Amplification of Genomic DNA for Decoy Receptor 3 Predicts Post-Resection Disease Recurrence in Breast Cancer Patients.

PubMed

Kanbayashi, Chizuko; Koyama, Yu; Ichikawa, Hiroshi; Sakata, Eiko; Hasegawa, Miki; Toshikawa, Chie; Manba, Naoko; Ikarashi, Mayuko; Kobayashi, Takashi; Minagawa, Masahiro; Kosugi, Shin-Ichi; Wakai, Toshifumi

2014-02-01

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, shows inhibitory effects on Fas-mediated apoptosis. Currently, data are lacking on the correlation between DcR3 and the recurrence of breast cancer. The authors examined DcR3 mRNA expression and genomic amplification in breast cancer, and investigated the effect of DcR3 gene amplification on prognosis of patients. A total of 95 patients formed the basis of the current retrospective study. DcR3 mRNA expression in breast cancer tissues was examined by RNase protection assay and in situ hybridization. DcR3 gene amplification was examined by quantitative polymerase chain reaction. The correlation between DcR3 gene amplification status and clinicopathological factors was examined and also the relationship between DcR3-Amp and relapse and survival. The relative copy numbers of DcR3 genomic DNA correlated significantly with the levels of DcR3 mRNA expression (ρ = 0.755, P = 0.0067). In addition, lymphatic invasion correlated significantly with DcR3 gene amplification (P = 0.012). However, there was no correlation between the remaining clinicopathological factors and DcR3 gene amplification. In the univariate analysis, the recurrence-free survival (RFS) rate of patients who were positive for DcR3 gene amplification was significantly lower than that of patients who were negative for DcR3 gene amplification (P = 0.0271). Multivariate analysis showed that DcR3 gene amplification (P = 0.028) and disease stage (P < 0.001) remained significant independent predictors of RFS. DcR3 gene amplification was significantly correlated with lymphatic invasion, and also DcR3 gene amplification predicts recurrence after resection, which may be an important prognostic factor in breast cancer patients.

Endoscopic dacryocystorhinostomy with and without silicone intubation: 4 years retrospective study.

PubMed

Longari, F; Dehgani Mobaraki, P; Ricci, A L; Lapenna, R; Cagini, C; Ricci, G

2016-08-01

The objective of this study is to assess different outcomes between endoscopic dacryocystorhinostomy (En-DCR) with and without silicone intubation. We retrospectively analyzed 84 patients (89 procedures), suffering from chronic epiphora for primary acquired nasolacrimal duct obstruction, treated with En-DCR and divided into two groups depending on silicone stent intubation. The surgical outcomes were evaluated at 7 post-operative controls using Munk's score criteria. Functional success was defined as absence of epiphora, no further episodes of dacryocystitis, and a patent ostium after fluorescein irrigation. 45 En-DCR with stent and 44 En-DCR without stent were performed. Success rate after 18 months follow-up were, respectively, 82.2 % in the stent group and 88.6 % in the non-stent group (OR 0.59) with no statistical differences. The ostial size reduction has been reported in higher percentage in the stent group, mainly due to peristomal granuloma (OR 3.64), scar tissue formation (OR 2.25), and turbinoseptal synaechia (OR 1.76). The benefits of non-intubation are less patient discomfort, reduced surgical time and costs, simpler follow-up regimen and less intubation-associated complications. En-DCR without silicone stent intubation should be the first choice of procedure, stent intubation should be reserved in selected cases with poor local conditions pre and intra-operatively assessed.

Decoy receptor 3 (DcR3) overexpression predicts the prognosis and pN2 in pancreatic head carcinoma.

PubMed

Zhou, Jian; Song, Shiduo; Li, Dechun; He, Songbing; Zhang, Bing; Wang, Zhenxin; Zhu, Xinguo

2014-03-05

This study was carried out to examine decoy receptor 3 (DcR3) expression and investigate its clinical and prognostic significance in patients with pancreatic head carcinoma. Tissue samples were obtained from 50 patients with pancreatic head carcinoma. DcR3 protein expression in tissues and sera was assessed by immunohistochemistry and ELISA. Correlations between DcR3 and clinicopathologic features and prognoses were analyzed statistically. Serum DcR3 levels were significantly elevated in patients with pancreatic head carcinoma compared with patients with cystadenoma and healthy individuals (P < 0.01 and P < 0.01, respectively). DcR3 overexpression correlated with lymph node metastases and TNM stages (P < 0.05 and P < 0.05, respectively). Median overall survival for the high DcR3 group was 16.3 months, compared to 21.6 months for the low DcR3 group (P < 0.05). In the low DcR3 group, no significant difference was found in the overall survival between patients who underwent standard pancreatoduodenectomy (SPD) and those who had radical pancreatoduodenectomy (RPD) (P > 0.05). In the high DcR3 group, the median overall survival rates were 16.8 months in the RPD group and 13.5 months in the SPD group (P < 0.05). We found that DcR3 was overexpressed in pancreatic head carcinoma. The patients with high DcR3 levels had higher pN2 stages than those with low DcR3 levels. Detecting serum DcR3 level preoperatively might be an additional approach for evaluating pN2 stage and guiding the range of lymphadenectomy.

The expression of death decoy receptor 3 was increased in the patients with primary Sjögren's syndrome.

PubMed

Liu, Jinlin; Zhao, Zhao; Zou, Yuqiong; Zhang, Mei; Zhou, Yonglie; Li, Yasong; Pang, Zhenzhen; Jin, Weidong

2015-05-01

Previous studies suggested a pathological role for the death decoy receptor 3 (DcR3) in systemic lupus erythematosus (SLE) and rheumatic arthritis (RA). Herein, the expression of DcR3 in primary Sjögren's syndrome (pSS) and the relationship with clinical characteristics were investigated. The serum DcR3 levels of pSS patients and healthy controls were measured by ELISA. Pearson's correlation analysis was used to evaluate the relationship between the DcR3 levels with the clinical characterstics of pSS patients. Additionally, the DcR3 expression in salivary glands of pSS patients was investigated by the immunohistochemistry method. The serum DcR3 expression in pSS patients was significantly higher than healthy controls (p < 0.001), especially in new onset pSS patients (p = 0.036). Moreover, Pearson's correlation analysis show that DcR3 levels were positively correlated with age (p = 0.013), platelet (PLT) (p = 0.002), hemoglobin (Hb) (p = 0.004), Sjögren's syndrome disease damage activity index (SSDAI) score (p = 0.005), Sjögren's syndrome disease damage index (SSDDI) score (p < 0.001) and EULAR Sjögren's syndrome disease activity index (ESSDAI) score (p = 0.010). Furthermore, the DcR3 levels were significantly lower when the pSS patients were treated with the disease-modifying anti-rheumatic drugs. At last, DcR3 expression in salivary glands of pSS patients was significantly higher than healthy controls. The DcR3 expression was significantly elevated in the pSS patients and positively correlated with the clinical characteristics, and it might be an important factor involved in the progression of pSS patients and could be a potential therapeutic target.

Decoy receptor 3: a pleiotropic immunomodulator and biomarker for inflammatory diseases, autoimmune diseases and cancer.

PubMed

Lin, Wan-Wan; Hsieh, Shie-Liang

2011-04-01

Recently, several decoy molecules belonging to tumor necrosis factor receptor superfamily (TNFRSF) have been identified, including decoy receptor 1 (DcR1), decoy receptor 2 (DcR2), and decoy receptor 3 (DcR3). One of the tumor necrosis factor superfamily (TNFSF) members, TNF-related apoptosis-inducing ligand (TRAIL), binds to DcR1 and DcR2, which are membranous receptors with a truncated cytoplasmic domain, thus unable to transduce TRAIL-mediated signaling. In contrast to DcR1 and DcR2, DcR3 is a soluble receptor capable of neutralizing the biological effects of three other TNFSF members: Fas ligand (FasL/TNFSF6/CD95L), LIGHT (TNFSF14) and TNF-like molecule 1A (TL1A/TNFSF15). Since FasL is a potent apoptosis- and inflammation-inducing factor, LIGHT is involved in apoptosis and inflammation, and TL1A is a T cell costimulator and is involved in gut inflammation, DcR3 can be defined as an immunomodulator on the basis of its neutralizing effects on FasL, LIGHT, and TL1A. Initial studies demonstrated that DcR3 expression is elevated in tumors cells; however, later work showed that DcR3 expression is also upregulated in inflammatory diseases, where serum DcR3 levels correlate with disease progression. In addition to its neutralizing effect, DcR3 also acts as an effector molecule to modulate cell function via 'non-decoy' activities. This review focuses on the immunomodulatory effects of DcR3 via 'decoy' and 'non-decoy' functions, and discusses the potential of DcR3 as a biomarker to predict cancer invasion and inflammation progression. We also discuss the possible utility of recombinant DcR3 as a therapeutic agent to control autoimmune diseases, as well as the potential to attenuate tumor progression by inhibiting DcR3 expression. Copyright © 2011 Elsevier Inc. All rights reserved.

Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2.

PubMed

Zhou, Xiao-Na; Li, Guang-Ming; Xu, Ying-Chen; Zhao, Tuan-Jie; Wu, Ji-Xiang

2016-11-05

Decoy receptor 3 (DcR3) binds to Fas ligand (FasL) and inhibits FasL-induced apoptosis. The receptor is overexpressed in hepatocellular carcinoma (HCC), and it is associated with the growth and metastatic spread of tumors. DcR3 holds promises as a new target for the treatment of HCC, but little is known regarding the molecular mechanisms underlying the oncogenic properties of DcR3. The present work, therefore, examined the role of DcR3 in regulating the growth and invasive property of liver cancer cell HepG2. HepG2 cells were stably transfected with lentivirus-based short hairpin RNA vector targeting DcR3. After the knockdown of DcR3 was confirmed, cell proliferation, clone formation, ability of migrating across transwell membrane, and wound healing were assessed in vitro. Matrix metalloproteinase-9 (MMP 9) and vascular epithelial growth factor (VEGF)-C and D expressions of the DcR3 knockdown were also studied. Comparisons between multiple groups were done using one-way analysis of variance (ANOVA), while pairwise comparisons were performed using Student's t test. P< 0.05 was regarded statistically significant. DcR3 was overexpressed in HepG2 compared to other HCC cell lines and normal hepatocyte Lo-2. Stable knockdown of DcR3 slowed down the growth of HepG2 (P < 0.05) and reduced the number of clones formed by 50% compared to those without DcR3 knockdown (P < 0.05). The knockdown also reduced the migration of HepG2 across transwell matrix membrane by five folds compared to the control (P < 0.05) and suppressed the closure of scratch wound (P < 0.05). In addition, the messenger RNA levels of MMP 9, VEGF-C, and VEGF-D were significantly suppressed by DcR3 knockdown by 90% when compared with the mock control (P < 0.05). Loss of DcR3 impaired the growth and invasive property of HCC cell line of HepG2. Targeting DcR3 may be a potential therapeutic approach for the treatment of HCC.

Knockdown of Decoy Receptor 3 Impairs Growth and Invasiveness of Hepatocellular Carcinoma Cell Line of HepG2

PubMed Central

Zhou, Xiao-Na; Li, Guang-Ming; Xu, Ying-Chen; Zhao, Tuan-Jie; Wu, Ji-Xiang

2016-01-01

Background: Decoy receptor 3 (DcR3) binds to Fas ligand (FasL) and inhibits FasL-induced apoptosis. The receptor is overexpressed in hepatocellular carcinoma (HCC), and it is associated with the growth and metastatic spread of tumors. DcR3 holds promises as a new target for the treatment of HCC, but little is known regarding the molecular mechanisms underlying the oncogenic properties of DcR3. The present work, therefore, examined the role of DcR3 in regulating the growth and invasive property of liver cancer cell HepG2. Methods: HepG2 cells were stably transfected with lentivirus-based short hairpin RNA vector targeting DcR3. After the knockdown of DcR3 was confirmed, cell proliferation, clone formation, ability of migrating across transwell membrane, and wound healing were assessed in vitro. Matrix metalloproteinase-9 (MMP 9) and vascular epithelial growth factor (VEGF)-C and D expressions of the DcR3 knockdown were also studied. Comparisons between multiple groups were done using one-way analysis of variance (ANOVA), while pairwise comparisons were performed using Student's t test. P < 0.05 was regarded statistically significant. Results: DcR3 was overexpressed in HepG2 compared to other HCC cell lines and normal hepatocyte Lo-2. Stable knockdown of DcR3 slowed down the growth of HepG2 (P < 0.05) and reduced the number of clones formed by 50% compared to those without DcR3 knockdown (P < 0.05). The knockdown also reduced the migration of HepG2 across transwell matrix membrane by five folds compared to the control (P < 0.05) and suppressed the closure of scratch wound (P < 0.05). In addition, the messenger RNA levels of MMP 9, VEGF-C, and VEGF-D were significantly suppressed by DcR3 knockdown by 90% when compared with the mock control (P < 0.05). Conclusions: Loss of DcR3 impaired the growth and invasive property of HCC cell line of HepG2. Targeting DcR3 may be a potential therapeutic approach for the treatment of HCC. PMID:27779171

High intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand TL1A in active ulcerative colitis.

PubMed

Bamias, Giorgos; Kaltsa, Garyfallia; Siakavellas, Spyros I; Papaxoinis, Kostis; Zampeli, Evanthia; Michopoulos, Spyros; Zouboulis-Vafiadis, Irene; Ladas, Spiros D

2010-11-01

Decoy receptor-3 (DcR3) is a member of the TNF receptor superfamily of proteins, which has been implicated in anti-apoptotic and anti-inflammatory pathways, via binding to TL1A, LIGHT and Fas-L. The role of the TL1A/DcR3 ligand/receptor pair in ulcerative colitis (UC) has not been studied. We investigated the systemic (peripheral blood) and local (large intestine) expression of DcR3 and TL1A in 64 patients with UC and 56 healthy controls. DcR3 serum concentrations were highly elevated in patients with active UC (P<0.0001 vs. healthy controls). This elevation was clearly related to the presence of intestinal inflammation as it was less frequently observed in patients in remission (P=0.003 vs. active UC) whereas effective treatment resulted in disappearance or significant decrease of serum DcR3 (P=0.006 vs. pre-treatment). Furthermore, DcR3 mRNA transcripts were significantly elevated in inflamed areas of the colon (P=0.002 vs. non-affected of the same patient). In addition to DcR3 elevation, we found increased circulating levels of TL1A in patients with either active or inactive UC in comparison to healthy controls (P<0.001 for both). We conclude that elevated serum DcR3 may serve as an indicator of active colonic inflammation in patients with UC. TL1A/DcR3-mediated pathways may participate in the pathogenesis of UC. Copyright © 2010 Elsevier Inc. All rights reserved.

Successes rate of endoscopic dacryocystorhinostomy at KMC.

PubMed

Shrestha, S; Kafle, P K; Pokhrel, S; Maharjan, M; Toran, K C

2010-01-01

Nasolacrimal duct obstruction is a common problem which can be corrected by dacryocystorhinostomy (DCR). The gold standard treatment for this is DCR operation through an external approach. Development of endoscopic sinus surgery and endoscopic DCR performed through intranasal route is a major recent development in this field. The aim of this study is to find out the success rate of endoscopic dacryocystorhinostomy without silicon stent intubation within the period of six month following surgery. A prospective study was done on 26 patients with obstruction of the nasolacrimal duct referred from eye out-patient department to ENT OPD during one year period from 2008 to 2009. All the cases had undergone endoscopic DCR operation which was regularly followed up for a period of six months. Postoperative patency of ostium was checked by sac syringing and endoscopic visualisation of ostium in the nasal cavity. The success of surgery was categorised as: complete cure, partial cure and no improvement depending upon symptomatic relief and clinical examination such as sac syringing and endoscopic examination following surgery. In six months' follow-up, 22 (84.5%) out of 26 patients had achieved the complete cure and 4 patients (15.5%) continued to have persistent epiphora. Endoscopic DCR is a beneficial procedure for nasolacrimal duct obstruction with no external scar on face and less bleeding. The success rate is as good as external DCR.

Management of functional epiphora in patients with an anatomically patent dacryocystorhinostomy.

PubMed

Shams, Pari N; Chen, Philip G; Wormald, Peter J; Sloan, Brian; Wilcsek, Geoff; McNab, Alan; Selva, Dinesh

2014-09-01

Approximately 5% to 10% of patients continue to experience persistent epiphora following an anatomically successful dacryocystorhinostomy (DCR) for nasolacrimal duct obstruction or stenosis. To investigate the management and success rate of so-called "functional failure" of DCR for nasolacrimal duct obstruction by experienced lacrimal surgeons. Multicenter retrospective case series including 5 Australian and New Zealand centers. Participants included 61 patients (71% women [n = 46]; mean age, 66 years) with functional epiphora after 65 DCRs (69% transnasal) who were recruited over a mean of 7.6 years. Inclusion criteria included confirmed preoperative diagnosis of nasolacrimal duct obstruction or stenosis, age greater than 18 years, recurrent or persistent epiphora after DCR, an anatomically successful DCR, and follow-up longer than 6 months. Exclusion criteria included evidence of lacrimal hypersecretion, eyelid malposition, and punctal or canalicular abnormalities. The number, type, timing, and success of all clinical interventions performed for the management of functional epiphora after DCR. Epiphora recurred a mean of 8.9 months after primary DCR; 89% of the cases (n = 58) had evidence of a patent ostium and 100% were patent on lacrimal irrigation. Intubation with a lacrimal stent was performed in 82% of the cases at the time of surgery, and all stents were removed a mean of 8 weeks postoperatively. Epiphora was reported immediately following DCR in 32% (n = 21) of the cases and within 6 weeks after removal of the stent in 31% (n = 20); late recurrence (>12 months after DCR) developed in 37% (n = 24) of the cases. In a total of 15% of the cases, participants declined any treatment following DCR. The remainder underwent a mean of 1.3 interventions (range, 1-3) during a mean of 23 to 41 months after primary DCR, following which 72% (n = 47) of the cases had a successful outcome; 12% (n = 8) failed to achieve improvement, and the patients declined further intervention. Thirty-nine interventions (60%) were intubation with a silicone stent with a 54% success rate. Almost half of those undergoing intubation elected to keep the stent permanently; 34% (n = 22) had an eyelid-tightening procedure with 50% success, and 15% (n = 10) required a Lester-Jones tube despite patent canaliculi, with a success rate of 90%. Functional epiphora after DCR among patients with preoperative nasolacrimal duct obstruction or stenosis appears to be uncommon. Benefits can be achieved in most patients with intubation (transient or permanent) or eyelid tightening. More than one procedure is often required.

Monitoring and Controlling an Underwater Robotic Arm

NASA Technical Reports Server (NTRS)

Haas, John; Todd, Brian Keith; Woodcock, Larry; Robinson, Fred M.

2009-01-01

The SSRMS Module 1 software is part of a system for monitoring an adaptive, closed-loop control of the motions of a robotic arm in NASA s Neutral Buoyancy Laboratory, where buoyancy in a pool of water is used to simulate the weightlessness of outer space. This software is so named because the robot arm is a replica of the Space Shuttle Remote Manipulator System (SSRMS). This software is distributed, running on remote joint processors (RJPs), each of which is mounted in a hydraulic actuator comprising the joint of the robotic arm and communicating with a poolside processor denoted the Direct Control Rack (DCR). Each RJP executes the feedback joint-motion control algorithm for its joint and communicates with the DCR. The DCR receives joint-angular-velocity commands either locally from an operator or remotely from computers that simulate the flight like SSRMS and perform coordinated motion calculations based on hand-controller inputs. The received commands are checked for validity before they are transmitted to the RJPs. The DCR software generates a display of the statuses of the RJPs for the DCR operator and can shut down the hydraulic pump when excessive joint-angle error or failure of a RJP is detected.

Serum decoy receptor 3 levels are associated with the disease activity of MPO-ANCA-associated renal vasculitis.

PubMed

Maruyama, Hiroshi; Hirayama, Kouichi; Nagai, Miho; Ebihara, Itaru; Shimohata, Homare; Kobayashi, Masaki

2016-10-01

Type 17 T-helper (Th17) cells have been suggested to be involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Th17 cell proliferation is promoted by tumor necrosis factor (TNF)-like ligand 1A (TL1A), which binds to death receptor 3 (DR3) expressed on Th17 cells. Decoy receptor 3 (DcR3) is known to block the TL1A-DR3 pathway by binding TL1A. To evaluate the Th17-TL1A systems as disease activity markers in AAV, we investigated the serum levels of TL1A and DcR3 in AAV patients. Serum IL-17, IL-23, TL1A, and DcR3 were measured by ELISA in 24 AAV patients with microscopic polyangiitis before the initial treatment, 24 AAV patients during remission, and 20 control subjects. There were no significant differences in serum IL-17, IL-23, and TL1A levels among the active-vasculitis patients, inactive-vasculitis patients, and controls. The mean serum DcR3 level was significantly higher in the active-vasculitis patients than in the inactive-vasculitis patients and controls (P < 0.0001, respectively). There were significant positive correlations between the serum DcR3 levels and Birmingham Vasculitis Activity Score (BVAS), myeloperoxidase (MPO)-ANCA titers, white blood cell counts, serum creatinine levels, and serum C-reactive protein levels. In a multiple regression analysis, there was a significant positive correlation between the serum DcR3 level and BVAS (β = 0.650, P = 0.0462). The mean BVAS level was significantly higher in the active-vasculitis patients with high serum DcR3 levels than in those with the low serum DcR3 levels (P = 0.0202). The serum level of DcR3 may be a useful marker for disease activity in AAV.

Propagation of spiking regularity and double coherence resonance in feedforward networks.

PubMed

Men, Cong; Wang, Jiang; Qin, Ying-Mei; Deng, Bin; Tsang, Kai-Ming; Chan, Wai-Lok

2012-03-01

We investigate the propagation of spiking regularity in noisy feedforward networks (FFNs) based on FitzHugh-Nagumo neuron model systematically. It is found that noise could modulate the transmission of firing rate and spiking regularity. Noise-induced synchronization and synfire-enhanced coherence resonance are also observed when signals propagate in noisy multilayer networks. It is interesting that double coherence resonance (DCR) with the combination of synaptic input correlation and noise intensity is finally attained after the processing layer by layer in FFNs. Furthermore, inhibitory connections also play essential roles in shaping DCR phenomena. Several properties of the neuronal network such as noise intensity, correlation of synaptic inputs, and inhibitory connections can serve as control parameters in modulating both rate coding and the order of temporal coding.

Serum decoy receptor 3 is a biomarker for disease severity in nonatopic asthma patients.

PubMed

Chen, Ming-Han; Kan, Hung-Tsai; Liu, Chun-Yu; Yu, Wen-Kuang; Lee, Shinn-Shing; Wang, Jia-Horng; Hsieh, Shie-Liang

2017-01-01

Decoy receptor 3 (DcR3), a soluble receptor of the tumor necrosis factor receptor superfamily, is a pleiotropic immunomodulator. The aim of this study was to investigate serum DcR3 levels in atopic and nonatopic asthma patients. The serum DcR3 levels of 70 adults with asthma and 20 healthy controls were determined by enzyme-linked immunosorbent assay (ELISA). The asthma patients were divided into atopic and nonatopic subgroups, based on the presence or absence of immunoglobulin E (IgE) specific to allergen. Correlations between serum DcR3 levels and blood total-eosinophil counts, forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), and Asthma Control Test (ACT) scores were analyzed. The mean serum DcR3 level was significantly higher in asthma patients than in healthy controls (266.1 ± 60.6 pg/mL vs. 63.7 ± 21.9 pg/mL, p = 0.003), but there was no significant difference between the mean serum DcR3 level of asthma patients with atopy (37 patients) and patients without atopy (33 patients; 298.7 ± 111.2 pg/mL vs. 230.6 ± 38.5 pg/mL, p = 0.064). However, the serum DcR3 level was positively correlated with the total eosinophil count (r = 0.448, p = 0.012) and inversely correlated with the percentages of predicted FEV1, FEV1/FVC, and ACT score (r = 0.409, p = 0.018; r = -0.399, p = 0.021; and r = -0.505, p = 0.003, respectively) in nonatopic asthma patients, but not in atopic patients. High serum DcR3 levels are associated with disease severity in nonatopic asthma patients, which suggests that DcR3 is a potential biomarker that can be used to predict the severity of nonatopic asthma. Copyright © 2016. Published by Elsevier B.V.

Office-based endoscopic revision using a microdebrider for failed endoscopic dacryocystorhinostomy.

PubMed

Park, Jongyeop; Kim, Hochang

2016-12-01

This article is to introduce office-based endoscopic revision surgery using a microdebrider for failed endoscopic dacryocystorhinostomy (EN-DCR). The authors conducted retrospective, non-comparative, interventional case series analysis of 27 eyes of 24 patients, treated by office-based revision EN-DCR using a microdebrider. After local anesthesia, anatomical failures (cicatrization, granuloma, synechia) after primary EN-DCR were treated with a microdebrider (Osseoduo 120, Bien-Air Surgery, Le Noirmont, Switzerland) in an office setting, and a bicanalicular silicone tube was placed. Anatomical improvement and functional relief of epiphora were evaluated at 6-months after revision. The causes of failed EN-DCR were rhinostomy site cicatrization (17/27, 63.0 %), granulomatous obstruction (7/27, 25.9 %) and synechial formation (3/27, 11.1 %). The anatomical success rate was 100 %, and 85.2 % cases achieved complete relief of epiphora. The surgery did not exceed 10 min in any case and no complications were observed. Office-based revision EN-DCR using a microdebrider provided prompt management of post-DCR epiphora. The portable nature and all-round ability of the microdebrider allowed office-based surgery, which offered advantage to work with the surgeon's own well-trained office staff. Office-based revision EN-DCR can be both time- and money-saving, and might be regarded the treatment of choice for failed EN-DCR.

EGFR-driven up-regulation of decoy receptor 3 in keratinocytes contributes to the pathogenesis of psoriasis.

PubMed

Wu, Nan-Lin; Huang, Duen-Yi; Hsieh, Shie-Liang; Hsiao, Cheng-Hsiang; Lee, Te-An; Lin, Wan-Wan

2013-10-01

Decoy receptor 3 (DcR3) is a soluble receptor of Fas ligand (FasL), LIGHT (TNFSF14) and TNF-like molecule 1A (TL1A) and plays pleiotropic roles in many inflammatory and autoimmune disorders and malignant diseases. In cutaneous biology, DcR3 is expressed in primary human epidermal keratinocytes and is upregulated in skin lesions in psoriasis, which is characterized by chronic inflammation and angiogenesis. However, the regulatory mechanisms of DcR3 over-expression in skin lesions of psoriasis are unknown. Here, we demonstrate that DcR3 can be detected in both dermal blood vessels and epidermal layers of psoriatic skin lesions. Analysis of serum samples showed that DcR3 was elevated, but FasL was downregulated in psoriatic patients compared with normal individuals. Additional cell studies revealed a central role of epidermal growth factor receptor (EGFR) in controlling the basal expression of DcR3 in keratinocytes. Activation of EGFR by epidermal growth factor (EGF) and transforming growth factor (TGF)-α strikingly upregulated DcR3 production. TNF-αenhanced DcR3 expression in both keratinocytes and endothelial cells compared with various inflammatory cytokines involved in psoriasis. Additionally, TNF-α-enhanced DcR3 expression in keratinocytes was inhibited when EGFR was knocked down or EGFR inhibitor was used. The NF-κB pathway was critically involved in the molecular mechanisms underlying the action of EGFR and inflammatory cytokines. Collectively, the novel regulatory mechanisms of DcR3 expression in psoriasis, particularly in keratinocytes and endothelial cells, provides new insight into the pathogenesis of psoriasis and may also contribute to the understanding of other diseases that involve DcR3 overexpression. Copyright © 2013 Elsevier B.V. All rights reserved.

Outcomes of revision external dacryocystorhinostomy and nasal intubation by bicanalicular silicone tubing under endonasal endoscopic guidance.

PubMed

Ari, Seyhmus; Kürşat Cingü, Abdullah; Sahin, Alparslan; Gün, Ramazan; Kiniş, Vefa; Caça, Ihsan

2012-01-01

To evaluate the long-term treatment outcomes in patients who underwent revision of external dacryocystorhinostomy (DCR) and nasal intubation by bicanalicular silicone tubing (BSTI) under endonasal endoscopic guidance. Data from 28 patients with recurrent dacryocystitis were retrospectively reviewed. Revision external DCR and bicanalicular nasal intubation by silicone tubing under endonasal endoscopic guidance was performed in 28 eyes of 28 patients. The patients were evaluated with respect to the reason of recurrence, time to recurrence, time to revision, duration of follow-up and surgical success. Endoscopic endonasal examination detected an osteotomy-side obstruction by the excessive granulation tissue in 24 patients (86%), nasal septal deviation in three patients (10%) and nasal polyp in one patient (4%). Recurrence occurred after a mean duration of 5.3±3.7 months following the first operation. The mean time between the first DCR operation and the revision DCR was 11.5 ± 9.3 months. After a mean follow-up of 14.9±7.8 months, the rate of anatomic success alone was 85% (24/28); the rate of subjective success was 78% (22/28). Revision external DCR and bicanalicular nasal intubation by silicone tubing under endonasal endoscopic guidance can be recommended in patients with recurrent dacryocystitis as a surgical approach that achieves satisfactory objective and subjective success rates.

Outcomes of revision external dacryocystorhinostomy and nasal intubation by bicanalicular silicone tubing under endonasal endoscopic guidance

PubMed Central

Ari, Şeyhmus; Kürşat Cingü, Abdullah; Şahin, Alparslan; Gün, Ramazan; Kiniş, Vefa; Çaça, İhsan

2012-01-01

AIM To evaluate the long-term treatment outcomes in patients who underwent revision of external dacryocystorhinostomy (DCR) and nasal intubation by bicanalicular silicone tubing (BSTI) under endonasal endoscopic guidance. METHODS Data from 28 patients with recurrent dacryocystitis were retrospectively reviewed. Revision external DCR and bicanalicular nasal intubation by silicone tubing under endonasal endoscopic guidance was performed in 28 eyes of 28 patients. The patients were evaluated with respect to the reason of recurrence, time to recurrence, time to revision, duration of follow-up and surgical success. RESULTS Endoscopic endonasal examination detected an osteotomy-side obstruction by the excessive granulation tissue in 24 patients (86%), nasal septal deviation in three patients (10%) and nasal polyp in one patient (4%). Recurrence occurred after a mean duration of 5.3±3.7 months following the first operation. The mean time between the first DCR operation and the revision DCR was 11.5 ± 9.3 months. After a mean follow-up of 14.9±7.8 months, the rate of anatomic success alone was 85% (24/28); the rate of subjective success was 78% (22/28). CONCLUSION Revision external DCR and bicanalicular nasal intubation by silicone tubing under endonasal endoscopic guidance can be recommended in patients with recurrent dacryocystitis as a surgical approach that achieves satisfactory objective and subjective success rates. PMID:22762058

Reduced signaling of PI3K-Akt and RAS-MAPK pathways is the key target for weight-loss-induced cancer prevention by dietary calorie restriction and/or physical activity.

PubMed

Standard, Joseph; Jiang, Yu; Yu, Miao; Su, Xiaoyu; Zhao, Zhihui; Xu, Jianteng; Chen, Jie; King, Brenee; Lu, Lizhi; Tomich, John; Baybutt, Richard; Wang, Weiqun

2014-12-01

Weight control through either dietary calorie restriction (DCR) or exercise has been associated with cancer prevention in animal models. However, the underlying mechanisms are not fully defined. Bioinformatics using genomics, proteomics and lipidomics was employed to elucidate the molecular targets of weight control in a mouse skin cancer model. SENCAR mice were randomly assigned into four groups for 10 weeks: ad-libitum-fed sedentary control, ad-libitum-fed exercise (AE), exercise but pair-fed isocaloric amount of control (PE) and 20% DCR. Two hours after topical TPA treatment, skin epidermis was analyzed by Affymetrix for gene expression, DIGE for proteomics and lipidomics for phospholipids. Body weights were significantly reduced in both DCR and PE but not AE mice versus the control. Among 39,000 transcripts, 411, 67 and 110 genes were significantly changed in DCR, PE and AE, respectively. The expression of genes relevant to PI3K-Akt and Ras-MAPK signaling was effectively reduced by DCR and PE but not AE as measured through GenMAPP software. Proteomics analysis identified ~120 proteins, with 27 proteins significantly changed by DCR, including up-regulated apolipoprotein A-1, a key antioxidant protein that decreases Ras-MAPK activity. Of the total 338 phospholipids analyzed by lipidomics, 57 decreased by PE including 5 phophatidylinositol species that serve as PI3K substrates. Although a full impact has not been determined yet, it appears that the reduction of both Ras-MAPK and PI3K-Akt signaling pathways is a cancer preventive target that has been consistently demonstrated by three bioinformatics approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

Reduced signaling of PI3K-Akt and RAS-MAPK pathways are the key targets for weight loss-induced cancer prevention by dietary calorie restriction and/or physical activity

PubMed Central

Standard, Joseph; Jiang, Yu; Yu, Miao; Su, Xiaoyu; Zhao, Zhihui; Xu, Jianteng; Chen, Jie; King, Brenee; Lu, Lizhi; Tomich, John; Baybutt, Richard; Wang, Weiqun

2014-01-01

Weight control through either dietary calorie restriction (DCR) or exercise has been associated with cancer prevention in animal models. However, the underlying mechanisms are not fully defined. Bioinformatics using genomics, proteomics, and lipidomics were employed to elucidate the molecular targets of weight control in a mouse skin cancer model. SENCAR mice were randomly assigned into 4 groups for 10 weeks: ad lib-fed sedentary control, ad lib-fed exercise (AE), exercise but pair-fed isocaloric amount of control (PE), and 20% DCR. Two hours after topical TPA treatment, skin epidermis was analyzed by Affymetrix for gene expression, DIGE for proteomics, and lipidomics for phospholipids. Body weights were significantly reduced in both DCR and PE but not AE mice versus the control. Among 39,000 transcripts, 411, 67, and 110 genes were significantly changed in DCR, PE, and AE, respectively. The expression of genes relevant to PI3K-Akt and Ras-MAPK signaling was effectively reduced by DCR and PE but not AE as measured through GenMAPP software. Proteomics analysis identified ~120 proteins, with 27 proteins significantly changed by DCR, including upregulated apolipoprotein A-1, a key antioxidant protein that decreases Ras-MAPK activity. Of the total 338 phospholipids analyzed by lipidomics, 57 decreased by PE including 5 phophatidylinositol species that serve as PI3K substrates. Although a full impact has not been determined yet, it appears the reduction of both Ras-MAPK and PI3K-Akt signaling pathways are cancer preventive targets that have been consistently demonstrated by three bioinformatics approaches. PMID:25283328

Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma.

PubMed

Boige, Valérie; Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

2012-01-01

Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. The 16W-DCR was 42% (95% confidence interval, 27%-57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3-4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation.

Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

PubMed Central

Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

2012-01-01

Objective. Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. Methods. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. Results. The 16W-DCR was 42% (95% confidence interval, 27%–57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3–4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Conclusion. Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation. PMID:22707516

Decoy receptor 3 suppresses B cell functions and has a negative correlation with disease activity in rheumatoid arthritis.

PubMed

Chen, Ming-Han; Liu, Po-Chun; Chang, Chien-Wen; Chen, Yi-Ann; Chen, Ming-Huang; Liu, Chun-Yu; Leu, Chuen-Miin; Lin, Hsiao-Yi

2014-01-01

The decoy receptor 3 (DcR3) is a member of the tumour necrosis factor (TNF) receptor superfamily and may regulate inflammation. The aim of this study was to investigate the role of DcR3 in B cell functions and its correlation to disease activity in patients with rheumatoid arthritis (RA). The concentrations of DcR3 and TNF-α were measured by ELISA. B cell proliferation was assessed by quantification of 3H-thymidine uptake. Staphylococcus aureus Cowan (SAC) strain were used to stimulate B cell proliferation and TNF-α production. Compared to the osteoarthritis (OA) patients, the RA group had higher synovial DcR3 levels (3273.6±1623.2 vs. 1594.8±1190.0 pg/ml, p=0.003), which were negatively correlated with the serum erythrocyte sedimentation rate and Disease Activity Score using 28 joint counts (DAS28) scores (r=-0.560, p=0.002; r=-0.579, p<0.001, respectively). Although the RA B cells have more active characteristics, B cell proliferation induced by SAC was successfully suppressed by recombinant DcR3.Fc fusion protein with an average inhibition of 44.8%. Moreover, DcR3.Fc fusion protein was found to suppress SAC-induced TNF-α production by B cells in 8 RA patients (average inhibition 47.0%). The results of our study indicated that the inhibition of B cell functions by DcR3 may partially explain the negative correlation between DcR3 level and disease activity in RA patients. Our findings imply that DcR3 may be used as a biomarker for disease activity and a potential therapeutic agent in the treatment of RA.

Diagnostic value of decoy receptor 3 combined with procalcitonin and soluble urokinase-type plasminogen activator receptor for sepsis.

PubMed

Zhao, Jing-Jing; Lou, Xiao-Li; Chen, Hong-Wei; Zhu, Feng-Ting; Hou, Yan-Qiang

2018-01-01

The levels of decoy receptor 3 (DcR3), soluble urokinase type plasminogen activator receptor (suPAR) and procalcitonin (PCT) are significantly increased in sepsis. We investigated the diagnostic value of DcR3 combined with suPAR and PCT in sepsis. Patients with sepsis, non-infectious systemic inflammatory response comprehensive syndrome (SIRS) and healthy controls were recruited according to the diagnostic standard. We measured DcR3, suPAR, PCT, interleukin-6 (IL-6) and C-reactive protein (CRP), and the diagnostic value was evaluated by receiver operating characteristics (ROC) curves. In our analysis, serum DcR3, suPAR and PCT levels of the sepsis group were significantly higher than those of the SIRS and control groups. However, IL-6, CRP and WBC showed no significant difference between the SIRS group and the sepsis group. The serum DcR3 level was positively correlated with the serum suPAR level ( r  = 0.37, p  = 0.0022) and PCT level ( r  = 0.37, p  = 0.0021). Using DcR3, suPAR and PCT to distinguish SIRS from sepsis, the area under the curve (AUC) values were 0.892, 0.778 and 0.692. When DcR3, suPAR and PCT combined were used for diagnosis of sepsis, the AUC was 0.933, at a cut-off point of 0.342. This combination improved the sensitivity and specificity of diagnosis of sepsis, suggesting that use of the combination of three indexes enhanced the efficiency of sepsis diagnosis.

Endoscopic dacryocystorhinostomy with silicone, polypropylene, and T-tube stents; randomized controlled trial of efficacy and safety.

PubMed

Okuyucu, Semsettin; Gorur, Hatice; Oksuz, Huseyin; Akoglu, Ertap

2015-01-01

To compare the efficacy and safety of endoscopic dacryocystorhinostomy (En-DCR) with different stent materials for lacrimal sac intubation in primary nasolacrimal ductal obstructions. Randomized controlled study with three parallel groups. Level of evidence is 1b. A total of 91 patients (five bilateral) with primary nasolacrimal duct obstruction (NLDO) at a tertiary referral center scheduled for En-DCR were to allocated into three stent groups with a sealed envelope and were randomized into three treatments: silicone, Prolene (polypropylene), and otologic T-tube. Ophthalmology and otolaryngology clinics evaluated the patients preoperatively and postoperatively with endoscopes, lacrimal system syringing, and dacryocystography. The success of the stents was evaluated 12 months after surgery with symptom relief and ostial patency. Complications were also noted. The overall success rate of the En-DCR in the stent groups was 78.1% (75/96); specifically, 87.5% (28/32) with silicone, 84.4% (27/32) with Prolene, and 62.5% (20/32) with T-tube. The efficacy of the procedures with the T-tube was significantly lower than that of the Prolene and silicone (p = .031, χ(2) test). There were no significant differences between the silicone and Prolene (p = .718, χ(2) test). Prolene was found to be related with orbital complications. Spontaneous loss is a particular complication of otologic T-tube and highly portends to failure. The results of our study suggest that efficacy, defined as anatomic and functional success, is equally high for silicone and Prolene stents and lower for otologic T-tube in En-DCR.

Endoscopic dacryocystorhinostomy without silicone stent.

PubMed

Yeon, Je Yeob; Shim, Woo Sub

2012-06-01

In nasolacrimal duct (NLD) obstruction patients that undergo endoscopic dacryocystorhinostomy (DCR), creation of a patent rhinostomy with adequate epithelialization can be accomplished without a stent. However, in common canalicular obstruction patients, a silicone stent seems to have a beneficial role and to bear more favorable results. The aim of this study was to evaluate the surgical outcome of endoscopic DCR without the use of a silicone stent. In all, 36 patients (41 eyes) who underwent endoscopic DCR were enrolled in this study. The patients were classified into a DCR with silicone stent group and a DCR without silicone stent group. Then each of the groups was subdivided into common canalicular obstruction group and NLD obstruction group. Surgical outcomes were evaluated by postoperative symptom improvement and patency of the rhinostomy under nasal endoscopic exam. The epiphora was improved in 84.2% of the silicone stent group and 81.8% of the non-silicone stent group. Categorized by the level of obstruction, in common canalicular obstruction, the success rate was 84.5% (11/13) in the silicone stent group and 57.1% (4/7) in the no stent group. In NLD obstruction, the success rate was 83.0% (5/6) in the silicone stent group and 93.3% (14/15) in the no stent group.

Lack of death receptor 4 (DR4) expression through gene promoter methylation in gastric carcinoma.

PubMed

Lee, Kyung Hwa; Lim, Sang Woo; Kim, Ho Gun; Kim, Dong Yi; Ryu, Seong Yeob; Joo, Jae Kyun; Kim, Jung Chul; Lee, Jae Hyuk

2009-07-01

To determine the underlying mechanism for the differential expression, the extent of promoter methylation in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-related genes acting downstream of TRAIL was examined in early and advanced gastric carcinomas. The extent of promoter methylation in the DR4, DR5, DcR1, DcR2, and CASP8 genes was quantified using bisulfite modification and methylation-specific polymerase chain reaction. The promoters for DcR1, DcR2, and CASP8 were largely unmethylated in early gastric carcinoma, advanced gastric carcinoma, and controls, with no significant difference among them. Protein levels of DR4, DcR1, and DcR2 as revealed by immunohistochemistry correlated with the extent of the respective promoter methylation (P < 0.05 in all cases). Hypomethylation, rather than hypermethylation, of the DR4 promoter was noted in invasive gastric malignancies, with statistical significance (P = 0.003). The promoter methylation status of TRAIL receptors in gastric carcinoma may have clinical implications for improving therapeutic strategies in patients with gastric carcinoma.

Endocanalicular diode laser dacryocystorhinostomy for nasolacrimal duct obstruction: short-term results of a new minimally invasive surgical technique.

PubMed

Özçimen, Muammer; Uysal, Ismail Onder; Eryılmaz, Mehmet Akif; Kal, Ali

2010-11-01

To evaluate the results, complications, effectiveness, and operative results of the endocanalicular laser dacryocystorhinostomy (ECL DCR) in the distal obstructions of the lacrimal drainage system. Sixty eyes of 57 patients who had a diagnosis of distal obstruction of the lacrimal drainage system were evaluated retrospectively in this study. All patients underwent ECL DCR by diode laser between October 2008 and July 2009. Forty-nine patients (86%) were females, 8 patients (14%) were males, and age distribution was between 3 and 84 years old (median, 40 y). The canaliculi were intubated by a silicone tube. The patency of the nasolacrimal system was controlled by lacrimal lavage, loss of epiphora, and endoscopic evaluation of the endonasal rhinostomy site with routine follow-up scheduled at first day and 1-week, 1-month, and 3-month postoperative intervals. After the 60 ECL DCRs, 10 patients underwent revision ECL DCR because of the persistent epiphora. The patency of the nasolacrimal duct or the decrease of the symptoms was assigned as success. There were no symptoms at all in 83.3% of the patients. The ECL DCR in the treatment of the distal obstructions of the lacrimal drainage system was easily tolerated by the patients, cosmetically preferred because there was no incision and scar formation with high success rates, and a minimally invasive alternative technique.

Catalytic Upgrading of Biomass Pyrolysis Oxygenates with Vacuum Gas Oil Using a Davison Circulating Riser Reactor

DOE PAGES

Jarvis, Mark W.; Olstad, Jessica; Parent, Yves; ...

2018-01-02

We investigate and quantitate the changes in hydrocarbon product composition while evaluating the performance and operability of the National Renewable Energy Laboratory's Davison Circulating Riser (DCR) reactor system when biomass model compounds are cofed with traditional fluid catalyst cracking (FCC) feeds and catalyst: vacuum gas oil (VGO) and equilibrium zeolite catalyst (E-Cat). Three compounds (acetic acid, guaiacol, and sorbitan monooleate) were selected to represent the major classes of oxygenates present in biomass pyrolysis vapors. These vapors can contain 30-50% oxygen as oxygenates, which create conversion complications (increased reactivity and coking) when integrating biomass vapors and liquids into fuel and chemicalmore » processes long dominated by petroleum feedstocks. We used these model compounds to determine the appropriate conditions for coprocessing with petroleum and ultimately pure pyrolysis vapors only as compared with standard baseline conditions obtained with VGO and E-Cat only in the DCR. Model compound addition decreased the DCR catalyst circulation rate, which controls reactor temperature and measures reaction heat demand, while increasing catalyst coking rates. Liquid product analyses included 2-dimensional gas chromatography time-of-flight mass spectroscopy (2D GCxGC TOFS), simulated distillation (SIM DIST), 13C NMR, and carbonyl content. Aggregated results indicated that the model compounds were converted during reaction, and despite functional group differences, product distributions for each model compound were very similar. In addition, we determined that adding model compounds to the VGO feed did not significantly affect the DCR's operability or performance. Future work will assess catalytic upgrading of biomass pyrolysis vapor to fungible hydrocarbon products using upgrading catalysts currently being developed at NREL and at Johnson Matthey.« less

Catalytic Upgrading of Biomass Pyrolysis Oxygenates with Vacuum Gas Oil Using a Davison Circulating Riser Reactor

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

Jarvis, Mark W.; Olstad, Jessica; Parent, Yves

We investigate and quantitate the changes in hydrocarbon product composition while evaluating the performance and operability of the National Renewable Energy Laboratory's Davison Circulating Riser (DCR) reactor system when biomass model compounds are cofed with traditional fluid catalyst cracking (FCC) feeds and catalyst: vacuum gas oil (VGO) and equilibrium zeolite catalyst (E-Cat). Three compounds (acetic acid, guaiacol, and sorbitan monooleate) were selected to represent the major classes of oxygenates present in biomass pyrolysis vapors. These vapors can contain 30-50% oxygen as oxygenates, which create conversion complications (increased reactivity and coking) when integrating biomass vapors and liquids into fuel and chemicalmore » processes long dominated by petroleum feedstocks. We used these model compounds to determine the appropriate conditions for coprocessing with petroleum and ultimately pure pyrolysis vapors only as compared with standard baseline conditions obtained with VGO and E-Cat only in the DCR. Model compound addition decreased the DCR catalyst circulation rate, which controls reactor temperature and measures reaction heat demand, while increasing catalyst coking rates. Liquid product analyses included 2-dimensional gas chromatography time-of-flight mass spectroscopy (2D GCxGC TOFS), simulated distillation (SIM DIST), 13C NMR, and carbonyl content. Aggregated results indicated that the model compounds were converted during reaction, and despite functional group differences, product distributions for each model compound were very similar. In addition, we determined that adding model compounds to the VGO feed did not significantly affect the DCR's operability or performance. Future work will assess catalytic upgrading of biomass pyrolysis vapor to fungible hydrocarbon products using upgrading catalysts currently being developed at NREL and at Johnson Matthey.« less

Pediatric endocanalicular diode laser dacryocystorhinostomy: results of a minimally invasive surgical technique.

PubMed

Uysal, Ismail Onder; Ozçimen, Muammer; Yener, Halil Ibrahim; Kal, Ali

2011-09-01

The purpose of this study was to evaluate the effectiveness of endocanalicular diode laser dacryocystorhinostomy (DCR), which is a minimally invasive surgical technique, in pediatric patients with congenital nasolacrimal duct obstruction (NLDO). A retrospective study was carried out on patients treated between October 2008 and August 2009 for nasolacrimal duct obstruction with an endocanalicular diode laser procedure. Patients diagnosed as having nasolacrimal duct obstruction were included in this study and an endocanalicular diode laser procedure was performed. The main outcome measures were patients' previous treatments, clinical presentation, operative and postoperative complications, postoperative follow-up and resolution of epiphora. Eighteen children (10 girls, 8 boys) with a mean age of 6.11 ± 2.08 years (range, 4-10) underwent 20 endocanalicular laser DCR operations for congenital NLDO. In all eyes (100%), there was a history of epiphora and chronic dacryocystitis; two (10%) presented with acute dacryocystitis. Previous procedures included probing and irrigation of all eyes (100%) and silicone tube intubation in nine eyes (45%). None of the patients underwent any previous DCR operations. During a mean postoperative follow-up period of 20.50 ± 3.24 months (range, 14-24 months), the anatomical success rate (patency of ostium on nasal endoscopy) was 100%, and the clinical success rate (resolution of epiphora) was 85%. Endocanalicular diode laser DCR is an effective treatment modality for pediatric patients with congenital NLDO that compares favorably with the reported success rates of external and endoscopic endonasal DCR. Moreover, it has an added advantage of shorter operative time, less morbidity and avoidance of overnight admission.

Changes in cytokines in tears after endoscopic endonasal dacryocystorhinostomy for primary acquired nasolacrimal duct obstruction.

PubMed

Lee, J K; Kim, T H

2014-05-01

We attempted to compare the cytokine composition of tears between primary acquired nasolacrimal duct (NLD) obstruction and normal controls. We investigated the changes in cytokines in tears after endoscopic endonasal dacryocystorhinostomy (DCR). Eighteen patients underwent endonasal DCR, with seven patients undergoing bilateral DCR, resulting in twenty-five DCRs in total. Eleven contralateral un-operated eyes were used as normal controls. Silicone stents were removed 3 months after surgery. Tear samples were collected from all eyes before surgery, and at 1 month, 2 months, 3 months, and 4 months after surgery. The level of interleukin (IL)-1β, IL-2, IL-6, IL-10, transforming growth factor (TGF)-β2, fibroblast growth factor (FGF)-2, and vascular endothelial growth factor (VEGF) in the tears was measured. The concentrations of IL-2, IL-6, IL-10, VEGF, and FGF-2 were significantly higher in eyes with NLD obstruction than controls before surgery (P=0.006, 0.018, 0.002, 0.048, and 0.039, respectively). Most inflammatory cytokines (IL-1β, IL-2, IL-6, VEGF, and FGF-2) were higher in the tears of the DCR group compared with the controls during the postoperative follow-up, but then rapidly decreased to the level of the controls after removal of the silicone stent. The recurred eyes showed a higher level of TGF-β2 and FGF-2 in tears compared with the eyes that showed good surgical results (P<0.005 and <0.005, respectively). The tear levels of inflammatory cytokines were higher in eyes with NLD obstruction than controls. The changes in cytokine level during the postoperative period showed the importance of cytokine analysis in understanding wound healing after DCR.

Noise characterization of a 512×16 spad line sensor for time-resolved spectroscopy applications

NASA Astrophysics Data System (ADS)

Finlayson, Neil; Usai, Andrea; Erdogan, Ahmet T.; Henderson, Robert K.

2018-02-01

Time-resolved spectroscopy in the presence of noise is challenging. We have developed a new 512 pixel line sensor with 16 single-photon-avalanche (SPAD) detectors per pixel and ultrafast in-pixel time-correlated single photon counting (TCSPC) histogramming for such applications. SPADs are near shot noise limited detectors but we are still faced with the problem of high dark count rate (DCR) SPADs. The noisiest SPADs can be switched off to optimise signal-to-noiseratios (SNR) at the expense of longer acquisition/exposure times than would be possible if more SPADs were exploited. Here we present detailed noise characterization of our array. We build a DCR map for the sensor and demonstrate the effect of switching off the noisiest SPADs in each pixel. 24% percent of SPADs in the array are measured to have DCR in excess of 1kHz, while the best SPAD selection per pixel reduces DCR to 53+/-7Hz across the entire array. We demonstrate that selection of the lowest DCR SPAD in each pixel leads to the emergence of sparse spatial sampling noise in the sensor.

2D dark-count-rate modeling of PureB single-photon avalanche diodes in a TCAD environment

NASA Astrophysics Data System (ADS)

Knežević, Tihomir; Nanver, Lis K.; Suligoj, Tomislav

2018-02-01

PureB silicon photodiodes have nm-shallow p+n junctions with which photons/electrons with penetration-depths of a few nanometer can be detected. PureB Single-Photon Avalanche Diodes (SPADs) were fabricated and analysed by 2D numerical modeling as an extension to TCAD software. The very shallow p+ -anode has high perimeter curvature that enhances the electric field. In SPADs, noise is quantified by the dark count rate (DCR) that is a measure for the number of false counts triggered by unwanted processes in the non-illuminated device. Just like for desired events, the probability a dark count increases with increasing electric field and the perimeter conditions are critical. In this work, the DCR was studied by two 2D methods of analysis: the "quasi-2D" (Q-2D) method where vertical 1D cross-sections were assumed for calculating the electron/hole avalanche-probabilities, and the "ionization-integral 2D" (II-2D) method where crosssections were placed where the maximum ionization-integrals were calculated. The Q-2D method gave satisfactory results in structures where the peripheral regions had a small contribution to the DCR, such as in devices with conventional deepjunction guard rings (GRs). Otherwise, the II-2D method proved to be much more precise. The results show that the DCR simulation methods are useful for optimizing the compromise between fill-factor and p-/n-doping profile design in SPAD devices. For the experimentally investigated PureB SPADs, excellent agreement of the measured and simulated DCR was achieved. This shows that although an implicit GR is attractively compact, the very shallow pn-junction gives a risk of having such a low breakdown voltage at the perimeter that the DCR of the device may be negatively impacted.

Diacerein niosomal gel for topical delivery: development, in vitro and in vivo assessment.

