gauge using the on-shell scheme renormalization for the Standard Model wave functions and parameters. We first show that the relative corrections to these anomalous couplings are rather small in most regions of the parameter space. We then analyze the effects of these anomalous couplings on certain observables such as top quark polarization in single top production through t−channel as well as W{sup ±} boson helicity fractions in top decay.

  17. Three-loop Neutrino Mass Model with Doubly Charged Particles from Iso-Doublets

    CERN Document Server

    Okada, Hiroshi

    2016-01-01

    We propose a new type of a three-loop induced neutrino mass model with dark matter candidates which are required for the neutrino mass generation. The smallness of neutrino masses can be naturally explained without introducing super heavy particles, namely, much heavier than a TeV scale and quite small couplings as compared to the gauge couplings. We find that as a bonus, the anomaly of the muon anomalous magnetic moment can simultaneously be explained by loop effects of new particles. In our model, there are doubly charged scalar bosons and leptons from isospin doublet fields which give characteristic collider signatures. In particular, the doubly charged scalar bosons can decay into the same sign dilepton with its chirality of both right-handed or left- and right-handed. This can be a smoking gun signature to identify our model and be useful to distinguish other models with doubly charged scalar bosons at collider experiments.

  18. Higgs boson pair production at a photon-photon collision in the two Higgs doublet model

    CERN Document Server

    Asakawa, Eri; Kanemura, Shinya; Okada, Yasuhiro; Tsumura, Koji

    2008-01-01

    We calculate the cross section of Higgs boson pair production at a photon collider in the two Higgs doublet model. We focus on the scenario in which the lightest CP even Higgs boson ($h$) has the standard model like couplings to the gauge bosons. We take into account the one-loop correction to the $hhh$ coupling as well as additional one-loop diagrams due to charged Higgs bosons to the $\\gamma\\gamma\\to hh$ helicity amplitudes. It is found that the full cross section can be enhanced by both these effects to a considerable level. We discuss the impact of these corrections on the $hhh$ coupling measurement at the photon collider.

  19. B → K*γDecay in Top-Quark Two-Higgs-Doublet Model

    Institute of Scientific and Technical Information of China (English)

    XIAO Zhen-Jun; CHENG Hui-Hui; L(U) Lin-Xia

    2006-01-01

    By employing the QCD factorization approach for the exclusive B → Vγ decays, we study the exclusive decay B → K*γ in the top-quark two-Higgs-doublet model (T2HDM). Within the considered parameter space, we find the following conclusions (a) A light charged-Higgs boson with a mass about 200 GeV is clearly excluded by the date of B → K*γ decay, and this lower limit is comparable with that from the inclusive B → Xsγ decay; (b) The theoretical predictions for CP asymmetry of B → K*γ in the T2HDM is always less than 1% in size; and (c) The isospin symmetry breaking for B → K*γ decay in the SM and T2HDM considered here is around 6% in size and well consistent with the data and the general expectations.

  20. Flavour-changing Higgs couplings in a class of two Higgs doublet models

    Energy Technology Data Exchange (ETDEWEB)

    Botella, F.J. [Universitat de Valencia-CSIC, Departament de Fisica Teorica y IFIC, Burjassot (Spain); Branco, G.C. [Universitat de Valencia-CSIC, Departament de Fisica Teorica y IFIC, Burjassot (Spain); Instituto Superior Tecnico (IST), Lisboa Univ., Departamento de Fisica and Centro de Fisica Teorica de Particulas (CFTP), Lisbon (Portugal); Nebot, M. [Instituto Superior Tecnico (IST), Lisboa Univ., Centro de Fisica Teorica de Particulas (CFTP), Lisbon (Portugal); Rebelo, M.N. [Instituto Superior Tecnico (IST), Lisboa Univ., Departamento de Fisica and Centro de Fisica Teorica de Particulas (CFTP), Lisbon (Portugal)

    2016-03-15

    We analyse various flavour-changing processes like t → hu, hc, h → τe, τμ as well as hadronic decays h @→ bs, bd, in the framework of a class of two Higgs doublet models where there are flavour-changing neutral scalar currents at tree level. These models have the remarkable feature of having these flavour-violating couplings entirely determined by the CKM and PMNS matrices as well as tan β. The flavour structure of these scalar currents results from a symmetry of the Lagrangian and there fore it is natural and stable under the renormalisation group. We show that in some of the models the rates of the above flavour-changing processes can reach the discovery level at the LHC at 13 TeV even taking into account the stringent bounds on low energy processes, in particular μ @→ eγ. (orig.)

  1. Big Dee upgrade of the Doublet III diagnostic data acquisition computer system

    Energy Technology Data Exchange (ETDEWEB)

    McHarg, B.B. Jr.

    1983-12-01

    The Big Dee upgrade of the Doublet III tokamak facility will begin operation in 1986 with an initial quantity of data expected to be 10 megabytes per shot and eventually attaining 20 to 25 megabytes per shot. This is in comparison to the 4 to 5 megabytes of data currently acquired. To handle this greater quantity of data and to serve physics needs for significantly improved between-shot processing of data will require a substantial upgrade of the existing data acquisition system. The key points of the philosophy that have been adopted for the upgraded system to handle the greater quantity of data are (1) preserve existing hardware; (2) preserve existing software; (3) configure the system in a modular fashion; and (4) distribute the data acquisition over multiple computers. The existing system using ModComp CLASSIC 16 bit minicomputers is capable of handling 5 megabytes of data per shot.