PubMed

El-Say, Khalid M; Abd-Allah, Fathy I; Lila, Ahmed E; Hassan, Abd El-Saboor A; Kassem, Alaa Eldin A

2016-01-01

The purpose of this study was to load diacerein (DCR) in niosomes by applying response surface methodology and incorporate these niosomes in gel base for topical delivery. Box-Behnken design was used to investigate the effect of charge-inducing agent (X1), surfactant HLB (X2) and sonication time (X3) on the vesicle size (Y1), entrapment efficiency (Y2) and cumulative drug released (Y3). DCR niosomal formulations were prepared by thin film hydration method. The optimized formula was incorporated in different gel bases. DCR niosomal gels were evaluated for homogeneity, rheological behavior; in vitro release and pharmacodynamic activity by carrageenan-induced hind paw edema method in the rat compared with DCR commercial gel. The results revealed that the mean vesicle sizes of the prepared niosomes ranged from 7.33 to 23.72 µm and the entrapment efficiency ranged from 9.52% to 58.43% with controlled release pattern over 8 h. DCR niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant, 37.66%, maximum inhibition of edema size in comparison with 20.83% for the commercial gel (p < 0.05). These results recommended the incorporation of DCR niosomes in 3% HPMC for topical application as a potent anti-inflammatory drug for the treatment of osteoarthritis.

Efficacy and safety of iodine-125 radioactive seeds brachytherapy for advanced non-small cell lung cancer-A meta-analysis.

PubMed

Zhang, Wenchao; Li, Jiawei; Li, Ran; Zhang, Ying; Han, Mingyong; Ma, Wei

This meta-analysis was conducted to investigate the efficacy and safety of 125 I brachytherapy for locally advanced non-small cell lung cancer (NSCLC). Trials comparing 125 I brachytherapy with chemotherapy in NSCLC were identified. Meta-analysis was performed to obtain pooled risk ratios for an overall response rate (ORR), disease control rate (DCR) and complications, and pooled hazard ratio for overall survival (OS). Fifteen studies including 1188 cases were included. The pooled result indicated that there were significant differences in ORR, DCR, and OS between 125 I brachytherapy combined with chemotherapy and chemotherapy alone, but no statistic differences in gastrointestinal symptoms, leukopenia, myelosuppression, and hemoglobin reduction. Patients treated with 125 I brachytherapy combined with chemotherapy have a higher relative risk of pneumothorax, bloody sputum, and pneumorrhagia compared with chemotherapy alone. Seeds migration only occurred in the group treated with 125 I brachytherapy. There were significant differences in ORR, DCR, and myelosuppression between 125 I brachytherapy alone and chemotherapy. 125 I brachytherapy combined with chemotherapy can significantly enhance the clinical efficacy and improve the OS of patients with advanced NSCLC without increasing the incidence of complications of chemotherapy. 125 I brachytherapy alone can significantly enhance the clinical efficacy and reduce the incidence of myelosuppression compared with chemotherapy. However, 125 I brachytherapy may cause lung injury. Large sample and higher-quality randomized controlled trials are needed to confirm the pooled results of complications. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

[Clinical Observation of Icotinib Hydrochloride for Advanced Non-small Cell Lung Cancer Patients with EGFR Status Identified].

PubMed

Li, Xi; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Xinyong; Lv, Jialin; Wu, Yuhua; Zhang, Hui; Nong, Jingying; Zhang, Quan; Zhang, Shucai

2015-12-01

Icotinib is the first self-developed small molecular drug in China for targeted therapy of lung cancer. Compared to the other two commercially available epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, icotinib is similar to them in chemical structure, mechanism of activity and therapeutic effects. To explore the efficacy and side effects of icotinib hydrochloride in the treatment of the advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation and wild-type. Patients with advanced NSCLC who were treated with icotinib hydrochloride in Beijing Chest Hospital were retrospective analyzed from March 2009 to December 2014. The clinical data of 124 patients (99 with EGFR mutation and 25 with wild type) with advanced NSCLC were enrolled in this study. The patients' overall objective response rate (ORR) was 51.6 % and the disease control rate (DCR) was 79.8%; The patients with EGFR mutation, ORR was 63.6%, DCR was 93.9%. The ORR was 4.0% and the DCR was 24.0% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 10.5 months and 1.0 month in wild-type patients. The major adverse events were mild skin rash (30.6%) and diarrhea (16.1%). Monotherapy with icotinib hydrochloride is effective and tolerable for the advanced NSCLC EGFR mutation patients.


Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

PubMed

Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

2015-09-03

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.

Damage control: Concept and implementation.

PubMed

Malgras, B; Prunet, B; Lesaffre, X; Boddaert, G; Travers, S; Cungi, P-J; Hornez, E; Barbier, O; Lefort, H; Beaume, S; Bignand, M; Cotte, J; Esnault, P; Daban, J-L; Bordes, J; Meaudre, E; Tourtier, J-P; Gaujoux, S; Bonnet, S

2017-12-01

The concept of damage control (DC) is based on a sequential therapeutic strategy that favors physiological restoration over anatomical repair in patients presenting acutely with hemorrhagic trauma. Initially described as damage control surgery (DCS) for war-wounded patients with abdominal penetrating hemorrhagic trauma, this concept is articulated in three steps: surgical control of lesions (hemostasis, sealing of intestinal spillage), physiological restoration, then surgery for definitive repair. This concept was quickly adapted for intensive care management under the name damage control resuscitation (DCR), which refers to the modalities of hospital resuscitation carried out in patients suffering from traumatic hemorrhagic shock within the context of DCS. It is based mainly on specific hemodynamic resuscitation targets associated with early and aggressive hemostasis aimed at prevention or correction of the lethal triad of hypothermia, acidosis and coagulation disorders. Concomitant integration of resuscitation and surgery from the moment of admission has led to the concept of an integrated DCR-DCS approach, which enables initiation of hemostatic resuscitation upon arrival of the injured person, improving the patient's physiological status during surgery without delaying surgery. This concept of DC is constantly evolving; it stresses management of the injured person as early as possible, in order to initiate hemorrhage control and hemostatic resuscitation as soon as possible, evolving into a concept of remote DCR (RDCR), and also extended to diagnostic and therapeutic radiological management under the name of radiological DC (DCRad). DCS is applied only to the most seriously traumatized patients, or in situations of massive influx of injured persons, as its universal application could lead to a significant and unnecessary excess-morbidity to injured patients who could and should undergo definitive treatment from the outset. DCS, when correctly applied, significantly improves the survival rate of war-wounded. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Decoy receptor 3 down-regulates centrosomal protein 70 kDa specifically in rheumatoid synovial fibroblasts.

PubMed

Fukuda, Koji; Miura, Yasushi; Maeda, Toshihisa; Hayashi, Shinya; Kuroda, Ryosuke

2018-03-01

Decoy receptor 3 (DcR3) competitively binds to Fas ligand, lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (LIGHT) and TNF-like ligand 1A (TL1A), thereby preventing their effects. Using a microarray assay, we previously newly identified centrosomal protein 70 kDa (CEP70) as one of the genes whose expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLS) is reduced by DcR3. Here, we investigated the significance of DcR3 regulation of CEP70 for RA-FLS. Synovial samples were obtained from RA patients who had never been treated with biologics and from osteoarthritis (OA) patients. CEP70 mRNA expression was quantified using RT-qPCR analysis. CEP70 protein expression was assessed using immunohistochemical and western blot analyses. CEP70 was expressed predominantly in the superficial lining layer in RA synovial tissue. CEP70 expression was dose-dependently downregulated by DcR3-Fc in RA-FLS but was not downregulated in OA-FLS. TL1A antibody prevented the DcR3-Fc inhibitory effects on CEP70 expression in RA-FLS. These results indicated that DcR3 reduces CEP70 expression in RA-FLS by binding to membrane-bound TL1A and may suppress RA-FLS proliferation. The reduction in CEP70 expression by DcR3/TL1A signaling may control the hyperplasia of RA synovium.

Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer.

PubMed

Gu, Aiqin; Shi, Chunlei; Xiong, Liwen; Chu, Tianqing; Pei, Jun; Han, Baohui

2013-02-01

To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05). The symptom improvement rate was 57.3% (51/89), and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 (33.7%)] and diarrhea [15/89 (16.9%)]. The level of toxicity was typically low. The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

Decoy receptor 3 polymorphisms are not associated with the risk of esophageal cancer in a Chinese population.

PubMed

Ren, Zhengbing; Zhu, Jingfeng; Gu, Haiyong; Liu, Ruiping; Chen, Suocheng; Rong, Guoxiang; Sun, Bin

2014-06-01

Esophageal cancer (EC) is the sixth most common cancer worldwide, and esophageal squamous-cell carcinoma (ESCC) accounts for more than 90% of ECs. We hypothesized that genetic factors might play an important role in ESCC carcinogenesis. We conducted a hospital-based case-control study to evaluate the association between two single nucleotide polymorphisms of decoy receptor 3 (DcR3), namely, rs2297441 G > A and rs2257440 T > C, on the ESCC risk. In all, 629 ESCC cases and 686 controls were included. Genotypes were determined using the ligation detection reaction method. When the DcR3 rs2297441 GG homozygote genotype was used as the reference group, the GA genotype showed no association with the ESCC risk (GA versus GG: adjusted OR = 1.11, 95% CI = 0.88-1.40, p = 0.396); similarly, even the TT genotype showed no association with the ESCC risk (AA versus GG: adjusted OR = 0.80, 95% CI = 0.55-1.18, p = 0.268). Logistic regression analyses revealed that the DcR3 rs2257440 T > C polymorphism was not associated with the ESCC risk. DcR3 rs2297441 G > A and DcR3 rs2257440 T > C polymorphisms may not contribute to the ESCC risk, and additional, larger studies are required to confirm our results.

Death decoy receptor overexpression and increased malignancy risk in colorectal cancer.

PubMed

Zong, Liang; Chen, Ping; Wang, Da-Xin

2014-04-21

To evaluate human epidermal growth factor receptor 2 (HER2) and death decoy receptor (DcR3) as colorectal cancer prognostic indicators. Colorectal carcinoma specimens from 300 patients were analyzed by immunohistochemistry to detect the staining patterns of HER2 and DcR3. Classification of HER2 staining was carried out using the United States Food and Drug Administration semi-quantitative scoring system, with scores of 0 or 1+ indicating a tumor-negative (normal expression) status and scores of 2+ and 3+ indicating a tumor-positive (overexpression) status. Classification of DcR3 was carried out by quantitating the percentage of positive cells within the stained section, with < 10% indicating a tumor-negative status and ≥ 10% indicating a tumor-positive status. Correlation of the HER2 and DcR3 staining status with clinicopathological parameters [age, sex, tumor size, differentiation, and the tumor, node, metastasis (pTNM) classification] and survival was statistically assessed. Tumor-positive status for HER2 and DcR3 was found in 18.33% and 58.33% of the 300 colorectal carcinoma specimens, respectively. HER2 tumor-positive status showed a significant correlation with tumor size (P = 0.003) but not with other clinicopathological parameters. DcR3 tumor-positive status showed a significant correlation with tumor differentiation (P < 0.001), pTNM stage (P < 0.001), and lymph node metastasis (P < 0.001). However, correlation coefficient analysis did not indicate that a statistically significant correlation exists between tumor-positive status for the HER2 and DcR3 overexpression (P = 0.236). Patients with specimens classified as DcR3-overexpressing had a significantly worse overall survival (OS) rate than those without DcR3 overexpression (median OS: 42.11 vs 61.21 mo; HR = 50.27, 95%CI: 44.90-55.64, P < 0.001). HER2 overexpression had no significant impact on median OS (35.10 mo vs 45.25 mo; HR = 44.40, 95%CI: 39.32-49.48, P = 0.344). However, patients with specimens classified as both HER2- and DcR3-overexpressing had a significantly poorer median OS than those with only HER2 overexpression (31.80 mo vs 52.20 mo; HR = 35.10, 95%CI: 22.04-48.16, P = 0.006). HER2 overexpression is not an independent prognostic marker of colorectal cancer, but DcR3 overexpression is highly correlated with lymph node metastasis and poor OS.

Prognosis of Combining Remaining Teeth and Implants in Double-Crown-Retained Removable Dental Prostheses: A Systematic Review and Meta-Analysis.

PubMed

Lian, Meifei; Zhao, Kai; Feng, Yunzhi; Yao, Qian

The reliability of combining natural teeth and implants in one removable prosthesis is controversial. This systematic review was conducted to evaluate the prognosis of combined tooth/implant-supported double-crown-retained removable dental prostheses (DCR-RDPs) and to compare them with solely implant-supported prostheses with a minimum observation period of 3 years. Electronic database (PubMed, Embase, Central, and SCI) and manual searches up to August 2016 were conducted to identify human clinical studies on tooth/implant-supported DCR-RDPs. Literature selection and data extraction were accomplished by two independent reviewers. Meta-analyses of survival and complication rates were performed separately for combined tooth/implant-supported and solely implant-supported DCRRDPs. Among the initially identified 366 articles, 17 were included in a quantitative analysis. The estimated overall cumulative survival rate (CSR) for implants in combined tooth/implant-supported DCRRDPs was 98.72% (95% confidence interval [95% CI]: 96.98% to 99.82%), and that for implants in solely implant-supported DCR-RDPs was 98.83% (95% CI: 97.45% to 99.75%). The summary CSR for abutment teeth was 92.96% (95% CI: 85.38% to 98.12%). Double-crown-retained dentures with both abutment types showed high CSRs, most of which were approximately 100%. Regarding prosthetic maintenance treatment, the estimated incidence for patients treated with combined tooth/implant-supported RDPs was 0.164 (95% CI: 0.089 to 0.305) per patient per year (T/P/Y) and that for patients restored with solely implant-supported RDPs was 0.260 (95% CI: 0.149 to 0.454) T/P/Y. Based on four studies with combined tooth/implant-supported DCR-RDPs, no intrusion phenomena were encountered. Subject to the limitations of the present review, combining remaining teeth and implants in DCR-RDPs is a reliable and predictable treatment modality for partially edentulous patients. Comparable high survival rates and minor biologic or technical complications are observed for combined tooth/implant-supported and solely implant-supported DCR-RDPs. Due to the heterogeneity of the included studies, the results must be interpreted with caution.

Decoy receptor 3: an endogenous immunomodulator in cancer growth and inflammatory reactions.

PubMed

Hsieh, Shie-Liang; Lin, Wan-Wan

2017-06-19

Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor (TNFR) superfamily member 6b (TNFRSF6B), is a soluble decoy receptor which can neutralize the biological functions of three members of tumor necrosis factor superfamily (TNFSF): Fas ligand (FasL), LIGHT, and TL1A. In addition to 'decoy' function, recombinant DcR3.Fc is able to modulate the activation and differentiation of dendritic cells (DCs) and macrophages via 'non-decoy' action. DcR3-treated DCs skew T cell differentiation into Th2 phenotype, while DcR3-treated macrophages behave M2 phenotype. DcR3 is upregulated in various cancer cells and several inflammatory tissues, and is regarded as a potential biomarker to predict inflammatory disease progression and cancer metastasis. However, whether DcR3 is a pathogenic factor or a suppressor to attenuate inflammatory reactions, has not been discussed comprehensively yet. Because mouse genome does not have DcR3, it is not feasible to investigate its physiological functions by gene-knockout approach. However, DcR3-mediated effects in vitro are determined via overexpressing DcR3 or addition of recombinant DcR3.Fc fusion protein. Moreover, CD68-driven DcR3 transgenic mice are used to investigate DcR3-mediated systemic effects in vivo. Upregulation of DcR3 during inflammatory reactions exerts negative-feedback to suppress inflammation, while tumor cells hijack DcR3 to prevent apoptosis and promote tumor growth and invasion. Thus, 'switch-on' of DcR3 expression may be feasible for the treatment of inflammatory diseases and enhance tissue repairing, while 'switch-off' of DcR3 expression can enhance tumor apoptosis and suppress tumor growth in vivo.

Serum decoy receptor 3, a potential new biomarker for sepsis.

PubMed

Hou, Yan-Qiang; Xu, Ping; Zhang, Mei; Han, Deping; Peng, Liang; Liang, Dong-Yu; Yang, Shanmin; Zhang, Zhenhuan; Hong, Jinsheng; Lou, Xiao-Li; Zhang, Lurong; Kim, Sunghee

2012-04-11

Sepsis, a common deadly systemic infection caused by a variety of pathogens, has some clinical symptoms similar to the systemic inflammatory response syndrome (SIRS), a whole-body non-infectious inflammatory reaction to severe insults, such as burn, trauma, hypotensive shock and so on. Treatment of sepsis depends mainly on anti-microbial, while remedy for SIRS might require steroids that could possibly enhance the spread of microbes. Unfortunately, it is very difficult to distinguish these two completely different serious conditions without blood culture, which takes days to grow and identify causative pathogens. We examined a biomarker, serum decoy receptor 3 (DcR3), was evaluated for its utility in the differential diagnosis between sepsis and SIRS. Serum DcR3 level in 118 healthy controls, 24 sepsis patients and 43 SIRS patients, was quantitatively measured by enzyme-linked immunosorbent assay (ELISA). The serum DcR3 was significantly increased in sepsis patients compared with SIRS patients and healthy controls (6.11±2.58 ng/ml vs 2.62±1.46 ng/ml, and 0.91±0.56 ng/ml, respectively, p<0.001). The areas under the receiver operating characteristic curve of DcR3 for the normal vs. SIRS, normal vs. sepsis and SIRS vs. sepsis were 0.910 (0.870-0.950), 0.992 (0.984-1.000) and 0.896 (0.820-0.973), respectively. In addition, the DcR3 exhibited a positive correlation coefficient with APACHE II score, a most commonly used index for the severity of sepsis (r=0.556, p=0.005). The serum DcR3 has a potential to serve as a new biomarker for sepsis with its high specificity and sensitivity. Copyright © 2012 Elsevier B.V. All rights reserved.

Prospective randomized comparison of mitomycin C application in endoscopic and external dacryocystorhinostomy.

PubMed

Mudhol, Rekha R; Zingade, N D; Mudhol, R S; Harugop, Anil S; Das, Amal T

2013-08-01

The aim of the study is to compare the subjective (relief of symptoms) and objective (endoscopic visualization of ostium patency at the time of syringing) outcomes at the end of two procedures-Endonasal DCR versus External DCR with Mitomycin C and to assess the role of Mitomycin C in maintaining patency of nasolacrimal drainage system. Prospective randomized comparative study was performed. Thirty-five patients were enrolled in each endoscopic and external dacryocystorhinostomy groups with Mitomycin C (MMC) application. The 37 eyes underwent endonasal DCR (28 unilateral primary eyes + 1 bilateral primary eyes + 5 unilateral revision eyes + 1 bilateral revision eye) while 35 eyes underwent external DCR (34 unilateral primary eyes + 1 unilateral revision eye). Mitomycin C 0.2 mg/ml was applied intra-operatively for 5 min to the ostium site at the end of endonasal or external DCR procedure. Objective assessment by syringing at the end of 1 year in the endonasal group showed 35 eyes (94%) were patent, 1 (3%) was partially blocked and 1(3%) was completely blocked; while in external group all 35 eyes (100%) were patent. Endoscopic visualization of the ostium at the time of syringing showed only one eye (3%) in the endonasal group was blocked while all the other eyes in both groups were patent. Both groups had a mean follow-up of 6-36 months. No complications were associated with use of Mitomycin C. In conclusion, intra-operative use of Mitomycin C in both endoscopic DCR and external DCR is safe and effective in increasing the success rate.

Comparison of therapeutic effects of EGFR-tyrosine kinase inhibitors on 19Del and L858R mutations in advanced lung adenocarcinoma and effect on cellular immune function.

PubMed

Zhou, Juan; Ben, Suqin

2018-02-01

We compared the therapeutic effect of EGFR-tyrosine kinase inhibitors (TKIs) on 19Del and L858R mutations in advanced lung adenocarcinoma on cellular immune function and explored the factors influencing the curative effect and prognosis. Clinical efficacy in the selected 71 patients with lung adenocarcinoma, including 52 patients with 19Del and L858R mutations and 19 wild type patients treated with EGFR-TKIs was retrospectively analyzed. The response rate (RR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and cellular immune function were analyzed. The RR, DCR, PFS, and OS of the 19Del group were higher than those of the L858R group; however, there were no statistically significant differences between the groups. χ 2 test results revealed that gender, smoking, and EGFR mutations were associated with DCR. Log-rank analytical results showed that EGFR mutation type was correlated to PFS and OS. Multivariate analysis implied that disease control and mutation type of EGFR were independent prognostic factors of OS. Following TKI treatment, the number of CD3+, CD4+, and NK cells and the CD4+/CD8+ratio increased in both mutation groups; however the results were not statistically significant. There was also no significant difference in the upregulation of immunological function observed, with 46.43% in the 19Del mutation and 45.83% in the L858R mutation group. EGFR 19Del and L858R mutations are good biomarkers for predicting the clinical response of EGFR-TKIs. 19Del mutations may have a better clinical outcome. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Mitomycin-C in dacryocystorhinostomy: From experimentation to implementation and the road ahead: A review.

PubMed

Nair, Akshay Gopinathan; Ali, Mohammad Javed

2015-04-01

Dacryocystorhinostomy (DCR) is the procedure of choice in patients with epiphora due to primary acquired nasolacrimal duct obstruction. The evolution of surgical tools, fiber-optic endoscopes, effective anesthesia techniques, and the adjunct use of antimetabolites intraoperatively; namely mitomycin-C (MMC) have significantly contributed to the advancement of DCR surgery. MMC is a systemic chemotherapeutic agent derived from Streptomyces caespitosus that inhibits the synthesis of DNA, cellular RNA, and protein by inhibiting the synthesis of collagen by fibroblasts. Even the cellular changes in the human nasal mucosal fibroblasts induced by MMC at an ultrastructural level have been documented. There, however, seems to be a lack of consensus regarding MMC: The dosage, the route of delivery/application, the time of exposure and subsequently what role each of these variables plays in the final outcome of the surgery. In this review, an attempt is made to objectively examine all the evidence regarding the role of MMC in DCR. MMC appears to improve the success rate of DCR.

Mitomycin-C in dacryocystorhinostomy: From experimentation to implementation and the road ahead: A review

PubMed Central

Nair, Akshay Gopinathan; Ali, Mohammad Javed

2015-01-01

Dacryocystorhinostomy (DCR) is the procedure of choice in patients with epiphora due to primary acquired nasolacrimal duct obstruction. The evolution of surgical tools, fiber-optic endoscopes, effective anesthesia techniques, and the adjunct use of antimetabolites intraoperatively; namely mitomycin-C (MMC) have significantly contributed to the advancement of DCR surgery. MMC is a systemic chemotherapeutic agent derived from Streptomyces caespitosus that inhibits the synthesis of DNA, cellular RNA, and protein by inhibiting the synthesis of collagen by fibroblasts. Even the cellular changes in the human nasal mucosal fibroblasts induced by MMC at an ultrastructural level have been documented. There, however, seems to be a lack of consensus regarding MMC: The dosage, the route of delivery/application, the time of exposure and subsequently what role each of these variables plays in the final outcome of the surgery. In this review, an attempt is made to objectively examine all the evidence regarding the role of MMC in DCR. MMC appears to improve the success rate of DCR. PMID:26044474

The Effects of Injury Preventive Warm-Up Programs on Knee Strength Ratio in Young Male Professional Soccer Players

PubMed Central

Daneshjoo, Abdolhamid; Mokhtar, Abdul Halim; Rahnama, Nader; Yusof, Ashril

2012-01-01

Purpose We aimed to investigate the effect of FIFA 11+ (11+) and HarmoKnee injury preventive warm-up programs on conventional strength ratio (CSR), dynamic control ratio (DCR) and fast/slow speed ratio (FSR) in young male professional soccer players. These ratios are related to the risk of injury to the knee in soccer players. Methods Thirty-six players were divided into 3 groups; FIFA 11+, HarmoKnee and control (n = 12 per group). These exercises were performed 3 times per week for 2 months (24 sessions). The CSR, DCR and FSR were measured before and after the intervention. Results After training, the CSR and DCR of knee muscles in both groups were found to be lower than the published normal values (0.61, 0.72, and 0.78 during 60°.s−1, 180°.s−1 and 300°.s−1, respectively). The CSR (60°.s−1) increased by 8% and FSR in the quadriceps of the non-dominant leg by 8% in the 11+. Meanwhile, the DCR in the dominant and non-dominant legs were reduced by 40% and 30% respectively in the 11+. The CSR (60°.s−1) in the non-dominant leg showed significant differences between the 11+, HarmoKnee and control groups (p = 0.02). As for the DCR analysis between groups, there were significant differences in the non-dominant leg between both programs with the control group (p = 0.04). For FSR no significant changes were found between groups. Conclusions It can be concluded that the 11+ improved CSR and FSR, but the HarmoKnee program did not demonstrate improvement. We suggest adding more training elements to the HarmoKnee program that aimed to enhance hamstring strength (CSR, DCR and FSR). Professional soccer players have higher predisposition of getting knee injuries because hamstring to quadriceps ratio were found to be lower than the average values. It seems that the 11+ have potentials to improve CSR and FSR as well as prevent knee injuries in soccer players. PMID:23226553

[Clinical effects for patients with recurrent advanced non-small cell lung cancer treated with icotinib hydrochloride].

PubMed

Nong, Jingying; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Hui; Wu, Yuhua; Lv, Jialin; Zhang, Quan; Zhang, Shucai

2013-05-01

Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC). Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. The overall response rate (ORR) was 45.0% and the disease control rate (DCR) was 80.0%. The median progression-free survival (PFS) time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively). RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively). RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, <0.001, 0.002, respectively). There was no statistical difference in RR and PFS between those age<65 and ≥65 or PS<2 and PS≥2. There was no statistical difference in RR and DCR between exon 19 deletion and exon 21 mutations, while the former had much longer PFS (P=0.020). EGFR mutation and exon 19 deletion are the independent prognostic factors to significantly improve the PFS (P=0.009, 0.012, respectively). The side effects were generally mild and consisted of rash and diarrhea. Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

A network meta-analysis on the efficacy of sixteen targeted drugs in combination with chemotherapy for treatment of advanced/metastatic colorectal cancer

PubMed Central

Ba-Sang, Dan-Zeng; Long, Zi-Wen; Teng, Hao; Zhao, Xu-Peng; Qiu, Jian; Li, Ming-Shan

2016-01-01

Objective A network meta-analysis was conducted comparing the short-term efficacies of 16 targeted drugs in combination with chemotherapy for treatment of advanced/metastatic colorectal cancer (CRC). Results Twenty-seven RCTs were ultimately incorporated into this network meta-analysis. Compared with chemotherapy alone, bevacizumab + chemotherapy, panitumumab + chemotherapy and conatumumab + chemotherapy had higher PR rate. Bevacizumab + chemotherapy, cetuximab + chemotherapy, panitumumab + chemotherapy, trebananib + chemotherapy and conatumumab + chemotherapy had higher ORR rate in comparison to chemotherapy alone. Furthermore, bevacizumab + chemotherapy had higher DCR rate than chemotherapy alone. The results of our cluster analysis showed that chemotherapy combined with bevacizumab, cetuximab, panitumumab, conatumumab, ganitumab, or brivanib + cetuximab had better efficacies for the treatment of advanced/metastatic CRC in comparison to chemotherapy alone. Materials and Methods Electronic databases were comprehensively searched for potential and related randomized controlled trials (RCTs). Direct and indirect evidence were incorporated for evaluation of stable disease (SD), progressive disease (PD), complete response (CR), partial response (PR), disease control rate (DCR) and overall response ratio (ORR) by calculating odds ratio (OR) and 95% confidence intervals (CI), and using the surface under the cumulative ranking curve (SUCRA). Conclusions These results indicated that bevacizumab + chemotherapy, panitumumab + chemotherapy, conatumumab + chemotherapy and brivanib + cetuximab + chemotherapy may have better efficacies for the treatment of advanced/metastatic CRC. PMID:27806321

Shoulder Dynamic Control Ratio and Rotation Range of Motion in Female Junior Elite Handball Players and Controls.

PubMed

van Cingel, Robert; Habets, Bas; Willemsen, Linn; Staal, Bart

2018-03-01

To compare glenohumeral range of motion and shoulder rotator muscle strength in healthy female junior elite handball players and controls. Cross-sectional case-control study. Sports medical center. Forty elite female handball players and 30 controls active in nonoverhead sports participated in this study. Passive external rotator (ER), internal rotator (IR), and total range of motion (TROM) of the dominant and nondominant arm were examined with a goniometer. An isokinetic dynamometer was used to evaluate concentric and eccentric rotator muscle strength at 60 and 120 degrees/s with dynamic control ratio (DCR = ERecc:IRcon) as the main outcome parameter. Except for the ER range of motion in the nondominant arm, no significant differences were found between groups for IR, ER of the dominant arm, and the TROM. Within the handball group, the side-to-side difference for IR of the dominant arm was -1.4 degrees. The ER and the TROM of the dominant arm were significantly larger, 6.3 and 4.9 degrees, respectively. For both groups, the DCR values were above 1 and no significant differences were found between the dominant and nondominant arm. The DCR values in the handball group were significantly lower than in the control group. Based on the adopted definitions for muscle imbalance, glenohumeral internal range of motion deficit and TROM deficit our elite female handball players seem not at risk for shoulder injuries. Prospective studies are needed to support the belief that a DCR below 1 places the shoulder at risk for injury.

Decoy Receptor 3 (DcR3) as a Biomarker of Tumor Deterioration in Female Reproductive Cancers: A Meta-Analysis.

PubMed

Jiang, Mengtong; Lin, Xiaomiao; He, Rongquan; Lin, Xinggu; Liang, Lu; Tang, Ruixue; Xiong, Dandan; Wei, Kanglai; Dang, Yiwu; Feng, Zhenbo; Chen, Gang

2016-06-01

BACKGROUND DcR3 (decoy receptor 3) has been proposed be involved in development and prognosis of female reproductive cancers, including cervical cancer, ovarian cancer, and breast cancer. The purpose of this meta-analysis was to explore the evidence for the correlation between DcR3 and the clinicopathological characteristics, as well as the overall survival time, in female reproductive cancers. MATERIAL AND METHODS Relevant studies were searched for in PubMed, Wiley Online Library, Web of Science, Science Direct, Cochrane Central Register of Controlled Trials, Google Scholar, EMBASE, Ovid, LILACS, Chinese CNKI, Chong Qing VIP, Wan Fang, and China Biology Medicine disc up to 30 September 2015. Data on the relationship between DcR3 expression and TNM stage, differentiation, lymph node metastasis, age, and overall survival time were extracted. Pooled odds ratios (ORs) and 95% CIs (confidence intervals) were estimated by forest plot. RESULTS Twelve studies with 1127 patients met the inclusion criteria for this meta-analysis. Overexpression of DcR3 was significantly related to the risk of female reproductive cancers (OR=10.69, 95% CI: 6.33-18.05), TNM stage (OR=5.51, 95% CI: 2.83-10.71), differentiation (OR=4.16, 95% CI: 2.28-7.60), lymph node metastasis (OR=5.89, 95% CI: 3.16-10.9), age (OR=0.85, 95% CI: 0.51-1.44), and overall survival time (OR=1.84, 95% CI: 0.58-5.83). Subgroup analyses showed that overexpression of DcR3 in cervical, ovarian, and breast cancer all had similar relationships with these clinicopathological parameters. CONCLUSIONS Our meta-analysis suggests that overexpression of DcR3 may play vital roles in the tumorigenesis and deterioration of female reproductive cancers. However, the relationship between DcR3 expression and prognosis needs further investigation.

'Decoy' and 'non-decoy' functions of DcR3 promote malignant potential in human malignant fibrous histiocytoma cells.

PubMed

Toda, Mitsunori; Kawamoto, Teruya; Ueha, Takeshi; Kishimoto, Kenta; Hara, Hitomi; Fukase, Naomasa; Onishi, Yasuo; Harada, Risa; Minoda, Masaya; Kurosaka, Masahiro; Akisue, Toshihiro

2013-09-01

Decoy receptor 3 (DcR3) is a soluble secreted protein that belongs to the tumor necrosis factor receptor (TNFR) superfamily. DcR3 inhibits the Fas ligand (FasL)/Fas apoptotic pathway by binding to FasL, competitively with Fas receptor. Previous studies have reported that overexpression of DcR3 has been detected in various human malignancies and that DcR3 functions as a 'decoy' for FasL to inhibit FasL-induced apoptosis. In addition, recent studies have revealed that DcR3 has 'non-decoy' functions to promote tumor cell migration and invasion, suggesting that DcR3 may play important roles in tumor progression by decoy and non-decoy functions. We have previously reported that overexpression of DcR3 was observed in human malignant fibrous histiocytoma (MFH), however, the roles of DcR3 in MFH have not been studied. In the present study, to elucidate the roles of DcR3 in tumor progression of MFH, we examined the effects of DcR3 inhibition on cell apoptosis, migration and invasion in human MFH cells. siRNA knockdown of DcR3 enhanced the FasL-induced apoptotic activity and significantly decreased cell migration and invasion with a decrease in the activation of phosphatidylinositol 3 kinase (PI3K)/Akt and matrix metalloproteinase (MMP)-2. The findings in this study strongly suggest that DcR3 plays important roles in tumor progression of human MFH by decoy as well as non-decoy functions and that DcR3 may serve as a potent therapeutic target for human MFH.

[Outpatient external dacryocystorhinostomy under regional anesthesia and sedation].

PubMed

Benatar-Haserfaty, J; Monleón de la Calle, M P; Sanz-López, A; Muriel García, A

2007-01-01

To assess the rate of early complications of outpatient external dacryocystorhinostomy (DCR) and patient satisfaction with the anesthetic technique. This prospective study enrolled 58 patients undergoing external DCR. We analyzed demographic variables, ASA physical status, level of sedation achieved, postoperative pain, systemic complications, intraoperative bleeding, duration of surgery, time until discharge home, and patient and surgeon satisfaction with the anesthetic technique. The mean (SD) level of satisfaction was 4.85 (0.80) points on the Iowa Satisfaction With Anesthesia Scale (ISAS). A positive association was found between postoperative pain and a lower ISAS score. There was also a positive association between use of rescue analgesia in the early postoperative period and a lower ISAS score. Mean blood loss per procedure was 178.9 (108.2) mL. The rate of minor systemic complications was 15.5%. The surgeon's rating of conditions in the surgical field was excellent or good in 89.6% of the cases. External DCR can be performed on an outpatient basis within a reasonable safety margin and with a low early postoperative complication rate. Patient satisfaction with anesthesia was high. Provision of preoperative information about the meaning of sedation, postoperative analgesia, and surgical bleeding are aspects to improve in this practice setting.

Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients

PubMed Central

Shen, Sipeng; Shi, Qianwen; Bai, Jianling; Li, Jin; Qin, Shukui; Yu, Hao; Chen, Feng

2017-01-01

Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis. PMID:27793017

Therapeutic effect of apatinib on overall survival is mediated by prolonged progression-free survival in advanced gastric cancer patients.

PubMed

Huang, Lihong; Wei, Yongyue; Shen, Sipeng; Shi, Qianwen; Bai, Jianling; Li, Jin; Qin, Shukui; Yu, Hao; Chen, Feng

2017-04-25

Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis.

Memory is Not Enough: The Neurobiological Substrates of Dynamic Cognitive Reserve.

PubMed

Serra, Laura; Bruschini, Michela; Di Domenico, Carlotta; Gabrielli, Giulia Bechi; Marra, Camillo; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

2017-01-01

Changes in the residual memory variance are considered as a dynamic aspect of cognitive reserve (d-CR). We aimed to investigate for the first time the neural substrate associated with changes in the residual memory variance overtime in patients with amnestic mild cognitive impairment (aMCI). Thirty-four aMCI patients followed-up for 36 months and 48 healthy elderly individuals (HE) were recruited. All participants underwent 3T MRI, collecting T1-weighted images for voxel-based morphometry (VBM). They underwent an extensive neuropsychological battery, including six episodic memory tests. In patients and controls, factor analyses were used on the episodic memory scores to obtain a composite memory score (C-MS). Partial Least Square analyses were used to decompose the variance of C-MS in latent variables (LT scores), accounting for demographic variables and for the general cognitive efficiency level; linear regressions were applied on LT scores, striping off any contribution of general cognitive abilities, to obtain the residual value of memory variance, considered as an index of d-CR. LT scores and d-CR were used in discriminant analysis, in patients only. Finally, LT scores and d-CR were used as variable of interest in VBM analysis. The d-CR score was not able to correctly classify patients. In both aMCI patients and HE, LT1st and d-CR scores showed correlations with grey matter volumes in common and in specific brain areas. Using CR measures limited to assess memory function is likely less sensitive to detect the cognitive decline and predict the evolution of Alzheimer's disease. In conclusion, d-CR needs a measure of general cognition to identify conversion to Alzheimer's disease efficiently.

Serum decoy receptor 3 is a useful predictor for the active status of chronic hepatitis B in hepatitis B e antigen-negative patients.

PubMed

Hou, Yanqiang; Xu, Ping; Lou, Xiaoli; Liang, Dongyu; Zhang, Mei; Zhang, Zhenhuan; Zhang, Lurong

2013-08-01

Hepatitis B virus (HBV) infection is a global public health problem, because patients with chronic hepatitis B (CHB) may progress to liver cirrhosis and eventually evolve into hepatocellular carcinoma. Decoy receptor 3 (DcR3) is a soluble receptor of the tumor necrosis factor receptor superfamily, and has been implicated in anti-apoptotic and anti-inflammatory pathways. In this study, we explored the clinical value of serum DcR3 in predicting the active status of CHB in hepatitis B e antigen-negative patients (active HBeAg (-) CHB), which was determined with ELISA. The serum level of DcR3 in active HBeAg (-) CHB patients (1.92 ± 0.68 ng/ml) was higher than that in healthy controls (0.80 ± 0.25 ng/ml, p < 0.0001) and that in inactive status of HBeAg (-) CHB (inactive hepatitis B surface antigen carrier, HBsAg-IaC) patients (0.95 ± 0.26 ng/ml, p < 0.0001). DcR3 level was correlated with HBV DNA level (r = 0.819, p < 0.0001) and alanine transaminase level (ALT, r = 0.704, p < 0.0001) in active HBeAg (-) CHB patients. The area under the Receiver Operating Characteristics curve of DcR3 for detecting the active status of HBeAg (-) CHB patients was 0.914 (95% confidence interval, 0.851-0.977). The optimal cut-off value for DcR3 to predict active HBeAg (-) CHB was 1.22 ng/ml, which had a sensitivity of 87.5% and a specificity of 84.4%. These results suggest that serum DcR3 level may be useful for detecting HBeAg (-) CHB in the active stage, which requires medical treatment.

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC.

PubMed

Liu, Yan-Ping; Zhu, Hui-Fang; Liu, Ding-Li; Hu, Zhi-Yan; Li, Sheng-Nan; Kan, He-Ping; Wang, Xiao-Yan; Li, Zu-Guo

2016-11-22

Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.

Decoy receptor 3 expression in esophageal squamous cell carcinoma: correlation with tumour invasion and metastasis.

PubMed

Xiong, Gang; Guo, Hong; Ge, Xiaodong; Xu, Xueqing; Yang, Xiaoya; Yang, Kang; Jiang, Yaoguang; Bai, Yun

2011-03-01

Decoy receptor 3 (DcR3) is a soluble receptor, which can bind to and inactivate the apoptosis-inducing ligands. We studied a possible association between DcR3 expression and clinicopathologic features in patients with esophageal squamous cell carcinoma (ESCC). The mRNA expression of DcR3 was examined by RT-PCR in 109 primary ESCC patients. For the 52 pairs of DcR3 positive tissues, the protein expression was determined by immunohistochemistry. There was a strong correlation among DcR3 mRNA expression and tumor invasion (P=0.01) and lymph node metastasis (P=0.036). We also found that there was a correlation between DcR3 overexpression with lymph node metastasis (P=0.014) in 52 pairs of DCR3 mRNA positive tissues. Our finding suggested that the overexpression of DcR3 is significantly related with ESCC clinical staging. DcR3 might be a candidate as a tumor specific biomarker for ESCC.

Quantum key distribution over a 72 dB channel loss using ultralow dark count superconducting single-photon detectors.

PubMed

Shibata, Hiroyuki; Honjo, Toshimori; Shimizu, Kaoru

2014-09-01

We report the first quantum key distribution (QKD) experiment over a 72 dB channel loss using superconducting nanowire single-photon detectors (SSPD, SNSPD) with the dark count rate (DCR) of 0.01 cps. The DCR of the SSPD, which is dominated by the blackbody radiation at room temperature, is blocked by introducing cold optical bandpass filter. We employ the differential phase shift QKD (DPS-QKD) scheme with a 1 GHz system clock rate. The quantum bit error rate (QBER) below 3% is achieved when the length of the dispersion shifted fiber (DSF) is 336 km (72 dB loss), which is low enough to generate secure keys.

DcR3 binds to ovarian cancer via heparan sulfate proteoglycans and modulates tumor cells response to platinum with corresponding alteration in the expression of BRCA1

PubMed Central

2012-01-01

Background Overcoming platinum resistance is a major obstacle in the treatment of Epithelial Ovarian Cancer (EOC). In our previous work Decoy Receptor 3 (DcR3) was found to be related to platinum resistance. The major objective of this work was to define the cellular interaction of DcR3 with EOC and to explore its effects on platinum responsiveness. Methods We studied cell lines and primary cultures for the expression of and the cells ability to bind DcR3. Cells were cultured with DcR3 and then exposed to platinum. Cell viability was determined by MTT assay. Finally, the cells molecular response to DcR3 was studied using real time RT-PCR based differential expression arrays, standard RT-PCR, and Western blot. Results High DcR3 in the peritoneal cavity of women with EOC is associated with significantly shorter time to first recurrence after platinum based therapy (p = 0.02). None-malignant cells contribute DcR3 in the peritoneal cavity. The cell lines studied do not secrete DcR3; however they all bind exogenous DcR3 to their surface implying that they can be effected by DcR3 from other sources. DcR3s protein binding partners are minimally expressed or negative, however, all cells expressed the DcR3 binding Heparan Sulfate Proteoglycans (HSPGs) Syndecans-2, and CD44v3. DcR3 binding was inhibited by heparin and heparinase. After DcR3 exposure both SKOV-3 and OVCAR-3 became more resistant to platinum with 15% more cells surviving at high doses. On the contrary CaOV3 became more sensitive to platinum with 20–25% more cell death. PCR array analysis showed increase expression of BRCA1 mRNA in SKOV-3 and OVCAR-3 and decreased BRCA1 expression in CaOV-3 after exposure to DcR3. This was confirmed by gene specific real time PCR and Western blot analysis. Conclusions Non-malignant cells contribute to the high levels of DcR3 in ovarian cancer. DcR3 binds readily to EOC cells via HSPGs and alter their responsiveness to platinum chemotherapy. The paradoxical responses seen were related to the expression pattern of HSPGs available on the cells surface to interact with. Although the mechanism behind this is not completely known alterations in DNA repair pathways including the expression of BRCA1 appear to be involved. PMID:22583667

Fiber-coupled superconducting nanowire single-photon detectors integrated with a bandpass filter on the fiber end-face

NASA Astrophysics Data System (ADS)

Zhang, W. J.; Yang, X. Y.; Li, H.; You, L. X.; Lv, C. L.; Zhang, L.; Zhang, C. J.; Liu, X. Y.; Wang, Z.; Xie, X. M.

2018-07-01

Superconducting nanowire single-photon detectors (SNSPDs) with both high system detection efficiency (SDE) and low dark count rate (DCR) play significant roles in quantum information processes and various applications. The background dark counts of SNSPDs originate from the room temperature blackbody radiation coupled to the device via a fiber. Therefore, a bandpass filter (BPF) operated at low temperature with minimal insert loss is necessary to suppress the background DCR. Herein, a low-loss BPF integrated on a single-mode fiber end-face was designed, fabricated and verified for the low temperature implement. The fiber end-face BPF was featured with a typical passband width about 40 nm in the 1550 nm telecom band and a peak transmittance of over 0.98. SNSPD with high SDE fabricated on a distributed Bragg reflector was coupled to the BPF. The device with such a BPF showed an SDE of 80% at a DCR of 0.5 Hz, measured at 2.1 K. Compared the same device without a BPF, the DCR was reduced by over 13 dB with an SDE decrease of <3%.

[Clinical observation of icotinib hydrochloride in first-line therapy for pulmonary adenocarcinoma].

PubMed

Yang, Xinjie; Zhang, Hui; Qin, Na; Li, Xi; Nong, Jingying; Lv, Jialin; Wu, Yuhua; Zhang, Quan; Zhang, Shucai

2013-07-01

It has been proven that icotinib hydrochloride, as a molecule targeted drug, can be safely and efficiently used to treat advanced non-small cell lung cancer (NSCLC) for second-line or third-line. This research was aimed to investigate the efficacy and toxicity of icotinib hydrochloride as the first-line therapy for pulmonary adenocarcinoma. Among the 56 patients, the tumor objective response rate (ORR) and disease control rate (DCR) was 46.4% (26/56) and 78.6% (46/56), respectively. Among the 20 patients with EGFR analyses, 18 patients were positive for a mutation, ORR was 66.7% (12/18), DCR was 94.4% (17/18) respectively. The ORR with no history of smoke. EGFR positive mutation and appearance of rash were significantly higher than those with smoker, wild type EGFR, no information about EGFR and no appearance of rash (P<0.05). The most common drug-related adverse events were mild skin rash (28.5%) and diarrhea (12%). Single agent treatment with icotinib hydrochloride is effective and tolerable in first-line therapy for pulmonary adenocarcinoma, especially with EGFR mutation.

The soluble Decoy Receptor 3 is regulated by a PI3K-dependent mechanism and promotes migration and invasion in renal cell carcinoma.

PubMed

Weissinger, Daniel; Tagscherer, Katrin E; Macher-Göppinger, Stephan; Haferkamp, Axel; Wagener, Nina; Roth, Wilfried

2013-10-10

Overexpression of Decoy Receptor 3 (DcR3), a soluble member of the tumor necrosis factor receptor superfamily, is a common event in several types of cancer. In renal cell carcinoma (RCC), DcR3 overexpression is associated with lymph node and distant metastasis as well as a poor prognosis. However, the functional role and regulation of DcR3 expression in RCC is so far unknown. Modulation of DcR3 expression by siRNA and ectopic gene expression, respectively, was performed in ACHN and 769-P RCC cell lines. Functional effects of a modulated DcR3 expression were analyzed with regard to migration, invasion, adhesion, clonogenicity, and proliferation. Furthermore, quantitative RT-PCR and immunoblot analyses were performed to evaluate the expression of downstream mediators of DcR3. In further experiments, luciferase assays, quantitative RT-PCR and immunoblot analyses were applied to study the regulation of DcR3 expression in RCC. Additionally, an ex vivo tissue slice culture technique combined with immunohistochemistry was used to study the regulation of DcR3 expression in human RCC specimens. Here, we show that DcR3 promotes adhesion, migration and invasiveness of RCC cells. The DcR3-dependent increase in cellular invasiveness is accompanied with an up-regulation of integrin alpha 4, matrixmetalloproteinase 7 and urokinase plasminogen activator (uPA). Further, we identified a signaling pathway regulating DcR3 expression in RCC. Using in vitro experiments as well as an ex vivo RCC tissue slice culture model, we demonstrate that expression of DcR3 is regulated in a PI3K/AKT-dependent manner involving the transcription factor nuclear factor of activated T-cells (NFAT). Taken together, our results identify DcR3 as a key driver of tumor cell dissemination and suggest DcR3 as a promising target for rational therapy of RCC.

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC

PubMed Central

Hu, Zhi-Yan; Li, Sheng-Nan; Kan, He-Ping; Wang, Xiao-Yan; Li, Zu-Guo

2016-01-01

Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells. PMID:27764793

Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis.

PubMed

Liang, DongYu; Hou, YanQiang; Lou, XiaoLi; Chen, HongWei

2015-01-01

Unbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP)-induced sepsis in mice. C57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation. Our results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05). Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis. Treatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis.

Bicanalicular Silicone Stents in Endonasal Dacryocystorhinostomy: Results of a Randomized Clinical Trial.

PubMed

Fayers, Tessa; Dolman, Peter J

2016-10-01

To assess whether the use of silicone lacrimal stents affects the long-term success of endonasal dacryocystorhinostomy (EN-DCR). Prospective, randomized, controlled, interventional trial. The subjects were adult patients older than 16 years undergoing primary EN-DCR for nasolacrimal duct obstruction who gave fully informed consent and who had no lid malpositions or canalicular pathology. In cases with bilateral surgery, only the right eyes were studied. Participants were randomized to receive stents (control group) or not (study group). Standardized nonendoscopic EN-DCR was performed by the senior author in all cases. When the ostium was completed, the randomization code was revealed as to whether a lacrimal stent was placed or not. Follow-up assessments were made at 3, 6, 9, and 12 months. Stents were removed at 3 months. The primary end point was symptoms of epiphora at 12 months, reported to the surgical booking clerk as (a) resolved, (b) significantly improved, (c) partially improved, or (d) no change or worse. The secondary end point was anatomic patency based on nasolacrimal syringing and categorized as (a) fully patent, minimal, or no reflux; (b) >50% patent but some reflux; (c) some patency but >50% reflux; or (d) nonpatent, 100% reflux. Complete success was defined as having resolved or significantly improved symptoms of watering and minimal or no reflux on nasolacrimal syringing. Partial success was defined as symptoms partially improved with a combination of patency and reflux on syringing. Failure was categorized as no change or worse symptoms of watering and 50% to 100% reflux on syringing. A total of 300 patients completed 12 months of follow-up. A total of 152 patients received tubes, and 148 patients did not. Overall success both subjectively and objectively was 94.7% in the stented group and 87.8% in the nonstented group (P = 0.034, Pearson chi-square 1-tailed test). The most common complications of stents included canalicular cheese-wiring and tube prolapse in approximately 4% each. There is a statistically significantly higher success rate in EN-DCR surgery with tubes compared with no tubes. The failure rate in this study was more than twice as high when tubes were not used (12.2% vs. 5.3%). Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The immunomodulator decoy receptor 3 improves locomotor functional recovery after spinal cord injury.

PubMed

Chiu, Chuan-Wen; Huang, Wen-Hung; Lin, Shao-Ji; Tsai, May-Jywan; Ma, Hsu; Hsieh, Shie-Liang; Cheng, Henrich

2016-06-17

Spinal cord injury (SCI) causes loss of neurons and axons and results in motor and sensory function impairments. SCI elicits an inflammatory response and induces the infiltration of immune cells, predominantly macrophages, to the injured site. Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member (TNFRSF)-6B, is a pleiotropic immunomodulator capable of inducing macrophage differentiation into the M2 phenotype and enhancing angiogenesis. Because M2 macrophages are crucial for the recovery of impaired motor functions, we ask whether DcR3 is beneficial for the functional recovery of locomotion in Sprague-Dawley (SD) rats after SCI. Contusion injury of the spinal cord was performed using a New York University impactor at the ninth thoracic vertebrae, followed by intrathecal injection of 15 μg recombinant protein comprising DcR3 (DcR3.Fc) in 5 μl of normal saline as the treatment, or 5 μl of normal saline as the control, into the injury epicenter. Functional recovery was evaluated using an open-field test weekly up to 6 weeks after injury. The cavity size and myelin sparing in the rostral-to-caudal region, including the epicenter of the injury, were then examined in SCI rats by histological staining. The expression of anti-inflammatory cytokines and the presence of M2 macrophages were determined by quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry at 7 day after SCI. Statistical analysis was performed using a two-tailed Student's t test. Intrathecal administration of DcR3.Fc significantly improved locomotor function and reduced secondary injury with a smaller wound cavity and increased myelin sparing at the lesion site. Compared with the control group, DcR3.Fc-treated rats had increased vascularization at the injury epicenter along with higher levels of interleukin (IL)-4 and IL-10 and lower level of IL-1β on DcR3.Fc-treated rats at day 7 after SCI. Moreover, higher levels of arginase I (Arg I) and CD206 (M2 macrophage markers) and RECA-1 (endothelial marker) were observed in the epicenter on day 7 after SCI by immunofluorescence staining. These results indicated that DcR3.Fc may promote the M2 macrophage infiltration and enhanced angiogenesis at the lesion site, thus preserving a greater amount of spinal cord tissues and enhancing functional recovery after SCI.

WSJointInv2D-MT-DCR: An efficient joint two-dimensional magnetotelluric and direct current resistivity inversion

NASA Astrophysics Data System (ADS)

Amatyakul, Puwis; Vachiratienchai, Chatchai; Siripunvaraporn, Weerachai

2017-05-01

An efficient joint two-dimensional direct current resistivity (DCR) and magnetotelluric (MT) inversion, referred to as WSJointInv2D-MT-DCR, was developed with FORTRAN 95 based on the data space Occam's inversion algorithm. Our joint inversion software can be used to invert just the MT data or the DCR data, or invert both data sets simultaneously to get the electrical resistivity structures. Since both MT and DCR surveys yield the same resistivity structures, the two data types enhance each other leading to a better interpretation. Two synthetic and a real field survey are used here to demonstrate that the joint DCR and MT surveys can help constrain each other to reduce the ambiguities occurring when inverting the DCR or MT alone. The DCR data increases the lateral resolution of the near surface structures while the MT data reveals the deeper structures. When the MT apparent resistivity suffers from the static shift, the DCR apparent resistivity can serve as a replacement for the estimation of the static shift factor using the joint inversion. In addition, we also used these examples to show the efficiency of our joint inversion code. With the availability of our new joint inversion software, we expect the number of joint DCR and MT surveys to increase in the future.

DcR3, a new biomarker for sepsis, correlates with infection severity and procalcitonin.

PubMed

Gao, Liqin; Yang, Bin; Zhang, Hairong; Ou, Qishui; Lin, Yulan; Zhang, Mei; Zhang, Zhenhuan; Kim, Sunghee; Wu, Bing; Wang, Zeng; Fu, Lengxi; Lin, Jingan; Chen, Ruiqing; Lan, Ruilong; Chen, Junying; Chen, Wei; Chen, Long; Zhang, Hengshan; Han, Deping; Chen, Jingrong; Okunieff, Paul; Lin, Jianhua; Zhang, Lurong

2018-02-16

Early diagnosis of sepsis is critical for successful treatment. The clinical value of DcR3 in early diagnosis of sepsis was determined in a dynamic follow-up study. Alterations in plasma levels of DcR3, PCT, CRP, and IL-6 were measured by ELISA and compared among patients with sepsis ( n = 134), SIRS ( n = 60) and normal adults ( n = 50). Correlations and dynamic patterns among the biomarkers, APACHE II scores, clinical outcomes, and pathogens were also examined. Plasma DcR3 was significantly increased in sepsis compared to SIRS and normal adults (median 3.87 vs. 1.28 and 0.17 ng/ml). The elevated DcR3 could be detected in 97.60% sepsis patients 1-2 days prior to the result of blood culture reported. For diagnosis of sepsis, the sensitivity was 97.69% and specificity 98.04%; and for differential diagnosis of sepsis from SIRS, the sensitivity was 90.77% and specificity 98.40%. DcR3 level was positively correlated with severity of sepsis ( r s = 0.82). In 41 patients who died of sepsis, DcR3 elevated as early as 1-2 days before blood culture and peaked on day 3 after blood culture performed. In 90% of sepsis patients, the dynamic alteration pattern of DcR3 was identical to that of PCT, while pattern of 10% patients differed in which clinical data was consistent with DcR3. In 13% sepsis patients, while PCT remained normal, DcR3 levels were at a high level. DcR3 levels had no difference among various pathogens infected. DcR3, a new biomarker, will aid in early diagnosis of sepsis and monitoring its outcome, especially when sepsis patients were PCT negative.

Postnatal Ablation of POMC Neurons Induces an Obese Phenotype Characterized by Decreased Food Intake and Enhanced Anxiety-Like Behavior

PubMed Central

Greenman, Yona; Drori, Yonat; Asa, Sylvia L.; Navon, Inbal; Forkosh, Oren; Gil, Shosh; Stern, Naftali

2013-01-01

Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus are central components of systems regulating appetite and energy homeostasis. Here we report on the establishment of a mouse model in which the ribonuclease III ribonuclease Dicer-1 has been specifically deleted from POMC-expressing neurons (POMCΔDCR), leading to postnatal cell death. Mice are born phenotypically normal, at the expected genetic ratio and with normal hypothalamic POMC-mRNA levels. At 6 weeks of age, no POMC neurons/cells could be detected either in the arcuate nucleus or in the pituitary of POMCΔDCR mice. POMCΔDCR develop progressive obesity secondary to decreased energy expenditure but unrelated to food intake, which was surprisingly lower than in control mice. Reduced expression of AgRP and ghrelin receptor in the hypothalamus and reduced uncoupling protein 1 expression in brown adipose tissue can potentially explain the decreased food intake and decreased heat production, respectively, in these mice. Fasting glucose levels were dramatically elevated in POMCΔDCR mice and the glucose tolerance test revealed marked glucose intolerance in these mice. Secondary to corticotrope ablation, basal and stress-induced corticosterone levels were undetectable in POMCΔDCR mice. Despite this lack of activation of the neuroendocrine stress response, POMCΔDCR mice exhibited an anxiogenic phenotype, which was accompanied with elevated levels of hypothalamic corticotropin-releasing factor and arginine-vasopressin transcripts. In conclusion, postnatal ablation of POMC neurons leads to enhanced anxiety and the development of obesity despite decreased food intake and glucocorticoid deficiency. PMID:23676213

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

Zhang, Yi; Li, Dechun; Zhao, Xin

Resistance to Fas Ligand (FasL) mediated apoptosis plays an important role in tumorigenesis. Decoy receptor 3 (DcR3) is reported to interact with FasL and is overexpressed in some malignant tumors. We sought to investigate the role of DcR3 in resistance to FasL in pancreatic cancer. We compared expression of apoptosis related genes between FasL-resistant SW1990 and FasL-sensitive Patu8988 pancreatic cell lines by microarray analysis. We explored the impact of siRNA knockdown of, or exogenous supplementation with, DcR3 on FasL-induced cell growth inhibition in pancreatic cancer cell lines and expression of proteins involved in apoptotic signaling. We assessed the level ofmore » DcR3 protein and ERK1/2 phosphorylation in tumor and non-tumor tissue samples of 66 patients with pancreatic carcinoma. RNAi knockdown of DcR3 expression in SW1990 cells reduced resistance to FasL-induced apoptosis, and supplementation of Patu8988 with rDcR3 had the opposite effect. RNAi knockdown of DcR3 in SW1990 cells elevated expression of caspase 3, 8 and 9, and reduced ERK1/2 phosphorylation (P < 0.05), but did not alter phosphorylated-Akt expression. 47 tumor tissue specimens, but only 15 matched non-tumor specimens stained for DcR3 (χ{sup 2} = 31.1447, P < 0.001). The proliferation index of DcR3 positive specimens (14.26  ±  2.67%) was significantly higher than that of DcR3 negative specimens (43.58  ±  7.88%, P < 0.01). DcR3 expression positively correlated with p-ERK1/2 expression in pancreatic cancer tissues (r = 0.607, P < 0.001). DcR3 enhances ERK1/2 phosphorylation and opposes FasL signaling in pancreatic cancer cells. - Highlights: • We investigated the role of DcR3 in FasL resistance in pancreatic cancer. • Knockdown of DcR3 in SW1990 cells reduced resistance to FasL-induced apoptosis. • DcR3 knockdown also elevated caspase expression, and reduced ERK1/2 phosphorylation. • Tumor and non-tumor tissues were collected from 66 pancreatic carcinoma patients. • 47 tumor tissue specimens, but only 15 matched non-tumor specimens contained DcR3.« less

Damage control resuscitation: history, theory and technique

PubMed Central

Ball, Chad G.

2014-01-01

Damage control resuscitation (DCR) represents the natural evolution of the initial concept of damage control surgery. It currently includes early blood product transfusion, immediate arrest and/or temporization of ongoing hemorrhage (i.e., temporary intravascular shunts and/or balloon tamponade) as well as restoration of blood volume and physiologic/hematologic stability. As a result, DCR addresses the early coagulopathy of trauma, avoids massive crystalloid resuscitation and leaves the peritoneal cavity open when a patient approaches physiologic exhaustion without improvement. This concept also applies to severe injuries within anatomical transition zones as well as extremities. This review will discuss each of these concepts in detail. PMID:24461267

Correlation of Hypertension and Proteinuria with Outcome in Elderly Bevacizumab-Treated Patients with Metastatic Colorectal Cancer

PubMed Central

Feliu, Jaime; Salud, Antonieta; Safont, Maria J.; García-Girón, Carlos; Aparicio, Jorge; Losa, Ferran; Bosch, Carlos; Escudero, Pilar; Casado, Enrique; Jorge, Monica; Bohn, Uriel; Pérez-Carrión, Ramon; Carmona, Alberto; Custodio, Ana B.; Maurel, Joan

2015-01-01

Background Studies suggest a relationship between hypertension and outcome in bevacizumab-treated patients with metastatic colorectal cancer (mCRC). We performed a retrospective analysis of two phase II studies (BECA and BECOX) to determine if hypertension and proteinuria predict outcome in elderly patients with mCRC treated with bevacizumab. Patients and Methods Patients ≥70 years of age received either capecitabine 1250 mg/m2 bid days 1–14 + bevacizumab 7.5 mg/kg day 1 every 21 days (BECA study) or capecitabine 1000 mg/m2 bid days 1–14 with bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 day 1 (BECOX study). The primary objective was to correlate hypertension and proteinuria with overall response rate (ORR), time to progression (TTP) and overall survival (OS). Secondary objectives included identification of risk factors associated with the development of hypertension and proteinuria and determining whether development of hypertension or proteinuria in the first 2 cycles was related to ORR, disease-control rate (DCR), TTP or OS. Results In total, 127 patients (median age 75.5 years) were included in the study. Hypertension correlated with DCR and OS; proteinuria correlated with ORR and DCR. Proteinuria or hypertension in the first 2 cycles did not correlate with efficacy. Risk factors for hypertension were female gender (odds ratio [OR] 0.241; P = 0.011) and more bevacizumab cycles (OR 1.112; P = 0.002); risk factors for proteinuria were diabetes (OR 3.869; P = 0.006) and more bevacizumab cycles (OR 1.181; P<0.0001). Multivariate analysis identified as having prognostic value: baseline lactate dehydrogenase, haemoglobin, number of metastatic lesions and DCR. Conclusion This analysis of two phase II studies suggests that hypertension is significantly correlated with OS but not with ORR and TTP, whereas proteinuria is correlated with ORR but not with OS and TTP. Both hypertension and proteinuria are associated with the duration of bevacizumab treatment and do not represent an independent prognostic factor. PMID:25602286

Serum decoy receptor 3 level: a predictive marker for nodal metastasis and survival among oral cavity cancer patients.

PubMed

Tu, Hsi-Feng; Liu, Chung-Ji; Liu, Shyun-Yeu; Chen, Yu-Ping; Yu, En-Hao; Lin, Shu-Chun; Chang, Kuo-Wei

2011-03-01

Validating markers for prediction of nodal metastasis could be beneficial in treatment of oral cavity cancer. Decoy receptor 3 (DcR3), locus on 20q13, functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor (TNFR) family. This study analyzed the serum level of DcR3 in relationship to the clinical parameters of oral cavity cancer patients together with detection of DcR3 genomic copy number in primary and recurrent tumors. Elevated serum DcR3 was associated with nodal metastasis and worse prognosis. Gain of DcR3 copy number was detected in 17% of primary tumor tissue but not found in healthy areca chewers. Tissue from recurrent tumors showed more frequent DcR3 copy number alteration (48%) than the paired primary tumor tissue. Serum DcR3 level is a predictor for the nodal metastasis and survival among oral cavity cancer patients and the DcR3 copy number alteration could underlie oral carcinogenesis progression. Copyright © 2010 Wiley Periodicals, Inc.

Silencing of decoy receptor 3 (DcR3) expression by siRNA in pancreatic carcinoma cells induces Fas ligand-mediated apoptosis in vitro and in vivo.

PubMed

Zhou, Jian; Song, Shiduo; He, Songbin; Wang, Zhenxin; Zhang, Bing; Li, Dechun; Zhu, Dongming

2013-09-01

Decoy receptor 3 (DcR3) is abundantly expressed in human tumors and protects cells from a wide range of apoptotic stimuli. In this study, we demonstrate that DcR3 is overexpressed in pancreatic carcinoma cells, and that the pancreatic carcinoma cell lines, Panc-1 and SW1990, are resistant to Fas ligand (FasL)-mediated apoptosis. To further define the function of DcR3 in cell growth and apoptosis, we used small interfering RNA (siRNA) to knockdown the expression of the DcR3 gene in Panc-1 and SW1990 cells. Our results revealed that the silencing of DcR3 expression enhanced the inhibitory effects of FasL and reduced the capabiltiy of the cells for proliferation and colony formation in vitro. In addition, the downregulation of DcR3 modulated the cell apoptotic regulators, Fas-associated death domain (FADD), caspase‑3 and caspase‑8, thus triggering cell apoptosis. Furthermore, the knockdown of DcR3 inhibited the growth of Panc-1 tumor xenografts. Taken together, our findings indicate that DcR3 is important in cancer progression and may be a used as a potential therapeutic target for the gene therapy of pancreatic carcinoma.

Decoy receptor 3 alleviates hepatic fibrosis through suppressing inflammation activated by NF-κB signaling pathway.

PubMed

Jin, Zhenjing; Liu, Siqi; Zhang, Qian; Shao, Xue; Ma, Jingting; Pan, Liulan

2018-03-20

Hepatic fibrosis is a reversible pathological process. Inflammatory responses are the prevailing reactions during hepatic fibrosis. Decoy receptor 3 (DcR3) has been reported to have an anti-inflammatory effect. The aim of the study was to investigate the preventive effects of DcR3 on hepatic fibrosis. Hepatic fibrosis was induced in rats by administering intraperitoneally (ip.) 1% dimethylnitrosamine (DMN). DcR3 plasmid was delivered into rats by intravenous injection. After 4 weeks, the expression of DcR3, TNF-like molecule 1A (TL1A) and α-SMA of the liver tissue were checked. The levels of inflammatory cytokines such as TNF-α, IL-6 and IL-1β were detected using western blotting and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Masson's trichrome staining for histopathological changes of the liver tissue was observed. Finally, the activity of NF-κB in the liver was examined by enzyme-linked immunosorbent assay (ELISA). A higher expression of DcR3 was observed in rats treated with DcR3 (p < 0.05). Histological results showed that DcR3 significantly attenuated pathology in hepatic fibrosis rats. Consistently, mRNA and protein levels of α-SMA, TL1A, TNF-α, IL-6, and IL-1β were repressed in the liver tissue after treatment with DcR3 (p < 0.05). Moreover, DcR3 also inhibited the activation of NF-κB in the liver tissue (p < 0.05). This study demonstrated that DcR3 attenuated liver injury and inflammatory responses in rats with hepatic fibrosis. We suggest DcR3 may be a prophylactic and promising therapeutic agent in the treatment of hepatic fibrosis.

Decoy receptor 3 is a prognostic factor in renal cell cancer.

PubMed

Macher-Goeppinger, Stephan; Aulmann, Sebastian; Wagener, Nina; Funke, Benjamin; Tagscherer, Katrin E; Haferkamp, Axel; Hohenfellner, Markus; Kim, Sunghee; Autschbach, Frank; Schirmacher, Peter; Roth, Wilfried

2008-10-01

Decoy receptor 3 (DcR3) is a soluble protein that binds to and inactivates the death ligand CD95L. Here, we studied a possible association between DcR3 expression and prognosis in patients with renal cell carcinomas (RCCs). A tissue microarray containing RCC tumor tissue samples and corresponding normal tissue samples was generated. Decoy receptor 3 expression in tumors of 560 patients was examined by immunohistochemistry. The effect of DcR3 expression on disease-specific survival and progression-free survival was assessed using univariate analysis and multivariate Cox regression analysis. Decoy receptor 3 serum levels were determined by ELISA. High DcR3 expression was associated with high-grade (P = .005) and high-stage (P = .048) RCCs. The incidence of distant metastasis (P = .03) and lymph node metastasis (P = .002) was significantly higher in the group with high DcR3 expression. Decoy receptor 3 expression correlated negatively with disease-specific survival (P < .001) and progression-free survival (P < .001) in univariate analyses. A multivariate Cox regression analysis retained DcR3 expression as an independent prognostic factor that outperformed the Karnofsky performance status. In patients with high-stage RCCs expressing DcR3, the 2-year survival probability was 25%, whereas in patients with DcR3-negative tumors, the survival probability was 65% (P < .001). Moreover, DcR3 serum levels were significantly higher in patients with high-stage localized disease (P = .007) and metastatic disease (P = .001). DcR3 expression is an independent prognostic factor of RCC progression and mortality. Therefore, the assessment of DcR3 expression levels offers valuable prognostic information that could be used to select patients for adjuvant therapy studies.

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study

PubMed Central

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-01-01

Background Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. Patients and methods This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Results Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63–7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Conclusion Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects. PMID:29075129

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study.

PubMed

Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-01-01

Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.

Gefitinib provides similar effectiveness and improved safety than erlotinib for advanced non-small cell lung cancer: A meta-analysis.

PubMed

Zhang, Wenxiong; Wei, Yiping; Yu, Dongliang; Xu, Jianjun; Peng, Jinhua

2018-04-01

The epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib are effective for advanced non-small cell lung cancer (NSCLC). This meta-analysis compared their effectiveness and safety. We searched systematically in PubMed, ScienceDirect, The Cochrane Library, Scopus, Ovid MEDLINE, EMBASE, Web of Science, and Google Scholar for relevant clinical trials regarding gefitinib versus erlotinib for NSCLC. Antitumor effectiveness (overall survival [OS], progression-free survival [PFS], objective response rate [ORR] and disease control rate [DCR]) and adverse effects [AEs]) were assessed. Forty studies comprising 9376 participants were included. The results suggested that gefitinib and erlotinib are effective for advanced NSCLC with comparable PFS (95% confidence intervals [CI]: 0.98-1.11, P = .15), OS (95% CI: 0.93-1.19, P = .45), ORR (95% CI: 0.99-1.16, P = .07), and DCR (95% CI: 0.92-1.03, P = .35). For erlotinib, dose reduction was significantly more frequent (95% CI: 0.10-0.57, P = .001) as were grade 3 to 5 AEs (95% CI: 0.36-0.79, P = .002). In the subgroup analysis, the erlotinib group had a significant higher rate and severity of skin rash, nausea/vomiting, fatigue, and stomatitis. Gefitinib was proven to be the better choice for advanced NSCLC, with equal antitumor effectiveness and fewer AEs compared with erlotinib. Further large-scale, well-designed randomized controlled trials are warranted to confirm our validation.

Temporal dependence of transient dark counts in an avalanche photodiode: A solution for power-law behavior of afterpulsing

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

Akiba, M., E-mail: akiba@nict.go.jp; Tsujino, K.

This paper offers a theoretical explanation of the temperature and temporal dependencies of transient dark count rates (DCRs) measured for a linear-mode silicon avalanche photodiode (APD) and the dependencies of afterpulsing that were measured in Geiger-mode Si and InGaAs/InP APDs. The temporal dependencies exhibit power-law behavior, at least to some extent. For the transient DCR, the value of the DCR for a given time period increases with decreases in temperature, while the power-law behavior remains unchanged. The transient DCR is attributed to electron emissions from traps in the multiplication layer of the APD with a high electric field, and itsmore » temporal dependence is explained by a continuous change in the electron emission rate as a function of the electric field strength. The electron emission rate is calculated using a quantum model for phonon-assisted tunnel emission. We applied the theory to the temporal dependence of afterpulsing that was measured for Si and InGaAs/InP APDs. The power-law temporal dependence is attributed to the power-law function of the electron emission rate from the traps as a function of their position across the p–n junction of the APD. Deviations from the power-law temporal dependence can be derived from the upper and lower limits of the electric field strength.« less

[Clinical observation of icotinib hydrochloride for patients with advanced non-small cell lung cancer].

PubMed

Li, Xi; Yang, Xin-jie; Sun, Yi-fen; Qin, Na; Lü, Jia-lin; Wu, Yu-hua; Zhang, Hui; Zhang, Quan; Zhang, Shu-cai

2012-08-01

To explore the efficacy and side effects of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The efficacy and side effects of icotinib hydrochloride in treatment of 59 cases with stage IV NSCIC and followed-up from March 2009 to January 2012 were retrospectively analyzed. Twenty seven patients (45.8%) showed partial response (PR), 17 patients (28.8%) achieved SD, and 15 (25.4%) had progressive disease. The objective response rate (ORR) was 45.8% (27/59), and disease control rate (DCR) was 74.6% (44/59). Among the 23 patients with EGFR mutation, ORR was 73.9% (17/23), and DCR was 95.7% (22/23). Thirty six patients (61.0%) achieved remission of symptoms to varying degrees. The main symptoms relieved were cough, asthmatic suffocating, pain and hoarseness. The major adverse events were mild skin rash (35.6%) and diarrhea (15.3%). Others were dry skin, nausea and stomach problems. The efficacy of icotinib hydrochloride were related to the ECOG performance status, smoking history, EGFR mutation and rash significantly (P < 0.05). Monotherapy with icotinib hydrochloride is effective and tolerable for patients with advanced NSCLC, especially with EGFR mutation.

Aberrant expression of decoy receptor 3 in human breast cancer: relevance to lymphangiogenesis.

PubMed

Wu, Qiuwan; Zheng, Yahong; Chen, Donghan; Li, Xiaohong; Lu, Chuanhui; Zhang, Zhiming

2014-05-15

Decoy receptor 3 (DcR3), a decoy receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily, is overexpressed in some forms of cancer. It was recently reported that DcR3 could protect endothelial cells from apoptosis, implying a potential role in the development of vessels, whereas its role in the lymphangiogenesis remains unclear. In the present study, we studied the DcR3 expression and its relationship with the lymphatic microvessel density (LMVD) to investigate if it played a role in the lymph metastasis of human breast cancer. Real-time polymerase chain reaction and immunohistochemistry were performed to measure the messenger RNA and protein expression of DcR3 in the breast cancer tissues, noncancerous counterparts, and axillary lymph node from 63 patients. LMVD in these specimens was assessed by counting the D2-40 labeled-microvessels. Furthermore, the correlations between DcR3 expression and LMVD and other clinicopathologic parameters were analyzed. DcR3 was overexpressed in the breast cancer tissue of 58 patients (92.1%) and was also expressed in vascular endothelial cells and tumor cells in the lymph nodes. LMVD in cancer tissue and lymph nodes were both positively correlated to the aberrant expression of DcR3. The relevance between DcR3 overexpression and LMVD revealed the existence of possible links between DcR3 and lymphangiogenesis. Based on these findings, it is important to further explore the regulation of lymphangiogenesis operated by the reverse tumor necrosis factor signaling of DcR3. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Humeral elevation reduces the dynamic control ratio of the shoulder muscles during internal rotation.

PubMed

Howard, William; Burgess, Jonathan; Vrhovnik, Borut; Stringer, Christian; Choy, Sherrie T; Marsden, Jonathan F; Gedikoglou, Ingrid A; Shum, Gary L

2017-04-01

To determine the differences in the dynamic control ratio of the glenohumeral joint rotators, during internal rotation at 20° and 60° of humeral elevation in the scapular plan. Dynamic control ratio (DCR) is defined as the ratio between eccentric action of the lateral rotators and the concentric action of the medial rotators. A cross-sectional laboratory study. Thirty asymptomatic participants (men n=14, women n=16, mean age=29.4±8.9years, BMI: 24.1±5.4) were tested. Peak torque generated by the concentric action of the MR and the eccentric action of the LR of the shoulder joint and the DCR were evaluated on the dominant arm using an isokinetic dynamometer at 20° and 60° of humeral elevation at a speed of 20°/s. There was a significant decrease in the DCR at 60° humeral elevation when compared to 20° humeral elevation (p<0.05). This decrease was due to the significant decrease in eccentric peak torques at 60° humeral elevation when compared to 20° (p<0.05). However, there was no significant difference in the concentric peak torques between 20° and 60° (p>0.05). The significant decrease in the DCR as a consequence of a decrease in the eccentric peak torque of the LR when the humerus is in a more elevated position suggests that the introduction of humeral elevation can be used as a progression for improving the eccentric action of the shoulder LR and subsequently the dynamic control of the shoulder. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Decoy receptor 3 regulates the expression of tryptophan hydroxylase 1 in rheumatoid synovial fibroblasts.

PubMed

Maeda, Toshihisa; Miura, Yasushi; Fukuda, Koji; Hayashi, Shinya; Kurosaka, Masahiro

2015-10-01

Decoy receptor 3 (DcR3) is expressed in rheumatoid arthritis fibroblast‑like synoviocytes (RA‑FLS) and downregulates the expression of tryptophan hydroxylase 1 (TPH1), which is the rate‑limiting enzyme in serotonin synthesis. The aim of the present study was to determine the specificity of the effects of DcR3 on TPH1 in RA‑FLS, and therefore determine whether DcR3 had the potential to modulate the pathogenesis of RA. The present study also aimed to compare the effects of DcR3 and inflammatory cytokines on the expression of TPH1 in RA‑FLS and osteoarthritis (OA)‑FLS. Primary cultured RA‑ or OA‑FLS were incubated with 1.0 µg/ml DcR3‑Fc protein or 1.0 µg/ml control immunoglobulin G (IgG)1 for 12 h, or with 1.0 ng/ml tumor necrosis factor (TNF)α, 1.0 ng/ml interleukin (IL)‑1β or serum‑free Opti‑MEM only, for 24 h. The relative mRNA expression levels of TPH1 were subsequently quantified using reverse transcription‑polymerase chain reaction. The expression of serotonin in RA or OA synovial tissue was detected using immunohistochemistry. The mRNA expression of TPH1 was observed in both RA‑ and OA‑FLS and was significantly decreased following treatment with DcR3 in the RA‑FLS, however, not in the OA‑FLS. The mRNA expression of TPH1 was significantly decreased following treatment with TNFα or IL‑1β in both the RA‑ and OA‑FLS. The expression of serotonin in the multi‑layered lining synovial cells of RA and the outer layer lining synovial cells of OA was detected using immunohistochemistry. The present study is the first, to the best of our knowledge, to demonstrate that the expression of TPH1 in FLS is downregulated by inflammatory cytokines, and that DcR3 suppressed the expression of TPH1 in RA‑FLS in a disease‑specific manner. These results suggested that synovial serotonin may be involved in the pathogenesis of RA, and that TPH1 and DcR3 may be potential therapeutic targets for the treatment of RA.

Correlation of Neutrophil to Lymphocyte Ratio and Absolute Neutrophil Count With Outcomes With PD-1 Axis Inhibitors in Patients With Advanced Non-Small-Cell Lung Cancer.

PubMed

Zer, Alona; Sung, Mike R; Walia, Preet; Khoja, Leila; Maganti, Manjula; Labbe, Catherine; Shepherd, Frances A; Bradbury, Penelope A; Feld, Ronald; Liu, Geoffrey; Iazzi, Melissa; Zawisza, Dianne; Nouriany, Nazanin; Leighl, Natasha B

2018-05-08

Programmed death-1 (PD-1) axis inhibitors have become standard therapy in advanced non-small-cell lung cancer (NSCLC). Response might be delayed and pseudo-progression occasionally occurs in patients who eventually benefit from treatment. Additional markers beyond programmed death ligand 1 (PD-L1) expression are needed to assist in patient selection, response evaluation, and treatment decisions. The relationship between prospectively collected clinical outcomes (response, disease control rate [DCR], treatment duration, overall survival) and hematologic parameters (neutrophil to lymphocyte ratio [NLR], absolute neutrophil count [ANC], and platelet to lymphocyte ratio [PLR]) was explored retrospectively in advanced NSCLC patients treated with PD-1 axis inhibitors at a major cancer center from May 2013 to August 2016. Hematologic parameters at baseline and during treatment (week 2 or 3 and week 8) were included. Of 88 patients treated with PD-1 axis inhibitors, 22 (25%) experienced partial response. Baseline NLR ≤4 was associated with superior DCR (74% vs. 50%; P = .025), treatment duration (P = .037), time to progression (P = .053), and overall survival (P = .019), with no differential association according to PD-L1 tumor expression. Lower NLR and ANC during treatment were also associated with response to treatment (P = .025 and P = .017, respectively), and treatment duration (P = .036 and P = .008). No association was found between baseline PLR and DCR, response, treatment duration, nor overall survival. Baseline NLR ≤4 and lower NLR and ANC during treatment might correlate with disease control and treatment response and should be explored further as potential predictors of treatment benefit in larger studies. Copyright © 2018. Published by Elsevier Inc.

Decoy receptor 3 suppresses TLR2-mediated B cell activation by targeting NF-κB.

PubMed

Huang, Zi-Ming; Kang, Jhi-Kai; Chen, Chih-Yu; Tseng, Tz-Hau; Chang, Chien-Wen; Chang, Yung-Chi; Tai, Shyh-Kuan; Hsieh, Shie-Liang; Leu, Chuen-Miin

2012-06-15

Decoy receptor 3 (DcR3) is a soluble protein in the TNFR superfamily. Its known ligands include Fas ligand, homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes, TNF-like molecule 1A, and heparan sulfate proteoglycans. DcR3 has been reported to modulate the functions of T cells, dendritic cells, and macrophages; however, its role in regulating B cell activation is largely unknown. In this study, we found that the DcR3.Fc fusion protein bound to human and mouse B cells and suppressed the activation of B cells. DcR3.Fc attenuated Staphylococcus aureus, IgM-, Pam(3)CSK(4)-, and LPS-mediated B cell proliferation but did not affect cytokine-induced B cell growth. In the presence of these mitogens, DcR3.Fc did not induce B cell apoptosis, suggesting that DcR3 may inhibit the signal(s) important for B cell activation. Because the combination of Fas.Fc, LT-βR.Fc (homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes receptor), and DR3.Fc (TNF-like molecule 1A receptor) did not suppress B cell proliferation and because the biological effect of DcR3.Fc on B cells was not blocked by heparin, we hypothesize that a novel ligand(s) of DcR3 mediates its inhibitory activity on B cells. Moreover, we found that TLR2-stimulated NF-κB p65 activation and NF-κB-driven luciferase activity were attenuated by DcR3.Fc. The TLR2-induced cytokine production by B cells was consistently reduced by DcR3. These results imply that DcR3 may regulate B cell activation by suppressing the activation of NF-κB.

Decoy receptor 3 suppresses FasL-induced apoptosis via ERK1/2 activation in pancreatic cancer cells.

PubMed

Zhang, Yi; Li, Dechun; Zhao, Xin; Song, Shiduo; Zhang, Lifeng; Zhu, Dongming; Wang, Zhenxin; Chen, Xiaochen; Zhou, Jian

2015-08-07

Resistance to Fas Ligand (FasL) mediated apoptosis plays an important role in tumorigenesis. Decoy receptor 3 (DcR3) is reported to interact with FasL and is overexpressed in some malignant tumors. We sought to investigate the role of DcR3 in resistance to FasL in pancreatic cancer. We compared expression of apoptosis related genes between FasL-resistant SW1990 and FasL-sensitive Patu8988 pancreatic cell lines by microarray analysis. We explored the impact of siRNA knockdown of, or exogenous supplementation with, DcR3 on FasL-induced cell growth inhibition in pancreatic cancer cell lines and expression of proteins involved in apoptotic signaling. We assessed the level of DcR3 protein and ERK1/2 phosphorylation in tumor and non-tumor tissue samples of 66 patients with pancreatic carcinoma. RNAi knockdown of DcR3 expression in SW1990 cells reduced resistance to FasL-induced apoptosis, and supplementation of Patu8988 with rDcR3 had the opposite effect. RNAi knockdown of DcR3 in SW1990 cells elevated expression of caspase 3, 8 and 9, and reduced ERK1/2 phosphorylation (P < 0.05), but did not alter phosphorylated-Akt expression. 47 tumor tissue specimens, but only 15 matched non-tumor specimens stained for DcR3 (χ(2) = 31.1447, P < 0.001). The proliferation index of DcR3 positive specimens (14.26  ±  2.67%) was significantly higher than that of DcR3 negative specimens (43.58  ±  7.88%, P < 0.01). DcR3 expression positively correlated with p-ERK1/2 expression in pancreatic cancer tissues (r = 0.607, P < 0.001). DcR3 enhances ERK1/2 phosphorylation and opposes FasL signaling in pancreatic cancer cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Interleukin‑12B is upregulated by decoy receptor 3 in rheumatoid synovial fibroblasts.

PubMed

Fukuda, Koji; Miura, Yasushi; Maeda, Toshihisa; Hayashi, Shinya; Kurosaka, Masahiro

2016-04-01

Decoy receptor 3 (DcR3) competitively binds to three ligands, Fas ligand, lymphotoxin‑related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells and tumor necrosis factor‑like ligand 1A (TL1A), to prevent their effects. Recent studies have suggested that DcR3 directly affects cells as a ligand. Using a microarray assay, our group newly identified interleukin (IL)‑12B, which encodes the p40 subunit common to IL‑12 and IL‑23, as one of the genes for which expression in fibroblast‑like synoviocytes from patients with rheumatoid arthritis (RA‑FLS) is induced by DcR3. The present study demonstrated that IL‑12B mRNA expression was upregulated by DcR3‑Fc in RA‑FLS in a dose‑dependent manner, but not in OA‑FLS. IL‑12B p40 protein in RA‑FLS was increased when stimulated with DcR3‑Fc. Pre‑treatment with anti‑TL1A antibody suppressed the upregulation of IL‑12B mRNA in RA‑FLS stimulated with DcR3‑Fc. DcR3 mRNA expression in RA‑FLS was induced by IL‑23, but not by IL‑12. These results indicated that DcR3 may increase IL‑12 or IL‑23 by inducing IL‑12B p40 expression via membrane‑bound TL1A on RA‑FLS and that IL‑23 reciprocally induces DcR3 expression in RA‑FLS. DcR3 and IL‑23 may interact in a feedback loop that aggravates local inflammation in patients with RA.

Suppression of dark current radiation in step-and-shoot intensity modulated radiation therapy by the initial pulse-forming network.

PubMed

Cheng, Chee-Wai; Das, Indra J; Ndlovu, Alois M

2002-09-01

The effect of the initial pulse forming network (IPFN) on the suppression of dark current is investigated for a Siemens Primus accelerator. The dark current produces a spurious radiation, which is referred to as dark current radiation (DCR) in this study. In the step-and-shoot delivery of an intensity modulated radiation therapy (IMRT), the DCR could be of some concern for whole body dose along with leakage radiation through collimator jaws or multileaf collimator. By adjusting the IPFN-to-PFN ratio to >0.8, the DCR can be measured with an ion chamber during the "PAUSE" state of the accelerator in the IMRT mode. For 15 MV x rays, the magnitude of the DCR is approximately equal to 0.7% of the dose at dmax for a 10 x 10 cm2 field. The DCR has a similar central axis depth dose as a 15 MV beam as determined from a water phantom scan. When the IPFN-to-PFN ratio is lowered to <0.8, no DCR is detected. For low energy x rays (6 MV), no DCR is detected regardless of the IPFN-to-PFN ratio. Although the DCR is studied only for the Siemens Primus model accelerator, the same precaution applies to other models of modern accelerators from other vendors. Due to the large number of field segments used in a step-and-shoot IMRT, it is imperative therefore, that dark current evaluation be part of machine commissioning and annual calibration for high-energy photon beams. Should DCR be detected, the medical physicist should work with a service engineer to rectify the problem. In view of DCR and whole body dose, low-energy photon beams are advisable for IMRT.

Damage Control for Vascular Trauma from the Prehospital to the Operating Room Setting.

PubMed

Pikoulis, Emmanouil; Salem, Karim M; Avgerinos, Efthymios D; Pikouli, Anastasia; Angelou, Anastasios; Pikoulis, Antreas; Georgopoulos, Sotirios; Karavokyros, Ioannis

2017-01-01

Early management of vascular injury, starting at the field, is imperative for survival no less than any operative maneuver. Contemporary prehospital management of vascular trauma, including appropriate fluid and volume infusion, tourniquets, and hemostatic agents, has reversed the historically known limb hemorrhage as a leading cause of death. In this context, damage control (DC) surgery has evolved to DC resuscitation (DCR) as an overarching concept that draws together preoperative and operative interventions aiming at rapidly reducing bleeding from vascular disruption, optimizing oxygenation, and clinical outcomes. This review addresses contemporary DCR techniques from the prehospital to the surgical setting, focusing on civilian vascular injuries.

Elevated serum levels of decoy receptor 3 are associated with disease severity in patients with hemorrhagic fever with renal syndrome.

PubMed

Dong, Yanying; Shi, Dongsha; Li, Man; Dai, Pengfei; Wang, Xiangling; Xie, Ming

2015-08-01

Hemorrhagic fever with renal syndrome (HFRS) is an acute viral infectious disease characterized by fever, hemorrhage and renal failure. HFRS has become a serious public health problem in China. Unfortunately, the pathogenesis of HFRS has not been completely clarified. The aim of this study is to investigate the changes of decoy receptor 3 (DcR3) and to further explore its potential roles in HFRS. The levels of serum DcR3 were measured by sandwich ELISA. We found serum DcR3 levels increased significantly, which reached peak value during the oliguric phase and in the critical group. Moreover, serum DcR3 levels were closely related to the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and parameters reflecting kidney injury including BUN, creatinine (Cr) and proteinuria. This study indicates that high levels of serum DcR3 have associations with the disease stages, severity and degree of kidney damage. Meanwhile, our results suggest that DcR3 may play a dual role in HFRS pathogenesis. First, DcR3 is involved in the inflammatory cascade response resulting in capillary permeability and kidney injury in the early stage. Secondly, HTNV infection induced DcR3 expression at the convalescent phase may act as a feed-back mechanism in anti-inflammatory response. Thus, a study of DcR3 is essential for a better understanding of HFRS pathogenesis.

Molecular interactions and immune responses between Maize fine streak virus and the leafhopper vector Graminella nigrifrons through differential expression and RNA interference.

PubMed

Chen, Y; Redinbaugh, M G; Michel, A P

2015-06-01

Graminella nigrifrons is the only known vector for Maize fine streak virus (MFSV). In this study, we used real-time quantitative PCR to compare the expression profiles of transcripts that putatively function in the insect immune response: four peptidoglycan recognition proteins (PGRP-SB1, -SD, -LC and LB), Toll, spaetzle, defensin, Dicer-2 (Dcr-2), Argonaut-2 (Ago-2) and Arsenic resistance protein 2 (Ars-2). Except for PGRP-LB and defensin, transcripts involved in humoral pathways were significantly suppressed in G. nigrifrons fed on MFSV-infected maize. The abundance of three RNA interference (RNAi) pathway transcripts (Dcr-2, Ago-2, Ars-2) was significantly lower in nontransmitting relative to transmitting G. nigrifrons. Injection with double-stranded RNA (dsRNA) encoding segments of the PGRP-LC and Dcr-2 transcripts effectively reduced transcript levels by 90 and 75% over 14 and 22 days, respectively. MFSV acquisition and transmission were not significantly affected by injection of either dsRNA. Knock-down of PGRP-LC resulted in significant mortality (greater than 90%) at 27 days postinjection, and resulted in more abnormal moults relative to those injected with Dcr-2 or control dsRNA. The use of RNAi to silence G. nigrifrons transcripts will facilitate the study of gene function and pathogen transmission, and may provide approaches for developing novel targets of RNAi-based pest control. © 2015 The Royal Entomological Society.

Systemic and local expression levels of TNF-like ligand 1A and its decoy receptor 3 are increased in primary biliary cirrhosis.

PubMed

Aiba, Yoshihiro; Harada, Kenichi; Komori, Atsumasa; Ito, Masahiro; Shimoda, Shinji; Nakamura, Hitomi; Nagaoka, Shinya; Abiru, Seigo; Migita, Kiyoshi; Ishibashi, Hiromi; Nakanuma, Yasuni; Nishida, Nao; Kawashima, Minae; Tokunaga, Katsushi; Yatsuhashi, Hiroshi; Nakamura, Minoru

2014-05-01

Through a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC. We analysed the systemic and local expression of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining. Serum TL1A levels were significantly increased in PBC patients at both early and late stages as compared with healthy controls, and its levels were significantly decreased in early-stage PBC patients after ursodeoxycholic acid (UDCA) treatment. TL1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA expression was increased in the PBC liver as compared with the non-diseased liver. Serum DcR3 levels were also significantly increased in PBC patients, and were significantly decreased after UDCA treatment in early-stage PBC patients. These results indicate that TL1A and DcR3 may play an important role in the pathogenesis of PBC. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Elevated Serum Levels of the Antiapoptotic Protein Decoy-Receptor 3 Are Associated with Advanced Liver Disease.

PubMed

Bamias, Giorgos; Gizis, Michalis; Delladetsima, Ioanna; Laoudi, Eyfrosyni; Siakavellas, Spyros I; Koutsounas, Ioannis; Kaltsa, Garyfallia; Vlachogiannakos, John; Vafiadis-Zouboulis, Irene; Daikos, George L; Papatheodoridis, George V; Ladas, Spiros D

2016-01-01

Background. Decoy-receptor 3 (DcR3) exerts antiapoptotic and immunomodulatory function and is overexpressed in neoplastic and inflammatory conditions. Serum DcR3 (sDcR3) levels during the chronic hepatitis/cirrhosis/hepatocellular carcinoma (HCC) sequence have not been explored. Objective. To assess the levels and significance of sDcR3 protein in various stages of chronic liver disease. Methods. We compared sDcR3 levels between healthy controls and patients with chronic viral hepatitis (CVH), decompensated cirrhosis (DC), and HCC. Correlations between sDcR3 levels and various patient- and disease-related factors were analyzed. Results. sDcR3 levels were significantly higher in patients with CVH than in controls (P < 0.01). sDcR3 levels were elevated in DC and HCC, being significantly higher compared not only to controls (P < 0.001 for both) but to CVH patients as well (P < 0.001 for both). In addition, DcR3 protein was detected in large quantities in the ascitic fluid of cirrhotics. In patients with CVH, sDcR3 significantly correlated to fibrosis severity, as estimated by Ishak score (P = 0.019) or by liver stiffness measured with elastography (Spearman r = 0.698, P < 0.001). In cirrhotic patients, significant positive correlations were observed between sDcR3 levels and markers of severity of hepatic impairment, including MELD score (r = 0.653, P < 0.001). Conclusions. Circulating levels of DcR3 are elevated during chronic liver disease and correlate with severity of liver damage. sDcR3 may serve as marker for liver fibrosis severity and progression to end-stage liver disease.

Aberrant expression and function of death receptor-3 and death decoy receptor-3 in human cancer.

PubMed

Ge, Zhicheng; Sanders, Andrew J; Ye, Lin; Jiang, Wen G

2011-03-01

Death receptor-3 (DR3) and death decoy receptor-3 (DcR3) are both members of the tumour necrosis factor receptor (TNFR) superfamily. The TNFR superfamily contains eight death domain-containing receptors, including TNFR1 (also called DR1), Fas (also called DR2), DR3, DR4, DR5, DR6, NGFR and EDAR. Upon the binding of these receptors with their corresponding ligands, the death domain recruits various proteins that mediate both the death and proliferation of cells. Receptor function is negatively regulated by decoy receptors (DcR1, DcR2, DcR3 and OPG). DR3/DcR3 are a pair of positive and negative players with which vascular endothelial growth inhibitor (VEGI) interacts. VEGI has been suggested to be a potential tumour suppressor. The inhibitory effects of VEGI on cancer are manifested in three main areas: a direct effect on cancer cells, an anti-angiogenic effect on endothelial cells, and the stimulation of dendritic cell maturation. A recent study indicated that DR3 may be a new receptor for E-selectin, which has been reported to be associated with cancer metastasis. DcR3 is a soluble receptor, highly expressed in various tumours, which lacks an apparent transmembrane segment, prevents cytokine response through ligand binding and neutralization, and is an inhibitor of apoptosis. DcR3 serves as a decoy receptor for FasL, LIGHT and VEGI. The cytokine LIGHT activates various anti-tumour functions and is expected to be a promising candidate for cancer therapy. Certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing DcR3, which blocks FasL function. DR3/DcR3 play profound roles in regulating cell death and proliferation in cancer. The present review briefly discusses DR3/DcR3 and attempts to elucidate the role of these negative and positive players in cancer.

Molecular cloning and preliminary expression analysis of banded dogfish (Triakis scyllia) TNF decoy receptor 3 (TNFRSF6B).

PubMed

Inoue, Yuuki; Morinaga, Akihiro; Takizawa, Fumio; Saito, Tsubasa; Endo, Mariko; Haruta, Chiaki; Nakai, Takeshi; Moritomo, Tadaaki; Nakanishi, Teruyuki

2008-03-01

Decoy receptor 3 (DcR3), a member of TNF receptor superfamily, is a soluble receptor without death domain and cytoplasmic domain, and secreted by cells and binds with FasL, LIGHT and TL1A. The principal function of DcR3 is the inhibition of apoptosis by the binding cytotoxic ligands. Expression of DcR3 has been reported in a wide array of normal human tissues as well as tumors and tumor cell lines. Recently, DcR3 was reported to modulate a variety of immune responses in mammals. TNFR or DcR3 has been identified in some teleost fishes. However, DcR3 is not reported in cartilaginous fish which is the lowest vertebrate possessing the adaptive immune system. Here we identified DcR3 cDNA in shark (Trsc-DcR3) from an SSH library prepared from peripheral white blood cells stimulated with PMA. Four cysteine-rich domains (CRDs) in common with TNF receptor family members are present in the Trsc-DcR3 sequence. The deduced amino acid sequence of Trsc-DcR3 showed highest identity with the chicken (50.4%), followed by human (46.8%) and rainbow trout (36.5%) DcR3. In a phylogenetic tree of known TNFRSF sequences, the Trsc-DcR3 grouped with the chicken and human DcR3. Trsc-DcR3 mRNA was detected strongly in the gill, moderately in the brain, and weakly in the kidney, thymus and leydig. These data strongly suggest that the gene encoding Trsc-DcR3 in banded dogfish is a homolog of the human gene. mRNA expression of Trsc-DcR3 in the thymus and leydig suggests that DcR3 may act as a modulator in the immune system even at the phylogenetic level of cartilaginous fish.

Decoy receptor 3 regulates the expression of various genes in rheumatoid arthritis synovial fibroblasts.

PubMed

Fukuda, Koji; Miura, Yasushi; Maeda, Toshihisa; Takahashi, Masayasu; Hayashi, Shinya; Kurosaka, Masahiro

2013-10-01

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor (TNF) receptor (TNFR) superfamily, lacks the transmembrane domain of conventional TNFRs in order to be a secreted protein. DcR3 competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT and TNF-like ligand 1A (TL1A). We previously reported that TNFα-induced DcR3 overexpression in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) protects cells from Fas-induced apoptosis. Previous studies have suggested that DcR3 acting as a ligand directly induces the differentiation of macrophages into osteoclasts. Furthermore, we reported that DcR3 induces very late antigen-4 (VLA--4) expression in THP-1 macrophages, inhibiting cycloheximide-induced apoptosis and that DcR3 binds to membrane-bound TL1A expressed on RA-FLS, resulting in the negative regulation of cell proliferation induced by inflammatory cytokines. In the current study, we used cDNA microarray to search for genes in RA-FLS whose expression was regulated by the ligation of DcR3. The experiments revealed the expression profiles of genes in RA-FLS regulated by DcR3. The profiles showed that among the 100 genes most significantly regulated by DcR3, 45 were upregulated and 55 were downregulated. The upregulated genes were associated with protein complex assembly, cell motility, regulation of transcription, cellular protein catabolic processes, cell membrane, nucleotide binding and glycosylation. The downregulated genes were associated with transcription regulator activity, RNA biosynthetic processes, cytoskeleton, zinc finger region, protein complex assembly, phosphate metabolic processes, mitochondrion, ion transport, nucleotide binding and cell fractionation. Further study of the genes detected in the current study may provide insight into the pathogenesis and treatment of rheumatoid arthritis by DcR3-TL1A signaling.

The solvent at antigen-binding site regulated C3d-CR2 interactions through the C-terminal tail of C3d at different ion strengths: insights from molecular dynamics simulation.

PubMed

Zhang, Yan; Guo, Jingjing; Li, Lanlan; Liu, Xuewei; Yao, Xiaojun; Liu, Huanxiang

2016-10-01

The interactions of complement receptor 2 (CR2) and the degradation fragment C3d of complement component C3 play important links between the innate and adaptive immune systems. Due to the importance of C3d-CR2 interaction in the design of vaccines and inhibitors, a number of studies have been performed to investigate C3d-CR2 interaction. Many studies have indicated C3d-CR2 interactions are ionic strength-dependent. To investigate the molecular mechanism of C3d-CR2 interaction and the origin of effects of ionic strength, molecular dynamics simulations for C3d-CR2 complex together with the energetic and structural analysis were performed. Our results revealed the increased interactions between charged protein and ions weaken C3d-CR2 association, as ionic strengths increase. Moreover, ion strengths have similar effects on antigen-binding site and CR2 binding site. Meanwhile, Ala17 and Gln20 will transform between the activated and non-activated states mediated by His133 and Glu135 at different ion strengths. Our results reveal the origins of the effects of ionic strengths on C3d-CR2 interactions are due to the changes of water, ion occupancies and distributions. This study uncovers the origin of the effect of ionic strength on C3d-CR2 interaction and deepens the understanding of the molecular mechanism of their interaction, which is valuable for the design of vaccines and small molecule inhibitors. Copyright © 2016 Elsevier B.V. All rights reserved.

The Arabidopsis DCR Encoding a Soluble BAHD Acyltransferase Is Required for Cutin Polyester Formation and Seed Hydration Properties1[C][W][OA

PubMed Central

Panikashvili, David; Shi, Jian Xin; Schreiber, Lukas; Aharoni, Asaph

2009-01-01

The cuticle covering every plant aerial organ is largely made of cutin that consists of fatty acids, glycerol, and aromatic monomers. Despite the huge importance of the cuticle to plant development and fitness, our knowledge regarding the assembly of the cutin polymer and its integration in the complete cuticle structure is limited. Cutin composition implies the action of acyltransferase-type enzymes that mediate polymer construction through ester bond formation. Here, we show that a member of the BAHD family of acyltransferases (DEFECTIVE IN CUTICULAR RIDGES [DCR]) is required for incorporation of the most abundant monomer into the polymeric structure of the Arabidopsis (Arabidopsis thaliana) flower cutin. DCR-deficient plants display phenotypes that are typically associated with a defective cuticle, including altered epidermal cell differentiation and postgenital organ fusion. Moreover, levels of the major cutin monomer in flowers, 9(10),16-dihydroxy-hexadecanoic acid, decreased to an almost undetectable amount in the mutants. Interestingly, dcr mutants exhibit changes in the decoration of petal conical cells and mucilage extrusion in the seed coat, both phenotypes formerly not associated with cutin polymer assembly. Excessive root branching displayed by dcr mutants and the DCR expression pattern in roots pointed to the function of DCR belowground, in shaping root architecture by influencing lateral root emergence and growth. In addition, the dcr mutants were more susceptible to salinity, osmotic, and water deprivation stress conditions. Finally, the analysis of DCR protein localization suggested that cutin polymerization, possibly the oligomerization step, is partially carried out in the cytoplasmic space. Therefore, this study extends our knowledge regarding the functionality of the cuticular layer and the formation of its major constituent the polymer cutin. PMID:19828672

The Arabidopsis DCR encoding a soluble BAHD acyltransferase is required for cutin polyester formation and seed hydration properties.

PubMed

Panikashvili, David; Shi, Jian Xin; Schreiber, Lukas; Aharoni, Asaph

2009-12-01

The cuticle covering every plant aerial organ is largely made of cutin that consists of fatty acids, glycerol, and aromatic monomers. Despite the huge importance of the cuticle to plant development and fitness, our knowledge regarding the assembly of the cutin polymer and its integration in the complete cuticle structure is limited. Cutin composition implies the action of acyltransferase-type enzymes that mediate polymer construction through ester bond formation. Here, we show that a member of the BAHD family of acyltransferases (DEFECTIVE IN CUTICULAR RIDGES [DCR]) is required for incorporation of the most abundant monomer into the polymeric structure of the Arabidopsis (Arabidopsis thaliana) flower cutin. DCR-deficient plants display phenotypes that are typically associated with a defective cuticle, including altered epidermal cell differentiation and postgenital organ fusion. Moreover, levels of the major cutin monomer in flowers, 9(10),16-dihydroxy-hexadecanoic acid, decreased to an almost undetectable amount in the mutants. Interestingly, dcr mutants exhibit changes in the decoration of petal conical cells and mucilage extrusion in the seed coat, both phenotypes formerly not associated with cutin polymer assembly. Excessive root branching displayed by dcr mutants and the DCR expression pattern in roots pointed to the function of DCR belowground, in shaping root architecture by influencing lateral root emergence and growth. In addition, the dcr mutants were more susceptible to salinity, osmotic, and water deprivation stress conditions. Finally, the analysis of DCR protein localization suggested that cutin polymerization, possibly the oligomerization step, is partially carried out in the cytoplasmic space. Therefore, this study extends our knowledge regarding the functionality of the cuticular layer and the formation of its major constituent the polymer cutin.

Decoy receptor 3, a novel inflammatory marker, and mortality in hemodialysis patients.

PubMed

Hung, Szu-Chun; Hsu, Ta-Wei; Lin, Yao-Ping; Tarng, Der-Cherng

2012-08-01

Inflammation is closely associated with cardiovascular disease, the leading cause of mortality in patients with CKD. Serum decoy receptor 3 (DcR3) is a member of the TNF receptor superfamily. CKD patients have higher levels of DcR3 than the general population, but whether DcR3 predicts mortality in CKD patients on hemodialysis has not been explored. DcR3 levels were measured in 316 prevalent hemodialysis patients who were followed up from November 1, 2004, to June 30, 2009, for cardiovascular and all-cause mortality. The baseline DcR3 concentration showed a strong positive correlation with inflammatory markers including high-sensitivity C-reactive protein, IL-6, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1). During a follow-up period of 54 months, 90 patients died (34 cardiovascular deaths). Kaplan-Meier survival analysis showed higher cardiovascular and all-cause mortality in patients with higher DcR3 levels. The hazard ratios (95% confidence intervals) of the highest versus lowest tertiles of DcR3 were 2.8 (1.1-7.3; P for trend=0.04) for cardiovascular mortality and 2.1 (1.1-3.7; P for trend=0.02) for all-cause mortality, respectively. Based on the minimal increase in the area under the receiver operating characteristic curve from 0.79 to 0.80, the addition of DcR3 to established risk factors including VCAM-1, albumin, and IL-6 does not improve the prediction of mortality. Higher DcR3 levels strongly correlate with inflammation and independently predict cardiovascular and all-cause mortality in CKD patients on hemodialysis.

Decoy receptor 3 attenuates collagen-induced arthritis by modulating T cell activation and B cell expansion.

PubMed

Cheng, Chia-Pi; Sytwu, Huey-Kang; Chang, Deh-Ming

2011-12-01

To investigate the immune-modulated effects of decoy receptor 3 (DCR3) in an experimental model of rheumatoid arthritis (RA). We delivered DCR3 plasmid into collagen-induced arthritis (CIA) mice using the hydrodynamic method and evaluated the serum level of DCR3 protein by ELISA. After immunization, we assessed disease severity of arthritis incidence, arthritis scores, paw thickness, and means of arthritic limbs, and used hematoxylin and eosin staining to observe synovial hyperplasia. We analyzed numbers of murine splenocytes and inguinal lymphocyte cells, cell populations, and serum proinflammatory cytokines by flow cytometry. We investigated B cell proliferation by carboxyfluorescein succinimidyl ester assay. We evaluated serum levels of total IgG2a and type II collagen-specific IgG and IgG2a using ELISA. DCR3 expression in sera significantly attenuated disease severity in CIA mice. We found that DCR3 inhibited the volume of inguinal lymph nodes, numbers of CD19+ B cells, and populations of interferon-γ, interleukin 4 (IL-4), IL-17A, and Foxp3-producing CD4+ T cell in vivo. We found that DCR3 inhibited Pam3CSK4 (Toll-like receptor 1/2 ligand)-induced B220+ B cell proliferation in vitro. DCR3 treatment reduced the serum level of IL-6, total IgG2a, and CII-specific IgG2a antibody. We postulated that the protective effects of DCR3 in CIA resulted from modulation of the immune system by maintaining the B/T cell balance and decreasing lymphocyte expansion. We suggest DCR3 as a prophylactic and potential therapeutic agent in the treatment of RA.