  2. $b \\rightarrow s \\gamma$ and $Z \\rightarrow b \\overline b$ Constraints on Two Higgs Doublet Model

    CERN Document Server

    Park, G T

    1994-01-01

    We perform a combined analysis of two stringent constraints on two Higgs doublet model, coming from the recently announced CLEO II bound on $B(b \\rightarrow s \\gamma)$ and $Z \\rightarrow b \\overline b$ and from the recent LEP data on the ratio $\\Gamma(Z\\rightarrow b\\overline b)\\over{\\Gamma(Z\\rightarrow hadrons)}$. We include one-loop vertex corrections to $Z \\rightarrow b \\overline b$ in the model. We find that although the CLEO II bound serves as the strongest constraint present in the charged Higgs sector of the model, the current LEP value for $R_b$ may also provide a further constraint for $\\tan\\beta<1$.

  3. $b \\rightarrow s \\gamma$ and $\\epsilon_b$ Constraints on Two Higgs Doublet Model

    CERN Document Server

    Park, G T

    1994-01-01

    We perform a combined analysis of two stringent constraints on the 2 Higgs doublet model, one coming from the recently announced CLEO II bound on $B(b \\rightarrow s \\gamma)$ and the other from the recent LEP data on $\\epsilon_b$. We have included one-loop vertex corrections to $Z \\rightarrow b \\overline b$ through $\\epsilon_b$ in the model. We find that the new $\\epsilon_b$ constraint excludes most of the less appealing window $\\tan\\beta\\lsim 1$ at $90\\%$C.~L. for $m_t=150\\GeV$. We also find that although $b \\rightarrow s \\gamma$ constraint is stronger for $\\tan\\beta>1$, $\\epsilon_b$ constraint is stronger for $\\tan\\beta\\lsim 1$, and therefore these two are the strongest and complimentary constraints present in the charged Higgs sector of the model.

  4. CP-violating phenomenology of flavor conserving two Higgs doublet models

    Science.gov (United States)

    Inoue, Satoru; Ramsey-Musolf, Michael J.; Zhang, Yue

    2014-06-01

    We analyze the constraints on CP-violating, flavor conserving two Higgs doublet models implied by measurements of Higgs boson properties at the Large Hadron Collider (LHC) and by the nonobservation of permanent electric dipole moments (EDMs) of molecules, atoms, and neutrons. We find that the LHC and EDM constraints are largely complementary, with the LHC studies constraining the mixing between the neutral CP-even states and the EDMs probing the effect of mixing between the CP-even and CP-odd scalars. Presently, the most stringent constraints are implied by the nonobservation of the ThO molecule EDM signal. Future improvements in the sensitivity of neutron and diamagnetic atom EDM searches could yield competitive or even more severe constraints. We analyze the quantitative impact of hadronic and nuclear theory uncertainties on the interpretation of the latter systems and conclude that these uncertainties cloud the impact of projected improvements in the corresponding experimental sensitivities.

  5. Radiative generation of quark masses and mixing angles in the two Higgs doublet model

    Directory of Open Access Journals (Sweden)

    Alejandro Ibarra

    2014-09-01

    Full Text Available We present a framework to generate the quark mass hierarchies and mixing angles by extending the Standard Model with one extra Higgs doublet. The charm and strange quark masses are generated by small quantum effects, thus explaining the hierarchy between the second and third generation quark masses. All the mixing angles are also generated by small quantum effects: the Cabibbo angle is generated at zeroth order in perturbation theory, while the remaining off-diagonal entries of the Cabibbo–Kobayashi–Maskawa matrix are generated at first order, hence explaining the observed hierarchy |Vub|,|Vcb|≪|Vus|. The values of the radiatively generated parameters depend only logarithmically on the heavy Higgs mass, therefore this framework can be reconciled with the stringent limits on flavor violation by postulating a sufficiently large new physics scale.

  6. Radiative Generation of Quark Masses and Mixing Angles in the Two Higgs Doublet Model

    CERN Document Server

    Ibarra, Alejandro

    2014-01-01

    We present a framework to generate the quark mass hierarchies and mixing angles by extending the Standard Model with one extra Higgs doublet. The charm and strange quark masses are generated by small quantum effects, thus explaining the hierarchy between the second and third generation quark masses. All the mixing angles are also generated by small quantum effects: the Cabibbo angle is generated at zero-th order in perturbation theory, while the remaining off-diagonal entries of the Cabibbo-Kobayashi-Maskawa matrix are generated at first order, hence explaining the observed hierarchy $|V_{ub}|,|V_{cb}|\\ll |V_{us}|$. The values of the radiatively generated parameters depend only logarithmically on the heavy Higgs mass, therefore this framework can be reconciled with the stringent limits on flavor violation by postulating a sufficiently large new physics scale.

  7. Treatment of FIGO stage IV ovarian carcinoma: results of primary surgery or interval surgery after neoadjuvant chemotherapy: a retrospective study.

    Science.gov (United States)

    Rafii, A; Deval, B; Geay, J-F; Chopin, N; Paoletti, X; Paraiso, D; Pujade-Lauraine, E

    2007-01-01

    The objective of the study is to determine whether surgery influences the outcome of stage IV ovarian cancer. The study design is as follows: From May 1995 to December 2000, 129 patients with FIGO stage IV ovarian cancer, recruited in 42 centers, were prospectively included in GINECO first-line randomized studies of platinum-based regimens with paclitaxel administered simultaneously or sequentially. In all, 109 were eligible for this study. Standard peritoneal cytoreductive surgery was defined as a procedure including at least total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and peritoneal debulking. Surgery was considered optimal if residual lesions were smaller than 1 cm. The Kaplan-Meier method was used to compare survival. Initial abdominopelvic cytoreductive surgery was considered standard in 55 (54%) patients. Abdominopelvic surgery was optimal in 29 patients and nonoptimal in 26. Twenty-two (22%) patients had a simple biopsy, and 25 (24%) patients underwent substandard surgery. Twenty-two of these 47 patients without initial standard surgery underwent a second surgical procedure, and 17 of the 22 patients completed standard surgery. The median overall survival time in the entire population was 24.3 months (95% confidence interval [CI], 19.5-29.1 months). Patients treated without a cytoreductive surgical procedure had significantly worse median survival (15.1 months; 95% CI, 5.4-24.9 months) than patients who had optimal primary surgery (22.9 months; 95% CI, 15.6-30.1 months), nonoptimal primary surgery (27.1 months; 95% CI, 21.2-32.9 months), or neoadjuvant chemotherapy followed by surgery (45.5 months; 95% CI, 23.5-67.5 months) (P= .001). In conclusion, this study shows a significant benefit of debulking surgery in stage IV ovarian cancer patients who responded to neoadjuvant chemotherapy. Neoadjuvant chemotherapy can help to select patients for surgery.