The dual combustor ramjet: A versatile propulsion system for hypersonic tactical missile applications

NASA Astrophysics Data System (ADS)

Waltrup, Paul J.

1992-09-01

Procedures for designing and maximizing the performance of Dual Combustor Ramjet (DCR) engines and vehicles powered by this engine are presented. Comparisons of DCR powered vehicles with scramjet powered vehicles for Mach 4 to 8 flight show that the DCR provides better performance at the Mach 4 flight condition, while the scramjet is better at Mach 8. Comparisons of the DCR with a ramjet for Mach 3 to 6 flight, with both having the same, but low, thrust level at Mach 3, show that the DCR exhibits better performance at and near the cruise condition at Mach 6 and similar performance during acceleration. Suggested additional comparisons to broaden the scope of the conclusions are also given.

The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans.

PubMed

Tabara, Hiroaki; Yigit, Erbay; Siomi, Haruhiko; Mello, Craig C

2002-06-28

Double-stranded (ds) RNA induces potent gene silencing, termed RNA interference (RNAi). At an early step in RNAi, an RNaseIII-related enzyme, Dicer (DCR-1), processes long-trigger dsRNA into small interfering RNAs (siRNAs). DCR-1 is also required for processing endogenous regulatory RNAs called miRNAs, but how DCR-1 recognizes its endogenous and foreign substrates is not yet understood. Here we show that the C. elegans RNAi pathway gene, rde-4, encodes a dsRNA binding protein that interacts during RNAi with RNA identical to the trigger dsRNA. RDE-4 protein also interacts in vivo with DCR-1, RDE-1, and a conserved DExH-box helicase. Our findings suggest a model in which RDE-4 and RDE-1 function together to detect and retain foreign dsRNA and to present this dsRNA to DCR-1 for processing.

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer

PubMed Central

Yang, R.F.; Yu, B.; Zhang, R.Q.; Wang, X.H.; Li, C.; Wang, P.; Zhang, Y.; Han, B.; Gao, X.X.; Zhang, L.; Jiang, Z.M.

2017-01-01

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC. PMID:29185589

Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer.

PubMed

Yang, R F; Yu, B; Zhang, R Q; Wang, X H; Li, C; Wang, P; Zhang, Y; Han, B; Gao, X X; Zhang, L; Jiang, Z M

2017-11-17

Non-small-cell lung cancer (NSCLC) patients who experience brain metastases are usually associated with poor prognostic outcomes. This retrospective study proposed to assess whether bevacizumab or gefitinib can be used to improve the effectiveness of whole brain radiotherapy (WBRT) in managing patients with brain metastases. A total of 218 NSCLC patients with multiple brain metastases were retrospectively included in this study and were randomly allocated to bevacizumab-gefitinib-WBRT group (n=76), gefitinib-WBRT group (n=77) and WBRT group (n=75). Then, tumor responses were evaluated every 2 months based on Response Evaluation Criteria in Solid Tumors version 1.0. Karnofsky performance status and neurologic examination were documented every 6 months after the treatment. Compared to the standard WBRT, bevacizumab and gefitinib could significantly enhance response rate (RR) and disease control rate (DCR) of WBRT (P<0.001). At the same time, RR and DCR of patients who received bevacizumab-gefitinib-WBRT were higher than those who received gefitinib-WBRT. The overall survival (OS) rates and progression-free survival (PFS) rates also differed significantly among the bevacizumab-gefitinib-WBRT (48.6 and 29.8%), gefitinib-WBRT (36.7 and 29.6%) and WBRT (9.8 and 14.6%) groups (P<0.05). Although bevacizumab-gefitinib-WBRT was slightly more toxic than gefitinib-WBRT, the toxicity was tolerable. As suggested by prolonged PFS and OS status, bevacizumab substantially improved the overall efficacy of WBRT in the management of patients with NSCLC.

Decoy receptor 3 suppresses RANKL-induced osteoclastogenesis via down-regulating NFATc1 and enhancing cell apoptosis.

PubMed

Cheng, Chia-Pi; Sheu, Ming-Jen; Sytwu, Huey-Kang; Chang, Deh-Ming

2013-04-01

Decoy receptor 3 (DCR3) has been known to modulate immune functions of monocyte or macrophage. In the present study, we investigated the mechanism and the effect of DCR3 on RANK ligand (RANKL)-induced osteoclastogenesis. We treated cells with DCR3 in RANKL-induced osteoclastogenesis to monitor osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast activity was assessed by pit formation assay. The mechanism of inhibition was studied by biochemical analysis such as RT-PCR and immunoblotting. In addition, cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis and apoptosis signalling were evaluated by immunoblotting and using flow cytometry. DCR3 inhibited RANKL-induced TRAP(+) multinucleated cells and inhibited RANKL-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation and nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) nuclear translocation in RAW264.7 cells. Also, DCR3 significantly inhibited the bone-resorbing activity of mature osteoclasts. Moreover, DCR3 enhanced RANKL-induced cell apoptosis and enhanced RANKL-induced Fas ligand expression. The mechanisms were mediated via the intrinsic cytochrome c and activated caspase 9 apoptosis pathway. We postulated that the inhibitory activity of DCR3 on osteoclastogenesis occurs via down-regulation of RANKL-induced NFATc1 expression and induction of cell apoptosis. Our results postulated DCR3 as a possible new remedy against inflammatory bone destruction.

CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials.

PubMed

Goss, G; Tsai, C-M; Shepherd, F A; Ahn, M-J; Bazhenova, L; Crinò, L; de Marinis, F; Felip, E; Morabito, A; Hodge, R; Cantarini, M; Johnson, M; Mitsudomi, T; Jänne, P A; Yang, J C-H

2018-03-01

Central nervous system (CNS) metastases are common in patients with non-small-cell lung cancer (NSCLC). Osimertinib has shown systemic efficacy in patients with CNS metastases, and early clinical evidence shows efficacy in the CNS. To evaluate osimertinib activity further, we present a pre-specified subgroup analysis of CNS response using pooled data from two phase II studies: AURA extension (NCT01802632) and AURA2 (NCT02094261). Patients with T790M-positive advanced NSCLC, who had progressed following prior epidermal growth factor receptor-tyrosine kinase inhibitor treatment, received osimertinib 80 mg od (n = 411). Patients with stable, asymptomatic CNS metastases were eligible for enrolment; prior CNS treatment was allowed. Patients with ≥1 measurable CNS lesion (per RECIST 1.1) on baseline brain scan by blinded independent central neuroradiology review (BICR) were included in the evaluable for CNS response set (cEFR). The primary outcome for this CNS analysis was CNS objective response rate (ORR) by BICR; secondary outcomes included CNS duration of response, disease control rate (DCR) and progression-free survival (PFS). Of 128 patients with CNS metastases on baseline brain scans, 50 were included in the cEFR. Confirmed CNS ORR and DCR were 54% [27/50; 95% confidence interval (CI) 39-68] and 92% (46/50; 95% CI 81-98), respectively. CNS response was observed regardless of prior radiotherapy to the brain. Median CNS duration of response (22% maturity) was not reached (range, 1-15 months); at 9 months, 75% (95% CI 53-88) of patients were estimated to remain in response. Median follow-up for CNS PFS was 11 months; median CNS PFS was not reached (95% CI, 7, not calculable). The safety profile observed in the cEFR was consistent with the overall patient population. Osimertinib demonstrated clinically meaningful efficacy against CNS metastases, with a high DCR, encouraging ORR, and safety profile consistent with that reported previously. NCT01802632; NCT02094261.

Irinotecan and temozolomide in recurrent Ewing sarcoma: an analysis in 51 adult and pediatric patients.

PubMed

Palmerini, E; Jones, R L; Setola, E; Picci, P; Marchesi, E; Luksch, R; Grignani, G; Cesari, M; Longhi, A; Abate, M E; Paioli, A; Szucs, Z; D'ambrosio, L; Scotlandi, K; Fagioli, F; Asaftei, S; Ferrari, S

2018-03-13

Data on temozolomide (TEM) and irinotecan (IRI) activity in recurrent Ewing sarcoma (EWS), especially in adult patients, are limited. Patients receiving TEM 100 mg/m 2 /day oral, and IRI 40 mg/m 2 /day intravenous, days 1-5, every 21 days, were included in this multi-institutional retrospective study. Disease control rate (DCR) [overall response rate (ORR) [complete response (CR) + partial response (PR)] + stable disease (SD)], 6-months progression-free survival (6-mos PFS) and 1-year overall survival (OS) were assessed. The median age of the 51 patients was 21 years (range 3-65 years): 34 patients (66%) were adults (≥18 years of age), 24 (48%) had ECOG 1 and 35 (69%) were presented with multiple site recurrence. TEMIRI was used at first relapse/progression in 13 (25%) patients, while the remainder received TEMIRI for second or greater relapse/progression. Fourteen (27%) patients had received prior myeloablative therapy with busulfan and melphalan. We observed five (10%) CR, 12 (24%) PR and 19 (37%) SD, with a DCR of 71%. 6-mos PFS was 49% (95% CI 35-63) and it was significantly influenced by ECOG (6-mos PFS 64% [95% CI 45-83] for ECOG 0, 34% [95% CI 14-54] for ECOG ≥1; p = .006) and LDH (6-mos PFS 62% [95% CI 44-79] for normal LDH, 22% [95% CI 3-42] for high LDH; p = .02), with no difference according to line of treatment, age and metastatic pattern. One-year OS was 55% (95% CI 39-70), with RECIST response (p = .001) and ECOG (p = .0002) independently associated with outcome. Grade 3 and 4 toxicity included neutropenia in 12% of patients, thrombocytopenia in 4%, diarrhea in 4%. This series confirms the activity of TEMIRI in both adults and pediatric patients. This schedule offers a 71% DCR, independently of the line of chemotherapy. Predictive factors of response are ECOG and LDH.

Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma.

PubMed

Ito, Yasuhiro; Onoda, Naoyoshi; Ito, Ken-Ichi; Sugitani, Iwao; Takahashi, Shunji; Yamaguchi, Iku; Kabu, Koki; Tsukada, Katsuya

2017-09-01

Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent. A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7-5.6], and median OS was 5.0 months [confidence interval 0.7-5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%. The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and radioactive iodine-refractory DTC.

The performance of DC restoration function for MODIS thermal emissive bands

NASA Astrophysics Data System (ADS)

Wang, Zhipeng; Xiong, Xiaoxiong Jack; Shrestha, Ashish

2017-09-01

The DC restore (DCR) process of MODIS instrument maintains the output of a detector at focal plane assembly (FPA) within the dynamic range of subsequent analog-to-digital converter, by adding a specific offset voltage to the output. The DCR offset value is adjusted per scan, based on the comparison of the detector response in digital number (DN) collected from the blackbody (BB) view with target DN saved as an on-board look-up table. In this work, the MODIS DCR mechanism is revisited, with the trends of DCR offset being provided for thermal emissive bands (TEB). Noticeable changes have been occasionally found which coincide with significant detector gain change due to various instrumental events such as safe-mode anomaly or FPA temperature fluctuation. In general, MODIS DCR functionality has been effective and the change of DCR offset has no impact to the quality of MODIS data. One exception is the Earth view (EV) data saturation of Aqua MODIS LWIR bands 33, 35 ad 36 during BB warm-up cool-down (WUCD) cycle which has been observed since 2008. The BB view of their detectors saturate when the BB temperature is above certain threshold so the DCR cannot work as designed. Therefore, the dark signal DN fluctuates with the cold FPA (CFPA) temperature and saturate for a few hours per WUCD cycle, which also saturate the EV data sector within the scan. The CFPA temperature fluctuation peaked in 2012 and has been reduced in recent years and the saturation phenomenon has been easing accordingly. This study demonstrates the importance of DCR to data generation.

Adverse effect on syngeneic islet transplantation by transgenic coexpression of decoy receptor 3 and heme oxygenase-1 in the islet of NOD mice.

PubMed

Huang, S-H; Lin, G-J; Chien, M-W; Chu, C-H; Yu, J-C; Chen, T-W; Hueng, D-Y; Liu, Y-L; Sytwu, H-K

2013-03-01

Decoy receptor 3 (DcR3) blocks both Fas ligand- and LIGHT-induced pancreatic β-cell damage in autoimmune diabetes. Heme oxygenase 1 (HO-1) possesses antiapoptotic, anti-inflammatory, and antioxidative effects that protect cells against various forms of attack by the immune system. Previously, we have demonstrated that transgenic islets overexpressing DcR3 or murine HO-1 (mHO-1) exhibit longer survival times than nontransgenic islets in syngeneic islet transplantation. In this study, we evaluated whether DcR3 and mHO-1 double-transgenic islets of NOD mice could provide better protective effects and achieve longer islet graft survival than DcR3 or mHO-1 single-transgenic islets after islet transplantation. We generated DcR3 and mHO-1 double-transgenic NOD mice that specifically overexpress DcR3 and HO-1 in islets. Seven hundred islets isolated from double-transgenic, single-transgenic, or nontransgenic NOD mice were syngeneically transplanted into the kidney capsules of newly diabetic female recipients. Unexpectedly, there was no significant difference in the survival time between double-transgenic or nontransgenic NOD islet grafts, and the survival times of double-transgenic NOD islet grafts were even shorter than those of DcR3 or mHO-1 single-transgenic islets. Our data indicate that transplantation of double-transgenic islets that coexpress HO-1 and DcR3 did not result in a better outcome. On the contrary, this strategy even caused an adverse effect in syngeneic islet transplantation. Copyright © 2013 Elsevier Inc. All rights reserved.

Decoy receptor 3 promotes cell adhesion and enhances endometriosis development.

PubMed

Tsai, Hsiao-Wen; Huang, Ming-Ting; Wang, Peng-Hui; Huang, Ben-Shian; Chen, Yi-Jen; Hsieh, Shie-Liang

2018-02-01

Endometriosis is a multifactorial inflammatory disease with persistent activation of the nuclear factor-κB (NF-κB) signalling pathway. Aberrant adhesion of endometrium is the essential step in the progression of endometriosis, but the molecular mechanism of ectopic growth of endometrium is still unclear. Decoy receptor 3 (DcR3)/TNFRSF6B, a pleiotropic immunomodulator regulated by oestrogen, is able to activate focal adhesion kinase to promote cell adhesion. We found that DcR3 is upregulated in human ectopic endometrial cells via activation of the Akt-NF-κB signalling pathway, and its expression level correlates positively with that of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and homing cell adhesion molecule (HCAM; CD44). In a multivariate regression model, DcR3 expression level was the most significant parameter associated with endometriosis severity. Knockdown of DcR3 not only downregulated the expression of ICAM-1 and HCAM, but also reduced cell adhesion and migration. In vivo investigation further showed that DcR3 promoted the growth and spread of endometrium, whereas knockdown of DcR3 by lentivirus-delivered short hairpin RNA inhibited ectopic adhesion of endometrium and abrogated endometriosis progression. These observations are in support of DcR3 playing a critical role in the pathogenesis of endometriosis, and the inhibition of DcR3 expression being a promising approach for the treatment of endometriosis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Decoy Receptor DcR1 Is Induced in a p50/Bcl3-Dependent Manner and Attenuates the Efficacy of Temozolomide.

PubMed

Mansour, Nassir M; Bernal, Giovanna M; Wu, Longtao; Crawley, Clayton D; Cahill, Kirk E; Voce, David J; Balyasnikova, Irina V; Zhang, Wei; Spretz, Ruben; Nunez, Luis; Larsen, Gustavo F; Weichselbaum, Ralph R; Yamini, Bakhtiar

2015-05-15

Temozolomide is used widely to treat malignant glioma, but the overall response to this agent is generally poor. Resistance to DNA-damaging drugs such as temozolomide has been related to the induction of antiapoptotic proteins. Specifically, the transcription factor NF-κB has been suggested to participate in promoting the survival of cells exposed to chemotherapy. To identify factors that modulate cytotoxicity in the setting of DNA damage, we used an unbiased strategy to examine the NF-κB-dependent expression profile induced by temozolomide. By this route, we defined the decoy receptor DcR1 as a temozolomide response gene induced by a mechanism relying upon p50/NF-κB1. A conserved NF-κB-binding sequence (κB-site) was identified in the proximal promoter and was demonstrated to be required for DcR1 induction by temozolomide. Loss-of-function and gain-of-function studies reveal that the atypical IκB protein, Bcl3, is also required for induction of DcR1 by temozolomide. Mechanistically, DcR1 attenuates temozolomide efficacy by blunting activation of the Fas receptor pathway in p53(+/+) glioma cells. Intracranial xenograft studies show that DcR1 depletion in glioma cells enhances the efficacy of temozolomide. Taken together, our results show how DcR1 upregulation mediates temozolomide resistance and provide a rationale for DcR1 targeting as a strategy to sensitize gliomas to this widely used chemotherapy. ©2015 American Association for Cancer Research.

Decoy receptor 3 inhibits renal mononuclear leukocyte infiltration and apoptosis and prevents progression of IgA nephropathy in mice.

PubMed

Ka, Shuk-Man; Hsieh, Tai-Tzu; Lin, Shih-Hua; Yang, Sung-Sen; Wu, Chin-Chen; Sytwu, Huey-Kang; Chen, Ann

2011-12-01

The progression of IgA nephropathy (IgAN), the most frequent type of primary glomerulonephritis, is associated with high levels of mononuclear leukocyte infiltration into the kidney. These cells consist mainly of T cells and macrophages. Our previous study showed that a decoy receptor 3 (DCR3) gene therapy can prevent the development of a mouse autoimmune glomerulonephritis model by its potent immune modulating effects (Ka SM, Sytwu HK, Chang DM, Hsieh SL, Tsai PY, Chen A. J Am Soc Nephrol 18: 2473-2485, 2007). Here, we tested the hypothesis that DCR3 might prevent the progression of IgAN, an immune complex-mediated primary glomerulonephritis, by inhibiting T cell activation, renal T cell/macrophage infiltration, and protecting the kidney from apoptosis. We used a progressive IgAN (Prg-IgAN) model in B cell-deficient mice, because the mice are characterized by a dramatic proliferation of activated T cells systemically and progressive NF-κB activation in the kidney. We treated the animals with short-term gene therapy with DCR3 plasmids by hydrodynamics-based gene delivery. When the mice were euthanized on day 21, we found that, compared with empty vector-treated (disease control) Prg-IgAN mice, DCR3 gene therapy resulted in 1) systemic inhibition of T cell activation and proliferation; 2) lower serum levels of proinflammatory cytokines; 3) improved proteinuria, renal function, and renal pathology (inhibiting the development of marked glomerular proliferation, crescent formation, glomerulosclerosis, and interstitial inflammation); 5) suppression of T cell and macrophage infiltration into the periglomerular interstitium of the kidney; and 5) a reduction in apoptotic figures in the kidney. On the basis of these findings, DCR3 might be useful therapeutically in preventing the progression of IgAN.

Reduction of Decoy Receptor 3 Enhances TRAIL-Mediated Apoptosis in Pancreatic Cancer

PubMed Central

Wang, Wei; Yang, Shanmin; Su, Ying; Zhang, Hengshan; Liu, Chaomei; Li, Xinfeng; Lin, Ling; Kim, Sunghee; Okunieff, Paul; Zhang, Zhenhuan; Zhang, Lurong

2013-01-01

Most human pancreatic cancer cells are resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. However, the mechanisms by which pancreatic cancer cells utilize their extracellular molecules to counteract the proapoptotic signaling mediated by the TNF family are largely unknown. In this study, we demonstrate for the first time that DcR3, a secreted decoy receptor that malignant pancreatic cancer cells express at a high level, acts as an extracellular antiapoptotic molecule by binding to TRAIL and counteracting its death-promoting function. The reduction of DcR3 with siRNA unmasked TRAIL and greatly enhanced TRAIL-induced apoptosis. Gemcitabine, a first-line drug for pancreatic cancer, also reduced the level of DcR3. The addition of DcR3 siRNA further enhanced gemcitabine-induced apoptosis. Notably, our in vivo study demonstrated that the therapeutic effect of gemcitabine could be enhanced via further reduction of DcR3, suggesting that downregulation of DcR3 in tumor cells could tip the balance of pancreatic cells towards apoptosis and potentially serve as a new strategy for pancreatic cancer therapy. PMID:24204567

Reduction of decoy receptor 3 enhances TRAIL-mediated apoptosis in pancreatic cancer.

PubMed

Wang, Wei; Zhang, Mei; Sun, Weimin; Yang, Shanmin; Su, Ying; Zhang, Hengshan; Liu, Chaomei; Li, Xinfeng; Lin, Ling; Kim, Sunghee; Okunieff, Paul; Zhang, Zhenhuan; Zhang, Lurong

2013-01-01

Most human pancreatic cancer cells are resistant to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. However, the mechanisms by which pancreatic cancer cells utilize their extracellular molecules to counteract the proapoptotic signaling mediated by the TNF family are largely unknown. In this study, we demonstrate for the first time that DcR3, a secreted decoy receptor that malignant pancreatic cancer cells express at a high level, acts as an extracellular antiapoptotic molecule by binding to TRAIL and counteracting its death-promoting function. The reduction of DcR3 with siRNA unmasked TRAIL and greatly enhanced TRAIL-induced apoptosis. Gemcitabine, a first-line drug for pancreatic cancer, also reduced the level of DcR3. The addition of DcR3 siRNA further enhanced gemcitabine-induced apoptosis. Notably, our in vivo study demonstrated that the therapeutic effect of gemcitabine could be enhanced via further reduction of DcR3, suggesting that downregulation of DcR3 in tumor cells could tip the balance of pancreatic cells towards apoptosis and potentially serve as a new strategy for pancreatic cancer therapy.

Endoscopic laser-assisted dacryocistorhinostomy DCR with the placement of a customised silicone and Teflon bicanalicular stent Endoscopic laser-assisted dacryocystorhinostomy (DCR).

PubMed

D'Ecclesia, A; Cocchi, R F; Giordano, F; Mazzilli, E; Longo, C; Laborante, A

We present our experience in endoscopic laser assisted dacryocystorhinostomy (DCR) analyzing the results obtained with a new technique that involves placing bicanalicolar silicone stent more Teflon tube, in combination with paraseptal silastic sheet. In our study 49 of 57 patients (85%) at a mean follow up of at least 12 months have not reported epiphora or more episodes of acute dacryocystitis. 49 out of the 57 patients (85%) in our group reported no additional epiphora or episodes of acute dacryocystitis. Endoscopic DCR is currently the gold standard for sac and post-sac stenosis given the minimal invasiveness of the procedure and the long-term results that appear comparable to those obtained with extrinsic DCR. The principal problem is cicatricial stenosis that can occlude the stoma over time.

Flexible ultrathin-body single-photon avalanche diode sensors and CMOS integration.

PubMed

Sun, Pengfei; Ishihara, Ryoichi; Charbon, Edoardo

2016-02-22

We proposed the world's first flexible ultrathin-body single-photon avalanche diode (SPAD) as photon counting device providing a suitable solution to advanced implantable bio-compatible chronic medical monitoring, diagnostics and other applications. In this paper, we investigate the Geiger-mode performance of this flexible ultrathin-body SPAD comprehensively and we extend this work to the first flexible SPAD image sensor with in-pixel and off-pixel electronics integrated in CMOS. Experimental results show that dark count rate (DCR) by band-to-band tunneling can be reduced by optimizing multiplication doping. DCR by trap-assisted avalanche, which is believed to be originated from the trench etching process, could be further reduced, resulting in a DCR density of tens to hundreds of Hertz per micrometer square at cryogenic temperature. The influence of the trench etching process onto DCR is also proved by comparison with planar ultrathin-body SPAD structures without trench. Photon detection probability (PDP) can be achieved by wider depletion and drift regions and by carefully optimizing body thickness. PDP in frontside- (FSI) and backside-illumination (BSI) are comparable, thus making this technology suitable for both modes of illumination. Afterpulsing and crosstalk are negligible at 2µs dead time, while it has been proved, for the first time, that a CMOS SPAD pixel of this kind could work in a cryogenic environment. By appropriate choice of substrate, this technology is amenable to implantation for biocompatible photon-counting applications and wherever bended imaging sensors are essential.

Crystal Structure of the Complex of Human FasL and Its Decoy Receptor DcR3.

PubMed

Liu, Weifeng; Ramagopal, Udupi; Cheng, Huiyong; Bonanno, Jeffrey B; Toro, Rafael; Bhosle, Rahul; Zhan, Chenyang; Almo, Steven C

2016-11-01

The apoptotic effect of FasL:Fas signaling is disrupted by DcR3, a unique secreted member of the tumor necrosis factor receptor superfamily, which also binds and neutralizes TL1A and LIGHT. DcR3 is highly elevated in patients with various tumors and contributes to mechanisms by which tumor cells to evade host immune surveillance. Here we report the crystal structure of FasL in complex with DcR3. Comparison of FasL:DcR3 structure with our earlier TL1A:DcR3 and LIGHT:DcR3 structures supports a paradigm involving the recognition of invariant main-chain and conserved side-chain functionalities, which is responsible for the recognition of multiple TNF ligands exhibited by DcR3. The FasL:DcR3 structure also provides insight into the FasL:Fas recognition surface. We demonstrate that the ability of recombinant FasL to induce Jurkat cell apoptosis is significantly enhanced by native glycosylation or by structure-inspired mutations, both of which result in reduced tendency to aggregate. All of these activities are efficiently inhibited by recombinant DcR3. Copyright © 2016 Elsevier Ltd. All rights reserved.

Crizotinib in patients with anaplastic lymphoma kinase-positive advanced non-small cell lung cancer versus chemotherapy as a first-line treatment.

PubMed

Zhou, Jianya; Zheng, Jing; Zhang, Xiaochen; Zhao, Jing; Zhu, Yanping; Shen, Qian; Wang, Yuehong; Sun, Ke; Zhang, Zeying; Pan, Zhijie; Shen, Yihong; Zhou, Jianying

2018-01-03

To compare the efficacy of crizotinib, pemetrexed and other chemotherapy regimens as a first-line treatment in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in real world clinical use and to evaluate the +86-571-87,236,876 predictive clinical factors of the efficacy of crizotinib. The 73 patients with ALK-positive advanced NSCLC were divided into three groups based on the first-line treatment: first-line crizotinib group (1-CRZ group, n = 32); first-line platinum-based pemetrexed treatment group (1-PP group, n = 28), and first-line chemotherapy platinum-based non-pemetrexed group (N1-PP, n = 12). Sixty eight of the 73 patients received crizotinib treatment and followed up in our hospital. Differences in the objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were compared in the different groups. The clinical factors were evaluated to predict the efficacy of crizotinib by the Kaplan-Meier survival analysis and Cox proportional hazards model. The PFS, ORR, DCR were 16.1 months, 78.1% (25/32) and 100% (32/32) in the 1-CRZ group; were 6.0 months, 17.9% (5/28) and 57.2% (16/28) in the 1-PP group; and were 2.9 months, 15.4% (2/13) and 46.2% (6/13) in the N1-PP group. The PFS of the 1-CRZ group was significantly longer than that of the 1-PP group (P < 0.001) and the N1-PP group (P < 0.001). The ORR and DCR of the 1-CRZ group was significantly greater than that of the 1-PP group and the N1-PP group (all the P < 0.001). Higher Eastern Cooperative Oncology Group (ECOG) performance status score (> = 2) (HR 2.345, 95% CI 1.137-4.834, P = 0.021) and patients received crizotinib after N1-PP chemotherapy (HR 2.345, 95% CI 1.137-4.834, P = 0.021) were two factors associated with shorter PFS after crizotinib treatment. In patients with ALK-positive NSCLC who did not receive previous treatment, crizotinib was superior to standard chemotherapy for the longer PFS and greater ORR and DCR. Higher ECOG score (> = 2) and patients received crizotinib after N1-PP chemotherapy predict poor efficacy of crizotinib.

Evaluation of dried vegetables residues for poultry: II. Effects of feeding cabbage leaf residues on broiler performance, ileal digestibility and total tract nutrient digestibility.

PubMed

Mustafa, A F; Baurhoo, B

2017-03-01

A study was conducted to investigate the effects of partial replacing corn and soybean meal with dried cabbage leaf residues (DCR) on broiler growth performance, apparent ileal nutrient digestibility, and apparent total tract nutrient utilization. Dietary treatments include 4 levels of DCR (0, 3, 6, and 9%). Two hundred and twenty-four day-old male broilers were randomly assigned to one of 4 groups (8 cage replicates; 7 birds/cage) and grown over a 35-d experimental period. Results showed that feeding DCR had no effects on daily body weigh gain (average 53.4 g/d), daily feed intake (average 94.9 g/d), and feed conversion ratio (average 1.78 g of feed/g of gain). Inclusion of DCR reduced apparent ileal DM (quadratic effect, P < 0.001), OM (linear effect, P = 0.012), and CP (quadratic effect, P = 0.001) digestibility of younger birds (d 21) while incremental levels of DCR had no effect on apparent ileal nutrient digestibilities of older birds (d 35). Apparent total tract digestibility of DM, OM, and CP increased (linear effect, P < 0.001) as the level of DCR increased. It was concluded that the inclusion of DCR in broiler diets up to 9% had no negative impact on bird performance and apparent ileal digestibility of older birds and improved apparent total tract nutrient digestibility. © 2016 Poultry Science Association Inc.

Serum and synovial fluid levels of tumor necrosis factor-like ligand 1A and decoy receptor 3 in rheumatoid arthritis.

PubMed

Xiu, Zijuan; Shen, Hui; Tian, Ye; Xia, Liping; Lu, Jing

2015-04-01

To measure the levels of Tumor necrosis factor (TNF)-like ligand 1A (TL1A) and decoy receptor 3 (DcR3) in serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA). To evaluate the effect of recombinant human (rh) TL1A on interleukin (IL)-17 production and IL-17mRNA expression. The serum and SF levels of TL1A and DcR3, and the production of IL-17 by rhTL1A-treated PBMC were measured by enzyme-linked immunosorbent assay (ELISA). The expression of IL-17 mRNA by rhTL1A-treated PBMC was measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR). We also tested the change of TL1A and DcR3 level following TNF-α blockade therapy. Serum TL1A and DcR3 levels were higher in RA patients. This increase was more significant in RF and anti-CCP positive patients. TL1A and DcR3 levels were higher in SF samples than in paired sera. TL1A and DcR3 decreased after anti-TNF treatment. rhTL1A increased the production of IL-17 protein and the expression of IL-17mRNA. TL1A and DcR3 may be of pathogenic and potentially of therapeutic importance in RA patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oxaliplatin-Based Doublets Versus Cisplatin or Carboplatin-Based Doublets in the First-Line Treatment of Advanced Nonsmall Cell Lung Cancer.

PubMed

Yu, Jing; Xiao, Jing; Yang, Yifan; Cao, Bangwei

2015-07-01

The efficacy and toxicity of oxaliplatin-based versus carboplatin/cisplatin-based doublets in patients with previously untreated nonsmall cell lung cancer (NSCLC) have been compared.We searched published randomized controlled trials of oxaliplatin-based or carboplatin/cisplatin-based medications for NSCLC. A fixed effect model was used to analyze outcomes which were expressed as the hazard ratio for overall survival (OS) and time-to-progression (TTP), relative risk, overall response rate (ORR), disease control rate (DCR), 1-year survival, and the odds ratios for toxicity were pooled.Eight studies involving 1047 patients were included. ORR tended to favor carboplatin/cisplatin but the effect was not significantly different compared with oxaliplatin doublets (P = 0.05). The effects of OS, TTP, DCR, and 1-year survival between the 2 regimens were comparable. Oxaliplatin doublets caused less grade 3/4 leukocytopenia and neutropenia. Grades 3 to 4 nonhematological toxicities and grades 3 to 4 hematological toxicities showed little difference between oxaliplatin doublets and carboplatin/cisplatin doublets.Meta-analysis shows that the efficacy of oxaliplatin doublets is similar to that of other currently used platinum doublets. The lack of significant differences in the statistic analysis does not preclude genuine differences in clinical efficacy, because higher diversities between the studies covered differences between the 2 groups in each study. Oxaliplatin combined with a third-generation agent should be considered for use as alternative chemotherapy in patients who cannot tolerate conventional platinum-based regimens because the toxicity profile is much more favorable.

Efficacy and safety of Apatinib in stage IV sarcomas: experience of a major sarcoma center in China.

PubMed

Li, Feng; Liao, Zhichao; Zhao, Jun; Zhao, Gang; Li, Xubin; Du, Xiaoling; Yang, Yun; Yang, Jilong

2017-09-08

This study was conducted to review the efficacy and safety of Apatinib in stage IV sarcoma patients who failed previous chemotherapy. The clinical information on 16 patients with stage IV sarcomas who failed in prior chemotherapy and subsequently received Apatinib treatment was collected. Apatinib was given 500mg/daily and 4 weeks as a cycle. All patients had at least one measurable extracranial tumor according to Response Evaluation Criteria In Solid Tumors 1.0 criteria. Progression free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment-related adverse effects (AEs) were reviewed and evaluated. Patients was administered Apatinib for 0 to 9 cycles with the median of 3.2 cycles. Median follow-up time was 8.4 months (1 to 12 months). Ten of 16 patients received at least 1 complete cycle of Apatinib treatment were eligible for the efficacy analysis. The median PFS was 8.84 months. Two patients achieved partial response (PR) and 6 patients achieved stable disease (SD). Two patients were evaluated as progression disease (PD) and one patient died of disease progression. The ORR was 20.0% (2/10) and the DCR was 80.0% (8/10). The most common grade 3/4 treatment-related AEs were hypertension (18.7%), hand-foot syndrome (12.5%) and proteinuria (6.3%). No drug-related severe AEs occurred. CApatinib treatment in this exploratory study exhibited objective efficacy and manageable toxicity in stage IV sarcoma patients who failed in chemotherapy. This result supports future random controlled trial to further define Apatinib activity in stage IV sarcomas.

Fully integrated free-running InGaAs/InP single-photon detector for accurate lidar applications.

PubMed

Yu, Chao; Shangguan, Mingjia; Xia, Haiyun; Zhang, Jun; Dou, Xiankang; Pan, Jian-Wei

2017-06-26

We present a fully integrated InGaAs/InP negative feedback avalanche diode (NFAD) based free-running single-photon detector (SPD) designed for accurate lidar applications. A free-piston Stirling cooler is used to cool down the NFAD with a large temperature range, and an active hold-off circuit implemented in a field programmable gate array is applied to further suppress the afterpulsing contribution. The key parameters of the free-running SPD including photon detection efficiency (PDE), dark count rate (DCR), afterpulse probability, and maximum count rate (MCR) are dedicatedly optimized for lidar application in practice. We then perform a field experiment using a Mie lidar system with 20 kHz pulse repetition frequency to compare the performance between the free-running InGaAs/InP SPD and a commercial superconducting nanowire single-photon detector (SNSPD). Our detector exhibits good performance with 1.6 Mcps MCR (0.6 μs hold-off time), 10% PDE, 950 cps DCR, and 18% afterpulse probability over 50 μs period. Such performance is worse than the SNSPD with 60% PDE and 300 cps DCR. However, after performing a specific algorithm that we have developed for afterpulse and count rate corrections, the lidar system performance in terms of range-corrected signal (Pr 2 ) distribution using our SPD agrees very well with the result using the SNSPD, with only a relative error of ∼2%. Due to the advantages of low-cost and small size of InGaAs/InP NFADs, such detector provides a practical solution for accurate lidar applications.

[Association of serum decoy receptor 3 protein level with the clinicopathologic features of bladder transitional cell carcinoma].

PubMed

Wang, Dong; Wang, Jian; Chen, Guojun

2013-12-01

To investigate the association of serum levels of decoy receptor 3(DcR3) protein and the clinicopathologic features of bladder transitional cell carcinoma. Enzyme-linked immunosorbent assay was used to examine the serum levels of DcR3 in patients with bladder transitional cell carcinoma for analysis of its association with the patients' age, gender, clinical stages and pathological classification. The patients with bladder transitional cell carcinoma showed a significantly elevated serum level of DcR3 (183.43 ∓78.45 pg/m1) compared with the normal level (116.65∓97.43 pg/m1, P<0.05). The serum level of DcR3 in the patients showed close correlations with the TNM stage and pathological classification of the tumor (P<0.05) but not with the patients' age or gender (P>0.05). In patients with bladder transitional cell carcinoma, a high serum level of DcR3 suggests a higher malignancy of the tumor.

A tissue microarray study of toll-like receptor 4, decoy receptor 3, and external signal regulated kinase 1/2 expressions in astrocytoma.

PubMed

Lin, Chih-Kung; Ting, Chun-Chieh; Tsai, Wen-Chiuan; Chen, Yuan-Wu; Hueng, Dueng-Yuan

2016-01-01

Decoy receptor 3 (DcR3) functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor family. It is highly expressed in many tumors and its expression can be regulated by the MAPK/ERK signaling pathway and ERK is a vital member of this pathway. Toll-like receptor 4 (TLR4) is expressed on immune cells. Increased TLR4 expression has been associated with various types of cancers. The study was conducted to investigate the expression of DcR3, ERK1/2, and TLR4 in astrocytomas and evaluate if they are validating markers for discriminating glioblastoma from anaplastic astrocytoma in limited surgical specimen. Expression of DcR3, ERK1/2, and TLR4 was determined by immunohistochemical staining of tissue microarray from 48 paraffin-embedded tissues. A binary logistic regression method was used to generate functions that discriminate between anaplastic astrocytomas and glioblastomas. The expression of TLR4 and DcR3 was significantly higher in glioblastomas than in anaplastic astrocytomas. DcR3 could discriminate anaplastic astrocytomas from glioblastomas with high sensitivity (93.8%), specificity (90%), and accuracy (92.3%). Our results suggest that DcR3 may be a useful marker for discriminating anaplastic astrocytomas from glioblastomas.

Mechanisms of the prevention and inhibition of the progression and development of non-alcoholic steatohepatitis by genetic and pharmacological decoy receptor 3 supplementation.

PubMed

Lee, Pei-Chang; Yang, Ling-Yu; Wang, Ying-Wen; Huang, Shiang-Fen; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Yang, Ying-Ying; Hsieh, Shie-Liang; Hou, Ming-Chih; Lin, Han-Chieh; Lee, Fa-Yuah; Lee, Shou-Dong

2017-11-01

Treatment of non-alcoholic steatohepatitis (NASH) is difficult due to the absence of a proven treatment and its comprehensive mechanisms. In the NASH animal model, upregulated hepatic inflammation and oxidative stress, with the resultant M1 polarization of macrophages as well as imbalanced adipocytokines, all accelerate NASH progression. As a member of the tumor necrosis factor receptor superfamily, decoy receptor 3 (DcR3) not only neutralizes the death ligands, but also performs immune modulations. In this study, we aimed to investigate the possible non-decoy effects of DcR3 on diet-induced NASH mice. Methionine- and choline-deficient (MCD) diet feeding for 9 weeks was applied to induce NASH in BALB/c mice. Decoy receptor 3 heterozygous transgenesis or pharmacological pretreatment with DcR3a for 1 month were designed as interventions. Intrahepatic inflammatory status as well as macrophage polarization, oxidative stress, and steatosis as well as lipogenic gene expression and fibrotic status were analyzed. Additionally, acute effects of DcR3a on HepG2 cells, Hep3B cells, and primary mouse hepatocytes in various MCD medium-stimulated changes were also evaluated. Both DcR3 genetic and pharmacologic supplement significantly reduced MCD diet-induced hepatic M1 polarization. In addition, DcR3 supplement attenuated MCD diet-increased hepatic inflammation, oxidative stress, adipocytokine imbalance, steatosis, and fibrogenesis. Moreover, acute DcR3a incubation in HepG2 cells, Hep3B cells, and mouse hepatocytes could normalize the expression of genes related to lipid oxidation along with inflammation and oxidative stress. The ability of DcR3 to attenuate hepatic steatosis and inflammation through its non-decoy effects of immune modulation and oxidative stress attenuation makes it a potential treatment for NASH. © 2017 The Japan Society of Hepatology.

Designing in vivo concentration gradients with discrete controlled release: a computational model

NASA Astrophysics Data System (ADS)

Walker, Edgar Y.; Barbour, Dennis L.

2010-08-01

One promising neurorehabilitation therapy involves presenting neurotrophins directly into the brain to induce growth of new neural connections. The precise control of neurotrophin concentration gradients deep within neural tissue that would be necessary for such a therapy is not currently possible, however. Here we evaluate the theoretical potential of a novel method of drug delivery, discrete controlled release (DCR), to control effective neurotrophin concentration gradients in an isotropic region of neocortex. We do so by constructing computational models of neurotrophin concentration profiles resulting from discrete release locations into the cortex and then optimizing their design for uniform concentration gradients. The resulting model indicates that by rationally selecting initial neurotrophin concentrations for drug-releasing electrode coatings in a square 16-electrode array, nearly uniform concentration gradients (i.e. planar concentration profiles) from one edge of the electrode array to the other should be obtainable. DCR therefore represents a promising new method of precisely directing neuronal growth in vivo over a wider spatial profile than would be possible with single release points.

Thalidomide combined with transcatheter artierial chemoembolzation for primary hepatocellular carcinoma: a systematic review and meta-analysis

PubMed Central

Cao, De-Dong; Xu, Hui-Lin; Liu, Liang; Zheng, Yong-Fa; Gao, Si-Fa; Xu, Xi-Ming; Ge, Wei

2017-01-01

Objective Transcatheter arterial chemoembolization (TACE) and thalidomide have been used for treating primary hepatocellular carcinoma(HCC). This study aims to evaluate the clinical efficacy and safety of thalidomide and TACE in primary HCC. Methods Randomized controlled trials(RCTs) about efficacy and safety of thalidomide combined with TACE for primary HCC were identified from the Cochrane Library, Pubmed, Embase, CNKI, and Wan Fang until August, 2016. The retrieved trials were reviewed and the data were extracted by two reviewers, independently. Combined analyses of survival rates, overall response rate(ORR), disease control rate(DCR), changes of KPS, parameters of cellular immunity and vascular endothelial growth factor(VEGF), and adverse events were performed using RevMan 5.3 software. Results A total of 23 RCTs involving 1836 patients were included. The results showed that thalidomide plus TACE was significantly superior in increasing 6-month survival rate(OR=1.79, 95% CI:1.02-3.15, P=0.04), 1-year survival rate(OR=1.76, 95% CI:1.38-2.24, P<0.0001), 1.5-year survival rate(OR=4.72, 95% CI:2.64-8.43, P<0.001), 2-year survival rate(OR=1.78, 95% CI:1.37-2.30, P<0.001), ORR(OR=1.89, 95% CI:1.48-2.42, P<0.0001), DCR(OR=2.62, 95% CI:1.90-3.63, P<0.001), improvement in cellular immunity(MD=0.63, 95% CI:0.45-0.80, P<0.0001), and reduction of VEGF(MD=-119.71, 95% CI:-135.75—103.68, P<0.0001), when compared with TACE group. The incidences of gastrointestinal reactions, myelosuppression, and liver dysfunction were similar between combination group and TACE group(P>0.05). However, compared to TACE, the combination of thalidomide and TACE had a higher incidence of drug rash(OR=6.35, 95% CI:2.75-14.68, P<0.0001). Conclusion Our findings suggest that thalidomide combined with TACE shows better clinical efficacy and tolerable adverse events in patients with primary HCC when compared with TACE alone. PMID:28402958

Radiation Tests of Single Photon Avalanche Diode for Space Applications

NASA Technical Reports Server (NTRS)

Moscatelli, Francesco; Marisaldi, Martino; MacCagnani, Piera; Labanti, Claudio; Fuschino, Fabio; Prest, Michela; Berra, Alessandro; Bolognini, Davide; Ghioni, Massimo; Rech, Ivan;

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation.

PubMed

Fabi, Alessandra; Metro, Giulio; Russillo, Michelangelo; Vidiri, Antonello; Carapella, Carmine Maria; Maschio, Marta; Cognetti, Francesco; Jandolo, Bruno; Mirri, Maria Alessandra; Sperduti, Isabella; Telera, Stefano; Carosi, Mariantonia; Pace, Andrea

2009-03-31

In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m(2) weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting. 40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m(2) to 100 mg/m(2). Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients. Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine. Low-dose fotemustine at 65-75 mg/m(2) (induction phase) followed by 75-85 mg/m(2) (maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.

Usefulness of Circulating Decoy Receptor 3 in Predicting Coronary Artery Disease Severity and Future Major Adverse Cardiovascular Events in Patients With Multivessel Coronary Artery Disease.

PubMed

Chang, Ting-Yung; Hsu, Chien-Yi; Huang, Po-Hsun; Chiang, Chia-Hung; Leu, Hsin-Bang; Huang, Chin-Chou; Chen, Jaw-Wen; Lin, Shing-Jong

2015-10-01

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an antiapoptotic soluble receptor considered to play an important role in immune modulation and has pro-inflammatory functions. This study was designed to test whether circulating DcR3 levels are associated with coronary artery disease (CAD) severity and predict future major adverse cardiovascular events (MACEs) in patients with CAD. Circulating DcR3 levels and the Syntax score (SXscore) were determined in patients with multivessel CAD. The primary end point was the MACE within 12 months. In total, 152 consecutive patients with angiographically confirmed multivessel CAD who had received percutaneous coronary intervention were enrolled and were divided into 3 groups according to CAD lesion severity. Group 1 was defined as low SXscore (≤13), group 2 as intermediate SXscore (>13 and ≤22), and group 3 as high SXscore (>22). DcR3 levels were significantly higher in the high SXscore group than the other 2 groups (13,602 ± 7,256 vs 8,025 ± 7,789 vs 4,637 ± 4,403 pg/ml, p <0.001). By multivariate analysis, circulating DcR3 levels were identified as an independent predictor for high SXscore (adjusted odds ratio 1.15, 95% confidence interval 1.09 to 1.21; p <0.001). The Kaplan-Meier analysis showed that increased circulating DcR3 levels are associated with enhanced 1-year MACE in patients with multivessel CAD (log-rank p <0.001). In conclusion, increased circulating DcR3 levels are associated with CAD severity and predict future MACE in patients with multivessel CAD. Copyright © 2015 Elsevier Inc. All rights reserved.

Interaction between geriatric nutritional risk index and decoy receptor 3 predicts mortality in chronic hemodialysis patients.

PubMed

Tsai, Ming-Tsun; Hu, Fen-Hsiang; Lien, Tse-Jen; Chen, Ping-Jen; Huang, Tung-Po; Tarng, Der-Cherng

2014-01-01

Protein-energy wasting (PEW) is common and associated with poor outcome in hemodialysis patients. In hemodialysis patients, geriatric nutritional risk index (GNRI) and decoy receptor 3 (DcR3) have been shown as the nutritional and inflammatory markers, respectively. The present study aimed to assess the predictive ability of GNRI and DcR3 for PEW status and long-term outcomes in chronic hemodialysis patients. A prospective cohort of 318 hemodialysis patients was conducted with a median follow-up of 54 months. Malnutrition-inflammation score (MIS) was used as the reference standard for the presence of PEW. Endpoints were cardiovascular and all-cause mortality. Baseline GNRI had a strong negative correlation with DcR3 and MIS score. For patients with age < or ≥60, high DcR3 and low GNRI were independent predictors for the presence of PEW at baseline. At the end of the study, 81 patients died (27 cardiovascular deaths). The adjusted hazard ratios (95% confidence intervals) of low GNRI and high DcR3 were 1.93 (1.1-4.8) and 2.53 (1.2-5.5) for cardiovascular mortality and 1.85 (1.1-3.2) and 2.37 (1.5-3.7) for all-cause mortality, respectively. While integrated into a model of conventional risk factors, GNRI together with DcR3 further significantly improved the predictability for overall mortality (c statistic, 0.823). Low GNRI and high DcR3 were the alternatives for identifying hemodialysis patients at risk of PEW and overall mortality. Further studies are needed to verify whether timely recognition of hemodialysis patients with a high malnutrition-inflammation risk could reduce their mortality by appropriate interventional strategies.

Studies of Human 2,4-Dienoyl CoA Reductase Shed New Light on Peroxisomal β-Oxidation of Unsaturated Fatty Acids

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

Hua, Tian; Wu, Dong; Ding, Wei

2012-10-15

Peroxisomes play an essential role in maintaining fatty acid homeostasis. Although mitochondria are also known to participate in the catabolism of fatty acids via β-oxidation, differences exist between the peroxisomal and mitochondrial β-oxidation. Only peroxisomes, but not mitochondrion, can shorten very long chain fatty acids. Here, we describe the crystal structure of a ternary complex of peroxisomal 2,4-dienoyl CoA reductases (pDCR) with hexadienoyl CoA and NADP, as a prototype for comparison with the mitochondrial 2,4-dienoyl CoA reductase (mDCR) to shed light on the differences between the enzymes from the two organelles at the molecular level. Unexpectedly, the structure of pDCRmore » refined to 1.84 Å resolution reveals the absence of the tyrosine-serine pair seen in the active site of mDCR, which together with a lysine and an asparagine have been deemed a hallmark of the SDR family of enzymes. Instead, aspartate hydrogen-bonded to the Cα hydroxyl via a water molecule seems to perturb the water molecule for protonation of the substrate. Our studies provide the first structural evidence for participation of water in the DCR-catalyzed reactions. Biochemical studies and structural analysis suggest that pDCRs can catalyze the shortening of six-carbon-long substrates in vitro. However, the Km values of pDCR for short chain acyl CoAs are at least 6-fold higher than those for substrates with 10 or more aliphatic carbons. Unlike mDCR, hinge movements permit pDCR to process very long chain polyunsaturated fatty acids.« less

Comparative Evaluation of the Ostium After External and Nonendoscopic Endonasal Dacryocystorhinostomy Using Image Processing (Matlabs and Image J) Softwares.

PubMed

Ganguly, Anasua; Kaza, Hrishikesh; Kapoor, Aditya; Sheth, Jenil; Ali, Mohammad Hasnat; Tripathy, Devjyoti; Rath, Suryasnata

The purpose of this study was to compare the characteristics of the ostium after external dacryocystorhinostomy and nonendoscopic endonasal dacryocystorhinostomy (NEN-DCR). This cross-sectional study included patients who underwent a successful external dacryocystorhinostomy or NEN-DCR and had ≥1 month follow up. Pictures of the ostium were captured with a nasal endoscope (4 mm, 30°) after inserting a lacrimal probe premarked at 2 mm. Image analyses were performed using Image J and Contour softwares. Of the 113 patients included, external dacryocystorhinostomy group had 53 patients and NEN-DCR group had 60 patients. The mean age of patients in the NEN-DCR group (38 years) was significantly (p < 0.05) lower than the external dacryocystorhinostomy group (50 years). There was no statistically significant difference (2 sample t test, p > 0.05) in mean follow up (6 vs. 4 months), maximum diameter of ostium (8 vs. 7 mm), perpendicular drawn to it (4 vs. 4 mm), area of ostium (43 vs. 36 mm), and the minimum distance between common internal punctum and edge of the ostium (1 vs. 1 mm) between the external and NEN-DCR groups. Image processing softwares offer simple and objective method to measure the ostium. While ostia are comparable in size, their relative position differs with posteriorly placed ostia in external compared with inferior in NEN-DCR.

Predictive value of decoy receptor 3 in postoperative nosocomial bacterial meningitis.

PubMed

Liu, Yong-Juan; Shao, Li-Hua; Wang, Qian; Zhang, Jian; Ma, Rui-Ping; Liu, Hai-Hong; Dong, Xiao-Meng; Ma, Li-Xian

2014-11-03

Nosocomial bacterial meningitis requires timely treatment, but what is difficult is the prompt and accurate diagnosis of this disease. The aim of this study was to assess the potential role of decoy receptor 3 (DcR3) levels in the differentiation of bacterial meningitis from non-bacterial meningitis. A total of 123 patients were recruited in this study, among them 80 patients being with bacterial meningitis and 43 patients with non-bacterial meningitis. Bacterial meningitis was confirmed by bacterial culture of cerebrospinal fluid (CSF) culture and enzyme-linked immunosorbent assay (ELISA) was used to detect the level of DcR3 in CSF. CSF levels of DcR3 were statistically significant between patients with bacterial meningitis and those with non-bacterial meningitis (p<0.001). A total of 48.75% of patients with bacterial meningitis received antibiotic>24 h before CSF sampling, which was much higher than that of non-bacterial meningitis. CSF leucocyte count yielded the highest diagnostic value, with an area under the receiver operating characteristic curve (ROC) of 0.928, followed by DcR3. At a critical value of 0.201 ng/mL for DcR3, the sensitivity and specificity were 78.75% and 81.40% respectively. DcR3 in CSF may be a valuable predictor for differentiating patients with bacterial meningitis from those with non-bacterial meningitis. Further studies are needed for the validation of this study.

The relationship of plasma decoy receptor 3 and coronary collateral circulation in patients with coronary artery disease.

PubMed

Yan, Youyou; Song, Dandan; Liu, Lulu; Meng, Xiuping; Qi, Chao; Wang, Junnan

2017-11-15

Previously, decoy receptor 3 (DcR3) was found to be a potential angiogenetic factor, while the relationship of DcR3 with coronary collateral circulation formation has not been investigated. In this study, we aimed to investigate whether plasma decoy receptor 3 levels was associated with CCC formation and evaluate its predictive power for CCC status in patients with coronary artery disease. Among patients who underwent coronary angiography with coronary artery disease and had a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrope Cohen classification. Patients with grade 2 or 3 collateral degree were enrolled in good CCC group and patients with grade 0 or 1 collateral degree were enrolled in poor CCC group. Plasma DcR3 level was significantly higher in good CCC group (328.00±230.82 vs 194.84±130.63ng/l, p<0.01) and positively correlated with Rentrope grade (p<0.01). In addition, plasma DcR3 was also positively correlated with VEGF-A. Both ROC (receiver operating characteristic curve) and multinomial logistical regression analysis showed that plasma DcR3 displayed potent predictive power for CCC status. Higher plasma DcR3 level was related to better CCC formation and displayed potent predictive power for CCC status. Copyright © 2017. Published by Elsevier Inc.

77 FR 44528 - Dry Cargo Residue Discharges in the Great Lakes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-30

...The Coast Guard proposes replacing its existing interim rule with a new rule to regulate the operation of U.S. and foreign vessels carrying bulk dry cargo such as limestone, iron ore, and coal on the U.S. waters of the Great Lakes, and the operation of U.S. bulk dry cargo vessels anywhere on the Great Lakes. Specifically, the Coast Guard proposes new requirements for the discharge of bulk dry cargo residue (DCR) on the U.S. waters of the Great Lakes. The Coast Guard also announces the availability of the tiered Draft Environmental Impact Statement (DEIS) prepared in support of this proposal. The proposed rule would continue to allow non-hazardous and non-toxic discharges of bulk DCR in limited areas of the Great Lakes. However, vessel owners and operators would need to minimize DCR discharges using methods they would be required to document in DCR management plans. The proposed rule would prohibit limestone and clean stone DCR discharges in some waters where they are now permitted. The proposed rule promotes the Coast Guard's strategic goals of maritime mobility and safety and protection of natural resources.

Decoy Strategies: The Structure of TL1A:DcR3 Complex

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

C Zhan; Y Patskovsky; Q Yan

2011-12-31

Decoy Receptor 3 (DcR3), a secreted member of the Tumor Necrosis Factor (TNF) receptor superfamily, neutralizes three different TNF ligands: FasL, LIGHT, and TL1A. Each of these ligands engages unique signaling receptors which direct distinct and critical immune responses. We report the crystal structures of the unliganded DcR3 ectodomain and its complex with TL1A, as well as complementary mutagenesis and biochemical studies. These analyses demonstrate that DcR3 interacts with invariant backbone and side-chain atoms in the membrane-proximal half of TL1A which supports recognition of its three distinct TNF ligands. Additional features serve as antideterminants that preclude interaction with other membersmore » of the TNF superfamily. This mode of interaction is unique among characterized TNF:TNFR family members and provides a mechanistic basis for the broadened specificity required to support the decoy function of DcR3, as well as for the rational manipulation of specificity and affinity of DcR3 and its ligands.« less

A phase II trial of carboplatin plus S-1 for elderly patients with advanced non-small-cell lung cancer with wild-type epidermal growth factor receptor: The Okayama Lung Cancer Study Group Trial 1202.

PubMed

Kuyama, Shoichi; Ochi, Nobuaki; Bessho, Akihiro; Hotta, Katsuyuki; Ikeda, Genyo; Kishino, Daizo; Kubo, Toshio; Harada, Daijiro; Fujimoto, Nobukazu; Nakanishi, Masamoto; Umeno, Takahiro; Okada, Toshiaki; Chikamori, Kenichi; Yamagishi, Tomoko; Ohashi, Kadoaki; Ichihara, Eiki; Takigawa, Nagio; Tanimoto, Mitsune; Kiura, Katsuyuki

2017-10-01

S-1 is an oral fluoropyrimidine-based combination of tegafur, gimeracil, and oteracil potassium. Although the combination of S-1 with carboplatin is a first-line chemotherapy regimen for advanced non-small cell lung cancer (NSCLC), the efficacy and safety of the regimen in the elderly remain unknown. The patient inclusion criteria were previously untreated advanced NSCLC, wild-type epidermal growth factor receptor, aged 70 years or more, and a performance status (PS) of 0-2. The patients received oral S-1 (40mg/m 2 , twice daily) for 2 weeks and carboplatin (area under the curve: 5) on day 1 every 4 weeks as induction treatment. After four induction cycles, S-1 alone (40mg/m 2 , twice daily) was administered for 2 weeks every 4 weeks as a maintenance therapy until disease progression. The primary endpoint was the overall response rate (ORR), which was expected to exceed 20%, and the secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and the toxicity profile. The associations between clinical outcomes and expression of genes such as thymidylate synthase and thymidine phosphorylase in the tumors were evaluated. Thirty-three patients were enrolled between March 2013 and June 2015. The median age was 78 (range 70-89) years, and 51.5% had a PS of 0. The ORR was 30.3% (95% confidence interval (CI): 14.6-46.0) and the DCR 57.6% (95% CI: 40.7-74.4). Grade 3/4 toxicities included thrombocytopenia (42.4%), neutropenia (33.3%), and anemia (27.3%). There was one treatment-related death due to aspiration pneumonia following febrile neutropenia. The median PFS and OS were 134days (95% CI: 79-173) and 479days (95% CI: 250-571), respectively. Low thymidine phosphorylase expression was associated with the DCR (P<0.01). This study met the predesigned primary endpoint, and the regimen seems to be a favorable treatment option. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of single agent versus combined chemotherapy in previously treated patients with advanced urothelial carcinoma: a meta-analysis.

PubMed

Wu, Xiao-Jun; Zhi, Yi; He, Peng; Zhou, Xiao-Zhou; Zheng, Ji; Chen, Zhi-Wen; Zhou, Zhan-Song

2016-01-01

Platinum-based chemotherapy is the standard treatment for advanced urothelial cancer (UC) and is generally used in the first-line setting. However, the optimal salvage treatment for previously treated UC patients is unclear. We conducted a systematic review of published clinical trials of single agent versus combined chemotherapy as salvage treatment in previously treated UC patients. Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All relevant studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS), and grade 3/4 toxicities were extracted and analyzed using Comprehensive Meta Analysis software (Version 2.0). Fifty cohorts with 1,685 patients were included for analysis: 814 patients were treated with single agent chemotherapy and 871 with combined chemotherapy. Pooled OS was significantly higher at 1 year for combined chemotherapy than for single agent (relative risk [RR] 1.52; 95% CI: 1.01-2.37; P=0.03) but not for 2-year OS (RR 1.31; 95% CI: 0.92-1.85; P=0.064). Additionally, combined chemotherapy significantly improved ORR (RR 2.25; 95% CI: 1.60-3.18; P<0.001) and DCR (RR 1.12; 95% CI: 1.01-1.25, P=0.033) compared to single agent for advanced UC patients. As for grade 3 and 4 toxicities, more frequencies of leukopenia and thrombocytopenia were observed in the combined chemotherapy than in single agent group, while equivalent frequencies of anemia, nausea, vomiting, and diarrhea were found between the two groups. In comparison with single agent alone, combined chemotherapy as salvage treatment for advanced UC patients significantly improved ORR, DCR, and 1-year OS, but not 2-year OS. Our findings support the need to compare combined chemotherapy with single agent alone in the salvage setting in large prospective trials due to its potential survival benefit in advanced UC patients.

A single-arm, multicenter, safety-monitoring, phase IV study of icotinib in treating advanced non-small cell lung cancer (NSCLC).

PubMed

Hu, Xingsheng; Han, Baohui; Gu, Aiqin; Zhang, Yiping; Jiao, Shun Chang; Wang, Chang-Li; He, Jintao; Jia, Xueke; Zhang, Li; Peng, Jiewen; Wu, Meina; Ying, Kejing; Wang, Junye; Ma, Kewei; Zhang, Shucai; You, Changxuan; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

2014-11-01

The phase 3 ICOGEN trial established the non-inferiority of icotinib to gefitinib in terms of progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients, and this led to the approval of icotinib for NSCLC by the China Food and Drug Administration. A phase 4 study was conducted to assess the safety and efficacy of icotinib in a broad range of patients with advanced NSCLC across China. This study retrospectively analyzed data from unresectable, recurrent, and/or advanced NSCLC patients who received oral icotinib 125 mg three times per day. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR) and disease control rate (DCR), which were investigated overall and in subgroups such as patients with an EGFR mutation and elderly patients. Between August, 2011 and August, 2012, a total of 6087 advanced NSCLC patients were registered in this study, of which 5549 were evaluable for safety and tumor response. The median age was 63 years (range 21-95 years), and 1571 (28.3%) patients were over the age of 70. The majority of patients were non-smokers, and had adenocarcinoma and stage IV disease. The overall incidence of adverse drug reactions (ADRs) of any grade was 31.5%. The most common ADRs included rash (17.4%) and diarrhea (8.5%), and three patients experienced interstitial lung disease (ILD). The ORR and DCR were 30.0% and 80.6%, respectively, for the overall population, and 33.4% and 81.2%, 30.3% and 80.3%, and 30.4% and 89.3%, for first-line, second-line, and third-line or multiple line subsets, respectively. In 665 EGFR-mutated patients who were evaluable for tumor response, the ORR and DCR were 49.2% (327/665) and 92.3% (614/665), respectively. The data from over 6000 patients was consistent with the results of the ICOGEN study. Icotinib demonstrated a favorable toxicity profile and efficacy in the routine clinical setting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Investigation of the Performance of an Ultralow-Dark-Count Superconducting Nanowire Single-Photon Detector

NASA Astrophysics Data System (ADS)

Subashchandran, Shanthi; Okamoto, Ryo; Zhang, Labao; Tanaka, Akira; Okano, Masayuki; Kang, Lin; Chen, Jian; Wu, Peiheng; Takeuchi, Shigeki

2013-10-01

The realization of an ultralow-dark-count rate (DCR) along with the conservation of high detection efficiency (DE) is critical for many applications using single photon detectors in quantum information technologies, material sciences, and biological sensing. For this purpose, a fiber-coupled superconducting nanowire single-photon detector (SNSPD) with a meander-type niobium nitride nanowire (width: 50 nm) is studied. Precise measurements of the bias current dependence of DE are carried out for a wide spectral range (from 500 to 1650 nm in steps of 50 nm) using a white light source and a laser line Bragg tunable band-pass filter. An ultralow DCR (0.0015 cps) and high DE (32%) are simultaneously achieved by the SNSPD at a wavelength of 500 nm.

NbN superconducting nanowire single-photon detector fabricated on MgF2 substrate

NASA Astrophysics Data System (ADS)

Wu, J. J.; You, L. X.; Zhang, L.; Zhang, W. J.; Li, H.; Liu, X. Y.; Zhou, H.; Wang, Z.; Xie, X. M.; Xu, Y. X.; Fang, W.; Tong, L. M.

2016-06-01

The performance of superconducting nanowire single-photon detectors (SNSPDs) relies on substrate materials. Magnesium fluoride (MgF2) exhibits outstanding optical properties, such as large optical transmission range and low refractive index (n = 1.38), making it an attractive substrate. We present the fabrication and the performance of SNSPDs made of a 4.5 nm thick NbN thin film deposited on MgF2 substrate for the wavelength of 1550 nm. The front-side illuminated SNSPDs without an optical cavity showed a maximal detection efficiency of 12.8% at a system dark count rate (DCR) of 100 Hz, while the backside illuminated SNSPDs with a SiO2/Au optical cavity atop displayed a maximal detection efficiency of 33% at a DCR of 100 Hz.

Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

PubMed Central

Fassan, Matteo; Indraccolo, Stefano; Calabrese, Fiorella; Favaretto, Adolfo; Bonanno, Laura; Polo, Valentina; Zago, Giulia; Lunardi, Francesca; Attili, Ilaria; Pavan, Alberto; Rugge, Massimo; Guarneri, Valentina; Conte, PierFranco; Pasello, Giulia

2017-01-01

Introduction Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm. Results Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm. Patients receiving first-line TKIs (N = 17) achieved median Progression Free Survival (PFS) and Overall Survival (OS) of 53 (IC 95%, 2–105) and 84 (CI 95%, 27–141) weeks respectively, without significant covariate impact. Response Rate and Disease Control Rate (DCR) were 47% and 65%, respectively. Uncommon exon 19 mutations achieved longer OS and PFS and higher DCR compared with exon 18 and 20 mutations. No additional gene mutation was discovered by MassARRAY analysis. TKIs were globally well tolerated. Materials and methods A retrospective review of advanced non-squamous NSCLC harbouring rare/complex EGFRm referred to our Center between 2010 and 2015 was performed. Additional molecular pathways disregulation was explored in selected cases, through MassARRAY analysis. Conclusions Peculiar clinical features and lower TKIs sensitivity of uncommon/complex compared with common EGFRm were shown. Exon 19 EGFRm achieved the best TKIs treatment outcome, while the optimal treatment of exon 18 and 20 mutations should be further clarified. PMID:28427238

Idiopathic pulmonary fibrosis fibroblasts become resistant to Fas ligand-dependent apoptosis via the alteration of decoy receptor 3.

PubMed

Im, Jintaek; Kim, Kyutae; Hergert, Polla; Nho, Richard Seonghun

2016-09-01

Idiopathic pulmonary fibrosis (IPF) is an irreversible lethal lung disease with an unknown etiology. IPF patients' lung fibroblasts express inappropriately high Akt activity, protecting them in response to an apoptosis-inducing type I collagen matrix. FasL, a ligand for Fas, is known to be increased in the lung tissues of patients with IPF, implicated with the progression of IPF. Expression of Decoy Receptor3 (DcR3), which binds to FasL, thereby subsequently suppressing the FasL-Fas-dependent apoptotic pathway, is frequently altered in various human disease. However, the role of DcR3 in IPF fibroblasts in regulating their viability has not been examined. We found that enhanced DcR3 expression exists in the majority of IPF fibroblasts on collagen matrices, resulting in the protection of IPF fibroblasts from FasL-induced apoptosis. Abnormally high Akt activity suppresses GSK-3β function, thereby accumulating the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) in the nucleus, increasing DcR3 expression in IPF fibroblasts. This alteration protects IPF cells from FasL-induced apoptosis on collagen. However, the inhibition of Akt or NFATc1 decreases DcR3 mRNA and protein levels, which sensitizes IPF fibroblasts to FasL-mediated apoptosis. Furthermore, enhanced DcR3 and NFATc1 expression is mainly present in myofibroblasts in the fibroblastic foci of lung tissues derived from IPF patients. Our results showed that when IPF cells interact with collagen matrix, aberrantly activated Akt increases DcR3 expression via GSK-3β-NFATc1 and protects IPF cells from the FasL-dependent apoptotic pathway. These findings suggest that the inhibition of DcR3 function may be an effective approach for sensitizing IPF fibroblasts in response to FasL, limiting the progression of lung fibrosis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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[Systematic review and Meta-analysis of Shenqi Fuzheng injection combined with first-line chemotherapy for non-small cell lung cancer].

PubMed

Hao, Teng-teng; Xie, Yan-ming; Liao, Xing; Wang, Jing

2015-10-01

The paper is to systematically evaluate the effect and safety of Shenqi Fuzheng injection (SFI) combined with first-line chemotherapy for non-small cell lung cancer (NSCLC). Randomized controlled trials (RCTs) on Shenqi Fuzheng injection (SFI) combined with first-line chemotherapy (experiment group) and chemotherapy alone group ( control group) were electronically retrieved from Medline, EMbase, Clinical Trials, Cochrane Library, CBM, CNKI, VIP, and Wanfang Data base. All trials were assessed for quality according to the Cochrane Reviewer's Handbook for Systematic Reviews of Intervention and then Meta-analysis was performed withRevMan5. 2 Software. A total of 43 RCTs (3433 patients) were included after screening and selecting. Results of Meta-analysis showed that: Objective remission rate (ORR): ORR of experimental group was about 20% higher than that of control group [RR = 1.23, 95% CI (1.11,1.35), P < 0.0001]. Disease control rate (DCR):DCR of SFI combined with first-line chemotherapy was 11% higher than that of first-line chemotherapy alone [RR = 1.11, 95% CI (1.07, 1.16), P < 0.000 01]. Life quality evaluated by Kosovan performance status (KPS) showed that: life quality improvement rate of experimental group was about twice of that in control group [RR = 2.02, 95% CI (1.81, 2.26), P < 0.000 01]. Toxic and side reaction analysis showed that: the incidence of side reactions in experimental group was about 50% lower than that in control group [RR = 0.59, 95% CI (0.53, 0.66), P < 0.000 01]. Immune function test showed that: the function of experimental group was 3.2 (standard deviations) times greater than that of control group [MD = 3.23, 95% CI (2.86, 3.60), P < 0.000 01]. We can see that SFI combined with first-line chemotherapy for NSCLC can increase objective efficacy, improve life quality, decrease toxic and side reactionsinduced by chemotherapy, and improve the immune functions. As most of the included studies in this systematic evaluation had poor quality, the evidence to support conclusion was weak, so it was necessary to conduct more multi-center clinical trials with high quality methods and rigorous design.

Predictive Value of Decoy Receptor 3 in Postoperative Nosocomial Bacterial Meningitis

PubMed Central

Liu, Yong-Juan; Shao, Li-Hua; Wang, Qian; Zhang, Jian; Ma, Rui-Ping; Liu, Hai-Hong; Dong, Xiao-Meng; Ma, Li-Xian

2014-01-01

Nosocomial bacterial meningitis requires timely treatment, but what is difficult is the prompt and accurate diagnosis of this disease. The aim of this study was to assess the potential role of decoy receptor 3 (DcR3) levels in the differentiation of bacterial meningitis from non-bacterial meningitis. A total of 123 patients were recruited in this study, among them 80 patients being with bacterial meningitis and 43 patients with non-bacterial meningitis. Bacterial meningitis was confirmed by bacterial culture of cerebrospinal fluid (CSF) culture and enzyme-linked immunosorbent assay (ELISA) was used to detect the level of DcR3 in CSF. CSF levels of DcR3 were statistically significant between patients with bacterial meningitis and those with non-bacterial meningitis (p < 0.001). A total of 48.75% of patients with bacterial meningitis received antibiotic >24 h before CSF sampling, which was much higher than that of non-bacterial meningitis. CSF leucocyte count yielded the highest diagnostic value, with an area under the receiver operating characteristic curve (ROC) of 0.928, followed by DcR3. At a critical value of 0.201 ng/mL for DcR3, the sensitivity and specificity were 78.75% and 81.40% respectively. DcR3 in CSF may be a valuable predictor for differentiating patients with bacterial meningitis from those with non-bacterial meningitis. Further studies are needed for the validation of this study. PMID:25372942

The TL1A/DR3/DcR3 pathway in autoimmune rheumatic diseases.

PubMed

Siakavellas, Spyros I; Sfikakis, Petros P; Bamias, Giorgos

2015-08-01

TNF-like cytokine 1A (TL1A) and its receptors, death receptor 3 (DR3) and decoy receptor 3 (DcR3) are members of the TNF and TNF receptor superfamilies of proteins, respectively. They constitute a cytokine system that actively interferes with the regulation of immune responses and may participate in the pathogenesis of autoimmune diseases. This review aims to present the current knowledge on the role of the TL1A/DR3/DcR3 system in the pathophysiology of autoimmune rheumatic diseases, with a focus on rheumatoid arthritis (RA). An extensive literature search was performed in the PubMed database using the following keywords: TL1A, death receptor 3, DR3, decoy receptor 3, DcR3, TNFSF15, TNFRSF25, and TNFSF6B. Studies were assessed and selected in view of their relevance to autoimmune rheumatic diseases. The TL1A/DR3/DcR3 axis is a novel immune pathway that participates in the pathogenesis of a variety of autoimmune rheumatic diseases. These molecules may be promising therapeutic targets for inflammatory arthritis. Copyright © 2015 Elsevier Inc. All rights reserved.

Significance of decoy receptor 3 (Dcr3) and external-signal regulated kinase 1/2 (Erk1/2) in gastric cancer.

PubMed

Yang, Donghai; Fan, Xin; Yin, Ping; Wen, Qiang; Yan, Feng; Yuan, Sibo; Liu, Bin; Zhuang, Guohong; Liu, Zhongchen

2012-06-06

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, is associated with anti-tumor immunity suppression. It is highly expressed in many tumors, and its expression can be regulated by the MAPK/MEK/ERK signaling pathway. The MAPK/MEK/ERK pathway has been reported to be a regulator in tumor occurrence, development and clonal expansion. External-signal regulated kinase (ERK) is a vital member of this pathway. The expression of DcR3 and ERK1/2 in tumor tissues of gastric cancer patients was significantly higher than the non-cancerous group (P < 0.05). There was no statistical difference among tumor tissues from patients with different ages or gender, and even of different differentiation (P > 0.05). However, in patients with stage I gastric cancer, the DcR3 and ERK1/2 levels were significantly lower than patients with more advanced stages. DcR3 and ERK1/2 play a vital role in the development of gastric cancer, and they may be new markers for indicating the efficiency of gastric cancer treatment in the future.

Decoy receptor 1 (DCR1) promoter hypermethylation and response to irinotecan in metastatic colorectal cancer

PubMed Central

Bosch, Linda J.W.; Coupé, Veerle M.H.; Mongera, Sandra; Haan, Josien C.; Richman, Susan D.; Koopman, Miriam; Tol, Jolien; de Meyer, Tim; Louwagie, Joost; Dehaspe, Luc; van Grieken, Nicole C.T.; Ylstra, Bauke; Verheul, Henk M.W.; van Engeland, Manon; Nagtegaal, Iris D.; Herman, James G.; Quirke, Philip; Seymour, Matthew T.; Punt, Cornelis J.A.; van Criekinge, Wim; Carvalho, Beatriz; Meijer, Gerrit A.

2017-01-01

Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients. Candidate genes were selected from 389 genes involved in DNA Damage Repair by correlation analyses between gene methylation status and drug response in 32 cell lines. A large series of samples (n=818) from two phase III clinical trials was used to evaluate these candidate genes by correlating methylation status to progression-free survival after treatment with first-line single-agent fluorouracil (Capecitabine or 5-fluorouracil) or combination chemotherapy (Capecitabine or 5-fluorouracil plus irinotecan (CAPIRI/FOLFIRI)). In the discovery (n=185) and initial validation set (n=166), patients with methylated Decoy Receptor 1 (DCR1) did not benefit from CAPIRI over Capecitabine treatment (discovery set: HR=1.2 (95%CI 0.7-1.9, p=0.6), validation set: HR=0.9 (95%CI 0.6-1.4, p=0.5)), whereas patients with unmethylated DCR1 did (discovery set: HR=0.4 (95%CI 0.3-0.6, p=0.00001), validation set: HR=0.5 (95%CI 0.3-0.7, p=0.0008)). These results could not be replicated in the external data set (n=467), where a similar effect size was found in patients with methylated and unmethylated DCR1 for FOLFIRI over 5FU treatment (methylated DCR1: HR=0.7 (95%CI 0.5-0.9, p=0.01), unmethylated DCR1: HR=0.8 (95%CI 0.6-1.2, p=0.4)). In conclusion, DCR1 promoter hypermethylation status is a potential predictive biomarker for response to treatment with irinotecan, when combined with capecitabine. This finding could not be replicated in an external validation set, in which irinotecan was combined with 5FU. These results underline the challenge and importance of extensive clinical evaluation of candidate biomarkers in multiple trials. PMID:28968978

Decoy receptor 1 (DCR1) promoter hypermethylation and response to irinotecan in metastatic colorectal cancer.

PubMed

Bosch, Linda J W; Trooskens, Geert; Snaebjornsson, Petur; Coupé, Veerle M H; Mongera, Sandra; Haan, Josien C; Richman, Susan D; Koopman, Miriam; Tol, Jolien; de Meyer, Tim; Louwagie, Joost; Dehaspe, Luc; van Grieken, Nicole C T; Ylstra, Bauke; Verheul, Henk M W; van Engeland, Manon; Nagtegaal, Iris D; Herman, James G; Quirke, Philip; Seymour, Matthew T; Punt, Cornelis J A; van Criekinge, Wim; Carvalho, Beatriz; Meijer, Gerrit A

2017-09-08

Diversity in colorectal cancer biology is associated with variable responses to standard chemotherapy. We aimed to identify and validate DNA hypermethylated genes as predictive biomarkers for irinotecan treatment of metastatic CRC patients. Candidate genes were selected from 389 genes involved in DNA Damage Repair by correlation analyses between gene methylation status and drug response in 32 cell lines. A large series of samples (n=818) from two phase III clinical trials was used to evaluate these candidate genes by correlating methylation status to progression-free survival after treatment with first-line single-agent fluorouracil (Capecitabine or 5-fluorouracil) or combination chemotherapy (Capecitabine or 5-fluorouracil plus irinotecan (CAPIRI/FOLFIRI)). In the discovery (n=185) and initial validation set (n=166), patients with methylated Decoy Receptor 1 ( DCR1) did not benefit from CAPIRI over Capecitabine treatment (discovery set: HR=1.2 (95%CI 0.7-1.9, p =0.6), validation set: HR=0.9 (95%CI 0.6-1.4, p =0.5)), whereas patients with unmethylated DCR1 did (discovery set: HR=0.4 (95%CI 0.3-0.6, p =0.00001), validation set: HR=0.5 (95%CI 0.3-0.7, p =0.0008)). These results could not be replicated in the external data set (n=467), where a similar effect size was found in patients with methylated and unmethylated DCR1 for FOLFIRI over 5FU treatment (methylated DCR1 : HR=0.7 (95%CI 0.5-0.9, p =0.01), unmethylated DCR1 : HR=0.8 (95%CI 0.6-1.2, p =0.4)). In conclusion, DCR1 promoter hypermethylation status is a potential predictive biomarker for response to treatment with irinotecan, when combined with capecitabine. This finding could not be replicated in an external validation set, in which irinotecan was combined with 5FU. These results underline the challenge and importance of extensive clinical evaluation of candidate biomarkers in multiple trials.

A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma.

PubMed

Hersh, E M; Del Vecchio, M; Brown, M P; Kefford, R; Loquai, C; Testori, A; Bhatia, S; Gutzmer, R; Conry, R; Haydon, A; Robert, C; Ernst, S; Homsi, J; Grob, J J; Kendra, K; Agarwala, S S; Li, M; Clawson, A; Brachmann, C; Karnoub, M; Elias, I; Renschler, M F; Hauschild, A

2015-11-01

The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS). A total of 529 patients were randomized to nab-paclitaxel (n = 264) or dacarbazine (n = 265). Baseline characteristics were well balanced. The majority of patients were men (66%), had an Eastern Cooperative Oncology Group status of 0 (71%), and had M1c stage disease (65%). The median PFS (primary end point) was 4.8 months with nab-paclitaxel and 2.5 months with dacarbazine [hazard ratio (HR), 0.792; 95.1% confidence interval (CI) 0.631-0.992; P = 0.044]. The median OS was 12.6 months with nab-paclitaxel and 10.5 months with dacarbazine (HR, 0.897; 95.1% CI 0.738-1.089; P = 0.271). Independently assessed overall response rate was 15% versus 11% (P = 0.239), and disease control rate (DCR) was 39% versus 27% (P = 0.004) for nab-paclitaxel versus dacarbazine, respectively. The most common grade ≥3 treatment-related adverse events were neuropathy (nab-paclitaxel, 25% versus dacarbazine, 0%; P < 0.001), and neutropenia (nab-paclitaxel, 20% versus dacarbazine, 10%; P = 0.004). There was no correlation between secreted protein acidic and rich in cysteine (SPARC) status and PFS in either treatment arm. nab-Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[Endonasal Dacryocystorhinostomy (DCR) with Transcanalicular Endoillumination (TCE) of the Saccus Lacrimalis].

PubMed

Hefner, J; Klask, J; Gerding, H

2016-04-01

Endonasal dacryocystorhinostomy (DCR) has been established as a standard procedure of lacrimal surgery, since it causes much less tissue damage than ab externo procedures. Diffiulties in visualization of the target area has been a limitation to the transnasal approach. An improvement of the classical endonasal DCR was achieved by the introduction of a transcanalicular endoillumination (TCE) of the lacrimal sac using a 23-Gauge vitreoretinal light probe, which can easily be intubated into the cannaliculi and advanced into the the lacrimal sac. Illumination of the lacrimal sac guides the endonasal approach and facilitates the creation of a lacrimal bypass. In our standard procedure a bicanalicular silicone intubation through the osteotomy is finally placed. Due to the introduction of TCE of the lacrimal sac, the surgical procedure of endonasal DCR became less traumatic and needed a significantly reduced operating time. Georg Thieme Verlag KG Stuttgart · New York.

Efficacy of Icotinib treatment in patients with stage IIIb/IV non-small cell lung cancer.

PubMed

Qin, Na; Yang, Xinjie; Zhang, Quan; Li, Xi; Zhang, Hui; Lv, Jialin; Wu, Yuhua; Wang, Jinghui; Zhang, Shucai

2014-05-01

To evaluate the efficacy and safety of Icotinib - an orally administered, highly potent selective inhibitor of epidermal growth factor receptor (EGFR) and its active mutations, in the treatment of patients with advanced non-small cell lung cancer (NSCLC). A total of 101 patients with stage IIIb/IV NSCLC were treated with 125 mg Icotinib three times a day until disease progression or intolerable toxicity. Response rate was evaluated using response evaluation criteria in solid tumors and progression-free survival (PFS) was collected. The overall response rate (ORR) and disease control rate (DCR) were 37.6% (38/101) and 79.2% (80/101), respectively. The median PFS was 6.5 months. Multivariate analysis showed that female gender (P= 0.048, 95% confidence interval [CI] 1.010-6.016) and occurrence of rash (P= 0.002, 95% CI 1.667-9.809) were the independent predictive factors for ORR, while a performance status (PS) score of 0-1 (P= 0.001, 95% CI 0.024-0.402) and rash (P= 0.042, 95% CI 1.089-76.557) were the independent predictive factors for DCR. In addition, PS scores of 0-1 (P <0.001, 95% CI 0.135-0.509), and non-smoking (P= 0.017, 95% CI 0.342-0.900) were found to be independent influencing factors for PFS. Moreover, patients with EGFR mutations had better PFS than patients with wild type EGFR, while patients with EGFR exon 19 deletion had better survival than those with EGFR exon 21 mutation. The most common adverse effects of Icotinib were rash (35.6%) and diarrhea (17.8%), which was tolerable. Treatment of stage IIIb/IV NSCLC patients with Icotinib was effective and tolerable, specifically in patients with EGFR mutation.

Temporal Characterization of Hydrates System Dynamics beneath Seafloor Mounds. Integrating Time-Lapse Electrical Resistivity Methods and In Situ Observations of Multiple Oceanographic Parameters

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

Lutken, Carol; Macelloni, Leonardo; D'Emidio, Marco

This study was designed to investigate temporal variations in hydrate system dynamics by measuring changes in volumes of hydrate beneath hydrate-bearing mounds on the continental slope of the northern Gulf of Mexico, the landward extreme of hydrate occurrence in this region. Direct Current Resistivity (DCR) measurements were made contemporaneously with measurements of oceanographic parameters at Woolsey Mound, a carbonate-hydrate complex on the mid-continental slope, where formation and dissociation of hydrates are most vulnerable to variations in oceanographic parameters affected by climate change, and where changes in hydrate stability can readily translate to loss of seafloor stability, impacts to benthic ecosystems,more » and venting of greenhouse gases to the water-column, and eventually, the atmosphere. We focused our study on hydrate within seafloor mounds because the structurally-focused methane flux at these sites likely causes hydrate formation and dissociation processes to occur at higher rates than at sites where the methane flux is less concentrated and we wanted to maximize our chances of witnessing association/dissociation of hydrates. We selected a particularly well-studied hydrate-bearing seafloor mound near the landward extent of the hydrate stability zone, Woolsey Mound (MC118). This mid-slope site has been studied extensively and the project was able to leverage considerable resources from the team’s research experience at MC118. The site exhibits seafloor features associated with gas expulsion, hydrates have been documented at the seafloor, and changes in the outcropping hydrates have been documented, photographically, to have occurred over a period of months. We conducted observatory-based, in situ measurements to 1) characterize, geophysically, the sub-bottom distribution of hydrate and its temporal variability, and 2) contemporaneously record relevant environmental parameters (temperature, pressure, salinity, turbidity, bottom currents) to detect short-term changes within the hydrates system, identify relationships/impacts of local oceanographic parameters on the hydrates system, and improve our understanding of how seafloor instability is affected by hydrates-driven changes. A 2009 DCR survey of MC118 demonstrated that we could image resistivity anomalies to a depth of 75m below the seafloor in water depths of 1km. We reconfigured this system to operate autonomously on the seafloor in a pre-programmed mode, for periods of months. We designed and built a novel seafloor lander and deployment capability that would allow us to investigate the seafloor at potential deployment sites and deploy instruments only when conditions met our criteria. This lander held the DCR system, controlling computers, and battery power supply, as well as instruments to record oceanographic parameters. During the first of two cruises to the study site, we conducted resistivity surveying, selected a monitoring site, and deployed the instrumented lander and DCR, centered on what appeared to be the most active locations within the site, programmed to collect a DCR profile, weekly. After a 4.5-month residence on the seafloor, the team recovered all equipment. Unfortunately, several equipment failures occurred prior to recovery of the instrument packages. Prior to the failures, however, two resistivity profiles were collected together with oceanographic data. Results show, unequivocally, that significant changes can occur in both hydrate volume and distribution during time periods as brief as one week. Occurrences appear to be controlled by both deep and near-surface structure. Results have been integrated with seismic data from the area and show correspondence in space of hydrate and structures, including faults and gas chimneys.« less

Long-term follow-up of external dacryocystorhinostomy and the factors affecting its success.

PubMed

Erdöl, Hidayet; Akyol, Nurettin; Imamoglu, Halil Ibrahim; Sözen, Engin

2005-06-01

To evaluate the long-term follow-up results of external dacryocystorhinostomy (Ex-DCR) and to assess the role of some factors in its success. Between January 1990 and November 2002, 437 nasolacrimal systems of 387 patients were operated on and included in the study. The success rates were determined on the basis of the last examinations of the patients, and the correlations between success rates and factors such as age, gender, the duration of obstruction, history of acute dacryocystitis, the side of obstruction, and the postoperative follow-up period were calculated. The mean follow-up period was 5.9 +/- 2.5 years. Fifty cases (12.9%) were operated bilaterally. The initial success rate was 91.5% and the last success rate was 98.4% after reoperations. We found meaningful correlations between success and duration of obstruction, age of the patient, and the duration of postoperative follow-up (r = 0.18, 0.17 and -0.14, p = 0.036, 0.001 and 0.002, respectively). In comparison to newly developed surgical techniques for the treatment of nasolacrimal duct obstruction, Ex-DCR still appears to offer higher success rates, even after long-term follow-up. In addition to being a cost-effective procedure, it requires no sophisticated instruments. In our opinion, the high success rates may be explained by the nature of the operation, which creates a fistula between the sac and the nasal mucosa.

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study

PubMed Central

Douillard, J-Y; Ostoros, G; Cobo, M; Ciuleanu, T; McCormack, R; Webster, A; Milenkova, T

2014-01-01

Background: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Methods: Treatment: gefitinib 250 mg day−1 until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. Results: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8% adenocarcinoma 97.2% never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5–77.7), DCR 90.6% (95% CI 83.5–94.8), median PFS 9.7 months (95% CI 8.5–11.0), median OS 19.2 months (95% CI 17.0–NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15% SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8–74.7). Conclusion: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable. PMID:24263064

[The Comparison of Clinical Effect of Rh-endostar on Retreated Non-Small Cell Lung Cancer and Colorectal Cancer.].

PubMed

Yang, Xueqin; Wang, Dong; Zhong, Zhaoyang; Jin, Feng; Shan, Jinlu; Wang, Ge; Wang, Zhengbo; Shen, Yibo

2009-11-20

Antiangiogenesis has become the fourth module of cancer therapy nowadays. However, its clinical effect varies from cancer to cancer. The aim of this study is to compare the clinical efficacy of rh-endostatin (YH-16, Endostar) on retreated non-small cell lung cancer and colorectal cancer. The patients including 17 cases of retreated non-small cell lung cancer (NSCLC) and 15 cases of retreated colorectal cancer were confirmed by histopathology or cytopathology. All the cases were administrated with rh-endostatin combining chemotherapy and radiotherapy. 7.5 mg/m(2) rhendostatin solved in 500 mL of normal saline was slow intravenously dropped from day 1 to day 14. The efficacy was evaluated strictly according to RECIST criteria and the quality of life (QOL) was based on the Karnofsky performance (KPS). The response rate (RR) of 17 cases of retreated NSCLC was 11.8% (2/17), and the disease control rate (DCR) was 41.2% (7/17). However, the RR and DCR of the 15 cases of retreated colorectal cancer were up to 40% (6/15) and 86.6% (13/15). There was significant difference between these two tumors (P<0.05). Moreover, significant difference was also found on the QOL of these two tumors [The improving and stable QOL was 41.2% (7/17) and 86.6% (13/15), respectively (P<0.05)]. The clinical efficacy of rh-endostatin on retreated colorectal cancer was better than on retreated non-small cell lung cancer, which suggested that it was necessary to perform more clinical observations on the digestive tumors.

Comparison of impact of four surgical methods on surgical outcomes in endoscopic dacryocystorhinostomy.

PubMed

Roh, Hyun Cheol; Baek, Sehyun; Lee, Hwa; Chang, Minwook

2016-06-01

To evaluate differences in the surgical outcomes of endoscopic dacryocystorhinostomy (DCR) according to four different surgical methods. This retrospective study included 222 patients who underwent endoscopic DCR from 2011 to 2013. All patients were assigned to one of four groups according to instruments for incision of nasal mucosa and the formation of mucosal flap: group 1, a sickle knife with mucosal flap; group 2, a sickle knife without mucosal flap; group 3, electrocautery with mucosal flap; and group 4, electrocautery without mucosal flap. The follow up period was at least 6 months. There were 33 eyes in group 1, 44 eyes in group 2, 49 eyes in group 3, and 97 eyes in group 4. There were no significant differences in success rate between groups (P = 0.878). Wound healing time was significantly different between groups (P < 0.001). In post hoc analysis, wound healing time was significantly shorter in group 1 and group 2 than in group 3 and group 4. The vertical ostium size and postsurgical complication were not significantly different between groups. The use of cold instruments such as sickle knife may be more helpful and effective for shortening wound healing time rather than making mucosal flaps in endoscopic DCR. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

The consequence of premature silicone stent loss after external dacryocystorhinostomy.

PubMed

Vicinanzo, Matthew G; McGwin, Gerald; Boyle, Michael; Long, John A

2008-07-01

To investigate the clinical affects of premature silicone stent loss after external dacryocystorhinostomy (DCR). Retrospective chart review. Two hundred thirty-three consecutive external dacryocystorhinostomies. Demographic information was recorded, including length to follow-up, age, gender, number of days until stent removal, and success of surgery. All patients who extruded their silicone stent prematurely were identified. All were primary DCRs (i.e., all reoperations were excluded). All patients had had documented nasolacrimal duct obstruction before surgery, with or without current or prior dacryocystitis. Failure of DCR surgery was accepted as symptomatic epiphora with notable nasolacrimal duct blockage and/or infection at long term follow-up. Of the 233 DCRs, 42 stents extruded or had to be removed before the planned 2-month period. The overall success rate of the surgery was 94.9%, with a 90.5% success for those who had early extrusion and 95.8% for those who did not (P = 0.24). Moreover, of the 4 people who had a failed surgery (of 42 early extrusions), none had a recurrent infection or pain, and only 1 opted to have a revision of the surgery. Patient age, gender, or timing of the extrusion was not found to affect surgical success significantly. Our experience and this study suggest that concerns over early stent extrusion or removal may not be wholly warranted. Moreover, our review of the literature shows no evidence-based recommendations that longer stent retention or reintubation after early extrusion results in a higher success rate. Although other surgeries (e.g., canalicular laceration, congenital epiphora) may benefit from intervention or reinsertion after early extrusion, we cannot extrapolate such a practice for the DCR.

Dose conversion ratio in hemodialysis patients switched from darbepoetin alfa to PEG-epoetin beta: AFFIRM study.

PubMed

Choi, Peter; Farouk, Mourad; Manamley, Nick; Addison, Janet

2013-11-01

There is limited information published on switching erythropoiesis-stimulating agent (ESA) treatment for anemia associated with chronic kidney disease (CKD) from darbepoetin alfa (DA) to methoxy polyethylene glycol-epoetin beta (PEG-Epo) outside the protocol of interventional clinical studies. AFFIRM (Aranesp Efficiency Relative to Mircera) was a retrospective, multi-site, observational study designed to estimate the population mean maintenance dose conversion ratio [DCR; dose ratio achieving comparable hemoglobin level (Hb) between two evaluation periods] in European hemodialysis patients whose treatment was switched from DA to PEG-Epo. Eligible patients had received hemodialysis for ≥ 12 months and DA for ≥ 7 months. Data were collected from 7 months before until 7 months after switching treatment. DCR was calculated for patients with Hb and ESA data available in both evaluation periods (EP; Months 1 and 2 were defined as the pre-switch EP, and Months 6 and 7 as the post-switch EP). Red blood cell transfusions pre- and post-switch were quantified. Of 302 patients enrolled, 206 had data available for DCR analysis. The geometric mean DCR was 1.17 (95% CI 1.05, 1.29). Regression analysis indicated a non-linear relationship between pre- and post-switch ESA doses; DCR decreased with increasing pre-switch DA dose. The geometric mean weekly ESA doses were 24.1 μg DA in the pre-switch EP and 28.6 μg PEG-Epo in the post-switch EP. Mean Hb was 11.5 g/dL in the pre-switch EP and 11.4 g/dL in the post-switch EP. There were 16 transfusions and 34 units transfused in the pre-switch period, versus 48 transfusions and 95 units transfused post-switch. Excluding patients receiving a transfusion within 90 days of or during either EP, the DCR was 1.21 (95% CI 1.09, 1.35). In these hemodialysis patients switched from DA to PEG-Epo the DCR was 1.17 and 1.21 after accounting for the effect of transfusions. The number of transfusions and units transfused increased approximately threefold from the pre-switch to the post-switch period.

Acquired fistula of the lacrimal sac and laisser-faire approach. Description of the natural history of acquired fistulas between the lacrimal sac and the skin occurring before planned endonasal dacryocystorhinostomy (DCR) and without any treatment of the fistula.

PubMed

Pison, A; Fau, J-L; Racy, E; Fayet, B

2016-10-01

The formation of a fistula between the lacrimal sac and the skin is a classic outcome of resistant lacrimal sac abscesses. There is currently no consensus about treatment in such cases. The goal of this study was to describe the natural history of acquired fistulas between the lacrimal sac and the skin, occurring before planned endonasal dacryocystorhinostomy (DCR) and without any treatment of the fistula. This prospective study was only descriptive and included patients between 1999 and 2012. The patients included were adults with a nasolacrimal duct (NLD) obstruction that was planned to be treated with endonasal DCR. A resistant lacrimal sac abscess appeared a few days before the planned surgery, and fistulized spontaneously despite medical treatment. The surgery was not delayed. The DCR was endoscopic. Nothing was done for the fistula. Its healing was spontaneous. The exclusion criteria were the following: congenital fistulas, post-traumatic and/or iatrogenic fistulas, fistulas which had regressed by the day of the surgery, postoperative follow-up less than 5 months, post-traumatic and/or iatrogenic fistulas, any history of previous DCR or any other lacrimal surgery, children. Twenty adults (25 cases) were included in the analysis. Mean age was 79 years old (from 41 to 90). The mean follow-up was 41 months (from 5 to 108 months). The fistula spontaneously disappeared in all cases, less than one month after it had appeared and in a permanent fashion. No unsightly scar developed. Spontaneously acquired fistulas between the lacrimal sac and the skin may occur in the natural course of abscessed acute dacryocystitis. Our study showed spontaneous healing of the fistula post-endoscopic DCR. Fistula excision in fistulous acute dacryocystitis does not seem essential to its healing. The laisser-faire approach appears adequate for aesthetic outcomes as well as for functional outcomes of DCR. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Axitinib after Sunitinib in Metastatic Renal Cancer: Preliminary Results from Italian "Real-World" SAX Study.

PubMed

D'Aniello, Carmine; Vitale, Maria G; Farnesi, Azzurra; Calvetti, Lorenzo; Laterza, Maria M; Cavaliere, Carla; Della Pepa, Chiara; Conteduca, Vincenza; Crispo, Anna; De Vita, Ferdinando; Grillone, Francesco; Ricevuto, Enrico; De Tursi, Michele; De Vivo, Rocco; Di Napoli, Marilena; Cecere, Sabrina C; Iovane, Gelsomina; Amore, Alfonso; Piscitelli, Raffaele; Quarto, Giuseppe; Pisconti, Salvatore; Ciliberto, Gennaro; Maiolino, Piera; Muto, Paolo; Perdonà, Sisto; Berretta, Massimiliano; Naglieri, Emanuele; Galli, Luca; Cartenì, Giacomo; De Giorgi, Ugo; Pignata, Sandro; Facchini, Gaetano; Rossetti, Sabrina

2016-01-01

Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib-axitinib sequence, were the primary endpoint. The mPFS was 5.83 months (95% CI 3.93-7.73 months). When patients was stratified by Heng score, mPFS was 5.73, 5.83, 10.03 months according to poor, intermediate, and favorable risk group, respectively. The mOS from the start of axitinib was 13.3 months (95% CI 8.6-17.9 months); the observed ORR and DCR were 25 and 71%, respectively. When stratified patients by subgroups defined by duration of prior therapy with Sunitinib (≤ vs. >median duration), there was a statistically significant difference in mPFS with 8.9 (95% CI 4.39-13.40 months) vs. 5.46 months (95% CI 4.04-6.88 months) for patients with a median duration of Sunitinib >13.2 months. DCR and ORR to previous Sunitinib treatment was associated with longer statistically mPFS, 7.23 (95% CI 3.95-10.51 months, p = 0.01) and 8.67 (95% CI 4.0-13.33 months, p = 0.008) vs. 2.97 (95% CI 0.65-5.27 months, p = 0.01) and 2.97 months (95% CI 0.66-5.28 months, p = 0.01), respectively. Overall Axitinib at standard schedule of 5 mg bid, was well-tolerated. The most common adverse events of all grades were fatig (25.6%), hypertension (22.6%), gastro-intestinal disorders (25.9%), and hypothyroidism (16.1%). The sequence Sunitinib-Axitinib was well-tolerated without worsening in side effects, with a median OS of 34.7 months (95% CI 18.4-51.0 months). Our results are consistent with the available literature; this retrospective analysis confirms that Axitinib is effective and safe in routine clinical practice.

Effect of HK2, PKM2 and LDHA on Cetuximab efficacy in metastatic colorectal cancer.

PubMed

Wang, Haohua; Peng, Roujun; Chen, Xiuxing; Jia, Rui; Huang, Chunyue; Huang, Yuanyuan; Xia, Liangping; Guo, Guifang

2018-04-01

Although hexokinase (HK) 2, pyruvate kinase muscle (PKM) isozyme 2 and lactate dehydrogenase (LDH) A predict the efficacy of medicines in various solid tumors, their ability to predict the efficacy of cetuximab in metastatic colorectal cancer (mCRC) remains unclear. mCRC patients with pathological specimens who received cetuximab and chemotherapy from 2005 to 2015 in the present institution were enrolled. Immunohistochemistry was used to detect HK2, PKM2 and LDHA expression. SPSS20 was used for statistical analysis. A total of 68 patients were included; 33 received cetuximab plus chemotherapy as first-line therapy, and the rest, as second- or later-line therapy. HK2 expression levels were increased in cancer compared with normal tissue (75.4% vs. 40%; P<0.001), however PKM2 (P=0.243) and LDHA (P=0.067) expression levels were not. For progression-free survival (PFS) with first-line cetuximab plus chemotherapy, patients with high HK2 expression exhibited longer PFS compared with those with low HK2 expression (23.9 months vs. 6.9 months; P=0.021). However, this positive association was absent in 35 cases administered first-line chemotherapy alone (13.4 months vs. 13.5 months; P=0.539). LDHA expression was associated with the PFS of patients receiving first-line chemotherapy (18.3 and 10.1 months for high and low expression, respectively; P=0.005), whereas this association was absent in cetuximab plus chemotherapy cases (19.9 months vs. 12 months; P=0.522). Furthermore, high LDHA expression correlated with high overall response rate (ORR) (72.2% vs. 15.4%, P=0.006) for chemotherapy, however not disease control rate (DCR) (P=0.074). Neither DCR nor ORR were associated with HK2 expression. PKM2 expression did not affect PFS, DCR or ORR. LDHA expression (P=0.005), pathological differentiation (P=0.019) and synchronous/metachronous metastasis (P=0.014) were independent predictive factors of PFS for all first-line patients, and tumor differentiation (P=0.002) was associated with overall survival (OS) in multivariate analysis. HK2, PKM2 and LDHA did not impact OS. It was concluded that HK2 expression was increased in colorectal cancer tissue and may predict cetuximab efficacy and LDHA for chemotherapy treatment of mCRC.

Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies.

PubMed

Bahleda, Rastislav; Grilley-Olson, Juneko E; Govindan, Ramaswamy; Barlesi, Fabrice; Greillier, Laurent; Perol, Maurice; Ray-Coquard, Isabelle; Strumberg, Dirk; Schultheis, Beate; Dy, Grace K; Zalcman, Gérard; Weiss, Glen J; Walter, Annette O; Kornacker, Martin; Rajagopalan, Prabhu; Henderson, David; Nogai, Hendrik; Ocker, Matthias; Soria, Jean-Charles

2017-06-06

To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway. Ten patients were evaluable in the 4 weeks on/2 weeks off schedule (terminated following limited tolerability) and 47 in the 3 days on/4 days off schedule dose-escalation cohorts. On the 3 days on/4 days off schedule, RP2D was 5 mg twice daily in solid tumours (n=40); undetermined in lymphoid malignancies (n=7). Common roniciclib-related adverse events included nausea (76.6%), fatigue (65.8%), diarrhoea (63.1%), and vomiting (57.7%). Roniciclib demonstrated rapid absorption and dose-proportional increase in exposure. One partial response (1.0%) was observed. In RP2D expansion cohorts, the disease control rate (DCR) was 40.9% for patients with ovarian cancer (n=25), 17.4% for patients with SCLC (n=33), and 33.3% for patients with CDK-related tumour mutations (n=6). Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.

2D Inversion of DCR and Time Domain IP data: an example from ore exploration

NASA Astrophysics Data System (ADS)

Adrian, J.; Tezkan, B.

2015-12-01

Ore deposits often appear as disseminated sulfidic materials. Exploring these deposits with the Direct Current Resistivity (DCR) method alone is challenging because the resistivity signatures caused by disseminated material is often hard to detect. The Time-domain Induced Polarization (TDIP) method, on the other hand, is qualified to detect areas with disseminated sulfidic ores due to large electrode polarization effects which result in large chargeability anomalies. By employing both methods we gain information about both, the resistivity and the chargeability distribution of the subsurface.On the poster we present the current state of the development of a 2D smoothness constraint inversion algorithm for DCR and TDIP data. The implemented forward algorithm uses a Finite Element approach with an unstructured mesh. The model parameters resistivity and chargeability are connected by either a simple conductivity pertubation approach or a complex conductivity approach.As a case study, the 2D inversion results of DCR/TDIP and RMT data obtained during a survey on a sulfidic copper ore deposit in Turkey are presented. The presence of an ore deposit is indicated by areas with low resistivity and significantly high chargeability in the inversion models.This work is part of the BMBF/TUEBITAK funded project ``Two-dimensional joint interpretation of Radiomagnetotellurics (RMT), Direct Current Resistivity (DCR) and Induced Polarization (IP) data: an example from ore exploration''.

Dermatux: phase IV trial of Cetuximab plus FOLFIRI in first-line metastatic colorectal cancer receiving a pre-defined skin care.

PubMed

Schimanski, Carl Christoph; Staib, Frank; Göhler, Thomas; Hebart, Holger; Heike, Michael; Neise, Michael; Rudi, Jochen; Geer, Thomas; Dingeldein, Gerrit; Lang, Claudia; Ehscheidt, Peter; Flohr, Thomas; Josten, Klaus Maria; Karthaus, Meinolf; Schmittel, Alexander; Wierecky, Jan; Boller, Emil; Indorf, Martin; Wörns, Marcus-Alexander; Galle, Peter R; Moehler, Markus

2017-06-01

Cetuximab-induced skin rash Gd3+ occurs in ≥16% patients (pts) (Heinemann et al., Lancet Oncol 15(10):1065-1075, 2014; Van Cutsem et al. J Clin Oncol 27(19):3117-25; 2009b). Survival, response, and toxicity parameters were re-evaluated under a pre-defined skin prophylaxis consistent of vitamin K1 ointment and oral doxycycline. This is a national, multicenter, phase 4, first-line mCRC (K-RAS wt) trial. Pts received irinotecan 180 mg/m² (d1), FA 400 mg/m² (d1), 5-FU 400 mg/m² (d1), 5-FU 2400 mg/m² (d1-2), and cetuximab [400 mg/m² (d1), and then 250 mg/m² qw], prophylactic 0.1% vitamin K1 ointment qd, and oral doxycycline 100 mg bid. 1-year PFS rate; secondary objectives: skin side-effects (grade, onset), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) time, and overall survival (OS) time and safety. Twenty centers recruited 55 patients. Recruitment started Q1 2011 and ended Q3 2013 due to slow accrual. Characteristics were in line with CRYSTAL trial except for age and colonic location. 1-year PFS rate was 25.9%, mOS 21.8 months (m), and mPFS 8.5 m. ORR was 63.0%, DCR 77.8%. Rash Gd2+ occurred in 42.6% [median onset was 4.0 weeks (w)]; paronychia Gd2+ occurred in 22.2% (median onset 15.4w.); skin fissures Gd2+ occurred in 31.5% (median onset 19.9 weeks) 7% pts abandoned cetuximab treatment due to toxicity. Our data reveal encouraging improvements in skin reactions and their time to occurrence due to a pre-defined skin care.

Comparison of effectiveness and adverse effects of gefitinib, erlotinib and icotinib among patients with non-small cell lung cancer: A network meta-analysis.