  8. Role of the human high-affinity copper transporter in copper homeostasis regulation and cisplatin sensitivity in cancer chemotherapy.

    Science.gov (United States)

    Kuo, Macus Tien; Fu, Siqing; Savaraj, Niramol; Chen, Helen H W

    2012-09-15

    The high-affinity copper transporter (Ctr1; SCLC31A1) plays an important role in regulating copper homeostasis because copper is an essential micronutrient and copper deficiency is detrimental to many important cellular functions, but excess copper is toxic. Recent research has revealed that human copper homeostasis is tightly controlled by interregulatory circuitry involving copper, Sp1, and human (hCtr1). This circuitry uses Sp1 transcription factor as a copper sensor in modulating hCtr1 expression, which in turn controls cellular copper and Sp1 levels in a 3-way mutual regulatory loop. Posttranslational regulation of hCtr1 expression by copper stresses has also been described in the literature. Because hCtr1 can also transport platinum drugs, this finding underscores the important role of hCtr1 in platinum-drug sensitivity in cancer chemotherapy. Consistent with this notion is the finding that elevated hCtr1 expression was associated with favorable treatment outcomes in cisplatin-based cancer chemotherapy. Moreover, cultured cell studies showed that elevated hCtr1 expression can be induced by depleting cellular copper levels, resulting in enhanced cisplatin uptake and its cell-killing activity. A phase I clinical trial using a combination of trientine (a copper chelator) and carboplatin has been carried out with encouraging results. This review discusses new insights into the role of hCtr1 in regulating copper homeostasis and explains how modulating cellular copper availability could influence treatment efficacy in platinum-based cancer chemotherapy through hCtr1 regulation.

  9. FGFR4 genetic polymorphisms determine the chemotherapy response of Chinese patients with non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Hong-mei FANG; Gang TIAN; Li-juan ZHOU; Han-ying ZHOU; Ying-zhi FANG

    2013-01-01

    Aim:To investigate the relationship of fibroblast growth factor receptor 4 (FGFR4) gene polymorphisms with the response of Chinese patients with non-small cell lung cancer (NSCLC) to chemotherapy.Methods:A total of 629 patients with Stage Ⅲ (A+B) or Ⅳ NSCLC,as well as 729 age-and gender-matched healthy controls were recruited.All the patients received platinum-based chemotherapy,and the therapeutic effects were evaluated.Three polymorphisms in the FGFR4 gene (rs351855G/A,rs145302848C/G,and rs147603016G/A) were genotyped,and the association between the 3 polymorphisms and the chemotherapy effect was analyzed using SPSS software,version 16.0.Results:The genotype frequencies of rs145302848C/G and rs147603016G/A were not significantly different between NSCLC patients and healthy controls on one hand,and between the responders and non-responders to the chemotherapy on the other hand.The distribution of AA genotype and A-allele of rs351855G/A was significantly lower in NSCLC patients than in healthy controls.Using patients with the GG genotype as a reference,the AA carrier had a significantly reduced risk for the development of NSCLC after normalizing to age,sex and smoking habits.In NSCLC patients,this genotype occurred more frequently in the responders to the chemotherapy than in non-responders.The chance of being a responder was significantly increased with the AA genotype as compared to G genotype.The AA genotype of rs351855G/A had a better prognosis compared with GA and GG genotype carriers:the over all survival of patients with the AA genotype of rs351855G/A was significantly longer than those with the GG+GA genotype (21.1 vs 16.5 months).Conclusion:The rs351855G/A polymorphisms of FGFR4 gene can be used to predict the occurrence,chemotherapy response and prognosis of NSCLC.

  10. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma.

    Science.gov (United States)

    Magarotto, Valeria; Bringhen, Sara; Offidani, Massimo; Benevolo, Giulia; Patriarca, Francesca; Mina, Roberto; Falcone, Antonietta Pia; De Paoli, Lorenzo; Pietrantuono, Giuseppe; Gentili, Silvia; Musolino, Caterina; Giuliani, Nicola; Bernardini, Annalisa; Conticello, Concetta; Pulini, Stefano; Ciccone, Giovannino; Maisnar, Vladimír; Ruggeri, Marina; Zambello, Renato; Guglielmelli, Tommasina; Ledda, Antonio; Liberati, Anna Marina; Montefusco, Vittorio; Hajek, Roman; Boccadoro, Mario; Palumbo, Antonio

    2016-03-03

    Lenalidomide-dexamethasone improved outcome in newly diagnosed elderly multiple myeloma patients. We randomly assigned 662 patients who were age ≥65 years or transplantation-ineligible to receive induction with melphalan-prednisone-lenalidomide (MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) or lenalidomide plus low-dose dexamethasone (Rd). The primary end point was progression-free survival (PFS) in triplet (MPR and CPR) vs doublet (Rd) lenalidomide-containing regimens. After a median follow-up of 39 months, the median PFS was 22 months for the triplet combinations and 21 months for the doublet (P = .284). The median overall survival (OS) was not reached in either arms, and the 4-year OS was 67% for the triplet and 58% for the doublet arms (P = .709). By considering the 3 treatment arms separately, no difference in outcome was detected among MPR, CPR, and Rd. The most common grade ≥3 toxicity was neutropenia: 64% in MPR, 29% in CPR, and 25% in Rd patients (P < .0001). Grade ≥3 nonhematologic toxicities were similar among arms and were mainly infections (6.5% to 11%), constitutional (3.5% to 9.5%), and cardiac (4.5% to 6%), with no difference among the arms. In conclusion, in the overall population, the alkylator-containing triplets MPR and CPR were not superior to the alkylator-free doublet Rd, which was associated with lower toxicity. This study was registered at www.clinicaltrials.gov as #NCT01093196.

  11. Cetuximab with radiotherapy in patients with loco-regionally advanced squamous cell carcinoma of head and neck unsuitable or ineligible for concurrent platinum-based chemo-radiotherapy: Ready for routine clinical practice?

    Directory of Open Access Journals (Sweden)

    J P Agarwal

    2011-01-01

    Full Text Available Purpose : To report outcomes of cetuximab concurrent with radiotherapy in advanced head-neck cancer unsuitable for platinum-based chemo-radiotherapy. Materials and Methods : Retrospective chart review of 37 patients treated with cetuximab and radiotherapy at a comprehensive cancer centre. Results : Median age of study cohort was 59 years. Thirty four (92% patients had advanced stage disease (stage III-IV. Reasons for ineligibility for platinum included impaired creatinine-clearance, old age, and/or co-morbidities. Thirty-two (86% patients completed planned radiotherapy without interruption; 29 (80% patients received ≥6 cycles of cetuximab. Fifteen patients (40.5% developed ≥grade 3 dermatitis; 9 patients (25% experienced ≥grade 3 mucositis. At a median follow-up of 16 months, the 2-year loco-regional control, disease-free survival, and overall survival was 35.5%, 29.5%, and 44.4% respectively. Stage grouping and severe dermatitis were significant predictors of outcome. Conclusions : Cetuximab concurrent with radiotherapy is a reasonable alternative in advanced head-neck cancer patients with acceptable compliance and outcomes, but higher skin toxicity.

  12. Breast Cancer Chemotherapy and Your Heart

    Science.gov (United States)

    ... American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , Sara ... cancer treatments. Breast cancer treatments include the following: Chemotherapy involves drugs that are intended to kill the ...

  13. Fertility preservation after chemotherapy for Hodgkin lymphoma

    NARCIS (Netherlands)

    van der Kaaij, Marleen A. E.; van Echten-Arends, Jannie; Simons, Arnold H. M.; Kluin-Nelemans, Hanneke C.

    2010-01-01

    Treatment for Hodgkin lymphoma can negatively affect fertility. This review summarizes data on fertility after chemotherapy in adult patients. Alkylating chemotherapy, especially if containing procarbazine and/or cyclophosphamide, is most harmful to gonadal functioning. Alkylating regimens cause pro

  14. Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy.

    Directory of Open Access Journals (Sweden)

    Maryam Ferdousi

    Full Text Available There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04 and warm sensation (P = 0.03 thresholds with a significantly reduced sural sensory (P<0.01 and peroneal motor (P<0.01 nerve conduction velocity, corneal nerve fibre density (CNFD, nerve branch density (CNBD and nerve fibre length (CNFL (P<0.0001. Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02, and CNFL (r = -0.8, P<0.0001 and CNBD (r = 0.63, P = 0.003 were related to the severity of lymph node involvement. After the 3rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003. Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.

  15. Congenital sacrococcygeal PNET and chemotherapy

    Directory of Open Access Journals (Sweden)

    Colin Patrick Hawkes

    2012-01-01

    Full Text Available We present the case of a congenital localised sacrococcygeal primitive neuroectodermal tumor treated aggressively with surgical resection and modified age-appropriate adjuvant chemotherapy. The conventional combination chemotherapy of vincristine, adriamycin, cyclophosphamide, ifosfamide and etoposide was modified to a regimen including vincristine, adriamicin, cyclophosphamide and actinomycin in order to minimise the predicted toxicity in this age group. Adjuvant "induction" chemotherapy commenced at 4 weeks of age and consisted of four cycles of vincristine, adriamycin and cyclophosphamide at 50%, 75%, 75% and 100% of recommended doses (vincristine 0.05 mg/kg, adriamycin 0.83 mg/kg daily × 2, cyclophosphamide 40 mg/kg at 3-weekly intervals. This was followed by four cycles of "maintenance" chemotherapy with vincristine (0.025 mg/kg, actinomycin (0.025 mg/kg and cyclophosphamide (36 mg/kg at full recommended doses. Cardioxane at a dose of 16.6 mg/kg was infused immediately prior to the adriamycin. Our patient is thriving at 19 months out from end of treatment.

  16. Chemotherapy of human african trypanosomiasis.

    Science.gov (United States)

    Bacchi, Cyrus J

    2009-01-01

    Human Africa trypanosomiasis is a centuries-old disease which has disrupted sub-Saharan Africa in both physical suffering and economic loss. This article presents an update of classic chemotherapeutic agents, in use for >50 years and the recent development of promising non-toxic combination chemotherapy suitable for use in rural clinics.

  17. Chemotherapy of Human African Trypanosomiasis

    Directory of Open Access Journals (Sweden)

    Cyrus J. Bacchi

    2009-01-01

    Full Text Available Human Africa trypanosomiasis is a centuries-old disease which has disrupted sub-Saharan Africa in both physical suffering and economic loss. This article presents an update of classic chemotherapeutic agents, in use for >50 years and the recent development of promising non-toxic combination chemotherapy suitable for use in rural clinics.