PubMed

Liu, Yuanyuan; Zhang, Yu; Feng, Gangling; Niu, Qiang; Xu, Shangzhi; Yan, Yizhong; Li, Shugang; Jing, Mingxia

2017-11-01

The present network meta-analysis aimed to compare the effectiveness and adverse effects of gefitinib, erlotinib and icotinib in the treatment of patients with non-small cell lung cancer (NSCLC). Two reviewers searched the Cochrane, PubMed, Embase, ScienceDirect, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals and Wanfang databases for relevant studies. Studies were then screened and evaluated, and data was extracted. End-points evaluated for NSCLC included complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), median survival time (MST) and adverse effects, including rash, diarrhea, nausea and vomiting, fatigue and abnormal liver function. For the analysis of incorporated studies, RevMan, SPSS, R and Stata software were used. A total of 43 studies with 7,168 patients were included in the network meta-analysis. No significant differences were observed in CR, PR, SD, PD, ORR or DCR between gefitinib, erlotinib and icotinib by using network meta analysis. Compared with gefitinib, erlotinib resulted in a higher rate of nausea and vomiting [adjusted odds ratio (OR)=2.0; 95% credible interval, 1.1-3.7]. However, no significant differences were observed in the rates of rash, diarrhea, fatigue or abnormal liver function using network meta-analysis. Compared with erlotinib, gefitinib resulted in a lower SD rate [OR=0.86; 95% confidence interval (CI): 0.75-0.99; P=0.04], and lower rates of rash (OR=0.45; 95% CI, 0.36-0.55; P<0.00001), diarrhea (OR=0.75; 95% CI, 0.61-0.92; P=0.005), nausea and vomiting (OR=0.47; 95% CI, 0.27-0.84; P=0.01) and fatigue (OR=0.43; 95% CI, 0.24-0.76; P=0.004) through meta-analysis of two congruent drugs. However, gefitinib resulted in a higher rate of rash compared with icotinib (OR=1.57; 95% CI, 1.18-2.09; P=0.002). Otherwise, no significant differences were observed in CR, PR, PD, ORR, DCR and abnormal liver function between gefitinib, erlotinib and icotinib through meta-analysis of two congruent drugs. The PFS rate for gefitinib, erlotinib and icotinib was 5.48, 5.15 and 5.81 months, respectively. The MST was 13.26, 13.52, 12.58 months for gefitinib, erlotinib and icotinib, respectively. Gefitinib and icotinib resulted in significantly higher PFS rates compared with erlotinib (P<0.05). Erlotinib resulted in a significantly longer MST compared with gefitinib and icotinib (P<0.05). In conclusion, gefitinib, erlotinib and icotinib had similar effectiveness for the treatment of patients with advanced NSCLC. However, gefitinib resulted in a lower frequency of fatigue, and nausea and vomiting, compared with the other two drugs. Icotinib resulted in a lower frequency of rash. Erlotinib resulted in a longer MST, but was also associated with a higher frequency of rash, and nausea and vomiting.

Comparison of effectiveness and adverse effects of gefitinib, erlotinib and icotinib among patients with non-small cell lung cancer: A network meta-analysis

PubMed Central

Liu, Yuanyuan; Zhang, Yu; Feng, Gangling; Niu, Qiang; Xu, Shangzhi; Yan, Yizhong; Li, Shugang; Jing, Mingxia

2017-01-01

The present network meta-analysis aimed to compare the effectiveness and adverse effects of gefitinib, erlotinib and icotinib in the treatment of patients with non-small cell lung cancer (NSCLC). Two reviewers searched the Cochrane, PubMed, Embase, ScienceDirect, China National Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals and Wanfang databases for relevant studies. Studies were then screened and evaluated, and data was extracted. End-points evaluated for NSCLC included complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), median survival time (MST) and adverse effects, including rash, diarrhea, nausea and vomiting, fatigue and abnormal liver function. For the analysis of incorporated studies, RevMan, SPSS, R and Stata software were used. A total of 43 studies with 7,168 patients were included in the network meta-analysis. No significant differences were observed in CR, PR, SD, PD, ORR or DCR between gefitinib, erlotinib and icotinib by using network meta analysis. Compared with gefitinib, erlotinib resulted in a higher rate of nausea and vomiting [adjusted odds ratio (OR)=2.0; 95% credible interval, 1.1–3.7]. However, no significant differences were observed in the rates of rash, diarrhea, fatigue or abnormal liver function using network meta-analysis. Compared with erlotinib, gefitinib resulted in a lower SD rate [OR=0.86; 95% confidence interval (CI): 0.75–0.99; P=0.04], and lower rates of rash (OR=0.45; 95% CI, 0.36–0.55; P<0.00001), diarrhea (OR=0.75; 95% CI, 0.61–0.92; P=0.005), nausea and vomiting (OR=0.47; 95% CI, 0.27–0.84; P=0.01) and fatigue (OR=0.43; 95% CI, 0.24–0.76; P=0.004) through meta-analysis of two congruent drugs. However, gefitinib resulted in a higher rate of rash compared with icotinib (OR=1.57; 95% CI, 1.18–2.09; P=0.002). Otherwise, no significant differences were observed in CR, PR, PD, ORR, DCR and abnormal liver function between gefitinib, erlotinib and icotinib through meta-analysis of two congruent drugs. The PFS rate for gefitinib, erlotinib and icotinib was 5.48, 5.15 and 5.81 months, respectively. The MST was 13.26, 13.52, 12.58 months for gefitinib, erlotinib and icotinib, respectively. Gefitinib and icotinib resulted in significantly higher PFS rates compared with erlotinib (P<0.05). Erlotinib resulted in a significantly longer MST compared with gefitinib and icotinib (P<0.05). In conclusion, gefitinib, erlotinib and icotinib had similar effectiveness for the treatment of patients with advanced NSCLC. However, gefitinib resulted in a lower frequency of fatigue, and nausea and vomiting, compared with the other two drugs. Icotinib resulted in a lower frequency of rash. Erlotinib resulted in a longer MST, but was also associated with a higher frequency of rash, and nausea and vomiting. PMID:29104622

TAF11 assembles RISC loading complex to enhance RNAi efficiency

PubMed Central

Liang, Chunyang; Wang, Yibing; Murota, Yukiko; Liu, Xiang; Smith, Dean; Siomi, Mikiko C.; Liu, Qinghua

2015-01-01

SUMMARY Assembly of the RNA-induced silencing complex (RISC) requires formation of the RISC loading complex (RLC), which contains Dicer-2(Dcr-2)-R2D2 complex and recruits duplex siRNA to Ago2 in Drosophila melanogaster. However, the precise composition and action mechanism of Drosophila RLC remain unclear. Here, we identified the missing factor of RLC as TATA-binding protein associated factor 11 (TAF11) by genetic screen. Although an annotated nuclear transcription factor, we found that TAF11 also associated with Dcr-2/R2D2 and localized to cytoplasmic D2 bodies. Consistent with defective RLC assembly in taf11−/− ovary extract, we reconstituted the RLC in vitro using recombinant Dcr-2-R2D2 complex, TAF11, and duplex siRNA. Furthermore, we showed that TAF11 tetramer facilitates Dcr-2-R2D2 tetramerization to enhance siRNA binding and RISC loading activities. Together, our genetic and biochemical studies define the molecular nature of Drosophila RLC and elucidate a novel cytoplasmic function of TAF11 in organizing RLC assembly to enhance RNAi efficiency. PMID:26257286

Selection and characterization of a mutant of feline immunodeficiency virus resistant to 2',3'-dideoxycytidine.

PubMed Central

Medlin, H K; Zhu, Y Q; Remington, K M; Phillips, T R; North, T W

1996-01-01

We have selected and plaque purified a mutant of feline immunodeficiency virus (FIV) that is resistant to 2',3'-dideoxycytidine (ddC). This mutant was selected in cultured cells in the continuous presence of 25 microM ddC. The mutant, designated DCR-5c, was fourfold resistant to ddC, threefold resistant to 2',3'-dideoxyinosine, and more than fourfold resistant to phosphonoformic acid. DCR-5c displayed little or no resistance to (-)-beta-2',3'-dideoxy-3'-thiacytidine, 3'-azido-3'-deoxythymidine, or 9-(2-phosphonylmethoxyethyl) adenine. Reverse transcriptase purified from DCR-5c was less susceptible to inhibition by ddCTP, phosphonoformic acid, ddATP, or azido-dTTP than the wild-type FIV reverse transcriptase. Sequence analysis of DCR-5c revealed a single base change (G to C at nucleotide 2342) in the reverse transcriptase-encoding region of FIV. This mutation results in substitution of His for Asp at codon 3 of FIV reverse transcriptase. The role of this mutation in ddC resistance was confirmed by site-directed mutagenesis. PMID:8849258

Biofilm Quantification on Nasolacrimal Silastic Stents After Dacryocystorhinostomy.

PubMed

Murphy, Jae; Ali, Mohammed Javed; Psaltis, Alkis James

2015-01-01

Biofilms are now recognized as potential factors in the pathogenesis of chronic inflammatory and infective diseases. The aim of this study was to examine the presence of biofilms and quantify their biomass on silastic nasolacrimal duct stents inserted after dacryocystorhinostomy (DCR). A prospective study was performed on a series of patients undergoing DCR with O'Donoghue stent insertion. After removal, the stents were subjected to biofilm analysis using standard protocols of confocal laser scanning microscopy (CLSM) and scanning electron microscopy. These stents were compared against negative controls and positive in vitro ones established using Staphylococcus aureus strain ATCC 25923. Biofilm quantification was performed using the COMSTAT2 software and the total biofilm biomass was calculated. A total of nine consecutive patient samples were included in this prospective study. None of the patients had any evidence of postoperative infection. All the stents demonstrated evidence of biofilm formation using both imaging modalities. The presence of various different sized organisms within a common exopolysaccharide matrix on CLSM suggested the existence of polymicrobial communities. The mean biomass of patient samples was 0.9385 μm³/μm² (range: 0.3901-1.9511 μm³/μm²). This is the first study to report the quantification of biomass on lacrimal stents. The presence of biofilms on lacrimal stents after DCR is a common finding but this need not necessarily translate to postoperative clinical infection.

BIM Gene Polymorphism Lowers the Efficacy of EGFR-TKIs in Advanced Nonsmall Cell Lung Cancer With Sensitive EGFR Mutations: A Systematic Review and Meta-Analysis.

PubMed

Huang, Wu Feng; Liu, Ai Hua; Zhao, Hai Jin; Dong, Hang Ming; Liu, Lai Yu; Cai, Shao Xi

2015-08-01

The strong association between bcl-2-like 11 (BIM) triggered apoptosis and the presence of epidermal growth factor receptor (EGFR) mutations has been proven in nonsmall cell lung cancer (NSCLC). However, the relationship between EGFR-tyrosine kinase inhibitor's (TKI's) efficacy and BIM polymorphism in NSCLC EGFR is still unclear.Electronic databases were searched for eligible literatures. Data on objective response rates (ORRs), disease control rates (DCRs), and progression-free survival (PFS) stratified by BIM polymorphism status were extracted and synthesized based on random-effect model. Subgroup and sensitivity analyses were conducted.A total of 6 studies that involved a total of 773 EGFR mutant advanced NSCLC patients after EGFR-TKI treatment were included. In overall, non-BIM polymorphism patients were associated with significant prolonged PFS (hazard ratio 0.63, 0.47-0.83, P = 0.001) compared to patients with BIM polymorphism. However, only marginal improvements without statistical significance in ORR (odds ratio [OR] 1.71, 0.91-3.24, P = 0.097) and DCR (OR 1.56, 0.85-2.89, P = 0.153) were observed. Subgroup analyses showed that the benefits of PFS in non-BIM polymorphism group were predominantly presented in pooled results of studies involving chemotherapy-naive and the others, and retrospective studies. Additionally, we failed to observe any significant benefit from patients without BIM polymorphism in every subgroup for ORR and DCR.For advanced NSCLC EGFR mutant patients, non-BIM polymorphism ones are associated with longer PFS than those with BIM polymorphism after EGFR-TKIs treatment. BIM polymorphism status should be considered an essential factor in studies regarding EGFR-targeted agents toward EGFR mutant patients.

A phase II study of apatinib in patients with recurrent epithelial ovarian cancer.

PubMed

Miao, Mingming; Deng, Guanming; Luo, Sujuan; Zhou, Jiajia; Chen, Le; Yang, Jun; He, Jie; Li, Junjun; Yao, Jing; Tan, Shanmei; Tang, Jie

2018-02-01

Antiangiogenic treatments have been implicated to play a major role in epithelial ovarian cancer (EOC). Apatinib, a novel oral antiangiogenic agent targeting vascular endothelial growth factor receptor (VEGFR2), is currently being studied in different tumor types and is already used in gastric adenocarcinoma. This study was performed to assess the efficacy and safety of apatinib in patients with recurrent, pretreated EOC. Patients with recurrent, platinum-resistant, pre-treated EOC who failed available standard chemotherapy were enrolled. Apatinib was administered as 500mg daily. Primary objective is the overall response rate (ORR) according to MASS criteria. Secondary objectives are progression free survival (PFS), overall survival (OS), disease control rate (DCR), safety and tolerability. The treatment duration is until disease progression or intolerability of apatinib. 29 eligible patients were enrolled in this multicenter, open-label, single arm study and received apatinib for a median of 36.8weeks (range 13-64.8weeks). Median follow-up time was 12months. 28 patients were eligible for efficacy analysis. ORR is 41.4% (95% confidence interval (CI), 23.3%-59.4%). DCR is 68.9% (95% CI, 52.1%-85.8%). Median PFS is 5.1months (95% CI, 3.8m-6.5m). Median OS is 14.5months (95% CI, 12.4m-16.4m). The most common treatment-related adverse events (AEs) were hand-foot syndrome (51.7%), hypertension (34.6%), nausea and vomiting (31.0%). 3 patients had no significant toxicity. 9 patients experienced grade 3 treatment-related AEs. Apatinib 500mg daily p.o. is a feasible treatment in patients with recurrent, platinum-resistant, pretreated EOC. Multi-center prospective studies enrolling more patients are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Overwhelming rapid metabolic and structural response to apatinib in radioiodine refractory differentiated thyroid cancer.

PubMed

Lin, Yansong; Wang, Chen; Gao, Wen; Cui, Ruixue; Liang, Jun

2017-06-27

Currently, patients with radioiodine refractory differentiated thyroid cancer (RAIR-DTC) have limited treatment options. In this study, we aimed to assess the short-term efficacy and safety of apatinib in RAIR-DTC. Ten adult patients were prospectively enrolled to receive oral apatinib (750 mg q.d). The primary endpoints were change in serum thyroglobulin (Tg) concentration, disease control rate (DCR) and objective response rate (ORR) based on RECIST 1.1 criteria. The secondary endpoints included change in glucose metabolism, evaluated by maximum standard uptake value (SUVmax), and safety. As early as 2 weeks after apatinib treatment, the serum Tg concentration decreased by 21.0% in 8 patients available for detection without interference, and a further sharp decline by 81.4% compared with the baseline level occurred at 8 weeks post-treatment. The DCR and ORR were 100% (10/10) and 90% (9/10), respectively. The sum of tumor diameter shrank to 22.8±8.1 mm from 38.8±15.7 mm (P=0.001). Moreover, a significant decrease in SUVmax was observed from 6.53±5.14 to 2.56±1.67 and 2.45±1.48 at 4-week and 8-week time-points after treatment (P=0.032 and 0.020), respectively. The common grade 3 adverse events (AEs) included hand-foot-skin reaction (50%), hypertension (30%), and hypocalcemia (20%). No severe AE related to apatinib was observed during treatment. Hence, apatinib seems to be a promising therapeutic option for RAIR-DTC patients. Apart from RECIST 1.1 criteria, the biochemical marker (Tg) and glucose metabolism index (SUVmax) could be adopted in assessing the early response to TKI in RAIR-DTC.

Overwhelming rapid metabolic and structural response to apatinib in radioiodine refractory differentiated thyroid cancer

PubMed Central

Gao, Wen; Cui, Ruixue; Liang, Jun

2017-01-01

Currently, patients with radioiodine refractory differentiated thyroid cancer (RAIR-DTC) have limited treatment options. In this study, we aimed to assess the short-term efficacy and safety of apatinib in RAIR-DTC. Ten adult patients were prospectively enrolled to receive oral apatinib (750 mg q.d). The primary endpoints were change in serum thyroglobulin (Tg) concentration, disease control rate (DCR) and objective response rate (ORR) based on RECIST 1.1 criteria. The secondary endpoints included change in glucose metabolism, evaluated by maximum standard uptake value (SUVmax), and safety. As early as 2 weeks after apatinib treatment, the serum Tg concentration decreased by 21.0% in 8 patients available for detection without interference, and a further sharp decline by 81.4% compared with the baseline level occurred at 8 weeks post-treatment. The DCR and ORR were 100% (10/10) and 90% (9/10), respectively. The sum of tumor diameter shrank to 22.8±8.1 mm from 38.8±15.7 mm (P=0.001). Moreover, a significant decrease in SUVmax was observed from 6.53±5.14 to 2.56±1.67 and 2.45±1.48 at 4-week and 8-week time-points after treatment (P=0.032 and 0.020), respectively. The common grade 3 adverse events (AEs) included hand-foot-skin reaction (50%), hypertension (30%), and hypocalcemia (20%). No severe AE related to apatinib was observed during treatment. Hence, apatinib seems to be a promising therapeutic option for RAIR-DTC patients. Apart from RECIST 1.1 criteria, the biochemical marker (Tg) and glucose metabolism index (SUVmax) could be adopted in assessing the early response to TKI in RAIR-DTC. PMID:28178685

Efficacy and safety of icotinib in treating non-small cell lung cancer: a systematic evaluation and meta-analysis based on 15 studies.

PubMed

Biaoxue, Rong; Hua, Liu; Wenlong, Gao; Shuanying, Yang

2016-12-27

Icotinib is a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that developed and used in China; this work was to evaluate its efficacy and safety in treating non-small cell lung cancer (NSCLC). Clinical studies evaluating the efficacy and safety of icotinib in treating NSCLC were identified from the databases of Medline, Web of Science, Embase and Cochrance Library. Pooled efficacy and safety of icotinib were calculated through a series of predefined search strategies. A total of 15 studies with 2,304 patients were involved in this study. The overall response rate (ORR) and disease control rate (DCR) of icotinib were 40.99% (95% CI: 33.77% to 48.22%) and 77.16% (95% CI: 51.43% to 82.31%). The pooled progression-free survival (PFS) and overall survival (OS) were 7.34 months (95% CI: 5.60 to 9.07) and 14.98 months (95% CI: 9.78 to 20.18). Patients with EGFR mutations exhibited better ORR (OR = 3.67, p < 0.001), DCR (OR = 1.39, p = 0.001) and PFS (11.0 ± 0.76 vs. 1.97 ± 0.82 months). Moreover, patients with rash had a higher ORR (OR = 2.14, p = 0.001) than those without rash. The common adverse effects (AEs) included skin rash (31.4%), diarrhea (14.2%), pruritus (6.7%) and hepatic toxicity (3.8%) and most of them were well tolerated. In conclusion, Icotinib is an effective and well tolerated regimen for Chinese patients with advanced NSCLC. Further randomized trials with large population are required to provide stronger evidence for icotinib in treating NSCLC.

Efficacy and safety of icotinib in treating non-small cell lung cancer: a systematic evaluation and meta-analysis based on 15 studies

PubMed Central

Biaoxue, Rong; Hua, Liu; Wenlong, Gao; Shuanying, Yang

2016-01-01

Icotinib is a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that developed and used in China; this work was to evaluate its efficacy and safety in treating non-small cell lung cancer (NSCLC). Clinical studies evaluating the efficacy and safety of icotinib in treating NSCLC were identified from the databases of Medline, Web of Science, Embase and Cochrance Library. Pooled efficacy and safety of icotinib were calculated through a series of predefined search strategies. A total of 15 studies with 2,304 patients were involved in this study. The overall response rate (ORR) and disease control rate (DCR) of icotinib were 40.99% (95% CI: 33.77% to 48.22%) and 77.16% (95% CI: 51.43% to 82.31%). The pooled progression-free survival (PFS) and overall survival (OS) were 7.34 months (95% CI: 5.60 to 9.07) and 14.98 months (95% CI: 9.78 to 20.18). Patients with EGFR mutations exhibited better ORR (OR = 3.67, p < 0.001), DCR (OR = 1.39, p = 0.001) and PFS (11.0 ± 0.76 vs. 1.97 ± 0.82 months). Moreover, patients with rash had a higher ORR (OR = 2.14, p = 0.001) than those without rash. The common adverse effects (AEs) included skin rash (31.4%), diarrhea (14.2%), pruritus (6.7%) and hepatic toxicity (3.8%) and most of them were well tolerated. In conclusion, Icotinib is an effective and well tolerated regimen for Chinese patients with advanced NSCLC. Further randomized trials with large population are required to provide stronger evidence for icotinib in treating NSCLC. PMID:27893423

Inaccuracy of diagnosis in a cohort of patients on the waiting list for dacryocystorhinostomy when the diagnosis was made by only syringing the lacrimal system.

PubMed

Beigi, B; Uddin, J M; McMullan, T F W; Linardos, E

2007-01-01

Accurate identification of the factors contributing to epiphora is essential in directing appropriate management and treatment strategies. The authors applied a methodical strategy of assessment for epiphora to patients who were already on the waiting list for dacryocystorhinostomy (DCR). The findings were compared to the original findings. Forty-four eyes of 35 patients listed for DCR were re-examined. All canaliculi were examined using four tests: dye disappearance, Jones 1 (dye retrieval), probing using Bowman probes, and syringing of the nasolacrimal duct (NLD) under local anesthesia. Some patients were examined using an endocanalicular mini-endoscope. Patients with NLD obstruction underwent DCR and those with canalicular and NLD stenosis underwent intubation of the lacrimal system-canaliculus, lacrimal sac, and nasolacrimal duct-using silicone stents. The authors refer to this as canaliculodacryocystoplasty (CDCP). The patients were assessed for symptoms of epiphora at 12 months. Forty-four eyes had been listed for DCR. They had been originally diagnosed, by means of lacrimal syringing, as NLD obstruction (24 eyes) or stenosis (12 eyes), and functional blocks (8 eyes). Four out of the original 44 planned DCR surgeries were performed after re-evaluation. After re-examination, 28 lacrimal systems were found to have canalicular stenosis, 4 NLD stenosis, 4 NLD obstruction, 4 punctal phimosis, 3 ocular surface disease, and 1 patient was asymptomatic. Twenty-eight lacrimal systems underwent CDCP, 4 underwent DCR, 4 had punctoplasty, and 4 had probing alone. Three had treatment for ocular surface disease and one patient required no treatment. After a follow-up of 12 months, 41 (93%) systems had improvement or were free of their Syringing of the lacrimal apparatus may result in a high false positive diagnosis of NLD obstruction. Canalicular pathology is not uncommon in this cohort of patients and may be underdiagnosed.

Patient satisfaction following endoscopic endonasal dacryocystorhinostomy: a quality of life study.

PubMed

Jutley, G; Karim, R; Joharatnam, N; Latif, S; Lynch, T; Olver, J M

2013-09-01

To assess the subjective success and quality of life of adult patients post endoscopic endonasal dacryocystorhinostomy (EE-DCR) for acquired nasolacrimal duct obstruction. Retrospective, questionnaire study performed at least 6 months post EE-DCR. Hundred and ten of the 282 consecutive patients who underwent EE-DCR. A standardised questionnaire (Glasgow Benefit Inventory, GBI) was used to analyse the quality of life. The questionnaire examines four parameters, providing total, subscale, social, and physical scores. We aimed to assess patient experience following EE-DCR surgery. Total GBI scores range from -100 to +100, the former reflecting maximal negative benefit and corresponding to subjective worsening of tearing and impact on quality of life. Any positive score reflects a satisfactory surgical outcome and +100 represents maximal positive benefit. A score of zero is no perceived benefit. The average age was 62 years, 63% were female. In three of the parameters measured, there was a subjective improvement post surgery: subscale score 22.16 (95% CI: 15.23-29.09), total score 15.04 (95% CI: 9.74-20.35), and social support score 4.67 (95% CI: 0.93-8.42). Physical health scored -4.47 (95% CI: -10.25 to 1.32). Secondary analyses demonstrate no statistical significance with respect to outcome whether a trainee or consultant performed the procedure. Younger patients (under split median of 63.5) had a better total score 19.04 (95% CI: 11.35-27.74) than those older than 63.5 years (11.04, 95% CI: 3.61-18.47). This study shows that EE-DCR gave patients improvement in quality of life, proven by a validated questionnaire. The mean total score of 15.04 found in our study compares with the 18.7 recorded by Feretis et al in 2009. Results were irrespective of the grade of surgeon, similar to the findings of Fayers et al for functional successes. This study supports the use of EE-DCR for the improvement of quality of life in adult patients.

Overexpression of decoy receptor 3 in synovial tissues of inflammatory arthritis.

PubMed

Chen, Ming-Han; Chen, Wei-Sheng; Tsai, Chang-Youh; Liao, Hsien-Tzung; Chen, Chun-Hsiung; Chou, Chung-Tei

2012-01-01

Decoy receptor 3 (DCR3) was a newly identified soluble receptor which was reported to modulate the function of T cells, dendritic cells and macrophages. The aim of this study was to investigate DCR3 expression on the synovial tissue in different types of arthritis. We obtained synovial tissues from 17 rheumatoid arthritis (RA), 17 ankylosing spondylitis (AS) and 17 osteoarthritis (OA) patients. Synovial specimens were stained with hematoxylin and eosin. The amount of lymphocytes and mononuclear cells infiltration and vascularity during light microscopic examination was scored from 0-4. The expression of CD3, CD4, CD8, CD68 and DCR3 in lining layer (LL) and sublining layer (SL) cells was stained using the immunohistochemical method and analysed by microscopic examination (score from 0-4, 0=absent, 1=slight, 2=moderate, 3=large, 4=extreme). OA patients were older than the RA and AS patients (65.9±10.3 years for OA, 58.4±17.7 for RA, and 43.2±16.4 for AS). Synovial tissues in RA patients had significantly increased mononuclear cells infiltration when compared to AS and OA patients (2.3±0.6, 1.9±0.5, 1.6±0.5, respectively, p<0.05). There was no striking difference in DCR3 expression in the synovial LL between RA, AS, and OA patients. CD4+ T cells and CD68+ monocytes/macrophages in the SL were more prominent in RA and AS than in OA (p<0.05). Similarly, DCR3 in the SL was more overexpressed in RA and AS than in OA (1.83±0.21, 1.71±0.36, 1.39±0.31, respectively, p<0.01). The increased synovial inflammatory cells infiltration in RA and AS was associated with the elevated DCR3 expression.

Expression of decoy receptor 3 in diffuse sclerosing variant of papillary thyroid carcinoma: correlation with M2 macrophage differentiation and lymphatic invasion.

PubMed

Chang, Wei-Chin; Chen, Jui-Yu; Lee, Chen-Hsen; Yang, An-Hang

2013-06-01

The diffuse sclerosing variant of papillary thyroid carcinoma (DSV-PTC) is a unique variant of PTC that is characterized by extensive lymphovascular invasion of tumor cells in a background of lymphocytic thyroiditis. The lymphatic emboli contain tumor cells as well as macrophages, but the recruitment of these macrophages is not well understood. The aim of this study was to determine the relationship between the expression of Decoy receptor 3 (DcR3), the recruitment of tumor-associated macrophages (TAMs), and lymphatic invasion in DSV-PTC. We retrospectively examined 14 cases of DSV-PTC using immunohistochemistry studies. The density of TAMs, lymphatic vessel density, lymphatic invasion, tumor emboli area, and DcR3 expression were assessed. Statistical analyses were performed using Fisher's exact test, unpaired t-test, and linear regression. The lymphatic tumor emboli contained a relatively higher density of TAMs than stroma and classical PTC (CPTC) areas. In addition, the number of lymphatic invasions and the size of the tumor emboli area were positively correlated with the number of M2 TAMs. A higher density of M2 TAMs was associated with older patients and larger tumor size. Moreover, DcR3 was expressed only in lymphatic tumor cells and squamous metaplastic tumor cells, but not in macrophages and CPTC. In addition, the preferential expression of DcR3 in tumors was associated with higher levels of M2 TAMs and lymphatic invasion. Despite the fact that the exact relationship between DcR3, M2 macrophages, and lymphatic invasion in DSV-PTC remains to be elucidated, our findings suggest that DcR3 expression in DSV-PTC tumor cells may promote the polarized macrophage differentiation toward the M2 phenotype. This phenomenon may further promote lymphatic invasion of DSV-PTC tumor cells.

Piezosurgery in External Dacryocystorhinostomy.

PubMed

Czyz, Craig N; Fowler, Amy M; Dutton, Jonathan J; Cahill, Kenneth V; Foster, Jill A; Hill, Robert H; Everman, Kelly R; Nabavi, Cameron B

Dacryocystorhinostomy (DCR) can be performed via an external or endoscopic approach. The use of ultrasonic or piezosurgery has been well described for endoscopic DCRs but is lacking for external DCRs. This study presents a case series of external DCRs performed using piezosurgery evaluating results and complications. Prospective, consecutive case series of patients undergoing primary external DCR for lacrimal drainage insufficiency. A standard external DCR technique was used using 1 of 2 piezosurgery systems for all bone incision. All patients received silicone intubation to the lacrimal system. Surgical outcome was measured in terms of patient-reported epiphora as follows: 1) complete resolution, 2) improvement >50%, 3) improvement <50%, and 4) No improvement. Intra and postoperative complications were also recorded. Fifty-two patients, 14 male and 38 female, were included in the study, with 2 patients having bilateral surgery. The average age of the patients was 55.8 years. The average length of follow up was 221 days. Surgical outcomes showed 72% of patients with complete resolution of epiphora and 21% with >50% improvement. There were 4 patients (7%) who had <50% improvement. There was 1 (2%) intraoperative complication and 2 (4%) postoperative complications recorded. Piezourgery is a viable modality for performing external DCRs. The lack of surgical complications shows a potential for decreased soft tissues damage. The surgical success rate based on patient-reported epiphora is similar to those published for mechanical external DCRs. This modality may benefit the novice surgeon in the reduction of soft and mucosal tissue damage.

Decoy receptor 3 analogous supplement protects steatotic rat liver from ischemia-reperfusion injury.

PubMed

Li, Tzu-Hao; Liu, Chih-Wei; Lee, Pei-Chang; Huang, Chia-Chang; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Yang, Ying-Ying; Hsieh, Shie-Liang; Lin, Han-Chieh; Tsai, Chang-Youh

2017-07-01

For steatotic livers, pharmacological approaches to minimize the hepatic neutrophil and macrophage infiltration, and cytokine and chemokine release in ischemia-reperfusion (IR) injury are still limited. Tumor necrosis factor (TNF)-α superfamily-stimulated pathogenic cascades and M1 macrophage/Kupffer cells (KC) polarization from Th1 cytokines are important in the pathogenesis of IR liver injury with hepatic steatosis (HS). Conversely, anti-inflammatory M2 macrophages produce Th2 cytokine (interleukin-4), which reciprocally enhances M2 polarization. Toll-like receptor 4-activated KCs can release proinflammatory mediators, skew M1 polarization and escalate liver IR injury. Decoy receptor 3 (DcR 3 ) could be potential agents simultaneously blocking the IR liver injury-related pathogenic changes and extend the survival of steatotic graft. Rats were fed with methionine and choline-deficient high-fat diet (MCD HFD) for 6 weeks to induce HS. Preliminary experiments with HS group and IR group were conducted, and either immunoglobulin G Fc protein or DcR3 analogue was treated for 14 days in all groups to evaluate the severity. In the Zucker rat-focused experiments, various serum and hepatic substances, M1 polarization, and hepatic microcirculation were assessed. We found that serum/hepatic DcR 3 levels were lower in nonalcoholic fatty liver disease patients with HS. DcR 3 a protected Zucker rats with HS from IR liver injury. The beneficial effects of DcR 3 a supplement were mediated by inhibiting hepatic M1 polarization of KCs, decreasing serum/hepatic TNFα, nitric oxide, nitrotyrosine, soluble TNF-like cytokine 1A, Fas ligand, and interferon-γ levels, neutrophil infiltration, and improving hepatic microcirculatory failure among rats with IR-injured steatotic livers. Additionally, downregulated hepatic TNF-like cytokine 1A/Fas-ligand and toll-like receptor 4/nuclear factor-κB signals were found to mediate the DcR 3 a-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR 3 a analogue was a potential agent to protect steatotic liver against IR injury by simultaneous blockade of the multiple IR injury-related pathogenic changes. Copyright © 2017. Published by Elsevier Taiwan LLC.

Isolation of epidermal cells and cDNA cloning of TNF decoy receptor 3 of conger eel, Conger myriaster.

PubMed

Tsutsui, Shigeyuki; Yoshino, Yuko; Matsui, Saho; Nakamura, Osamu; Muramoto, Koji; Watanabe, Tasuku

2008-03-01

By using EDTA and a trypsin solution, we established a method for isolating the epidermal cells of the conger eel, Conger myriaster. We then identified TNF decoy receptor (DcR) cDNA in the species from a suppression subtractive hybridization library prepared from the epidermal cells stimulated with LPS. The full-length cDNA of conger TNF DcR (conDcR) consisted of 1479 base pairs, and the protein comprised 286 amino acid residues. Phylogenetic analysis indicated that conDcR was clustered into a DcR3 branch. ConDcR is likely to act as an important immune-regulating factor in inhibiting the apoptosis-inducing effect of TNF in the skin of conger eel.

Efficacy of Icotinib treatment in patients with stage IIIb/IV non-small cell lung cancer

PubMed Central

Qin, Na; Yang, Xinjie; Zhang, Quan; Li, Xi; Zhang, Hui; Lv, Jialin; Wu, Yuhua; Wang, Jinghui; Zhang, Shucai

2014-01-01

Background To evaluate the efficacy and safety of Icotinib – an orally administered, highly potent selective inhibitor of epidermal growth factor receptor (EGFR) and its active mutations, in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Methods A total of 101 patients with stage IIIb/IV NSCLC were treated with 125 mg Icotinib three times a day until disease progression or intolerable toxicity. Response rate was evaluated using response evaluation criteria in solid tumors and progression-free survival (PFS) was collected. Results The overall response rate (ORR) and disease control rate (DCR) were 37.6% (38/101) and 79.2% (80/101), respectively. The median PFS was 6.5 months. Multivariate analysis showed that female gender (P= 0.048, 95% confidence interval [CI] 1.010–6.016) and occurrence of rash (P= 0.002, 95% CI 1.667–9.809) were the independent predictive factors for ORR, while a performance status (PS) score of 0–1 (P= 0.001, 95% CI 0.024–0.402) and rash (P= 0.042, 95% CI 1.089–76.557) were the independent predictive factors for DCR. In addition, PS scores of 0–1 (P <0.001, 95% CI 0.135–0.509), and non-smoking (P= 0.017, 95% CI 0.342–0.900) were found to be independent influencing factors for PFS. Moreover, patients with EGFR mutations had better PFS than patients with wild type EGFR, while patients with EGFR exon 19 deletion had better survival than those with EGFR exon 21 mutation. The most common adverse effects of Icotinib were rash (35.6%) and diarrhea (17.8%), which was tolerable. Conclusion Treatment of stage IIIb/IV NSCLC patients with Icotinib was effective and tolerable, specifically in patients with EGFR mutation. PMID:26767007

Electrostatic Steering Accelerates C3d:CR2 Association.

PubMed

Mohan, Rohith R; Huber, Gary A; Morikis, Dimitrios

2016-08-25

Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts.

Local versus general anesthesia for external dacryocystorhinostomy in young patients.

PubMed

Ciftci, Ferda; Pocan, Sibel; Karadayi, Koray; Gulecek, Oguz

2005-05-01

To compare the effectiveness, complications, and patient acceptance of local anesthesia with general anesthesia in young patients for external dacryocystorhinostomy (DCR). Data were prospectively collected over an 8-year period (1996-2004) on young patients (mean age: 22.64+/-1.71) undergoing external DCR in Gulhane Military Medical Academy. Patients were randomly allocated in two groups: general anesthesia (GA) and local anesthesia (LA). Of the 480 DCR procedures, 182 were performed with general anesthesia (44 bilateral), 298 were performed with local anesthesia (32 bilateral). Visual analogue scales were recorded in the postoperative 2-hour period. Postoperative nausea and vomiting (PONV), epistaxis, length of hospital stay, and intraoperative bleeding were noted. Patients in both groups reported being comfortable during and immediately after surgery. Only 2 patients in the LA group required additional local anesthetic because of pain. Intraoperative bleeding was lower in the LA group. Analgesic requirement and signs of nausea and vomiting in the GA group were higher in the early postoperative period (p<0.05). The incidence of PONV was higher (p<0.05) in the GA group. Postoperative epistaxis was observed in 12 patients in the GA group and just 2 patients in the LA group. Length of hospital stay was 2.29+/-0.46 days in the GA group, and 1.23+/-0.42 days in the LA group (p<0.01). Local anesthesia in DCR is safe and comfortable when proper anatomical approach to nerve blocks is performed correctly. Local anesthesia in young patients undergoing external DCR is a good alternative because it is cost-effective and it eliminates the complications of general anesthesia.

Pain during external dacryocystorhinostomy with local anesthesia.

PubMed

Knežević, Miroslav M; Stojković, Milenko Ž; Vlajković, Gordana P; Jovanović, Miloš B; Rašić, Dejan M

2011-06-01

External dacryocystorhinostomy (DCR) is often performed under local anesthesia (LA) without adequate knowledge of the pain experienced by the patient. We subdivided our surgical technique into stages easily understood by the patients (introducing cotton tipped applicators, performing parabulbar injection, creating the incision, bone cracking (opening the ostium), manipulating the nose, intubating, closing the wound, and packing with gauze). A total of 50 patients ranging in age from 31 to 83 years of age (63.64±9.64) underwent external DCR. Each patient was asked 30 minutes after surgery to indicate the intensity of pain experienced at each stage of the surgery and during intramuscular (i.m.) injection of an antibiotic using a visual analog scale (VAS). Analysis of the VAS-based pain scores indicated 3 statistically equal occurrences of pain coinciding with the opening of the ostium, and receiving both parabulbar anesthetic and i.m. antibiotic injections. The level of pain experienced during the most unpleasant stage of external DCR (ostium opening) was similar to the pain experienced from an i.m. injection. Patients can be informed that pain during external DCR with local anesthesia is comparable to receiving an i.m. gluteal injection.

TAF11 Assembles the RISC Loading Complex to Enhance RNAi Efficiency.

PubMed

Liang, Chunyang; Wang, Yibing; Murota, Yukiko; Liu, Xiang; Smith, Dean; Siomi, Mikiko C; Liu, Qinghua

2015-09-03

Assembly of the RNA-induced silencing complex (RISC) requires formation of the RISC loading complex (RLC), which contains the Dicer-2 (Dcr-2)-R2D2 complex and recruits duplex siRNA to Ago2 in Drosophila melanogaster. However, the precise composition and action mechanism of Drosophila RLC remain unclear. Here we identified the missing factor of RLC as TATA-binding protein-associated factor 11 (TAF11) by genetic screen. Although it is an annotated nuclear transcription factor, we found that TAF11 also associated with Dcr-2/R2D2 and localized to cytoplasmic D2 bodies. Consistent with defective RLC assembly in taf11(-/-) ovary extract, we reconstituted the RLC in vitro using the recombinant Dcr-2-R2D2 complex, TAF11, and duplex siRNA. Furthermore, we showed that TAF11 tetramer facilitates Dcr-2-R2D2 tetramerization to enhance siRNA binding and RISC loading activities. Together, our genetic and biochemical studies define the molecular nature of the Drosophila RLC and elucidate a cytoplasmic function of TAF11 in organizing RLC assembly to enhance RNAi efficiency. Copyright © 2015 Elsevier Inc. All rights reserved.

The RNA methyltransferase Dnmt2 is required for efficient Dicer-2-dependent siRNA pathway activity in Drosophila.

PubMed

Durdevic, Zeljko; Mobin, Mehrpouya Balaghy; Hanna, Katharina; Lyko, Frank; Schaefer, Matthias

2013-09-12

Transfer RNA (tRNA) fragmentation in response to stress conditions has been described in many organisms. tRNA fragments have been found in association with small interfering RNA (siRNA) components, but the biological role of these interactions remains unclear. We report here that the tRNA methyltransferase Dnmt2 is essential for efficient Dicer-2 (Dcr-2) function in Drosophila. Using small RNA (sRNA) sequencing, we confirmed that Dnmt2 limits the extent of tRNA fragmentation during the heat-shock response. tRNAs as well as tRNA fragments serve as Dcr-2 substrates, and Dcr-2 degrades tRNA-derived sequences, especially under heat-shock conditions. tRNA-derived RNAs are able to inhibit Dcr-2 activity on long double-stranded RNAs (dsRNAs). Consequently, heat-shocked Dnmt2 mutant animals accumulate dsRNAs, produce fewer siRNAs, and show misregulation of siRNA pathway-dependent genes. These results reveal the impact of tRNA fragmentation on siRNA pathways and implicate tRNA modifications in the regulation of sRNA homeostasis during the heat-shock response. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Organ donation in trauma victims: A systematic review and meta-analysis.

PubMed

Cameron, Adam; Erdogan, Mete; Lanteigne, Sara; Hetherington, Alexandra; Green, Robert S

2018-06-01

Although trauma patients represent a large pool of potential organ donors (PODs), the donor conversion rates (DCRs) in this population are unclear. Our primary objective was to synthesize published evidence on DCRs in trauma patients. As a secondary objective, we investigated factors that affect organ donation (OD) in the trauma population. We searched four electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) and gray literature for articles on OD in trauma patients (PROSPERO 2017: CRD42017070388). Articles were excluded if it was not possible to calculate the DCR (actual organ donors divided by PODs). We pooled DCRs and performed subgroups analysis by trauma subpopulation, patients' age, and study publication date. We identified 27 articles with a total of 123,142 participants. Cohorts ranged in size from 28 to 120,512 patients (median, 132), with most studies performed in the United States. Conversion rates among individual studies ranged from 14.0% to 75.2% (median, 49.3%). All 27 studies were included in the meta-analysis. We found a pooled DCR of 48.1% using the random effects model. There was a high level of heterogeneity between studies (I = 97.4%). Upon subgroup analysis, we found DCRs were higher in head trauma patients compared with traumatic cardiac arrest patients (45.3% vs 20.9%, p < 0.001), in pediatric patients compared with adults (61.0% vs 38.0%, p = 0.018), and in studies published after 2007 compared with those published before (50.8% vs 43.9%, p < 0.001). Few studies assessed for factors associated with OD in trauma patients. We found variation in DCRs among trauma patients (range, 14.0-75.2%) and estimated a pooled DCR of 48.1%. Our results are limited by heterogeneity across studies, which may be attributable to differences in study design and population, definitions of a POD, and in the institutional criteria and processes regarding OD. Systematic reviews and meta-analyses level III.

Pazopanib in Metastatic Renal Cancer: A "Real-World" Experience at National Cancer Institute "Fondazione G. Pascale".

PubMed

Cecere, Sabrina C; Rossetti, Sabrina; Cavaliere, Carla; Della Pepa, Chiara; Di Napoli, Marilena; Crispo, Anna; Iovane, Gelsomina; Piscitelli, Raffaele; Sorrentino, Domenico; Ciliberto, Gennaro; Maiolino, Piera; Muto, Paolo; Perdonà, Sisto; Berretta, Massimiliano; Pignata, Sandro; Facchini, Gaetano; D'Aniello, Carmine

2016-01-01

Pazopanib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma. The present study analyzed the outcomes of pazopanib in first-line treatment of mRCC, in a single Italian cancer center. In the light of the retrospective, observational nature and the unselected population, our experience can be defined a "real-world" study. The medical records of 38 mRCC patients treated with front-line pazopanib were retrospectively reviewed and analyzed. The progression free survival (PFS) and the overall survival (OS) were the primary endpoints, while secondary objectives included objective response rate (ORR), disease control rate (DCR), and treatment tolerability. Pazopanib achieved a median PFS (mPFS) of 12.7 months (95% CI, 6.9-18.5 months). The median OS (mOS) was 26.2 months (95% CI, 12.6-39.9 months); the observed ORR and DCR were 30.3 and 72.7%, respectively, with a median duration of response of 11 weeks. mPFS appeared not to be influenced by number of co-morbidities (< 3 vs. ≥3), gender, Fuhrman grade and age. Conversely, the ORR and the DCR positively affect the mPFS (HR = 0.05 [95% CI, 0.05-0.55], p = 0.01; HR = 0.10 [95% CI, 0.02-0.43], p = 0.002, respectively). A worse outcome was associated with a lower mPFS in patients with liver metastases (p = 0.2) and with a high tumor burden (number of metastatic sites < 6 vs. ≥6) (p = 0.08). Worst OS was observed in patients aged ≥70 years old (HR = 6.91 [95% CI, 1.49-31.91], p = 0.01). The treatment was well-tolerated: no grade 4 adverse events, nor discontinuation due to toxicities was reported. Grade 3 hypertension affected positively the OS reaching the statistical significance (HR = 0.22 [95% CI, 0.05-0.8], p = 0.03). Thyroid dysfunction (hypo and hyperthyroidism) seems to correlate with better outcome in terms of a longer mPFS (HR = 0.12 [95% CI, 0.02-0.78], p = 0.02). Our results are consistent with those reported in prospective phase III trials and the published retrospective "real world" experiences. This analysis confirms the safety and efficacy of pazopanib in first-line setting, both in frail patients with multiple co-morbidities and Karnofsky PS < 80% and in younger, healthier patients with a number of metastatic sites < 6.

Pazopanib in Metastatic Renal Cancer: A “Real-World” Experience at National Cancer Institute “Fondazione G. Pascale”

PubMed Central

Cecere, Sabrina C.; Rossetti, Sabrina; Cavaliere, Carla; Della Pepa, Chiara; Di Napoli, Marilena; Crispo, Anna; Iovane, Gelsomina; Piscitelli, Raffaele; Sorrentino, Domenico; Ciliberto, Gennaro; Maiolino, Piera; Muto, Paolo; Perdonà, Sisto; Berretta, Massimiliano; Pignata, Sandro; Facchini, Gaetano; D'Aniello, Carmine

2016-01-01

Pazopanib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) and soft tissue sarcoma. The present study analyzed the outcomes of pazopanib in first-line treatment of mRCC, in a single Italian cancer center. In the light of the retrospective, observational nature and the unselected population, our experience can be defined a “real-world” study. The medical records of 38 mRCC patients treated with front-line pazopanib were retrospectively reviewed and analyzed. The progression free survival (PFS) and the overall survival (OS) were the primary endpoints, while secondary objectives included objective response rate (ORR), disease control rate (DCR), and treatment tolerability. Pazopanib achieved a median PFS (mPFS) of 12.7 months (95% CI, 6.9–18.5 months). The median OS (mOS) was 26.2 months (95% CI, 12.6–39.9 months); the observed ORR and DCR were 30.3 and 72.7%, respectively, with a median duration of response of 11 weeks. mPFS appeared not to be influenced by number of co-morbidities (< 3 vs. ≥3), gender, Fuhrman grade and age. Conversely, the ORR and the DCR positively affect the mPFS (HR = 0.05 [95% CI, 0.05–0.55], p = 0.01; HR = 0.10 [95% CI, 0.02–0.43], p = 0.002, respectively). A worse outcome was associated with a lower mPFS in patients with liver metastases (p = 0.2) and with a high tumor burden (number of metastatic sites < 6 vs. ≥6) (p = 0.08). Worst OS was observed in patients aged ≥70 years old (HR = 6.91 [95% CI, 1.49–31.91], p = 0.01). The treatment was well-tolerated: no grade 4 adverse events, nor discontinuation due to toxicities was reported. Grade 3 hypertension affected positively the OS reaching the statistical significance (HR = 0.22 [95% CI, 0.05–0.8], p = 0.03). Thyroid dysfunction (hypo and hyperthyroidism) seems to correlate with better outcome in terms of a longer mPFS (HR = 0.12 [95% CI, 0.02–0.78], p = 0.02). Our results are consistent with those reported in prospective phase III trials and the published retrospective “real world” experiences. This analysis confirms the safety and efficacy of pazopanib in first-line setting, both in frail patients with multiple co-morbidities and Karnofsky PS < 80% and in younger, healthier patients with a number of metastatic sites < 6. PMID:27630568

Adjusted Indirect Comparison Using Propensity Score Matching of Osimertinib to Platinum-Based Doublet Chemotherapy in Patients with EGFRm T790M NSCLC Who Have Progressed after EGFR-TKI.

PubMed

Mann, Helen; Andersohn, Frank; Bodnar, Carolyn; Mitsudomi, Tetsuya; Mok, Tony S K; Yang, James Chih-Hsin; Hoyle, Christopher

2018-04-01

An adjusted indirect comparison was conducted to assess efficacy outcomes, particularly overall survival (OS), of osimertinib versus platinum-based doublet chemotherapy in patients with epidermal growth factor receptor-mutated (EGFRm) T790M mutation-positive non-small-cell lung cancer (NSCLC) who had progressed following an EGFR tyrosine kinase inhibitor (TKI). Analysis of treatment effect from two separate trials had the potential to more accurately estimate the magnitude of OS benefit due to absence of confounding due to treatment switching from the control arm to the osimertinib arm of the ongoing randomized control trial, AURA3. Two non-randomized individual datasets were compared: pooled patients from the AURA extension and AURA2 trials (osimertinib 80 mg, n = 405, with a confirmed T790M mutation using tissue samples), and patients from the control arm of the IMPRESS study (platinum-based doublet chemotherapy, n = 61, with a confirmed T790M mutation using plasma circulating tumour DNA [ctDNA]). A propensity score-based approach was used to account for differences in baseline demographics and disease characteristics. After adjustment for baseline differences between the two groups, osimertinib demonstrated a statistically significant improvement in progression-free survival (PFS) versus platinum-based doublet chemotherapy (hazard ratio [HR] = 0.278, 95% confidence interval [CI] 0.188-0.409, p < 0.0001; median PFS 10.9 vs. 5.3 months). Improvements were also observed for objective response rate (ORR) and disease control rate (DCR) (ORR: 64.3 vs. 33.3%; odds ratio [OR] = 5.31, 95% CI 2.47-11.40, p < 0.001; DCR: 92.1 vs. 75.0%; OR = 4.72, 95% CI 1.92-11.58, p < 0.001). Similar results were obtained for patients who received osimertinib as second-line treatment only. A statistically significant improvement in OS was observed for the osimertinib group (HR = 0.412, 95% CI 0.273-0.622, p < 0.0001). Median OS for osimertinib was not reached. In this indirect comparison, osimertinib showed a statistically significant improvement in efficacy outcomes versus platinum-based doublet chemotherapy in patients with EGFRm T790M NSCLC who had progressed after EGFR-TKI therapy.

Absolute quantification of DcR3 and GDF15 from human serum by LC-ESI MS

PubMed Central

Lancrajan, Ioana; Schneider-Stock, Regine; Naschberger, Elisabeth; Schellerer, Vera S; Stürzl, Michael; Enz, Ralf

2015-01-01

Biomarkers are widely used in clinical diagnosis, prognosis and therapy monitoring. Here, we developed a protocol for the efficient and selective enrichment of small and low concentrated biomarkers from human serum, involving a 95% effective depletion of high-abundant serum proteins by partial denaturation and enrichment of low-abundant biomarkers by size exclusion chromatography. The recovery of low-abundance biomarkers was above 97%. Using this protocol, we quantified the tumour markers DcR3 and growth/differentiation factor (GDF)15 from 100 μl human serum by isotope dilution mass spectrometry, using 15N metabolically labelled and concatamerized fingerprint peptides for the both proteins. Analysis of three different fingerprint peptides for each protein by liquid chromatography electrospray ionization mass spectrometry resulted in comparable concentrations in three healthy human serum samples (DcR3: 27.23 ± 2.49 fmol/ml; GDF15: 98.11 ± 0.49 fmol/ml). In contrast, serum levels were significantly elevated in tumour patients for DcR3 (116.94 ± 57.37 fmol/ml) and GDF15 (164.44 ± 79.31 fmol/ml). Obtained data were in good agreement with ELISA and qPCR measurements, as well as with literature data. In summary, our protocol allows the reliable quantification of biomarkers, shows a higher resolution at low biomarker concentrations than antibody-based strategies, and offers the possibility of multiplexing. Our proof-of-principle studies in patient sera encourage the future analysis of the prognostic value of DcR3 and GDF15 for colon cancer patients in larger patient cohorts. PMID:25823874

Electrostatic Steering Accelerates C3d:CR2 Association

PubMed Central

2016-01-01

Electrostatic effects are ubiquitous in protein interactions and are found to be pervasive in the complement system as well. The interaction between complement fragment C3d and complement receptor 2 (CR2) has evolved to become a link between innate and adaptive immunity. Electrostatic interactions have been suggested to be the driving factor for the association of the C3d:CR2 complex. In this study, we investigate the effects of ionic strength and mutagenesis on the association of C3d:CR2 through Brownian dynamics simulations. We demonstrate that the formation of the C3d:CR2 complex is ionic strength-dependent, suggesting the presence of long-range electrostatic steering that accelerates the complex formation. Electrostatic steering occurs through the interaction of an acidic surface patch in C3d and the positively charged CR2 and is supported by the effects of mutations within the acidic patch of C3d that slow or diminish association. Our data are in agreement with previous experimental mutagenesis and binding studies and computational studies. Although the C3d acidic patch may be locally destabilizing because of unfavorable Coulombic interactions of like charges, it contributes to the acceleration of association. Therefore, acceleration of function through electrostatic steering takes precedence to stability. The site of interaction between C3d and CR2 has been the target for delivery of CR2-bound nanoparticle, antibody, and small molecule biomarkers, as well as potential therapeutics. A detailed knowledge of the physicochemical basis of C3d:CR2 association may be necessary to accelerate biomarker and drug discovery efforts. PMID:27092816

Endoscopic endonasal dacryocystorhinostomy combined with canaliculus repair for the management of dacryocystitis with canalicular obstruction.

PubMed

Tu, Yunhai; Qian, Zhenbin; Zhang, Jiao; Wu, Wencan; Xiao, Tianlin

2015-01-01

Purpose. The aim of this study is to propose a simple and efficient combination surgery for the management of dacryocystitis with canalicular obstruction. Methods. A retrospective noncomparative case series of dacryocystitis with canalicular obstruction has been studied. Twelve patients with dacryocystitis and canalicular obstruction underwent a conventional endoscopic endonasal dacryocystorhinostomy (EE-DCR) combined with a modified canalicular repair. Postoperative observations included slit lamp, fluorescein dye disappearance test, lacrimal syringing, lacrimal endoscopy, and nasal endoscopy. Results. After 6-18 months of postoperative follow-up, the symptoms of epiphora and mucopurulent discharge disappeared completely in 10 patients, and occasional or intermittent epiphora remained in 2 patients. All of the twelve patients showed an opened intranasal ostium and normal fluorescein dye disappearance test. Patent bicanalicular irrigation was achieved in 9 patients. One patient had a partial and the other two had a complete reobstruction by lacrimal irrigation to their repaired lower canaliculus; however, all of them had a patent lacrimal irrigation to upper canaliculus. The functional success rate for the combination surgery is 83% (10/12), and anatomical success rate is 75% (9/12). Conclusion. EE-DCR combined with modified canalicular repair is a simple and efficient method for the management of dacryocystitis with canalicular obstruction.

A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia.