  18. Managing Chemotherapy Side Effects: Diarrhea

    Science.gov (United States)

    ... such as Pedialyte ® ••Tea (without caffeine) ••Water ••Applesauce ••Bananas ••Crackers ••Cream of wheat or rice cereal ••Eggs •• ... has a series of 18 Chemotherapy Side Effects Sheets at: www.cancer.gov/chemo-side-effects

  19. Chemotherapy-associated recurrent pneumothoraces in lymphangioleiomyomatosis.

    LENUS (Irish Health Repository)

    Kelly, Emer

    2012-02-01

    Lymphangioleiomyomatosis is a rare cause of pneumothorax in women. We present the case of a 48-year-old woman with lymphangioleiomyomatosis, who had never had a pneumothorax prior to commencing chemotherapy for breast cancer. During chemotherapy she developed 3 pneumothoraces and 2 episodes of pneumomediastinum. We suggest that the pneumothoraces were caused by the chemotherapy. To our knowledge, this is the first reported case of chemotherapy triggering pneumothoraces in a woman with lymphangioleiomyomatosis.

  20. Chemotherapy and You: Support for People with Cancer

    Science.gov (United States)

    ... Terms Blogs and Newsletters Health Communications Publications Reports Chemotherapy and You: Support for People With Cancer Chemotherapy ... ePub This booklet covers: Questions and answers about chemotherapy. Answers common questions, such as what chemotherapy is ...

  1. Arterial occlusion precipitated by cisplatinbased chemotherapy

    OpenAIRE

    2010-01-01

    Cisplatin-based therapy is curative in testicular cancer. Adverse effects of cisplatin-based chemotherapy include dose-dependent myelosuppression, nephrotoxicity, neurotoxicity, and ototoxicity. By contrast, chemotherapy-associated vascular complications are unpredictable. Few incidents of digital gangrene with cisplatin have been reported. Here, we present a patient who developed arterial occlusion leading to gangrene of the toe after cisplatinbased chemotherapy.

  2. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review th...

  3. Chemotherapy e-prescribing: opportunities and challenges

    Directory of Open Access Journals (Sweden)

    Elsaid KA

    2015-05-01

    Full Text Available Khaled A Elsaid,1,2 Steven Garguilo,1 Christine M Collins2 1Department of Pharmaceutical Sciences, School of Pharmacy, MCPHS University, Boston, MA, 2Pharmacy Services, Rhode Island Hospital, Providence, RI, USA Abstract: Chemotherapy drugs are characterized by low therapeutic indices and significant toxicities at clinically prescribed doses, raising serious issues of drug safety. The safety of the chemotherapy medication use process is further challenged by regimen complexity and need to tailor treatment to patient status. Errors that occur during chemotherapy prescribing are associated with serious and life-threatening outcomes. Computerized provider order entry (CPOE systems were shown to reduce overall medication errors in ambulatory and inpatient settings. The adoption of chemotherapy CPOE is lagging due to financial cost and cultural and technological challenges. Institutions that adopted infusional or oral chemotherapy electronic prescribing modified existing CPOE systems to allow chemotherapy prescribing, implemented chemotherapy-specific CPOE systems, or developed home-grown chemotherapy electronic prescribing programs. Implementation of chemotherapy electronic prescribing was associated with a significant reduction in the risk of prescribing errors, most significantly dose calculation and adjustment errors. In certain cases, implementation of chemotherapy CPOE was shown to improve the chemotherapy use process. The implementation of chemotherapy CPOE may increase the risk of new types of errors, especially if processes are not redesigned and adapted to CPOE. Organizations aiming to implement chemotherapy CPOE should pursue a multidisciplinary approach engaging all stakeholders to guide system selection and implementation. Following implementation, organizations should develop and use a risk assessment process to identify and evaluate unanticipated consequences and CPOE-generated errors. The results of these analyses should serve to

  4. Yukawa Corrections to Single Top Quark Production at the Fermilab Tevatron in the Two-Higgs-Doublet Models

    CERN Document Server

    Li, C S; Yang, J M; Li, Chong Sheng; Oakes, Robert J.; Yang, Jin Min

    1997-01-01

    We calculate Yukawa corrections of order $\\alpha_{ew} M_t^2/M_W^2$ to s= ingle top quark production via $q \\bar q'\\rightarrow t \\bar b$ at the Fermilab Tevatron in the two-Higgs-doublet models. In our calculation we also keep= the terms proportional to $ M_b^2 \\tan^2 \\beta$ since their effects may becom= e rather important for large $\\tan\\beta$. The corrections can amount to mor= e than a 15\\% reduction in the production cross section relative to the tree lev= el result in the general two-Higgs-doublet model, and a 10\\% enhancement in = the minimal supersymmetric model, which might be observable at a high-luminos= ity Tevatron.

  5. Discriminators of 2 Higgs Doublets at the LHC14, ILC and MuonCollider(125): A Snowmasss White Paper

    CERN Document Server

    Barger, Vernon; Logan, Heather E; Shaughnessy, Gabe

    2013-01-01

    The historic LHC discovery of the 125 GeV particle with properties that closely resemble the Standard Model (SM) Higgs boson verifies our understanding of electroweak symmetry breaking, but solidifies the need for a resolution to the hierarchy problem. Many extensions of the SM that address the hierarchy problem contain a non-minimal Higgs sector. Therefore, as a benchmark alternative to the SM Higgs mechanism, we study a general 2 Higgs doublet model (2HDM-G) framework for evaluating future sensitivity to Higgs couplings. We study how well it can be distinguished from the SM Higgs boson by future measurements at LHC14, ILC (250, 500,1000 GeV) and a Muon Collider (125 GeV). Additionally, our study bears on singlet Higgs extensions of two Higgs doublet models through predicted coupling relationships.

  6. Chiral U(1) flavor models and flavored Higgs doublets: the top FB asymmetry and the W jj

    Energy Technology Data Exchange (ETDEWEB)

    Ko, P.; Omura, Yuji; Yu, Chaehyun

    2012-01-01

    We present U(1) flavor models for leptophobic Z' with flavor dependent couplings to the right-handed up-type quarks in the Standard Model (SM), which can accommodate the recent data on the top forward-backward (FB) asymmetry and the dijet resonance associated with a W boson reported by CDF Collaboration. Such flavor-dependent leptophobic charge assignments generally require extra chiral fermions for anomaly cancellation. Also the chiral nature of U(1)' flavor symmetry calls for new U(1)'-charged Higgs doublets in order for the SM fermions to have realistic renormalizable Yukawa couplings. The stringent constraints from the top FB asymmetry at the Tevatron and the same sign top pair production at the LHC can be evaded due to contributions of the extra Higgs doublets. We also show that the extension could realize cold dark matter candidates.

  7. Sphaleron and critical bubble in the scale invariant two Higgs doublet model

    Directory of Open Access Journals (Sweden)

    Kaori Fuyuto

    2015-07-01

    Full Text Available We revisit the electroweak phase transition and the critical bubble in the scale invariant two Higgs doublet model in the light of recent LHC data. Moreover, the sphaleron decoupling condition is newly evaluated in this model. The analysis is done by using the resummed finite-temperature one-loop effective potential. It is found that the 125 GeV Higgs boson inevitably leads to the strong first-order electroweak phase transition, and the strength of which is always large enough to satisfy the sphaleron decoupling condition, vN/TN>1.2, where TN denotes a nucleation temperature and vN is the Higgs vacuum expectation value at TN. In this model, even if the Higgs boson couplings to gauge bosons and fermions are similar to the standard model values, the signal strength of the Higgs decay to two photons is reduced by 10% and the triple Higgs boson coupling is enhanced by 82% compared to the standard model prediction.

  8. Competition between Quadrupole and Magnetic Kondo Effects in Non-Kramers Doublet Systems

    Science.gov (United States)

    Kusunose, Hiroaki; Onimaru, Takahiro

    2015-03-01

    We discuss possible competition between magnetic and quadrupole Kondo effects in non-Kramers doublet systems in cubic symmetry. The quadrupole Kondo effect leads to non-Fermi-liquid (NFL) ground state, while the magnetic one favors ordinary Fermi-liquid (FL) ground state. In terms of the j-j coupling scheme, we argue that the orbital fluctuation must develop in the vicinity of the NFL-FL boundary. A change of temperature dependence of the f-electron entropy in both the FL and NFL regimes is demonstrated by the Wilson's numerical renormalization-group (NRG) method on the basis of the extended two-channel Kondo exchange model. We present implications to PrT2X20 (T=Ti, V, Ir; X=Al, Zn) systems which exhibit both quadrupole ordering and peculiar superconductivity. We discuss how the magnetic field lifts the non-Kramers degeneracy. Our model also represents the alternative FL state accompanied by a free magnetic spin, as a consequence of stronger competition between the magnetic and the quadrupole Kondo effects.

  9. Light A physics in the lepton-specific two-Higgs doublet model

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    We examine various direct and indirect constraints on the lepton-specific two-Higgs doublet model and discuss its phenomenology at colliders in the allowed parameter space.The constraints we consider come from the precision electroweak data,the direct search for Higgs boson,the muon anomalous magnetic moment,as well as some theoretical consistency requirements.We find that in the allowed parameter space the CP-odd Higgs boson A is rather light (m A < 30 GeV with 95% possibility),which is composed dominantly by the leptonic Higgs and decays dominantly into τ + τ;while the SM-like Higgs boson h (responsible largely for electroweak symmetry breaking) decays dominantly in the mode h → AA → 4τ with a large decay width,which will make the Higgs discovery more difficult at the LHC.Whereas,this scenario predicts rare Z decays Z → AAA and Z →τ + τA with their branching ratios ranging from 10-8 to 10-and 10-5 to 10-4 respectively,which may be accessible at the GigaZ option of the ILC.

  10. A nomenclature for Λ-doublet levels in rotating linear molecules

    Science.gov (United States)

    Alexander, M. H.; Andresen, P.; Bacis, R.; Bersohn, R.; Comes, F. J.; Dagdigian, P. J.; Dixon, R. N.; Field, R. W.; Flynn, G. W.; Gericke, K.-H.; Grant, E. R.; Howard, B. J.; Huber, J. R.; King, D. S.; Kinsey, J. L.; Kleinermanns, K.; Kuchitsu, K.; Luntz, A. C.; McCaffery, A. J.; Pouilly, B.; Reisler, H.; Rosenwaks, S.; Rothe, E. W.; Shapiro, M.; Simons, J. P.; Vasudev, R.; Wiesenfeld, J. R.; Wittig, C.; Zare, R. N.

    1988-08-01

    It is proposed that the two Λ-doublet levels of linear molecules with nonzero electronic orbital angular momentum be labeled Λ(A') and Λ(A`), e.g., Π(A') and Π(A`) for Π states, etc., according to the following prescription: All series of levels in which the electronic wave function at high J is symmetric with reflection of the spatial coordinates of the electrons in the plane of rotation will be designated Λ(A') for all values of J, and all those for which the electronic wave function is antisymmetric with respect to reflection will be denoted Λ(A`). It is emphasized that this notation is meant to supplement, and not replace, the accepted spectroscopic e/f labeling and the parity quantum number. The utility of the Λ(A')/Λ(A`) notation is that it is of most relevance in the mechanistic interpretation of reactive or photodissociative processes involving open-shell molecules.