PubMed

Marriott, Helen M; Daigneault, Marc; Thompson, Alfred A R; Walmsley, Sarah R; Gill, Sharonjit K; Witcher, Derrick R; Wroblewski, Victor J; Hellewell, Paul G; Whyte, Moira K B; Dockrell, David H

2012-11-01

Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility. Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a. During established pneumonia, neutrophils became the predominant cell in the airway and gld mice were less able to clear bacteria from the lungs, demonstrating localised impairment of pulmonary neutrophil function in comparison to lpr or wild-type mice. T-cells from gld mice had enhanced activation and reduced apoptosis in comparison to wild-type and lpr mice during established pneumonia. Treatment with DcR3-a reduced T-cell activation and corrected the defect in pulmonary bacterial clearance in gld mice. The results suggest that imbalance in tumour necrosis factor superfamily signalling and excessive T-cell activation can impair bacterial clearance in the lung but that DcR3-a treatment can reduce T-cell activation, restore optimal pulmonary neutrophil function and enhance bacterial clearance during S pneumoniae infection.

Resuscitation and Transfusion Principles for Traumatic Hemorrhagic Shock

DTIC Science & Technology

2009-11-01

hyperfibrinolysis. We also describe the concept of damage control resuscitation (DCR), an early and aggressive prevention and treatment of hemorrhagic shock... prevention and treatment of acidosis, hypothermia, and hypocalcemia, avoidance of hemodilution, and hemostatic resuscitation with transfusion of red...are potentially preventable and 66–80% of these deaths occur from hemorrhage.3,4 Rural civilian data indicate that approximately 10% of traumatic

Systemic bioinformatics analysis of skeletal muscle gene expression profiles of sepsis

PubMed Central

Yang, Fang; Wang, Yumei

2018-01-01

Sepsis is a type of systemic inflammatory response syndrome with high morbidity and mortality. Skeletal muscle dysfunction is one of the major complications of sepsis that may also influence the outcome of sepsis. The aim of the present study was to explore and identify potential mechanisms and therapeutic targets of sepsis. Systemic bioinformatics analysis of skeletal muscle gene expression profiles from the Gene Expression Omnibus was performed. Differentially expressed genes (DEGs) in samples from patients with sepsis and control samples were screened out using the limma package. Differential co-expression and coregulation (DCE and DCR, respectively) analysis was performed based on the Differential Co-expression Analysis package to identify differences in gene co-expression and coregulation patterns between the control and sepsis groups. Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways of DEGs were identified using the Database for Annotation, Visualization and Integrated Discovery, and inflammatory, cancer and skeletal muscle development-associated biological processes and pathways were identified. DCE and DCR analysis revealed several potential therapeutic targets for sepsis, including genes and transcription factors. The results of the present study may provide a basis for the development of novel therapeutic targets and treatment methods for sepsis. PMID:29805480

Real world study of regimen containing bevacizumab as first-line therapy in Chinese patients with advanced non-small cell lung cancer.

PubMed

Xing, Puyuan; Mu, Yuxin; Wang, Yan; Hao, Xuezhi; Zhu, Yixiang; Hu, Xingsheng; Wang, Hongyu; Liu, Peng; Lin, Lin; Wang, Zhijie; Li, Junling

2018-05-16

Large scale randomized controlled trials have demonstrated that the use of bevacizumab in addition to chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) conveys significant survival benefits. We explored the clinical impact of a first-line regimen containing bevacizumab (B+) versus a non-bevacizumab regimen (non-B) in advanced non-squamous NSCLC (NS-NSCLC) patients in a real world setting. The medical records of patients with advanced NS-NSCLC who received first-line therapy with or without bevacizumab were retrospectively collected. The primary outcome was progression-free survival (PFS), with secondary objectives of objective response rate (ORR), disease control rate (DCR), and safety. Exploratory analysis of EGFR and ALK status was conducted in subgroup. One hundred and forty-nine patients met the selection criteria: 62 in the B+ and 87 in the non-B group. The baseline characteristics were well balanced. In the overall population, the median PFS was significantly longer in the B+ than in the non-B group (9.7 vs. 7.0 months, hazard ratio [HR] 0.52, 95% confidence interval [CI] 0.30-0.91; P = 0.0184). Improved trends in both ORR and DCR were observed in the B+ group. In wild-type patients, the median PFS of the B+ was 11.3 compared to 5.5 months in the non-B group (HR 0.43, 95% CI 0.20-0.91; P = 0.0234). In wild type and unknown populations, the median PFS was 11.3 (B+) compared to 6.0 months (non-B) (HR 0.53; 95% CI 0.28-1.02; P = 0.0520). The safety profile was acceptable in both groups and no unexpected findings were observed. Our analysis confirmed that a first-line regimen containing bevacizumab showed superior clinical benefits over a non-bevacizumab regimen in Chinese patients with advanced NS-NSCLC in a real world setting. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Do incident and new subsequent cases of non-melanoma skin cancer registered in a Danish prospective cohort study have different 10-year mortality?

PubMed

Jensen, Annette Østergaard; Olesen, Anne Braae; Dethlefsen, Claus; Sørensen, Henrik Toft

2007-01-01

The Danish Gerda Frentz Cohort (GFC) was created for registering all incident and new subsequent cases of non-melanoma skin cancer (NMSC) among patients seen by Danish dermatologists in 1995. We have recently found, in this cohort, a lower 10-year mortality than in the general population in patients with basal cell carcinoma (BCC). Differences in mortality between incident and new subsequent cases, incomplete registration or selection bias may be responsible for this finding. We aimed to quantify differences in mortality between incident and new subsequent cases of NMSC in the GFC and to compare mortality among incident cases recorded in the GFC and those recorded in the Danish Cancer Registry (DCR). We followed 10,830 skin cancer patients and 106,696 age-, gender- and residence-matched population controls through 2006 and computed their cumulative mortality and mortality rate ratio (MRR). One-, 5-, and 10-year cumulative mortality of incident and new subsequent cases of BCC and SCC in the GFC were similar. Likewise, MRR for incident BCC (MRR=0.91; 95% CI 0.84-0.98) and incident SCC (MRR=1.29; 95% CI 1.05-1.56) among patients registered in the GFC were similar to their counterparts in the DCR (MRR=0.96; 95% CI 0.91-1.00 and MRR=1.36; 95% CI 1.22-1.52). Mortality of incident and new subsequent cases of NMSC was similar and thus did not explain the reduced mortality of BCC patients.

Comparison of 32 x 128 and 32 x 32 Geiger-mode APD FPAs for single photon 3D LADAR imaging

NASA Astrophysics Data System (ADS)

Itzler, Mark A.; Entwistle, Mark; Owens, Mark; Patel, Ketan; Jiang, Xudong; Slomkowski, Krystyna; Rangwala, Sabbir; Zalud, Peter F.; Senko, Tom; Tower, John; Ferraro, Joseph

2011-05-01

We present results obtained from 3D imaging focal plane arrays (FPAs) employing planar-geometry InGaAsP/InP Geiger-mode avalanche photodiodes (GmAPDs) with high-efficiency single photon sensitivity at 1.06 μm. We report results obtained for new 32 x 128 format FPAs with 50 μm pitch and compare these results to those obtained for 32 x 32 format FPAs with 100 μm pitch. We show excellent pixel-level yield-including 100% pixel operability-for both formats. The dark count rate (DCR) and photon detection efficiency (PDE) performance is found to be similar for both types of arrays, including the fundamental DCR vs. PDE tradeoff. The optical crosstalk due to photon emission induced by pixel-level avalanche detection events is found to be qualitatively similar for both formats, with some crosstalk metrics for the 32 x 128 format found to be moderately elevated relative to the 32 x 32 FPA results. Timing jitter measurements are also reported for the 32 x 128 FPAs.

Neural Imaging Using Single-Photon Avalanche Diodes

PubMed Central

Karami, Mohammad Azim; Ansarian, Misagh

2017-01-01

Introduction: This paper analyses the ability of single-photon avalanche diodes (SPADs) for neural imaging. The current trend in the production of SPADs moves toward the minimum dark count rate (DCR) and maximum photon detection probability (PDP). Moreover, the jitter response which is the main measurement characteristic for the timing uncertainty is progressing. Methods: The neural imaging process using SPADs can be performed by means of florescence lifetime imaging (FLIM), time correlated single-photon counting (TCSPC), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). Results: This trend will result in more precise neural imaging cameras. While achieving low DCR SPADs is difficult in deep submicron technologies because of using higher doping profiles, higher PDPs are reported in green and blue part of light. Furthermore, the number of pixels integrated in the same chip is increasing with the technology progress which can result in the higher resolution of imaging. Conclusion: This study proposes implemented SPADs in Deep-submicron technologies to be used in neural imaging cameras, due to the small size pixels and higher timing accuracies. PMID:28446946

Pattern of Retained Contrast on Immediate Postprocedure Computed tomography (CT) After Particle Embolization of Liver Tumors Predicts Subsequent Treatment Response

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

Wang Xiaodong, E-mail: wangxde@gmail.com; Erinjeri, Joseph P., E-mail: erinjerj@mskcc.org; Jia Xiaoyu, E-mail: jiax@mskcc.org

2013-08-01

PurposeTo determine if the pattern of retained contrast on immediate postprocedure computed tomography (CT) after particle embolization of hepatic tumors predicts modified Response Evaluation Criteria in Solid Tumors (mRECIST) response.Materials and MethodsThis study was approved by the Institutional Review Board with a waiver of authorization. One hundred four liver tumors were embolized with spherical embolic agents (Embospheres, Bead Block, LC Bead) and polyvinyl alcohol. Noncontrast CT was performed immediately after embolization to assess contrast retention in the targeted tumors, and treatment response was assessed by mRECIST criteria on follow-up CT (average time 9.0 {+-} 7.7 weeks after embolization). Tumor contrastmore » retention (TCR) was determined based on change in Hounsfield units (HUs) of the index tumors between the preprocedure and immediate postprocedure scans; vascular contrast retention (VCR) was rated; and defects in contrast retention (DCR) were also documented. The morphology of residual enhancing tumor on follow-up CT was described as partial, circumferential, or total. Association between TCR variables and tumor response were assessed using multivariate logistic regression.ResultsOf 104 hepatic tumors, 51 (49 %) tumors had complete response (CR) by mRECIST criteria; 23 (22.1 %) had partial response (PR); 21 (20.2 %) had stable disease (SD); and 9 (8.7 %) had progressive disease (PD). By multivariate analysis, TCR, VCR, and tumor size are independent predictors of CR (p = 0.02, 0.05, and 0.005 respectively). In 75 tumors, DCR was found to be an independent predictor of failure to achieve complete response (p < 0.0001) by imaging criteria.ConclusionTCR, VCR, and DCR on immediate posttreatment CT are independent predictors of CR by mRECIST criteria.« less

The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small-Cell Lung Cancer.

PubMed

Papadimitrakopoulou, Vassiliki; Lee, J Jack; Wistuba, Ignacio I; Tsao, Anne S; Fossella, Frank V; Kalhor, Neda; Gupta, Sanjay; Byers, Lauren Averett; Izzo, Julie G; Gettinger, Scott N; Goldberg, Sarah B; Tang, Ximing; Miller, Vincent A; Skoulidis, Ferdinandos; Gibbons, Don L; Shen, Li; Wei, Caimiao; Diao, Lixia; Peng, S Andrew; Wang, Jing; Tam, Alda L; Coombes, Kevin R; Koo, Ja Seok; Mauro, David J; Rubin, Eric H; Heymach, John V; Hong, Waun Ki; Herbst, Roy S

2016-08-01

By applying the principles of real-time biopsy, biomarker-based, adaptively randomized studies in non-small-cell lung cancer (NSCLC) established by the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, we conducted BATTLE-2 (BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer), an umbrella study to evaluate the effects of targeted therapies focusing on KRAS-mutated cancers. Patients with advanced NSCLC (excluding sensitizing EGFR mutations and ALK gene fusions) refractory to more than one prior therapy were randomly assigned, stratified by KRAS status, to four arms: (1) erlotinib, (2) erlotinib plus MK-2206, (3) MK-2206 plus AZD6244, or (4) sorafenib. Tumor gene expression profiling-targeted next-generation sequencing was performed to evaluate predictive and prognostic biomarkers. Two hundred patients, 27% with KRAS-mutated (KRAS mut+) tumors, were adaptively randomly assigned to erlotinib (n = 22), erlotinib plus MK-2206 (n = 42), MK-2206 plus AZD6244 (n = 75), or sorafenib (n = 61). In all, 186 patients were evaluable, and the primary end point of an 8-week disease control rate (DCR) was 48% (arm 1, 32%; arm 2, 50%; arm 3, 53%; and arm 4, 46%). For KRAS mut+ patients, DCR was 20%, 25%, 62%, and 44% whereas for KRAS wild-type patients, DCR was 36%, 57%, 49%, and 47% for arms 1, 2, 3, and 4, respectively. Median progression-free survival was 2.0 months, not different by KRAS status, 1.8 months for arm 1, and 2.5 months for arms 2 versus arms 3 and 4 in KRAS mut+ patients (P = .04). Median overall survival was 6.5 months, 9.0 and 5.1 months for arms 1 and 2 versus arms 3 and 4 in KRAS wild-type patients (P = .03). Median overall survival was 7.5 months in mesenchymal versus 5 months in epithelial tumors (P = .02). Despite improved progression-free survival on therapy that did not contain erlotinib for KRAS mut+ patients and improved prognosis for mesenchymal tumors, better biomarker-driven treatment strategies are still needed. © 2016 by American Society of Clinical Oncology.

The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer

PubMed Central

Lee, J. Jack; Wistuba, Ignacio I.; Tsao, Anne S.; Fossella, Frank V.; Kalhor, Neda; Gupta, Sanjay; Byers, Lauren Averett; Izzo, Julie G.; Gettinger, Scott N.; Goldberg, Sarah B.; Tang, Ximing; Miller, Vincent A.; Skoulidis, Ferdinandos; Gibbons, Don L.; Shen, Li; Wei, Caimiao; Diao, Lixia; Peng, S. Andrew; Wang, Jing; Tam, Alda L.; Coombes, Kevin R.; Koo, Ja Seok; Mauro, David J.; Rubin, Eric H.; Heymach, John V.; Hong, Waun Ki; Herbst, Roy S.

2016-01-01

Purpose By applying the principles of real-time biopsy, biomarker-based, adaptively randomized studies in non–small-cell lung cancer (NSCLC) established by the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, we conducted BATTLE-2 (BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer), an umbrella study to evaluate the effects of targeted therapies focusing on KRAS-mutated cancers. Patients and Methods Patients with advanced NSCLC (excluding sensitizing EGFR mutations and ALK gene fusions) refractory to more than one prior therapy were randomly assigned, stratified by KRAS status, to four arms: (1) erlotinib, (2) erlotinib plus MK-2206, (3) MK-2206 plus AZD6244, or (4) sorafenib. Tumor gene expression profiling–targeted next-generation sequencing was performed to evaluate predictive and prognostic biomarkers. Results Two hundred patients, 27% with KRAS-mutated (KRAS mut+) tumors, were adaptively randomly assigned to erlotinib (n = 22), erlotinib plus MK-2206 (n = 42), MK-2206 plus AZD6244 (n = 75), or sorafenib (n = 61). In all, 186 patients were evaluable, and the primary end point of an 8-week disease control rate (DCR) was 48% (arm 1, 32%; arm 2, 50%; arm 3, 53%; and arm 4, 46%). For KRAS mut+ patients, DCR was 20%, 25%, 62%, and 44% whereas for KRAS wild-type patients, DCR was 36%, 57%, 49%, and 47% for arms 1, 2, 3, and 4, respectively. Median progression-free survival was 2.0 months, not different by KRAS status, 1.8 months for arm 1, and 2.5 months for arms 2 versus arms 3 and 4 in KRAS mut+ patients (P = .04). Median overall survival was 6.5 months, 9.0 and 5.1 months for arms 1 and 2 versus arms 3 and 4 in KRAS wild-type patients (P = .03). Median overall survival was 7.5 months in mesenchymal versus 5 months in epithelial tumors (P = .02). Conclusion Despite improved progression-free survival on therapy that did not contain erlotinib for KRAS mut+ patients and improved prognosis for mesenchymal tumors, better biomarker-driven treatment strategies are still needed. PMID:27480147

CpG-island methylation study of liver fluke-related cholangiocarcinoma

PubMed Central

Sriraksa, R; Zeller, C; El-Bahrawy, M A; Dai, W; Daduang, J; Jearanaikoon, P; Chau-in, S; Brown, R; Limpaiboon, T

2011-01-01

Background: Genetic changes have been widely reported in association with cholangiocarcinoma (CCA), while epigenetic changes are poorly characterised. We aimed to further evaluate CpG-island hypermethylation in CCA at candidate loci, which may have potential as diagnostic or prognostic biomarkers. Methods: We analysed methylation of 26 CpG-islands in 102 liver fluke related-CCA and 29 adjacent normal samples using methylation-specific PCR (MSP). Methylation of interest loci was confirmed using pyrosequencing and/or combined bisulfite restriction analysis, and protein expression by immunohistochemistry. Results: A number of CpG-islands (OPCML, SFRP1, HIC1, PTEN and DcR1) showed frequency of hypermethylation in >28% of CCA, but not adjacent normal tissues. The results showed that 91% of CCA were methylated in at least one CpG-island. The OPCML was the most frequently methylated locus (72.5%) and was more frequently methylated in less differentiated CCA. Patients with methylated DcR1 had significantly longer overall survival (Median; 41.7 vs 21.7 weeks, P=0.027). Low-protein expression was found in >70% of CCA with methylation of OPCML or DcR1. Conclusion: Aberrant hypermethylation of certain loci is a common event in liver fluke-related CCA and may potentially contribute to cholangiocarcinogenesis. The OPCML and DcR1 might serve as methylation biomarkers in CCA that can be readily examined by MSP. PMID:21448164

The serologic decoy receptor 3 (DcR3) levels are associated with slower disease progression in HIV-1/AIDS patients.

PubMed

Lin, Yu-Ting; Yen, Chia-Hung; Chen, Heng-Li; Liao, Yi-Jen; Lin, I-Feng; Chen, Marcelo; Lan, Yu-Ching; Chuang, Shao-Yuan; Hsieh, Shie-Liang; Chen, Yi-Ming Arthur

2015-06-01

The decoy receptor 3 (DcR3) is a member of the tumor necrosis factor receptor (TNFR) super-family. It counteracts the biological effects of Fas ligands and inhibits apoptosis. The goals of this study were to understand the associations between serologic DcR3 (sDcR3) levels and different human immunodeficiency virus type 1 (HIV-1) subtypes, as well as the AIDS disease progression. Serum samples from 61 HIV/AIDS patients, who had been followed up every 6 months for 3 years, were collected. sDcR3 levels were quantified using an enzyme immunoassay (EIA). The sDcR3 levels in patients with HIV-1 subtype B were significantly higher than those in patients infected with subtype CRF01_AE (p < 0.001). In addition, multivariable linear mixed model analysis demonstrated that HIV-1 subtype B and slow disease progression were associated with higher levels of sDcR3, adjusting for potential predictors (p = 0.0008 and 0.0455, respectively). HIV-1-infected cells may gain a survival advantage by activating DcR3, which prevents infected cell detection by the host immune system. These data indicate that the sDcR3 level is a biomarker for AIDS disease progression. Copyright © 2013. Published by Elsevier B.V.

Exploratory cohort study and meta-analysis of BIM deletion polymorphism in patients with epidermal growth factor receptor-mutant non-small-cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors

PubMed Central

Sun, Si; Yu, Hui; Wang, Huijie; Zhao, Xinmin; Zhao, Xintai; Wu, Xianghua; Qiao, Jie; Chang, Jianhua; Wang, Jialei

2017-01-01

Background Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations might develop primary and secondary resistance to tyrosine kinase inhibitors (TKIs). The proapoptotic protein Bcl-2-like 11 (BIM) is a key modulator of apoptosis triggered by EGFR-TKIs. The recent studies have indicated that some patients with positive EGFR mutations were refractory to EGFR-TKIs if they harbored a BIM deletion polymorphism. The purpose of this study was to investigate whether BIM polymorphism predicts treatment efficacy of EGFR-TKIs in Chinese NSCLC patients. Patients and methods A cohort of advanced NSCLC patients with EGFR mutations and treated with EGFR-TKIs (gefitinib or erlotinib) were recruited. We drew peripheral blood to determinate BIM deletion status and then compared patients’ clinical outcomes according to the BIM deletion status. Additionally, we electronically searched eligible cohort studies and conducted a meta-analysis to pool event risk. Results The exploratory cohort study included 140 patients. Patients with and without the BIM deletion polymorphism had similar objective response rates (ORRs, 48.5 vs 63.0%, P=0.16), disease control rate (DCR, 93.9 vs 97.0%, P=0.60) and adverse reactions. Similar progression-free survival (PFS) and overall survival (OS) were noted in overall population (P=0.27 for PFS and P=0.61 for OS) and prespecified patient subgroups. The meta-analysis included 10 eligible cohort studies involving 1,317 NSCLC patients. It showed the positive BIM deletion was associated with shorter PFS (hazard ratio =1.45; P=0.02). Nonsignificant differences existed for ORR, DCR and OS. Conclusion The expanded meta-analysis results demonstrated the positive BIM deletion predicts shorter PFS in NSCLC patients after treatment with EGFR-TKIs while other clinical measures do not. A large multicenter well-designed cohort study involving other concurrent genetic alterations is warranted. PMID:28435285

Exploratory cohort study and meta-analysis of BIM deletion polymorphism in patients with epidermal growth factor receptor-mutant non-small-cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors.

PubMed

Sun, Si; Yu, Hui; Wang, Huijie; Zhao, Xinmin; Zhao, Xintai; Wu, Xianghua; Qiao, Jie; Chang, Jianhua; Wang, Jialei

2017-01-01

Non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor ( EGFR ) mutations might develop primary and secondary resistance to tyrosine kinase inhibitors (TKIs). The proapoptotic protein Bcl-2-like 11 (BIM) is a key modulator of apoptosis triggered by EGFR-TKIs. The recent studies have indicated that some patients with positive EGFR mutations were refractory to EGFR-TKIs if they harbored a BIM deletion polymorphism. The purpose of this study was to investigate whether BIM polymorphism predicts treatment efficacy of EGFR-TKIs in Chinese NSCLC patients. A cohort of advanced NSCLC patients with EGFR mutations and treated with EGFR-TKIs (gefitinib or erlotinib) were recruited. We drew peripheral blood to determinate BIM deletion status and then compared patients' clinical outcomes according to the BIM deletion status. Additionally, we electronically searched eligible cohort studies and conducted a meta-analysis to pool event risk. The exploratory cohort study included 140 patients. Patients with and without the BIM deletion polymorphism had similar objective response rates (ORRs, 48.5 vs 63.0%, P =0.16), disease control rate (DCR, 93.9 vs 97.0%, P =0.60) and adverse reactions. Similar progression-free survival (PFS) and overall survival (OS) were noted in overall population ( P =0.27 for PFS and P =0.61 for OS) and prespecified patient subgroups. The meta-analysis included 10 eligible cohort studies involving 1,317 NSCLC patients. It showed the positive BIM deletion was associated with shorter PFS (hazard ratio =1.45; P =0.02). Nonsignificant differences existed for ORR, DCR and OS. The expanded meta-analysis results demonstrated the positive BIM deletion predicts shorter PFS in NSCLC patients after treatment with EGFR-TKIs while other clinical measures do not. A large multicenter well-designed cohort study involving other concurrent genetic alterations is warranted.

Final Results of the Randomized Phase II NorCap-CA223 Trial Comparing First-Line All-Oral Versus Taxane-Based Chemotherapy for HER2-Negative Metastatic Breast Cancer.

PubMed

Cinieri, Saverio; Chan, Arlene; Altundag, Kadri; Vandebroek, An; Tubiana-Mathieu, Nicole; Barnadas, Agusti; Dodyk, Patricia; Lazzarelli, Silvia; Botha, Michiel; Rauch, Daniel; Villanova, Gustavo; Coskun, Ugur

2017-04-01

The purpose of this study was to evaluate the efficacy of 3 first-line chemotherapy combination regimens for HER2-negative metastatic breast cancer (mBC). In this open-label, 3-arm, randomized phase II trial, patients were randomized to all-oral NORCAP (vinorelbine/capecitabine), GEMPAC (gemcitabine/paclitaxel), or GEMDOC (gemcitabine/docetaxel) as first-line chemotherapy for HER2-negative mBC. Stratification factors were center, previous (neo)adjuvant anthracycline, and age. The primary end point was disease control rate (DCR; complete or partial response, or stable disease for ≥3 months). The DCR was 73% (95% confidence interval [CI], 59-85) with NORCAP (36 of 49 patients), 78% (95% CI, 64-88) with GEMPAC (39 of 50 patients), and 80% (95% CI, 66-90) with GEMDOC (40 of 50 patients). Objective response rates were 33% (16 of 49 patients), 24% (12 of 50 patients), and 50% (25 of 50 patients), respectively; median progression-free survival was 7.6, 9.0, and 11.4 months, respectively. Median overall survival was 30 to 31 months with all regimens. The most common Grade ≥3 adverse event with each regimen was neutropenia (24 patients [50%], 23 patients [46%], and 43 patients [86%], respectively). The most common nonhematological Grade ≥3 adverse event was fatigue. Grade 2 alopecia occurred in 36 patients (72%) who received GEMPAC and 38 patients (76%) who received GEMDOC, but only 4 patients (8%) who received NORCAP. There was no evidence of a detrimental effect of NORCAP on quality of life. All-oral NORCAP is an active first-line chemotherapy regimen and might be offered as an alternative to first-line taxane-based therapy for HER2-negative mBC, particularly if patients wish to avoid alopecia or frequent intravenous administrations. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy, safety and predictive indicators of apatinib after multilines treatment in advanced nonsquamous nonsmall cell lung cancer: Apatinib treatment in nonsquamous NSCLC.

PubMed

Wu, Di; Liang, Li; Nie, Ligong; Nie, Jun; Dai, Ling; Hu, Weiheng; Zhang, Jie; Chen, Xiaoling; Han, Jindi; Ma, Xiangjuan; Tian, Guangming; Han, Sen; Long, Jieran; Wang, Yang; Zhang, Ziran; Xin, Tao; Fang, Jian

2018-03-24

Patients with advanced nonsquamous nonsmall cell lung cancer (NSCLC) who experienced progression with two or more lines chemotherapy have no treatment options that clearly confer a survival benefit. As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, apatinib has a certain antitumor effect for various solid tumors. The present study evaluated the efficacy and safety of apatinib in advanced nonsquamous NSCLC as salvage treatment in Chinese real-world practice. Twenty-eight patients were enrolled in this observational study from October 2015 to May 2017. Progression-free survival (PFS) and overall survival (OS) were graphed by Kaplan-Meier curve and intergroup comparisons were carried out by log-rank test. Objective response rate (ORR), disease control rate (DCR) and adverse effects (AEs) were also evaluated. Seven patients obtained partial response, and 18 obtained stable disease, representing an ORR of 26% and a DCR of 93%. Median PFS and OS were 3 (95% confidence interval [CI] 2.6-3.4) and 7.4 (95% CI 1.3-13.5) months, respectively. The efficacy analysis showed that Eastern Cooperative Oncology Group (ECOG) performance status 0-1 was correlated with prolonged OS and PFS (P < 0.05), and hypertension during apatinib treatment was correlated with prolonged OS (P < 0.05). Cox regression showed that ECOG performance status (P < 0.01) (RR = 0.231) (95% CI 0.083-0.642) and hypertension during apatinib treatment (P = 0.05) were predictive indicators for apatinib treatment. Grade 3-4 AEs with incidences of 10% or greater were hypertension (21%), hand-foot syndrome (14%) and proteinuria (11%) which could be relieved by dose reduction. In conclusion, apatinib has a certain therapeutic effect in patients with advanced nonsquamous NSCLC. ECOG performance status and hypertension during apatinib might be predictive indicators for treatment efficacy. © 2018 John Wiley & Sons Australia, Ltd.

[Efficacy of icotinib for advanced non-small cell lung cancer patients with EGFR status identified].

PubMed

Song, Zhengbo; Yu, Xinmin; Cai, Jufen; Shao, Lan; Lin, Baochai; He, Chunxiao; Zhang, Beibei; Zhang, Yiping

2013-03-01

As the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in China, icotinib shows promising anticancer activity in vitro and vivo. The phase III clinical study (ICOGEN) showed that icotinib has a good efficacy and tolerability in Chinese patients with advanced non-small cell lung cancer (NSCLC) compared with gefitinib. This retrospective study aims to evaluate the efficacy and tolerability of icotinib monotherapy for advanced NSCLC patients with EGFR mutation and wild-type patients in our hospital. Patients with advanced NSCLC who were treated with icotinib in Zhejiang Cancer Hospital were retrospectively analyzed from August, 2011 to August, 2012. Survival was estimated using Kaplan-Meier analysis and Log-rank tests. The clinical data of 49 patients (13 with wild-type and 36 with EGFR mutation) with NSCLC were enrolled in the current study. The patients' overall objective response rate (ORR) was 58.3% and the disease control rate (DCR) in 36 EGFR mutation patients was 88.9%. The ORR was 7.7% and DCR was 53.8% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 9.5 months and 2.2 months in wild-type patients (P<0.001). Nineteen patients with EGFR mutation received icotinib as first-line and 17 in further-line treatment. The PFS was 9.5 months in the first-line and 8.5 months for second-line or further-line patients (P=0.41). Median overall survival (OS) in EGFR mutation patients was not reached, but was 12.6 months in wild-type patients. Most of the drug-related adverse events were mild (grade I or II) and reversible with no grade IV toxicity. Icotinib monotherapy showed significant antitumor activity in advanced NSCLC EGFR mutation patients. The toxicity was well tolerated and acceptable.

Introduction of Two Novel Stiffness Parameters and Interpretation of Air Puff-Induced Biomechanical Deformation Parameters With a Dynamic Scheimpflug Analyzer.

PubMed

Roberts, Cynthia J; Mahmoud, Ashraf M; Bons, Jeffrey P; Hossain, Arif; Elsheikh, Ahmed; Vinciguerra, Riccardo; Vinciguerra, Paolo; Ambrósio, Renato

2017-04-01

To investigate two new stiffness parameters and their relationships with the dynamic corneal response (DCR) parameters and compare normal and keratoconic eyes. Stiffness parameters are defined as Resultant Pressure at inward applanation (A1) divided by corneal displacement. Stiffness parameter A1 uses displacement between the undeformed cornea and A1 and stiffness parameter highest concavity (HC) uses displacement from A1 to maximum deflection during HC. The spatial and temporal profiles of the Corvis ST (Oculus Optikgeräte, Wetzlar, Germany) air puff were characterized using hot wire anemometry. An adjusted air pressure impinging on the cornea at A1 (adjAP1) and an algorithm to biomechanically correct intraocular pressure based on finite element modelling (bIOP) were used for Resultant Pressure calculation (adjAP1 - bIOP). Linear regression analyses between DCR parameters and stiffness parameters were performed on a retrospective dataset of 180 keratoconic eyes and 482 normal eyes. DCR parameters from a subset of 158 eyes of 158 patients in each group were matched for bIOP and compared using t tests. A P value of less than .05 was considered statistically significant. All DCR parameters evaluated showed significant differences between normal and keratoconic eyes, except peak distance. Keratoconic eyes had lower stiffness parameter values, thinner pachymetry, shorter applanation lengths, greater absolute values of applanation velocities, earlier A1 times and later second applanation times, greater HC deformation amplitudes and HC deflection amplitudes, and lower HC radius of concave curvature (greater concave curvature). Most DCR parameters showed a significant relationship with both stiffness parameters in both groups. Keratoconic eyes demonstrated less resistance to deformation than normal eyes with similar IOP. The stiffness parameters may be useful in future biomechanical studies as potential biomarkers. [J Refract Surg. 2017;33(4):266-273.]. Copyright 2017, SLACK Incorporated.

Connecting the Molecular Structure of Cutin to Ultrastructure and Physical Properties of the Cuticle in Petals of Arabidopsis.

PubMed

Mazurek, Sylwester; Garroum, Imène; Daraspe, Jean; De Bellis, Damien; Olsson, Vilde; Mucciolo, Antonio; Butenko, Melinka A; Humbel, Bruno M; Nawrath, Christiane

2017-02-01

The plant cuticle is laid down at the cell wall surface of epidermal cells in a wide variety of structures, but the functional significance of this architectural diversity is not yet understood. Here, the structure-function relationship of the petal cuticle of Arabidopsis (Arabidopsis thaliana) was investigated. Applying Fourier transform infrared microspectroscopy, the cutin mutants long-chain acyl-coenzyme A synthetase2 (lacs2), permeable cuticle1 (pec1), cyp77a6, glycerol-3-phosphate acyltransferase6 (gpat6), and defective in cuticular ridges (dcr) were grouped in three separate classes based on quantitative differences in the ν(C=O) and ν(C-H) band vibrations. These were associated mainly with the quantity of 10,16-dihydroxy hexadecanoic acid, a monomer of the cuticle polyester, cutin. These spectral features were linked to three different types of cuticle organization: a normal cuticle with nanoridges (lacs2 and pec1 mutants); a broad translucent cuticle (cyp77a6 and dcr mutants); and an electron-opaque multilayered cuticle (gpat6 mutant). The latter two types did not have typical nanoridges. Transmission electron microscopy revealed considerable variations in cuticle thickness in the dcr mutant. Different double mutant combinations showed that a low amount of C16 monomers in cutin leads to the appearance of an electron-translucent layer adjacent to the cuticle proper, which is independent of DCR action. We concluded that DCR is not only essential for incorporating 10,16-dihydroxy C16:0 into cutin but also plays a crucial role in the organization of the cuticle, independent of cutin composition. Further characterization of the mutant petals suggested that nanoridge formation and conical cell shape may contribute to the reduction of physical adhesion forces between petals and other floral organs during floral development. © 2017 American Society of Plant Biologists. All Rights Reserved.

Connecting the Molecular Structure of Cutin to Ultrastructure and Physical Properties of the Cuticle in Petals of Arabidopsis1[OPEN

PubMed Central

Mazurek, Sylwester; Garroum, Imène; Daraspe, Jean; De Bellis, Damien; Olsson, Vilde; Butenko, Melinka A.; Humbel, Bruno M.

2017-01-01

The plant cuticle is laid down at the cell wall surface of epidermal cells in a wide variety of structures, but the functional significance of this architectural diversity is not yet understood. Here, the structure-function relationship of the petal cuticle of Arabidopsis (Arabidopsis thaliana) was investigated. Applying Fourier transform infrared microspectroscopy, the cutin mutants long-chain acyl-coenzyme A synthetase2 (lacs2), permeable cuticle1 (pec1), cyp77a6, glycerol-3-phosphate acyltransferase6 (gpat6), and defective in cuticular ridges (dcr) were grouped in three separate classes based on quantitative differences in the ν(C=O) and ν(C-H) band vibrations. These were associated mainly with the quantity of 10,16-dihydroxy hexadecanoic acid, a monomer of the cuticle polyester, cutin. These spectral features were linked to three different types of cuticle organization: a normal cuticle with nanoridges (lacs2 and pec1 mutants); a broad translucent cuticle (cyp77a6 and dcr mutants); and an electron-opaque multilayered cuticle (gpat6 mutant). The latter two types did not have typical nanoridges. Transmission electron microscopy revealed considerable variations in cuticle thickness in the dcr mutant. Different double mutant combinations showed that a low amount of C16 monomers in cutin leads to the appearance of an electron-translucent layer adjacent to the cuticle proper, which is independent of DCR action. We concluded that DCR is not only essential for incorporating 10,16-dihydroxy C16:0 into cutin but also plays a crucial role in the organization of the cuticle, independent of cutin composition. Further characterization of the mutant petals suggested that nanoridge formation and conical cell shape may contribute to the reduction of physical adhesion forces between petals and other floral organs during floral development. PMID:27994007

Targeted resequencing identifies defective variants of decoy receptor 3 in pediatric-onset inflammatory bowel disease.

PubMed

Cardinale, C J; Wei, Z; Panossian, S; Wang, F; Kim, C E; Mentch, F D; Chiavacci, R M; Kachelries, K E; Pandey, R; Grant, S F A; Baldassano, R N; Hakonarson, H

2013-10-01

Genome-wide association studies have implicated common variation at the 20q13 locus in inflammatory bowel disease, particularly for the pediatric Crohn's form. This locus harbors tumor necrosis factor receptor superfamily (TNFRSF6B), encoding a secreted protein, decoy receptor 3 (DcR3), which binds to and neutralizes pro-inflammatory cytokines of the tumor necrosis factor superfamily. We sought to further the evidence of DcR3's role in pediatric IBD by identifying missense mutations with functional significance within TNFRSF6B. We sequenced the exons of the gene in 528 Caucasian pediatric IBD cases and 549 Caucasian healthy controls to establish the frequency of such events in each population. Sequencing revealed that our IBD cohort harbored a greater number of missense variants, yielding an odds ratio of 3.9 (P-value=0.005). Using functional assays, we established that the frequency of mutants defective in secretion from cultured cells was greater in the Crohn's category than in the controls, yielding an odds ratio of 7.1 (P-value=0.004). These results suggest that rare defective variants in TNFRSF6B have a role in the pathogenesis of some cases of IBD and that interventions targeting this group of tumor necrosis factor-family members may benefit patients with IBD.

Comparison of Dengue Virus Type 2-Specific Small RNAs from RNA Interference-Competent and –Incompetent Mosquito Cells

PubMed Central

Scott, Jaclyn C.; Brackney, Doug E.; Campbell, Corey L.; Bondu-Hawkins, Virginie; Hjelle, Brian; Ebel, Greg D.; Olson, Ken E.; Blair, Carol D.

2010-01-01

The exogenous RNA interference (RNAi) pathway is an important antiviral defense against arboviruses in mosquitoes, and virus-specific small interfering (si)RNAs are key components of this pathway. Understanding the biogenesis of siRNAs in mosquitoes could have important ramifications in using RNAi to control arbovirus transmission. Using deep sequencing technology, we characterized dengue virus type 2 (DENV2)-specific small RNAs produced during infection of Aedes aegypti mosquitoes and A. aegypti Aag2 cell cultures and compared them to those produced in the C6/36 Aedes albopictus cell line. We show that the size and mixed polarity of virus-specific small RNAs from DENV-infected A. aegypti cells indicate that they are products of Dicer-2 (Dcr2) cleavage of long dsRNA, whereas C6/36 cells generate DENV2-specific small RNAs that are longer and predominantly positive polarity, suggesting that they originate from a different small RNA pathway. Examination of virus-specific small RNAs after infection of the two mosquito cell lines with the insect-only flavivirus cell fusing agent virus (CFAV) corroborated these findings. An in vitro assay also showed that Aag2 A. aegypti cells are capable of siRNA production, while C6/36 A. albopictus cells exhibit inefficient Dcr2 cleavage of long dsRNA. Defective expression or function of Dcr2, the key initiator of the RNAi pathway, might explain the comparatively robust growth of arthropod-borne viruses in the C6/36 cell line, which has been used frequently as a surrogate for studying molecular interactions between arboviruses and cells of their mosquito hosts. PMID:21049014

Aedes aegypti uses RNA interference in defense against Sindbis virus infection.

PubMed

Campbell, Corey L; Keene, Kimberly M; Brackney, Douglas E; Olson, Ken E; Blair, Carol D; Wilusz, Jeffrey; Foy, Brian D

2008-03-17

RNA interference (RNAi) is an important anti-viral defense mechanism. The Aedes aegypti genome encodes RNAi component orthologs, however, most populations of this mosquito are readily infected by, and subsequently transmit flaviviruses and alphaviruses. The goal of this study was to use Ae. aegypti as a model system to determine how the mosquito's anti-viral RNAi pathway interacts with recombinant Sindbis virus (SINV; family Togaviridae, genus Alphavirus). SINV (TR339-eGFP) (+) strand RNA, infectious virus titers and infection rates transiently increased in mosquitoes following dsRNA injection to cognate Ago2, Dcr2, or TSN mRNAs. Detection of SINV RNA-derived small RNAs at 2 and 7 days post-infection in non-silenced mosquitoes provided important confirmation of RNAi pathway activity. Two different recombinant SINV viruses (MRE16-eGFP and TR339-eGFP) with significant differences in infection kinetics were used to delineate vector/virus interactions in the midgut. We show virus-dependent effects on RNAi component transcript and protein levels during infection. Monitoring midgut Ago2, Dcr2, and TSN transcript levels during infection revealed that only TSN transcripts were significantly increased in midguts over blood-fed controls. Ago2 protein levels were depleted immediately following a non-infectious bloodmeal and varied during SINV infection in a virus-dependent manner. We show that silencing RNAi components in Ae. aegypti results in transient increases in SINV replication. Furthermore, Ae. aegypti RNAi is active during SINV infection as indicated by production of virus-specific siRNAs. Lastly, the RNAi response varies in a virus-dependent manner. These data define important features of RNAi anti-viral defense in Ae. aegypti.

Combination TS-1 plus EGFR-tyrosine kinase inhibitors (TKIs) for the treatment of non-small cell lung cancer after progression on first-line or further EGFR-TKIs: A phase II, single-arm trial.

PubMed

Yang, Lu; Yang, Sheng; Liu, Yutao; Li, Junling; Hu, Xingsheng; Wang, Yalei; Zhang, Yan; Wang, Yan

2018-06-01

EGFR-tyrosine kinase inhibitors (TKIs) combined with TS-1 might overcome EGFR-TKI resistance, which has been indicated by several preclinical studies. We investigated the synergistic efficacy and safety of the combination therapy of EGFR-TKIs and TS-1 in non-small cell lung cancer (NSCLC) patients with acquired resistance to previous EGFR-TKI therapy. This was a phase II, single-arm and single-center prospective study. Stage IIIB-IV NSCLC patients with acquired resistance to prior EGFR-TKI treatment were enrolled. All patients were administered combination therapy of TS-1 and continuing EGFR-TKIs in this study. The primary endpoints were progression-free survival (PFS), while overall survival (OS), disease control rate (DCR), and safety were secondary endpoints. A total of 42 patients with acquired resistance to EGFR-TKIs were eligible for this study. The median PFS for all patients was five months (95% confidence interval [CI] 3.6-5.4). The OS and DCR were 31.9 (95% CI 17.8-46.0) months and 69.0% (29/42), respectively. No grade 4 toxicity or grade 3 hematologic toxicity was observed in this study. One patient (2%) experienced grade 3 elevated total serum bilirubin. The combination treatment of TS-1 and EGFR-TKIs was effective and well tolerated by patients who had experienced prior EGFR-TKI treatment failure. Our results need to be validated by larger prospective clinical trials. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

3D Silicon Coincidence Avalanche Detector (3D-SiCAD) for charged particle detection

NASA Astrophysics Data System (ADS)

Vignetti, M. M.; Calmon, F.; Pittet, P.; Pares, G.; Cellier, R.; Quiquerez, L.; Chaves de Albuquerque, T.; Bechetoille, E.; Testa, E.; Lopez, J.-P.; Dauvergne, D.; Savoy-Navarro, A.

2018-02-01

Single-Photon Avalanche Diodes (SPADs) are p-n junctions operated in Geiger Mode by applying a reverse bias above the breakdown voltage. SPADs have the advantage of featuring single photon sensitivity with timing resolution in the picoseconds range. Nevertheless, their relatively high Dark Count Rate (DCR) is a major issue for charged particle detection, especially when it is much higher than the incoming particle rate. To tackle this issue, we have developed a 3D Silicon Coincidence Avalanche Detector (3D-SiCAD). This novel device implements two vertically aligned SPADs featuring on-chip electronics for the detection of coincident avalanche events occurring on both SPADs. Such a coincidence detection mode allows an efficient discrimination of events related to an incoming charged particle (producing a quasi-simultaneous activation of both SPADs) from dark counts occurring independently on each SPAD. A 3D-SiCAD detector prototype has been fabricated in CMOS technology adopting a 3D flip-chip integration technique, and the main results of its characterization are reported in this work. The particle detection efficiency and noise rejection capability for this novel device have been evaluated by means of a β- strontium-90 radioactive source. Moreover the impact of the main operating parameters (i.e. the hold-off time, the coincidence window duration, the SPAD excess bias voltage) over the particle detection efficiency has been studied. Measurements have been performed with different β- particles rates and show that a 3D-SiCAD device outperforms single SPAD detectors: the former is indeed capable to detect particle rates much lower than the individual DCR observed in a single SPAD-based detectors (i.e. 2 to 3 orders of magnitudes lower).

Efficiency of low dosage apatinib in post-first-line treatment of advanced lung adenocarcinoma.

PubMed

Zeng, Da-Xiong; Wang, Chang-Guo; Lei, Wei; Huang, Jian-An; Jiang, Jun-Hong

2017-09-12

Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial response and 8 patients showed stable diseases response to apatinib, with a medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was 68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome, proteinuria and thrombocytopenia which were tolerable and manageable. So, apatinib might be an optional choice for post-first-line treatment of EGFR wild-type advanced lung adenocarcinoma patients.

Microbial community production, respiration, and structure of the microbial food web of an ecosystem in the northeastern Atlantic Ocean

NASA Astrophysics Data System (ADS)

Maixandeau, Anne; LefèVre, Dominique; Karayanni, Hera; Christaki, Urania; van Wambeke, France; Thyssen, Melilotus; Denis, Michel; FernáNdez, Camila I.; Uitz, Julia; Leblanc, Karine; QuéGuiner, Bernard

2005-07-01

Gross community production (GCP), dark community respiration (DCR), and the biomass of the different size classes of organisms in the microbial community were measured in the northeastern Atlantic basin as part of the Programme Océan Multidisciplinaire Méso Echelle (POMME) project. The field experiment was conducted during three seasons (winter, spring, and late summer-fall) in 2001. Samples were collected from four different mesoscale structures within the upper 100 m. GCP rates increased from winter (101 ± 24 mmol O2 m-2 d-1) to spring (153 ± 27 mmol O2 m-2 d-1) and then decreased from spring to late summer (44 ± 18 mmol O2 m-2 d-1). DCR rates increased from winter (-47 ± 18 mmol O2 m-2 d-1) to spring (-97 ± 7 mmol O2 m-2 d-1) and then decreased from spring to late summer (50 ± 7 mmol O2 m-2 d-1). The onset of stratification depended on latitude as well as on the presence of mesoscale structures (eddies), and this largely contributed to the variability of GCP. The trophic status of the POMME area was defined as net autotrophic, with a mean annual net community production rate of +38 ± 18 mmol O2 m-2 d-1, exhibiting a seasonal variation from +2 ± 20 mmol O2 m-2 d-1 to +57 ± 20 mmol O2 m-2 d-1. This study highlights that small organisms (picoautotrophs, nanoautotrophs, and bacteria) are the main organisms contributing to biological fluxes throughout the year and that episodic blooms of microphytoplankton are related to mesoscale structures.

[Damage control resuscitation of severe multiple trauma in the pelvic fractures].

PubMed

Fu, Chang-guo

2015-05-01

To discuss the clinical effects of damage control resuscitation (DCR) in treating severe multiple trauma in the pelvic fractures. From March 2009 to September 2013, a restrospective analysis was conducted on the clinical data of 28 patients with multiple trauma in the pelvic fractures, including 19 males and 9 females, ranging in age from 21 to 51 years old with an average of 32.5 years old. According to Tile classification of pelvic fractures, 16 cases were type B and 12 cases were type C. Injury severity score (ISS) averaged 32.0±3.4. All cases were treated with damage contral orthopaedics and DCR strategy, namely that used immediately with small capacity of balanced salt solution on admission so as to maintain the blood pressure between 80 to 90 mmHg. At the same time, emergency phase I simple debridement plus external fixator or bundled with fixed pelvic was done, and the chest or abdomen combined injury was treated at first. And limbs fracture was temporary dealing with bone traction or plaster external fixation, etc. After bleeding was controlled by operation, fluid resuscitation was done as fast as possible and the plasma was transfused early according to the proportion of plasma and red cell suspension (2 U:1 U-3 U:2 U). Dosage of balanced salt solution and blood before remedy shock was recorded, and the removal of time of lactic acid and coagulation were observed. Five cases were died after 4 to 15 hours into hospital (3 cases died for severe trauma-hemorrhagic shock and 2 cases for acute respiratory distress syndrome). Twenty-three cases were remedy shock at 1.6 to 4.3 hours after injury with an average of 2.4 hours. Period I operation duration was (78.2±10.3) minutes. Dosage of balanced salt solution was (3,798±340) ml and red cell suspension was 14 to 18 U, fresh frozen plasma (FFP) was (1,267±58) ml (1U FFP=100 ml), blood platelet was 8 to 12 U for 9 patients. The removal time of lactic acid and PT-APTT was (11.4±2.1) hours and (4.3±0.8) hours. Measures were taken to correct electrolyte and acid-base imbalance was normal. The success rat of recovery was 82.2% (23/28). Damage control resuscitation (DCR) integrates the main links such as damage control operation and allowable low blood pressure (or limited liquid resuscitation) and hemostatic control resuscitation, was early effective treatment measures for the patients with severe multiple trauma in the pelvic fractures.

Decoy receptors block TRAIL sensitivity at a supracellular level: the role of stromal cells in controlling tumour TRAIL sensitivity.

PubMed

O'Leary, L; van der Sloot, A M; Reis, C R; Deegan, S; Ryan, A E; Dhami, S P S; Murillo, L S; Cool, R H; Correa de Sampaio, P; Thompson, K; Murphy, G; Quax, W J; Serrano, L; Samali, A; Szegezdi, E

2016-03-10

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand cytokine known for its cytotoxic activity against malignantly transformed cells. TRAIL induces cell death through binding to death receptors DR4 and DR5. The inhibitory decoy receptors (DcR1 and DcR2) co-expressed with death receptor 4 (DR4)/DR5 on the same cell can block the transmission of the apoptotic signal. Here, we show that DcRs also regulate TRAIL sensitivity at a supracellular level and thus represent a mechanism by which the microenvironment can diminish tumour TRAIL sensitivity. Mathematical modelling and layered or spheroid stroma-extracellular matrix-tumour cultures were used to model the tumour microenvironment. By engineering TRAIL to escape binding by DcRs, we found that DcRs do not only act in a cell-autonomous or cis-regulatory manner, but also exert trans-cellular regulation originating from stromal cells and affect tumour cells, highlighting the potent inhibitory effect of DcRs in the tumour tissue and the necessity of selective targeting of the two death-inducing TRAIL receptors to maximise efficacy.

Increased sensitivity of RT-PCR for Potato virus Y detection using RNA isolated by a procedure with differential centrifugation.

PubMed

Zhang, Jianhua; Nie, Xianzhou; Boquel, Sébastien; Al-Daoud, Fadi; Pelletier, Yvan

2015-12-01

The sensitivity of reverse transcription-polymerase chain reaction (RT-PCR) for virus detection is influenced by many factors such as specificity of primers and quality of templates. These factors become extremely important for successful detection when virus concentration is low. Total RNA isolated from Potato virus Y (PVY)-infected potato plants using the sodium sulfite RNA isolation method or RNeasy plant mini kit contains a high proportion of host RNA and may also contain trace amount of phenolic and polysaccharide residues, which may inhibit RT-PCR. The goal of this study was to enhance the sensitivity of PVY detection by reducing host RNA in the extract by differential centrifugation followed by extraction using an RNeasy mini kit (DCR method). One-step RT-PCR had relatively low amplification efficiency for PVY RNA when a high proportion of plant RNA was present. SYBR Green-based real time RT-PCR showed that the RNA isolated by the DCR method had a higher cycle threshold value (Ct) for the elongation factor 1-α mRNA (Ef1α) of potato than the Ct value of the RNA extracted using the RNeasy plant mini kit, indicating that the DCR method significantly reduced the proportion of potato RNA in the extract. The detectable amount of RNA extracted using the DCR method was <0.001ng when plant sap from 10 PVY-infected and PVY-free potato leaflets in a 1.5:100 fresh weight ratio was extracted, compared with 0.01 and 0.02ng of RNA using the RNeasy plant mini kit and sodium sulfite RNA isolation methods, respectively. Copyright © 2015. Published by Elsevier B.V.

Etiologic analysis of 100 anatomically failed dacryocystorhinostomies

PubMed Central

Dave, Tarjani Vivek; Mohammed, Faraz Ali; Ali, Mohammad Javed; Naik, Milind N

2016-01-01

Background The aim of this study was to assess the etiological factors contributing to the failure of a dacryocystorhinostomy (DCR). Patients and methods Retrospective review was performed in 100 consecutive patients who were diagnosed with anatomically failed DCR at presentation to a tertiary care hospital over a 5-year period from 2010 to 2015. Patient records were reviewed for demographic data, type of past surgery, preoperative endoscopic findings, previous use of adjuvants such as intubation and mitomycin C, and intraoperative notes during the re-revision. The potential etiological factors for failure were noted. Results Of the 100 patients with failed DCRs, the primary surgery was an external DCR in 73 and endoscopic DCR in 27 patients. Six patients in each group had multiple revisions. The mean ages at presentation in the external and endoscopic groups were 39.41 years and 37.19 years, respectively. All patients presented with epiphora. The most common causes of failure were inadequate osteotomy (69.8% in the external group and 85.1% in the endoscopic group, P=0.19) followed by inadequate or inappropriate sac marsupialization (60.2% in the external group and 77.7% in the endoscopic group, P=0.16) and cicatricial closure of the ostium (50.6% in the external group and 55.5% in the endoscopic group, P=0.83). The least common causes such as ostium granulomas and paradoxical middle turbinate (1.37%, n=1) were noted in the external group only. Conclusion Inadequate osteotomy, incomplete sac marsupialization, and cicatricial closure of the ostium were the most common causes of failure and did not significantly differ in the external and endoscopic groups. Meticulous evaluation to identify causative factors for failure and addressing them are crucial for subsequent successful outcomes. PMID:27555748

Changes in everyday life after discharge from day care rehabilitation

PubMed Central

Tollén, Anita; Kamwendo, Kitty; Ivarsson, Ann-Britt

2011-01-01

Community-based day care that provides rehabilitation (DCR) targets elderly people with physical disabilities. The goal of these programmes is mainly to improve physical ability in order to enable participants to remain in their ordinary homes. Knowledge of the outcomes of DCR is limited as well as knowledge of what it is that makes a difference for the individual. The aim of this study was to describe what changes in everyday life elderly persons experienced after discharge from a community-based day care rehabilitation centre and to give possible explanations for these changes. Fifteen elderly people were interviewed after that they had been discharged from DCR. A narrative approach was used for analysing the interview data. Four case stories constitute the findings, each of them with unique descriptions of changes in everyday life as well as possible explanations for these changes. The first case story described resumption of daily activities that made the days more eventful and meaningful. The second described how everyday life became an arena for exercising, which create confidence for the future. The third described how an increased sense of certainty and security in the movements led to an increased appetite for life. Finally, the fourth case story described both the stay at the DCR centre and the promise of a new period there as uplifting that made the days easier. Concerning possible explanations for these changes, the findings indicate that it was a combination of several events that together contributed to the changes. Examples were physical training, counselling about how to live in an active and healthy lifestyle, and socialisation with other patients in formal as well as in informal sessions. PMID:21423596

Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Clinical Experience from an Expanded Access Study in the United States.