  11. Renormalization of seesaw neutrino masses in the standard model with two-Higgs doublets

    Indian Academy of Sciences (India)

    N Nimai Singh; S Biramani Singh

    2000-02-01

    Using the theoretical ambiguities inherent in the seesaw mechanism, we derive the new analytic expressions for both quadratic and linear seesaw formulae for neutrino masses at low energies, with either up-type quark masses or charged lepton masses. This is possible through full radiative corrections arising out of the renormalizations of the Yukawa couplings, the coefficients of the neutrino-mass-operator in the standard model with two-Higgs doublets, and also the QCD–QED rescaling factors below the top-quark mass scale, at one-loop level. We also investigate numerically the unification of top-- Yukawa couplings at the scale =0.59× 108GeV for a fixed value of tan =58.77, and then evaluate the seesaw neutrino masses which are too large in magnitude to be compatible with the presently available solar and atmospheric neutrino oscillation data. However, if we consider a higher but arbitrary value of =0.59× 1011GeV, the predictions from linear seesaw formulae with charged lepton masses, can accommodate simultaneousely both solar atmospheric neutrino oscillation data.

  12. Polarization dependence of transition intensities in double resonance experiments: unresolved spin doublets.

    Science.gov (United States)

    Petrović, Vladimir S; Field, Robert W

    2008-01-07

    The polarization dependence of transition intensities in multiple resonance spectroscopic experiments can provide information useful for making rotational assignments. A formalism to describe the polarization dependence of transition intensities in multiple resonance experiments, particularly for cases when two rotational/fine structure quantum numbers are needed to specify the state of the system, is presented. The formalism is presented in a form usable both when the transitions between the underlying fine structure components are experimentally resolved, as well as when they are unresolved, to form composite lines. This sort of treatment is necessary for cases when the two quantum numbers that specify the fine structure differ significantly, such as is the case at low N, when the difference between J and N becomes comparable to the value of J. Ratios of transition intensities in different experimentally convenient polarization arrangements are evaluated for the case of composite N transitions formed by combining the spin components of a doublet system. The formalism is expressed in a form easily extendable to accommodate experimental cases of more than two excitation steps, or a combination of excitation steps and an external static electric field. This polarization diagnostic has been experimentally applied to assign spectral features in double resonance Rydberg spectra of CaF.

  13. Higgs potential and hidden light Higgs scenario in two Higgs doublet models

    CERN Document Server

    Chang, Sanghyeon; Lee, Jong-Phil; Song, Jeonghyeon

    2015-01-01

    In two Higgs doublet models (2HDM), there exists an interesting possibility, the hidden light Higgs scenario, that the discovered SM-like Higgs boson is the heavier CP-even Higgs boson $H^0$ and the lighter CP-even $h^0$ has not been observed yet in any experiment. We study the current status of this scenario in Types I, II, X, and Y, through the scans of the 2HDM parameters with all relevant theoretical and experimental constraints. We employ not only the most up-to-date Higgs signal strength measurements with the feed-down effects, but also all the available LHC exclusion limits from heavy Higgs searches. Adjusting the heavier $H^0$ to the 125 GeV state while hiding the lighter $h^0$ from the LEP Higgs search prohibits the extreme decoupling limit: there exist upper bounds on the masses of the pseudoscalar $A^0$ and the charged Higgs $H^\\pm$ below about 550 GeV. In addition, the $Z_2$ symmetry, which was introduced to avoid the tree-level FCNC, is shown to be a good approximate symmetry since the soft $Z_2$...

  14. Interference contributions to gluon initiated heavy Higgs production in the two-Higgs-doublet model

    Energy Technology Data Exchange (ETDEWEB)

    Greiner, Nicolas [DESY, Hamburg (Germany); Universitaet Zuerich, Physik-Institut, Zuerich (Switzerland); Liebler, Stefan; Weiglein, Georg [DESY, Hamburg (Germany)

    2016-03-15

    We discuss the production of a heavy neutral Higgs boson of a CP-conserving two-Higgs-doublet model in gluon fusion and its decay into a four-fermion final state, gg(→ VV) → e{sup +}e{sup -}μ{sup +}μ{sup -}/e{sup +}e{sup -}ν{sub l} anti ν{sub l}. We investigate the interference contributions to invariant mass distributions of the four-fermion final state and other relevant kinematical observables. The relative importance of the different contributions is quantified for the process in the on-shell approximation, gg → ZZ. We show that interferences of the heavy Higgs with the light Higgs boson and background contributions are essential for a correct description of the differential cross section. Even though they contribute below O(10%) to those heavy Higgs signal cross sections, to which the experiments at the Large Hadron Collider were sensitive in its first run, we find that they are sizable in certain regions of the parameter space that are relevant for future heavy Higgs boson searches. In fact, the interference contributions can significantly enhance the experimental sensitivity to the heavy Higgs boson. (orig.)

  15. Generation of doublet spectral lines at self-seeded X-ray FELs

    CERN Document Server

    Geloni, Gianluca; Saldin, Evgeni

    2010-01-01

    Self-seeding schemes, consisting of two undulators with a monochromator in between, aim to reduce the bandwidth of SASE X-ray FELs. We recently proposed a new method of monochromatization exploiting a single crystal in Bragg-transmission geometry for self-seeding in the hard X-ray range. A straightforward extension is to use such kind of monochromator setup with two -or more- crystals arranged in a series to spectrally filter the SASE radiation at two closely-spaced wavelengths within the FEL gain band. This allows for the production of doublet -or multiplet- spectral lines. Applications involve any process with a large change in cross section over a narrow wavelength range, as in multiple wavelength anomalous diffraction. Here we consider the simultaneous operation of the LCLS hard X-ray FEL at two closely spaced wavelengths. We present simulation results for the LCLS baseline, yielding fully coherent radiation shared between two longitudinal modes. Mode spacing can be easily tuned within the FEL gain band. ...

  16. Tectonic Implication of the 5th March 2005, Doublet Earthquake in Ilan, Taiwan

    Directory of Open Access Journals (Sweden)

    En-Chao Yeh

    2016-01-01

    Full Text Available The 5th March 2005 earthquake doublet focal mechanism was determined as strike-slip faulting from Harvard and BATS moment tensor inversion. However, based on first motion polarities, the first shock has a normal focal mechanism (Wu et al. 2008a. This discrepancy has caused a debate over the focal mechanism solution because different focal mechanisms have different tectonic implications. Based on the dislocation determination from Global Position System (GPS measurements, we find this event includes both tensile and strike-slip components. This finding illustrates the reason for the differences in the determined focal mechanisms using two different types of seismic data and analyzing methods. Field mapping and microstructure examination results indicate that the ductile deformation around the study area was characterized by the evolution from transpression to transtension with a predominant strike-slip component, but present-day active structures may be dominated by normal faulting. Thus, the active tensile slip result determined from dislocation modeling strongly suggests that the back arc extension of the Okinawa trough influences the stress state in this region, and changes the major transtension from strike-slip faulting to normal faulting.

  17. Copernicus observations of the N v resonance doublet in 53 early-type stars

    Science.gov (United States)

    Abbott, D. C.; Bohlin, R. C.; Savage, B. D.

    1982-01-01

    UV spectra in the wavelength interval 1170-1270 A are presented for 53 early-type stars ranging in spectral type from O6.5 V to B2.5 IV. The sample includes four Wolf-Rayet stars, seven known Oe-Be stars, and six galactic halo OB stars. A qualitative analysis of the stellar N v doublet reveals that: (1) N v is present in all stars hotter and more luminous than type B0 for the main sequence, B1 for giants, and B2 for supergiants; (2) shell components of N v and an unidentified absorption feature at 1230 A are present in about half of the stars; (3) the column density of N v is well correlated with bolometric luminosity over the spectral range O6 to B2; and (4) the ratio of emission to absorption equivalent width is a factor of 2 smaller in the main sequence stars than in supergiants, which suggests that the wind structure changes as a star evolves. For several stars, this ratio is too small to be explained by traditional wind models.

  18. Exploring the Inert Doublet Model through the dijet plus missing transverse energy channel at the LHC

    Directory of Open Access Journals (Sweden)

    P. Poulose

    2017-02-01

    Full Text Available In this study of the Inert Doublet Model (IDM, we propose that the dijet + missing transverse energy channel at the Large Hadron Collider (LHC will be an effective way of searching for the scalar particles of the IDM. This channel receives contributions from gauge boson fusion, and t-channel production, along with contributions from H+ associated production. We perform the analysis including study of the Standard Model (SM background with assumed systematic uncertainty, and optimise the selection criteria employing suitable cuts on the kinematic variables to maximise the signal significance. We find that with high luminosity option of the LHC, this channel has the potential to probe the IDM in the mass range of up to about 400 GeV, which is not accessible through other leptonic channels. In a scenario with light dark matter of mass about 65 GeV, charged Higgs in the mass range of around 200 GeV provides the best possibility with a signal significance of about 2σ at an integrated luminosity of about 3000 fb−1.

  19. On the Doublet Formation in the Flocculation Process of the Yeast Cells

    CERN Document Server

    Stan, S; Stan, Silvia; Despa, Florin

    2000-01-01

    The combination of single cells to form doublets is regarded as the rate-limiting step of flocculation and requires the presence of surface proteins in active form. The process of activation of the flocculation proteins of yeast cells is described in the frame of the autocrine interaction regime (Cantrell, D. A. and Smith, K. A., 1984, Science 224, 1312-1316). The influence of several effectors (the cell efficiency to use sugars, the calcium content in the external medium and the probability that free cells collide each other under thermal motion conditions) on the initial rate of flocculation and on the fraction of remaining free cells in the steady state is briefly discussed in the paper. The present model offers an useful tool for further quantitative investigations in this topic. Also, it indicates qualitatively a way in which the regulation of flocculation might be controlled at the level of the expression of cell-surface activation abilities. Keywords: flocculation; yeast; autocrine binding; lectin hypo...

  20. Calculation of doublet capture rate for muon capture in deuterium within chiral effective field theory

    Science.gov (United States)

    Adam, J.; Tater, M.; Truhlík, E.; Epelbaum, E.; Machleidt, R.; Ricci, P.

    2012-03-01

    The doublet capture rate Λ1 / 2 of the negative muon capture in deuterium is calculated employing the nuclear wave functions generated from accurate nucleon-nucleon (NN) potentials constructed at next-to-next-to-next-to-leading order of heavy-baryon chiral perturbation theory and the weak meson exchange current operator derived within the same formalism. All but one of the low-energy constants that enter the calculation were fixed from pion-nucleon and nucleon-nucleon scattering data. The low-energy constant dˆR (cD), which cannot be determined from the purely two-nucleon data, was extracted recently from the triton β-decay and the binding energies of the three-nucleon systems. The calculated values of Λ1 / 2 show a rather large spread for the used values of the dˆR. Precise measurement of Λ1 / 2 in the future will not only help to constrain the value of dˆR, but also provide a highly nontrivial test of the nuclear chiral EFT framework. Besides, the precise knowledge of the constant dˆR will allow for consistent calculations of other two-nucleon weak processes, such as proton-proton fusion and solar neutrino scattering on deuterons, which are important for astrophysics.