PubMed

Pal, Sumanta Kumar; Hoffman-Censits, Jean; Zheng, Hanzhe; Kaiser, Constanze; Tayama, Darren; Bellmunt, Joaquim

2018-05-01

Atezolizumab (anti-programmed death-ligand 1) was approved in the USA, Europe, and elsewhere for treatment-naive and platinum-treated locally advanced/metastatic urothelial carcinoma (mUC). To report efficacy and safety from an atezolizumab expanded access study. This single-arm, open-label study enrolled 218 patients at 36 US sites. Key eligibility criteria included progression during/following ≥1 platinum-based chemotherapy for mUC or in perioperative setting (progression within 12 mo) and Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2. Patients received atezolizumab1200mg intravenously every 3 wk until loss of clinical benefit, unacceptable toxicity, consent withdrawal, decision to discontinue, death, atezolizumab commercial availability, or study closure. Key end points reported herein included Response Evaluation Criteria in Solid Tumors v1.1 objective response rate and duration, disease control rate (DCR; response or stable disease), and safety. All patients received prior systemic therapy (68% mUC; 27% adjuvant; and 26% neoadjuvant). At baseline, 57% of 214 treated patients had ECOG PS ≥1, 19% had hemoglobin <10g/dl, and 25% had liver metastases. Median treatment duration was 9 wk (interquartile range [IQR], 6-12 wk). Median follow-up duration was 2.3 mo (IQR, 1.6-3.4 mo) overall and 2.7 mo (IQR, 2.0-3.5 mo) in patients not known to have died. Seventeen of 114 evaluable patients (15%) had objective responses (16 ongoing at study termination). DCR was 49%. Treatment-related adverse events (mostly fatigue) occurred in 98 of 214 treated patients. The benefit/risk profile of atezolizumab was consistent with that observed in previous studies, despite pretreatment and poor prognostic factors. These results suggest a potential role for atezolizumab in a broader patient range than typically eligible for phase 1-3 studies. In this expanded access study, atezolizumab was active and tolerable in a range of patients with platinum-treated metastatic urothelial carcinoma. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Acquisition of a Thermophoresis Instrument for Molecular Association Thermodynamic Studies

DTIC Science & Technology

2015-05-20

using NAMD.27 Crystallographic structures of C3d ( PDB code 1C3D) and C3d-CR2 ( PDB code 3OED) were obtained from the protein data bank ( PDB ).28 Missing...This project is funded by DTRA (Defense Threat Reduction Agency) and aims to develop new multienzyme structures for the controlled destruction of...enable detection. Pharmacophore models were developed based on known C3d-ligand interactions and information from computational analysis of structural

TRAIL Death Receptor-4, Decoy Receptor-1 and Decoy Receptor-2 Expression on CD8+ T Cells Correlate with the Disease Severity in Patients with Rheumatoid Arthritis

PubMed Central

2010-01-01

Background Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disorder. Although the pathogenesis of disease is unclear, it is well known that T cells play a major role in both development and perpetuation of RA through activating macrophages and B cells. Since the lack of TNF-Related Apoptosis Inducing Ligand (TRAIL) expression resulted in defective thymocyte apoptosis leading to an autoimmune disease, we explored evidence for alterations in TRAIL/TRAIL receptor expression on peripheral T lymphocytes in the molecular mechanism of RA development. Methods The expression of TRAIL/TRAIL receptors on T cells in 20 RA patients and 12 control individuals were analyzed using flow cytometry. The correlation of TRAIL and its receptor expression profile was compared with clinical RA parameters (RA activity scored as per DAS28) using Spearman Rho Analysis. Results While no change was detected in the ratio of CD4+ to CD8+ T cells between controls and RA patient groups, upregulation of TRAIL and its receptors (both death and decoy) was detected on both CD4+ and CD8+ T cells in RA patients compared to control individuals. Death Receptor-4 (DR4) and the decoy receptors DcR1 and DcR2 on CD8+ T cells, but not on CD4+ T cells, were positively correlated with patients' DAS scores. Conclusions Our data suggest that TRAIL/TRAIL receptor expression profiles on T cells might be important in revelation of RA pathogenesis. PMID:20799941

Military-to-civilian translation of battlefield innovations in operative trauma care.

PubMed

Haider, Adil H; Piper, Lydia C; Zogg, Cheryl K; Schneider, Eric B; Orman, Jean A; Butler, Frank K; Gerhardt, Robert T; Haut, Elliott R; Mather, Jacques P; MacKenzie, Ellen J; Schwartz, Diane A; Geyer, David W; DuBose, Joseph J; Rasmussen, Todd E; Blackbourne, Lorne H

2015-12-01

Historic improvements in operative trauma care have been driven by war. It is unknown whether recent battlefield innovations stemming from conflicts in Iraq/Afghanistan will follow a similar trend. The objective of this study was to survey trauma medical directors (TMDs) at level 1-3 trauma centers across the United States and gauge the extent to which battlefield innovations have shaped civilian practice in 4 key domains of trauma care. Domains were determined by the use of a modified Delphi method based on multiple consultations with an expert physician/surgeon panel: (1) damage control resuscitation (DCR), (2) tourniquet use, (3) use of hemostatic agents, and (4) prehospital interventions, including intraosseous catheter access and needle thoracostomy. A corresponding 47-item electronic anonymous survey was developed/pilot tested before dissemination to all identifiable TMD at level 1-3 trauma centers across the US. A total of 245 TMDs, representing nearly 40% of trauma centers in the United States, completed and returned the survey. More than half (n = 127; 51.8%) were verified by the American College of Surgeons. TMDs reported high civilian use of DCR: 95.1% of trauma centers had implemented massive transfusion protocols and the majority (67.7%) tended toward 1:1:1 packed red blood cell/fresh-frozen plasma/platelets ratios. For the other 3, mixed adoption corresponded to expressed concerns regarding the extent of concomitant civilian research to support military research and experience. In centers in which policies reflecting battlefield innovations were in use, previous military experience frequently was acknowledged. This national survey of TMDs suggests that military data supporting DCR has altered civilian practice. Perceived relevance in other domains was less clear. Civilian academic efforts are needed to further research and enhance understandings that foster improved trauma surgeon awareness of military-to-civilian translation. Copyright © 2015 Elsevier Inc. All rights reserved.

Optic Nerve Decompression

MedlinePlus

... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Optic Nerve Decompression John Lee, MD Introduction Optic nerve decompression is a surgical procedure aimed at ...

Bilateral congenital lacrimal fistulas in an adult as part of ectrodactyly-ectodermal dysplasia-clefting syndrome: A rare anomaly.

PubMed

Ghosh, Debangshu; Saha, Somnath; Basu, Sumit Kumar

2015-10-01

Ectrodactyly-ectodermal dysplasia and clefting syndrome or "Lobster claw" deformity is a rare congenital anomaly that affects tissues of ectodermal and mesodermal origin. Nasolacrimal duct (NLD) obstruction with or without atresia of lacrimal passage is a common finding of such a syndrome. The authors report here even a rarer presentation of the syndrome which manifested as bilateral NLD obstruction and lacrimal fistula along with cleft lip and palate, syndactyly affecting all four limbs, mild mental retardation, otitis media, and sinusitis. Lacrimal duct obstruction and fistula were managed successfully with endoscopic dacryocystorhinostomy (DCR) which is a good alternative to lacrimal probing or open DCR in such a case.

Tryptophol induces death receptor (DR) 5-mediated apoptosis in U937 cells.

PubMed

Inagaki, Shyuichiro; Morimura, Shigeru; Tang, Yueqin; Akutagawa, Hiroshi; Kida, Kenji

2007-08-01

Tryptophol is a natural component isolated from vinegar produced from the boiled extract of black soybean. We have reported that tryptophol induces apoptosis in U937 cells via activation of caspase-8 followed by caspase-3. Tryptophol, however, did not affect human peripheral blood lymphocytes (PBL). In this study, we found that tryptophol enhances formation of a death-inducing signaling complex including death receptor (DR) 5. Cell viability and induction of apoptosis by tryptophol was reduced by transfection with decoy receptor (DcR) 1. These results indicate that tryptophol induces apoptosis through DR5 and that the resistance of PBL to tryptophol-induced apoptosis might be due to competition from DcR1.

Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

PubMed

Tang, Ning; Guo, Jun; Zhang, Qianqian; Wang, Yali; Wang, Zhehai

2016-01-19

Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P < 0.01). For patients with EGFR-mutated NSCLC, the efficacy of TKI treatment was not statistically better than that of chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P < 0.01). The local response rate (RR)and disease control rate (DCR)with regimen including pemetrexed were greater than those with regimen including paclitaxel (P < 0.05). Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

Aspirin Desensitization

MedlinePlus

... Nerve Decompression Dacryocystorhinostomy (DCR) Disclosure Statement Printer Friendly Aspirin Desensitization Kevin C. Welch, MD Zara Patel, MD Introduction The term "aspirin-sensitive asthma" (also known as "aspirin triad" or " ...

[Damage Control Surgery in Polytrauma Patients with Pelvic Fractures. Is It Possible to Use Internal Fixation?

PubMed

Havlůj, L; Džupa, V; Gürlich, R

2017-01-01

Current polytrauma management is multidisciplinary, with Damage Control Surgery (DCS), Damage Control Orthopaedics (DCO) and Damage Control Resuscitation (DCR) being applied in the first few hours after injury. The most severe group of polytrauma patients are those with circulatory instability and massive blood loss as a consequence of unstable pelvic fractures. In treating these patients, of crucial importance is the speed and quality of stabilisation of pelvic fracture fragments. The authors present two case reports of polytrauma patients with unstable pelvic fractures, in whom open reduction and internal fixation was performed on the anterior fracture segment through extended laparotomy in order to stop bleeding into the abdominopelvic cavity as part of the DCS approach. Key words: exsanguination, polytrauma, unstable pelvic fracture, plate fixation.

Randomized, double-blind phase II study to compare nitroglycerin plus oral vinorelbine plus cisplatin with oral vinorelbine plus cisplatin alone in patients with stage IIIB/IV non-small cell lung cancer (NSCLC).

PubMed

Reinmuth, N; Meyer, A; Hartwigsen, D; Schaeper, C; Huebner, G; Skock-Lober, R; Bier, A; Gerecke, U; Held, C-P; Reck, M

2014-03-01

Adding nitroglycerin to the combination of vinorelbine plus cisplatin has been reported to improve the overall survival (OS) of Asian patients with stage IIIB/IV non-small cell lung cancer (NSCLC) probably due to better drug delivery based on changed vascular tonus. The main objective of our study was to evaluate the effect of adding nitroglycerin to vinorelbine and cisplatin in a Caucasian population. 66 chemonaïve patients with stage IIIB/IV NSCLC received oral vinorelbine (first cycle 60 mg/m(2), subsequent cycles: 80 mg/m(2) in the absence of any hematological toxicity ≥ grade 3 in cycle 1) once daily on days 1 and 8 of each cycle and cisplatin (80 mg/m(2) i.v.) on day 1 of each cycle (q3w). Nitroglycerin (arm A, n=34) or placebo patches (arm B, n=32) were administered once daily from day -3 to day 2 of each cycle and were removed about 12h after administration. One nitroglycerin patch contained 25mg nitroglycerin. Median age was 62.5 (33-82) years. In the overall population (n=66), the objective response rate (ORR) was 27.3% (all PR; 95%CI: 17.0-39.6), with a disease control rate (DCR) of 57.6% (95%CI: 44.8-69.7), a median time to progression (TTP) of 4.8 months (n=58; 95%CI: 3.4-5.9) and a median overall survival (OS) of 11.5 months (95%CI: 7.9-13.6). ORR and DCR were numerically higher in arm A than in arm B (35.3% vs. 18.8% and 61.8% vs. 53.1%, respectively), whereas TTP and OS were comparable. The main hematological and non-hematological toxicities grade ≥ 3 were moderate with no significant differences between the two treatment arms. Overall, oral vinorelbine plus cisplatin showed a high level of efficacy and adequate tolerability in first line treatment of NSCLC. Despite the low sample size per group the results seem to confirm the previous results reported in Asian patients. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02-14 Study).

PubMed

Auliac, Jean-Bernard; Monnet, Isabelle; Dubos-Arvis, Catherine; Chiappa, Anne Marie; Baize, Nathalie; Bota, Suzana; Vergnenegre, Alain; Doubre, Helene; Locher, Chrystele; Bizieux, Acya; Robinet, Gilles; Chouaid, Christos

2017-12-01

Chromosomal translocations involving the anaplastic lymphoma kinase gene (ALK) are rare oncogenic events found in 3-5% of non-small-cell lung cancers (NSCLC). Limited data have been published on the management of these patients outside clinical trials. To investigate the clinical characteristics and management of patients with NSCLC harboring ALK translocations (ALK+) in a real-life setting in France. This multicenter, observational, retrospective study included all NSCLC patients harboring ALK translocations diagnosed in participating centers between January 2012 and December 2014. Patient data include clinical characteristics, disease management, and outcomes [progression-free survival (PFS) and overall survival (OS)]. The 31 participating centers reported data on 132 patients, of whom 51% (n = 67) were male. The median age was 60.1 ± 14.5 (standard deviation) years; 89% (n = 106/119) had performance status 0/1 at diagnosis; 79% (n = 103/130) were non- or former smokers; 93% (n = 120/129) had adenocarcinomas and 74%(n = 97)/19%(n = 25)/7%(n = 10) had disease stages IV/III/I-II at diagnosis, respectively; co-mutations included EGFR (n = 2), BRAF (n  = 2), KRAS (n = 1), and HER2 (n = 1). Of the patients with stage IV NSCLC (n = 97), 96% received first-line treatment [75% chemotherapy-based, 21% ALK tyrosine kinase inhibitor (TKI)], with an associated response rate (RR), disease-control rate (DCR), and PFS of 42%, 64%, and 7.5 [95% confidence interval (CI) 5.9-9.5] months, respectively; 62% received second-line treatment (28% chemotherapy, 72% ALK TKI) with an associated RR, DCR, and PFS of 43.4%, 70%, and 4.7 (95% CI 4.0-8.1) months, respectively. The 2-year OS was 56.7% (95% CI 45.5-70.4%); median OS was not reached. The results of this real-life analysis suggest that the prognosis of NSCLC patients with theALK translocation may be better than that of the overall NSCLC population, but the outcomes were poorer than those of ALK+ NSCLC patients included in clinical studies.

Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope

PubMed Central

Cremolini, Chiara; Aprile, Giuseppe; Lonardi, Sara; Orlandi, Armando; Mennitto, Alessia; Berenato, Rosa; Antoniotti, Carlotta; Casagrande, Mariaelena; Marsico, Valentina; Marmorino, Federica; Cardellino, Giovanni Gerardo; Bergamo, Francesca; Tomasello, Gianluca; Formica, Vincenzo; Longarini, Raffaella; Giommoni, Elisa; Caporale, Marta; Di Bartolomeo, Maria; Loupakis, Fotios; de Braud, Filippo

2015-01-01

Background. No prospective trials have specifically addressed the efficacy and safety of panitumumab in elderly patients with metastatic colorectal cancer (CRC). We aimed at assessing the efficacy and safety of single agent panitumumab in “frail” elderly patients diagnosed with metastatic RAS and BRAF wild-type CRC. Materials and Methods. Forty elderly patients (aged ≥75 years) with metastatic RAS-BRAF wild-type CRC received off-label prescriptions of single-agent panitumumab at seven Italian institutions. Treatment was administered as first line in patients with absolute contraindication to any chemotherapy or as second-line treatment after failure of a fluoropyrimidine-based treatment, in the presence of contraindication to irinotecan. The outcome measures included objective response rate (ORR), as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results. The median PFS and OS were 6.4 months (95% confidence interval [CI]: 4.9–8 months) and 14.3 months (95% CI: 10.9–17.7 months), respectively. ORR was 32.5%, and DCR was 72.5%. Dose reductions related to adverse events (AEs) were reported in 9 (23%) patients, but no permanent treatment discontinuation caused by was reported. The most frequent grade 3 AE was skin rash, with an incidence of 20%. Conclusion. Panitumumab is effective and well-tolerated in frail elderly patients with RAS-BRAF wild-type metastatic CRC and deemed unfit for chemotherapy. A randomized study is needed to confirm these data. Implications for Practice: Treatment of elderly patients with metastatic colorectal cancer represents a difficult challenge in clinical practice. A significant proportion of frail elderly patients do not receive treatment, reflecting ongoing uncertainty of clinical benefit and toxicity of chemotherapy. Unfit condition in this cohort of patients further limits antineoplastic prescription and consequently patient survival. RAS and BRAF wild-type status could help select an elderly and unfit population that could benefit from anti-epidermal growth factor receptor single agent therapy. In the present study, single-agent off-label panitumumab was effective and well-tolerated as first-line treatment in frail elderly patients deemed unfit for chemotherapy for metastatic RAS and BRAF wild-type colorectal cancer. PMID:26446234

Multicenter phase II study of apatinib in non-triple-negative metastatic breast cancer.

PubMed

Hu, Xichun; Cao, Jun; Hu, Wenwei; Wu, Changping; Pan, Yueyin; Cai, Li; Tong, Zhongsheng; Wang, Shusen; Li, Jin; Wang, Zhonghua; Wang, Biyun; Chen, Xiaoyu; Yu, Hao

2014-11-07

Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). This study was conducted to assess the efficacy and safety of apatinib in patients with non-triple-negative metastatic breast cancer who had received prior chemotherapy for their metastatic disease. This multicenter, open-label, single arm study enrolled patients with non-triple-negative breast cancer, pretreated with anthracycline, taxanes and capecitabine, and who failed in the metastatic setting at least 1 and at most 4 prior chemotherapy regimens and at least one endocrine drug for hormone receptor-positive patients as well as at least one anti-Her2 drug for Her2-positive patients. The primary end point of this study was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Apatinib was administered as 500 mg daily on days 1 through 28 of each 4-week cycle. 38 patients were enrolled with a median age of 49 years (range, 35 to 62 years) and received apatinib for a median of 4 cycles (range from 0 to 10 cycles). 18 (47.4%) patients experienced dose reduction during treatment. The median relative dose intensity (relative to assigned dose for each cycle) was 82% (range, 45.0% to 100.0%). Median follow-up time was 10.1 months. Median PFS of all 38 patients was 4.0 months (95% confidence interval (CI), 2.8 m - 5.2 m). 36 patients were eligible for efficacy analysis. ORR was 16.7% (6/36). DCR was 66.7% (24/36). Median OS was 10.3 months (95% CI, 9.1 m - 11.6 m). The most common grade 3/4 treatment-related AEs were hypertension (20.5%), hand-foot syndrome (10.3%), and proteinuria (5.1%). Of three possibly drug-related SAEs recorded in the study, 2 (3.4%) deaths occurred within 28 days of last treatment and were both considered to be the result of disease progression. The other one was grade 2 diarrhea needing hospitalization. Apatinib exhibited objective efficacy in heavily pretreated, metastatic non-triple-negative breast cancer with manageable toxicity, and it might be better to be tested in breast cancer with high angiogenesis dependency. ClinicalTrials.gov: NCT01653561.

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Defective in Cuticular Ridges (DCR) of Arabidopsis thaliana, a Gene Associated with Surface Cutin Formation, Encodes a Soluble Diacylglycerol Acyltransferase*

PubMed Central

Rani, Sapa Hima; Krishna, T. H. Anantha; Saha, Saikat; Negi, Arvind Singh; Rajasekharan, Ram

2010-01-01

A key step in the triacylglycerol (TAG) biosynthetic pathway is the final acylation of diacylglycerol (DAG) by DAG acyltransferase. In silico analysis has revealed that the DCR (defective in cuticular ridges) (At5g23940) gene has a typical HX4D acyltransferase motif at the N-terminal end and a lipid binding motif VX2GF at the middle of the sequence. To understand the biochemical function, the gene was overexpressed in Escherichia coli, and the purified recombinant protein was found to acylate DAG specifically in an acyl-CoA-dependent manner. Overexpression of At5g23940 in a Saccharomyces cerevisiae quadruple mutant deficient in DAG acyltransferases resulted in TAG accumulation. At5g23940 rescued the growth of this quadruple mutant in the oleate-containing medium, whereas empty vector control did not. Lipid particles were localized in the cytosol of At5g23940-transformed quadruple mutant cells, as observed by oil red O staining. There was an incorporation of 16-hydroxyhexadecanoic acid into TAG in At5g23940-transformed cells of quadruple mutant. Here we report a soluble acyl-CoA-dependent DAG acyltransferase from Arabidopsis thaliana. Taken together, these data suggest that a broad specific DAG acyltransferase may be involved in the cutin as well as in the TAG biosynthesis by supplying hydroxy fatty acid. PMID:20921218

Defective in cuticular ridges (DCR) of Arabidopsis thaliana, a gene associated with surface cutin formation, encodes a soluble diacylglycerol acyltransferase.

PubMed

Rani, Sapa Hima; Krishna, T H Anantha; Saha, Saikat; Negi, Arvind Singh; Rajasekharan, Ram

2010-12-03

A key step in the triacylglycerol (TAG) biosynthetic pathway is the final acylation of diacylglycerol (DAG) by DAG acyltransferase. In silico analysis has revealed that the DCR (defective in cuticular ridges) (At5g23940) gene has a typical HX(4)D acyltransferase motif at the N-terminal end and a lipid binding motif VX(2)GF at the middle of the sequence. To understand the biochemical function, the gene was overexpressed in Escherichia coli, and the purified recombinant protein was found to acylate DAG specifically in an acyl-CoA-dependent manner. Overexpression of At5g23940 in a Saccharomyces cerevisiae quadruple mutant deficient in DAG acyltransferases resulted in TAG accumulation. At5g23940 rescued the growth of this quadruple mutant in the oleate-containing medium, whereas empty vector control did not. Lipid particles were localized in the cytosol of At5g23940-transformed quadruple mutant cells, as observed by oil red O staining. There was an incorporation of 16-hydroxyhexadecanoic acid into TAG in At5g23940-transformed cells of quadruple mutant. Here we report a soluble acyl-CoA-dependent DAG acyltransferase from Arabidopsis thaliana. Taken together, these data suggest that a broad specific DAG acyltransferase may be involved in the cutin as well as in the TAG biosynthesis by supplying hydroxy fatty acid.

The benefits of modified FOLFIRINOX for advanced pancreatic cancer and its induced adverse events: a systematic review and meta-analysis.

PubMed

Tong, Hongxuan; Fan, Zhu; Liu, Biyuan; Lu, Tao

2018-06-06

FOLFIRINOX has been one of the first-line options for advanced pancreatic cancer, even though it induces significant adverse effects. Several institutions have begun using modified FOLFIRINOX to decrease its side effects and increase its tolerability. We systematically investigated the outcome from patients who initially received modified FOLFIRINOX as a chemotherapy regimen for advanced pancreatic cancer. We used the random-model generic inverse variance method to analyse the binary data with 95% confidence intervals (CIs). Eleven studies were included in the meta-analysis with 563 total patients. The 6-month and 1-year overall survival (OS) rates of locally advanced pancreatic cancer (LAPC) were 90.9% and 76.2%. The 6-month and 1-year progression-free survival (PFS) rates of LAPC were 81.5% and 48.5%. The 6-month and 1-year OS rates of metastatic pancreatic cancer (MPC) were 79.7% and 47.6%. The 6-month and 1-year PFS rates of MPC were 56.3% and 20.6%. The following rates were also calculated: complete response rate (CR): 2.9%; partial response rate (PR): 35.9%; stable disease rate (SD): 41.2%; overall response rate (OR): 34.6%; disease control rate (DCR): 76.7%; progressive disease: 23.1%; and grade III/IV adverse events (AEs): neutropenia 23.1%, febrile neutropenia 4.8%, thrombocytopenia 4.8%, anaemia 5.7%, fatigue 11.5%, nausea 9.1%, diarrhoea 10.1%, vomiting 5.7%, neuropathy 3.8%, and increased ALT 5.7%. In conclusion, modified FOLFIRINOX could provide comparative survival benefits with fewer adverse events compared to the conventional dosage.

A comparison of DSM-III-R and ICD-10 personality disorder criteria in an out-patient population.

PubMed

Sara, G; Raven, P; Mann, A

1996-01-01

This study reports the results of a comparison of DSM-III-R and ICD-10 personality disorder criteria by application of both sets of criteria to the same group of patients. Despite the clinical relevance of these disorders and the need for reliable diagnostic criteria, such a comparison has not previously been reported. DSM-III-R and ICD-10 have converged in their classification of personality disorders, but some important differences between the two systems remain. Personality disorder diagnoses from both systems were obtained in 52 out-patients, using the Standardized Assessment of Personality (SAP), a brief, informant-based interview which yields diagnoses in both DSM-III-R and ICD-10. For individual personality disorder diagnoses, agreement between systems was limited. Thirty-four subjects received a personality disorder diagnosis that had an equivalent form in both systems, but only 10 subjects (29%) received the same primary diagnosis in each system. There was a difference in rate of diagnosis, with ICD-10 making significantly more personality disorder diagnoses. The lower diagnostic threshold of the ICD-10 contributed most of this effect. Further modifications in ICD-10 Diagnostic Criteria for Research (DCR) and DSM-IV to the personality disorder category have been considered. The omission in DSM-IV of three categories unique to that system and the raising of the threshold in ICD-10 DCR, do seem to have been helpful in promoting convergence.

Epigenetic regulation of the TRAIL/Apo2L apoptotic pathway by histone deacetylase inhibitors: an attractive approach to bypass melanoma immunotherapy resistance

PubMed Central

Jazirehi, Ali R; Arle, Dylan

2013-01-01

TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) is a major cytotoxic mechanism employed by cytotoxic T lymphocytes (CTL) and natural killer (NK) cells to eradicate malignant cells. TRAIL/Apo2L interacts with its cognate receptors located on tumor cell surface namely, TRAIL-R1 (DR4), TRAIL-R2 (DR5), TRAIL-R3 (DcR1), TRAIL-R4 (DcR2) and osteoprotegerin (OPG). The exact function of DcR1 and DcR2 remains elusive. TRAIL/Apo2L or agonistic monoclonal antibodies directed against TRAIL/Apo2L death-inducing receptors (DR4, DR5) have become an attractive immunological therapeutic tools in clinical oncology due to their selective killing of tumors and lack of affinity towards healthy cells. Though a potent anti-cancer modality, some cancer cells exhibit inherent or acquired resistance to TRAIL/Apo2L. Postulated resistance mechanisms include up-regulation of c-FLIP, down-regulation of caspase-8, down-regulation/shedding of death receptors and an imbalanced ratio of pro- to anti-apoptotic genes due to aberrant activity of cellular survival signal transduction pathways. The development of resistance has spurred the use of combination therapy, in particular using small molecule sensitizing agents, to restore apoptosis sensitivity. A novel category of such compounds is histone deacetylase inhibitors (HDACi), which block HDACs from removing acetyl groups from histone tails thereby preventing silencing of pro-apoptotic genes and regulating the expression of non-histone proteins (i.e., apoptosis-associated genes), are effective agents in some malignancies. Some HDACi, such as Suberoylanilide Hydroxamic Acid (SAHA), have received FDA approval for cancer treatment. In various melanoma preclinical models, HDACi in conjunction with TRAIL/Apo2L, via modulation of apoptotic machinery, have proven to overcome acquired/inherent resistance to either agent. Here, we discuss recent findings on the role of TRAIL/Apo2L and its agonistic mAbs in melanoma immunotherapy with discussions on potential cellular and molecular events by which HDACi can sensitize metastatic melanoma to TRAIL/Apo2L-mediated immune-therapy, thereby, overcoming resistance. PMID:23885325

Endoscopic Dacrocystorhinostomy in Lacrimal Canalicular Trauma

PubMed Central

Khan, Humayun A; Bayat, Aredeshir; De Carpentier, JP

2007-01-01

A case is presented where the common insertion of the upper and lower canaliculus of the lacrimal sac was repaired using endoscopic dacrocystorhinostomy (DCR) techniques, with silicone stenting and securing of stents intranasally. PMID:17316509

Analysis of InP-based single photon avalanche diodes based on a single recess-etching process

NASA Astrophysics Data System (ADS)

Lee, Kiwon

2018-04-01

Effects of the different etching techniques have been investigated by analyzing electrical and optical characteristics of two-types of single-diffused single photon avalanche diodes (SPADs). The fabricated two-types of SPADs have no diffusion depth variation by using a single diffusion process at the same time. The dry-etched SPADs show higher temperature dependence of a breakdown voltage, larger dark-count-rate (DCR), and lower photon-detection-efficiency (PDE) than those of the wet-etched SPADs due to plasma-induced damage of dry-etching process. The results show that the dry etching damages can more significantly affect the performance of the SPADs based on a single recess-etching process.

Tranexamic Acid for Lower GI Hemorrhage: A Randomized Placebo-Controlled Clinical Trial.

PubMed

Smith, Stephen R; Murray, David; Pockney, Peter G; Bendinelli, Cino; Draganic, Brian D; Carroll, Rosemary

2018-01-01

Lower GI hemorrhage is a common source of morbidity and mortality. Tranexamic acid is an antifibrinolytic that has been shown to reduce blood loss in a variety of clinical conditions. Information regarding the use of tranexamic acid in treating lower GI hemorrhage is lacking. The aim of this trial was to determine the clinical efficacy of tranexamic acid when used for lower GI hemorrhage. This was a prospective, double-blind, placebo-controlled, randomized clinical trial. The study was conducted at a tertiary referral university hospital in Australia. Consecutive patients aged >18 years with lower GI hemorrhage requiring hospital admission from November 2011 to January 2014 were screened for trial eligibility (N = 265). A total of 100 patients were recruited after exclusions and were randomly assigned 1:1 to either tranexamic acid or placebo. The primary outcome was blood loss as determined by reduction in hemoglobin levels. The secondary outcomes were transfusion rates, transfusion volume, intervention rates for bleeding, length of hospital stay, readmission, and complication rates. There was no difference between groups with respect to hemoglobin drop (11 g/L of tranexamic acid vs 13 g/L of placebo; p = 0.9445). There was no difference with respect to transfusion rates (14/49 tranexamic acid vs 16/47 placebo; p = 0.661), mean transfusion volume (1.27 vs 1.93 units; p = 0.355), intervention rates (7/49 vs 13/47; p = 0.134), length of hospital stay (4.67 vs 4.74 d; p = 0.934), readmission, or complication rates. No complications occurred as a direct result of tranexamic acid use. A larger multicenter trial may be required to determine whether there are more subtle advantages with tranexamic acid use in some of the secondary outcomes. Tranexamic acid does not appear to decrease blood loss or improve clinical outcomes in patients presenting with lower GI hemorrhage in the context of this trial. see Video Abstract at http://links.lww.com/DCR/A453.

76 FR 22730 - Notice of Determinations Regarding Eligibility To Apply for Worker Adjustment Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-22

.... 75,041 Lockheed Martin, Mission Systems & Sensors, Eagan, MN Leased Workers DCR and Caribou Thunder. 75,214 Foodswing, Inc Cambridge, MD....... 75,221 World Color (USA), LLC, World Color (USA) Lebanon...

External dacryocystorhinostomy for the treatment of epiphora in patients with patent but non-functioning lacrimal systems.

PubMed

Peter, Neena M; Pearson, Andrew R

2010-02-01

To assess the outcome of external dacryocystorhinostomies (DCRs) in patients with patent but non-functional lacrimal drainage systems and to identify any preoperative clinical or dacryocystography (DCG) and lacrimal scintigraphy (LS) factors associated with successful surgery. A retrospective study of 46 DCRs with silicone intubation performed for patients with epiphora associated with a clinically patent lacrimal drainage system. All patients underwent preoperative DCG and LS which were evaluated for presence, site and severity of delayed clearance. DCGs were also evaluated for reflux and anatomical abnormalities. Postoperative success was determined by subjective resolution of epiphora. Patients with persistent symptoms were offered Lester Jones Tube (LJT) insertion after establishment of a patent anastomosis to syringing and normal ostium on nasal endoscopy. Statistical analysis was performed using the chi2 and Fisher exact tests to determine whether there was any association between surgical outcome and preoperative resistance to lacrimal syringing, DCG and LS findings. 29 cases (63%) reported subjective surgical success after 11 months' average follow-up. There was a statistically significant association between increased resistance to syringing preoperatively and successful DCR (p=0.012). Of the 17 eyes that failed, all had patent anastomoses, and seven went on to have LJT insertion with complete resolution of symptoms. The majority of patients with patent but non-functional lacrimal drainage systems will be helped by DCR surgery, with greater success rates in those with significant reflux on preoperative syringing. For patients with residual epiphora, functional success can reach 100% with subsequent LJT insertion.

Sodium valproate, a histone deacetylase inhibitor, modulates the vascular endothelial growth inhibitor-mediated cell death in human osteosarcoma and vascular endothelial cells.

PubMed

Yamanegi, Koji; Kawabe, Mutsuki; Futani, Hiroyuki; Nishiura, Hiroshi; Yamada, Naoko; Kato-Kogoe, Nahoko; Kishimoto, Hiromitsu; Yoshiya, Shinichi; Nakasho, Keiji

2015-05-01

The level of vascular endothelial growth inhibitor (VEGI) has been reported to be negatively associated with neovascularization in malignant tumors. The soluble form of VEGI is a potent anti-angiogenic factor due to its effects in inhibiting endothelial cell proliferation. This inhibition is mediated by death receptor 3 (DR3), which contains a death domain in its cytoplasmic tail capable of inducing apoptosis that can be subsequently blocked by decoy receptor 3 (DcR3). We investigated the effects of sodium valproate (VPA) and trichostatin A (TSA), histone deacetylase inhibitors, on the expression of VEGI and its related receptors in human osteosarcoma (OS) cell lines and human microvascular endothelial (HMVE) cells. Consequently, treatment with VPA and TSA increased the VEGI and DR3 expression levels without inducing DcR3 production in the OS cell lines. In contrast, the effect on the HMVE cells was limited, with no evidence of growth inhibition or an increase in the DR3 and DcR3 expression. However, VPA-induced soluble VEGI in the OS cell culture medium markedly inhibited the vascular tube formation of HMVE cells, while VEGI overexpression resulted in enhanced OS cell death. Taken together, the HDAC inhibitor has anti-angiogenesis and antitumor activities that mediate soluble VEGI/DR3-induced apoptosis via both autocrine and paracrine pathways. This study indicates that the HDAC inhibitor may be exploited as a therapeutic strategy modulating the soluble VEGI/DR3 pathway in osteosarcoma patients.

Structure of RDE-4 dsRBDs and mutational studies provide insights into dsRNA recognition in the Caenorhabditis elegans RNAi pathway.

PubMed

Chiliveri, Sai Chaitanya; Deshmukh, Mandar V

2014-02-15

The association of RDE-4 (RNAi defective 4), a protein containing two dsRBDs (dsRNA-binding domains), with long dsRNA and Dcr-1 (Dicer1 homologue) initiates the siRNA pathway in Caenorhabditis elegans. Unlike its homologues in higher eukaryotes, RDE-4 dsRBDs possess weak (micromolar) affinity for short dsRNA. With increasing length of dsRNA, RDE-4 exhibits enhanced affinity due to co-operativity. The linker and dsRBD2 are indispensable for RDE-4's simultaneous interaction with dsRNA and Dcr-1. In the present study, we have determined the solution structures of RDE-4 constructs that contain both dsRBDs and the linker region. In addition to the canonical dsRBD fold, both dsRBDs of RDE-4 show modified structural features such as truncation in the β1-β2 loop that rationalize RDE-4's relatively weak dsRNA affinity. Structure and binding studies demonstrate that dsRBD2 plays a decisive role in the RDE-4-dsRNA interaction; however, in contrast with previous findings, we found ephemeral interaction of RDE-4 dsRBD1 with dsRNA. More importantly, mutations in two tandem lysine residues (Lys217 and Lys218) in dsRBD2 impair RDE-4's dsRNA-binding ability and could obliterate RNAi initiation in C. elegans. Additionally, we postulate a structural basis for the minimal requirement of linker and dsRBD2 for RDE-4's association with dsRNA and Dcr-1.

[Clinical observation of apatinib mesylate for the treatment of multi-drug resistant advanced breast cancer].

PubMed

Lü, H M; Zhang, M W; Niu, L M; Zeng, H A; Yan, M

2018-04-24

Objective: To assess the clinical efficacy and adverse outcomes of apatinib mesylate for the treatment of multi-drug resistant advanced breast cancer. Methods: A total of 24 patients with multi-drug-resistant advanced breast cancer who underwent apatinib mesylate treatment were retrospectively analyzed at the Diagnosis and Treatment Center for Breast Cancer of Henan Cancer Hospital. Patients were reviewed every 4 weeks after initial treatment and then every 8 weeks after stable disease. Objective response rate (ORR), progression free survival (PFS), overall survival (OS) , toxicity and adverse outcomes of apatinib mesylate treatment were evaluated by imaging examinations. Results: Totally, 24 patients received apatinib mesylate at a dose of 500 mg QD. Out of the 24 patients treated, complete remission (CR) occurred in none of the patients, partial remission (PR) in 10 cases, stable disease (SD) in 10 cases, progressive disease (PD) in 4 cases, and drug with drawal in 2 cases due to adverse outcomes. Treatment with apatinib mesylate resulted in an ORR of 41.7% (10/24), disease control rate (DCR) of 83.3%, PFS of 4.7 months, and OS of 8.0 months. Adverse outcomes included proteinuria, high blood pressure, fatigue, hand-foot skin reaction (HFSR), hyperbilirubinemia, leukopenia, hair/skin pigmentation decreased. Most of the adverse events were tolerable and can be controlled after symptomatic management. Conclusions: Single-agent apatinib mesylate demonstrated the good short-term efficacy for multi-drug resistant advanced breast cancer in patients who previously underwent multiple line treatment failures. Adverse effects were controllable after symptomatic management. Treatment with apatinib mesylate maybe a viable option when other treatment modalities failed.

[The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

PubMed

Chen, H; Wang, H P; Zhang, L; Si, X Y

2017-01-01

Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95% CI 13.5-16.3) and the OS was 37.0 weeks (95% CI 27.9-46.1). Patients with brain metastases showed higher ORR( P =0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P =0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

[Religiousness of patients with diagnosis of schizophrenia. Wide-ranging studies].

PubMed

Tomczak, Piotr

2006-01-01

(1) The correlations between: (1.1) various aspects of religiousness and (1.2) age, anxiety-state, anxiety-trait, locus of control, and, in the group of patients with shizophrenia: span of treatment, rate of therapy, ego psychopathology, paranoid and depression dimensions, self-rating of state of self-feeling, state of feeling of illness, and quality of life and (2) the comparison of various aspects of religiousness of patients with schizophrenia and healthy people were studied. The Scale of Christian Religiousness, Individual Religiousness Scale, Intrinsic, Extrinsic and Quest Religious Orientation Scales, Scale of Fundamentalism, State-Trait Anxiety Inventory, Rotter's questionnaire of locus of control, Scharfetter's questionnaire of ego psychopathology, Paranoid-Depresivity Scale-abridgment, Frankfurt Self-feeling Scale-abridgment, visual analogy of self-feeling, visual analogy of feeling of illness, and questionnaire of quality of life (WHOQOL-BREF) were used in the study. 91 adults both of sexes, 60 patients with a diagnosis of schizophrenia according to ICD-10 and DCR-10 in the diagnostic group and 31 healthy persons were studied. It was noticed that: (1) various correlations are manifested between religiousness and psychopathology of patients with schizophrenia; (2) patients diagnosed as having schizophrenia have a significantly higher level of extrinsic religiousness and fundamentalism than healthy individuals; (3) many results pointed out in the bibliography had no verification in these studies. Intrinsic, extrinsic, quest, and orthodox religiousness and fundamentalism realize significant functions in psychopathology of schizophrenia disorder. The knowledge about religiousness of schizophrenia patients can be important for diagnostic and therapeutic processes of the disorder.

The relationship between BIM deletion polymorphism and clinical significance of epidermal growth factor receptor-mutated non-small cell lung cancer patients with epidermal growth factor receptor-tyrosine kinase inhibitor therapy: a meta-analysis.

PubMed

Zou, Qian; Zhan, Ping; Lv, Tangfeng; Song, Yong

2015-12-01

BIM deletion polymorphism is a germline that might lead to little or no BH3 expression, which affects epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) related apoptosis. Recent studies show that BIM deletion polymorphism might be a critical factor leading to the resistance of EGFR-TKIs in EGFR mutation-positive non-small cell lung cancer (NSCLC) patients. Thus, a meta-analysis was conducted by combing seven original eligible studies including 778 NSCLC patients to investigate a steady and reliable conclusion. Our study indicated that BIM deletion polymorphism was significantly associated with the poor objective response rate (ORR) of EGFR-TKIs in EGFR-mutated NSCLC patients [odds ratios (OR) =0.55, 95% confidence interval (CI), 0.33-0.92]. And disease control rate (DCR) in EGFR-mutate NSCLC patients treated with EGFR-TKIs was significantly decreased in patients with BIM deletion polymorphism (OR=0.55, 95% CI, 0.27-1.12). Moreover, the progression-free survival (PFS) of patients with BIM deletion polymorphism is shorter. These findings suggested that BIM deletion polymorphism might be a genetic cause of intrinsic resistance to TKI therapy and it could be emerged as an independent predictor to identify patients who would benefit from TKI targeted therapy in EGFR-mutated NSCLC.

Proteus mirabilis and its role in dacryocystitis.

PubMed

Borgman, Christopher J

2014-09-01

Dacryocystitis is a common inflammation of the lacrimal sac, usually from an underlying bacterial infection. Most cases can be attributed to common ocular flora such as Staphylococcus aureus or Streptococcus pneumoniae; however, uncommon bacterial causes such as Proteus mirabilis can still occur. P. mirabilis is a gram-negative bacillus that is found abundantly in people who have undergone long-term catheterization and is uncommonly found in or around the eyes except in people who have undergone long-term catheterization. Proteus species can cause conjunctivitis, canaliculitis, and dacryocystitis and have the ability to manifest into preseptal cellulitis; therefore, timely recognition and treatment are important to prevent potential further complications. An 84-year-old white man had several recurrences of acute dacryocystitis that had marginal improvement with empiric antibiotic treatment. Resultant culture of the ocular discharge revealed an uncommon bacterium, P. mirabilis. Successful dosing of oral antibiotics resolved the infection but ultimately the patient required an external dacryocystorhinostomy (DCR) procedure to maintain patency of the nasolacrimal lacrimal system and prevent recurrence. At 3 months after external DCR, the patient was symptom free with no recurrences. Dacryocystitis has a distinctive clinical presentation and is usually easily treated when appropriate oral antibiotics are directed at the underlying pathogen. In nonresponsive cases, culturing of the ocular discharge should be performed to identify the underlying pathogen. Cases of dacryocystitis caused by Proteus species are usually responsive to several standard antibiotics used orally in eye care; however, culturing and susceptibility testing can streamline the diagnostic and management sequence considerably in unclear or unresponsive cases. Typically, patients with dacryocystitis return to normal after appropriate treatment, but chronic recurrences and epiphora are potential sequelae. Patients should be educated that a DCR surgical procedure may be needed to prevent future recurrences in some cases.

Trajectory optimization for dynamic couch rotation during volumetric modulated arc radiotherapy

NASA Astrophysics Data System (ADS)

Smyth, Gregory; Bamber, Jeffrey C.; Evans, Philip M.; Bedford, James L.

2013-11-01

Non-coplanar radiation beams are often used in three-dimensional conformal and intensity modulated radiotherapy to reduce dose to organs at risk (OAR) by geometric avoidance. In volumetric modulated arc radiotherapy (VMAT) non-coplanar geometries are generally achieved by applying patient couch rotations to single or multiple full or partial arcs. This paper presents a trajectory optimization method for a non-coplanar technique, dynamic couch rotation during VMAT (DCR-VMAT), which combines ray tracing with a graph search algorithm. Four clinical test cases (partial breast, brain, prostate only, and prostate and pelvic nodes) were used to evaluate the potential OAR sparing for trajectory-optimized DCR-VMAT plans, compared with standard coplanar VMAT. In each case, ray tracing was performed and a cost map reflecting the number of OAR voxels intersected for each potential source position was generated. The least-cost path through the cost map, corresponding to an optimal DCR-VMAT trajectory, was determined using Dijkstra’s algorithm. Results show that trajectory optimization can reduce dose to specified OARs for plans otherwise comparable to conventional coplanar VMAT techniques. For the partial breast case, the mean heart dose was reduced by 53%. In the brain case, the maximum lens doses were reduced by 61% (left) and 77% (right) and the globes by 37% (left) and 40% (right). Bowel mean dose was reduced by 15% in the prostate only case. For the prostate and pelvic nodes case, the bowel V50 Gy and V60 Gy were reduced by 9% and 45% respectively. Future work will involve further development of the algorithm and assessment of its performance over a larger number of cases in site-specific cohorts.

TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

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

Sanlioglu, Ahter D.; Department of Medical Biology and Genetics, Akdeniz University Faculty of Medicine, Antalya; Korcum, Aylin F.

2007-11-01

Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, thismore » study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma.« less

A retrospective analysis of efficacy and safety of adding bevacizumab to chemotherapy as first- and second-line therapy in advanced non-small-cell lung cancer (NSCLC).

PubMed

Quan, Rencui; Huang, Jiaxing; Chen, Nan; Fang, Wenfeng; Hu, Zhihuang; Zhan, Jianhua; Zhou, Ting; Zhang, Li; Zhang, Hongyu

2016-08-01

Several phase III clinical trials had authenticated that the addition of bevacizumab to paclitaxel plus carboplatin or gemcitabine plus cisplatin showed encouraging efficacy as first-line therapy for advanced NSCLC patients. However, the benefits of adding bevacizumab to other chemotherapy regimens in first- or second-line therapy have not been reported. To compare the clinical efficacy and safety of bevacizumab concomitant with chemotherapy regimens in patients with advanced NSCLC as first- or second-line therapy, we retrospectively reviewed the effects of adding bevacizumab to chemotherapy regimens in naive-chemotherapy and pre-chemotherapy patients with advanced non-squamous NSCLC. A total of 79 patients with advanced non-squamous NSCLC received at least two cycles of bevacizumab with chemotherapy between October 2010 and December 2013 were selected. Our primary end points were overall response rate (ORR) and disease control rate (DCR). The secondary objective was overall survival (OS) and safety. Seventy-nine patients were included in this study. Overall response rates at first evaluation (after 2 cycles) were 23.1 % (9/39) and 5.0 % (2/40) in first- and second-line therapy (P = 0.020), respectively. And disease control rates were 84.6 % (33/39) and 50 % (20/40), respectively (P = 0.001). The median OS were 27.2 months (95 % CI 13.3-41.1 months) and 29.6 months (95 % CI 6.7-52.5 months), respectively (P = 0.740). Grade 3-4 adverse events included leukopenia (2/39), and neutropenia (3/39) in first-line therapy versus neutropenia (1/40) and thrombocytopenia (2/40) in second-line treatment. In our experience, combination of bevacizumab and chemotherapy had encouraging anti-tumor efficacy as both first- and second-line therapy.

Endoscopic guided single self-linking silicone stent in pediatric external dacryocystorhinostomy.

PubMed

Ali, Mohammad Javed; Gupta, Himika; Naik, Milind N; Honavar, Santosh G

2013-09-01

To study the efficacy of a new technique of single self-linking silicone stent exclusively in pediatric external dacryocystorhinostomy (DCR) and to report the new use and advantages of endoscopic guidance for the same. Prospective interventional case series, including 11 eyes of ten patients with nasolacrimal duct obstruction. Data collected included demographic data, clinical presentation, laterality, status of lids and puncta, syringing findings, probing interpretations, types and duration of intubation. Consecutive pediatric patients with post-saccal obstruction who underwent an external dacryocystorhinostomy were included. Exclusion criteria included patients who had undergone a DCR in the past by any route via external, endonasal or transcanalicular. Primary outcome measures were stent retention and ease of stent removal. Secondary outcome measures were anatomic patency of the passage and resolution of symptoms. There were three male and seven female patients. Mean age was 9.4 years (range 6-15). A total of 11 procedures were carried out. Following placement of self-linked stents, the removal was done at a mean duration of 13.2 weeks (range:12-16 weeks). None of the patients had a stent prolapse during this period. All stents were removed in the outpatient without the use of general anesthesia with minimal endoscopic guidance. A minimum follow-up of three months following removal was considered for final analysis. Follow-up ranged from three months to six months after tube removal. The anatomical and functional success rate was 91%. There was one anatomical failure three months following tube removal and the remaining patients were free of symptoms at the last follow-up. Self-linking stents are a useful modality in pediatric patients not only to prevent stent prolapse but also to allow easy removal with minimum discomfort. Endoscopic guidance is a useful addition to this technique.

Aggregate freeze-thaw testing and d-cracking field performance : 30 years later : [summary].

DOT National Transportation Integrated Search

2014-09-01

Premature deterioration of concrete pavement due to D-cracking has been a problem in : Kansas since the 1930s. The Kansas Department of Transportation (KDOT) has made : significant efforts, including five extensive studies into the phenomenon of D-Cr...

RNA-seq of Rice Yellow Stem Borer Scirpophaga incertulas Reveals Molecular Insights During Four Larval Developmental Stages

PubMed Central

Renuka, Pichili; Madhav, Maganti S.; Padmakumari, Ayyagari Phani; Barbadikar, Kalyani M.; Mangrauthia, Satendra K.; Vijaya Sudhakara Rao, Kola; Marla, Soma S.; Ravindra Babu, Vemuri

2017-01-01

The yellow stem borer (YSB), Scirpophaga incertulas, is a prominent pest in rice cultivation causing serious yield losses. The larval stage is an important stage in YSB, responsible for maximum infestation. However, limited knowledge exists on the biology and mechanisms underlying the growth and differentiation of YSB. To understand and identify the genes involved in YSB development and infestation, so as to design pest control strategies, we performed de novo transcriptome analysis at the first, third, fifth, and seventh larval developmental stages employing Illumina Hi-seq. High-quality reads (HQR) of ∼229 Mb were assembled into 24,775 transcripts with an average size of 1485 bp. Genes associated with various metabolic processes, i.e., detoxification mechanism [CYP450, GSTs, and carboxylesterases (CarEs)], RNA interference (RNAi) machinery (Dcr-1, Dcr-2, Ago-1, Ago-2, Sid-1, Sid-2, Sid-3, and Sid-1-related gene), chemoreception (CSPs, GRs, OBPs, and ORs), and regulators [transcription factors (TFs) and hormones] were differentially regulated during the developmental stages. Identification of stage-specific transcripts made it possible to determine the essential processes of larval development. Comparative transcriptome analysis revealed that YSB has not evolved much with respect to the detoxification mechanism, but showed the presence of distinct RNAi machinery. The presence of strong specific visual recognition coupled with chemosensory mechanisms supports the monophagous nature of YSB. Designed expressed sequenced tags-simple-sequence repeats (EST-SSRs) will facilitate accurate estimation of the genetic diversity of YSB. This is the first report on characterization of the YSB transcriptome and the identification of genes involved in key processes, which will help researchers and industry to devise novel pest control strategies. This study also opens up a new avenue to develop next-generation resistant rice using RNAi or genome editing approaches. PMID:28717048

Development Communication Report, No. 41, March 1983.

ERIC Educational Resources Information Center

Development Communication Report, 1983

1983-01-01

This newsletter on development projects in developing nations include the following major articles: (1) "An Insider's Perspective: Dr. Henry Cassirer Talks to DCR about Development Communication and Unesco"; (2) "Comic Books Carry Health Messages to Rural Children in Honduras," by Oscar Vigano; (3) "Computers Come to the…

chroma: Chromatic effects for LSST weak lensing

NASA Astrophysics Data System (ADS)

Meyers, Joshua E.; Burchat, Patricia R.

2018-04-01

Chroma investigates biases originating from two chromatic effects in the atmosphere: differential chromatic refraction (DCR), and wavelength dependence of seeing. These biases arise when using the point spread function (PSF) measured with stars to estimate the shapes of galaxies with different spectral energy distributions (SEDs) than the stars.

Prospective randomized phase II study of FOLFIRI versus FOLFOX7 in advanced gastric adenocarcinoma: a Chinese Western Cooperative Gastrointestinal Oncology Group Study

PubMed Central

Qiu, Meng; Liu, Jiyan; Chen, Jing; Yi, Cheng; Li, Zhiping; Luo, Deyun; Xu, Feng; Cai, Xiaohong; Bi, Feng

2017-01-01

Until now, no standard chemotherapy has been widely accepted for advanced gastric cancer (GC). The current research aimed to compare folinic acid, fluorouracil with irinotecan (mFOLFIRI) or with oxaliplatin (mFOLFOX7) as first-line treatments in patients with locally advanced GC in an open, randomized, phase II study. Previously untreated metastatic or recurrent GC patients with measurable disease received mFOLFIRI (arm A) or mFOLFOX7 (arm B) every 2 weeks. The defined second-line treatment was mFOLFOX7 for arm A and mFOLFIRI for arm B. Primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), disease control rate (DCR) and toxicity. The evaluable population consisted of 128 patients (54 in arm A; 74 in arm B). Median PFS of arm A was 2.9 months (m) (95% confidence interval, CI, 1.9 to 4.1 m) versus 4.1 m (95% CI, 3.2 to 4.8 m) for arm B (p = 0.109). Median OS was 9.9 months (95% CI, 6.0 to 13.5 m) for arm A versus 12.0 m for arm B (95% CI, 10.3 to 13.7m; p = 0.431). DCRs for arm A and arm B were 59.3% and 66.3%, respectively (p = 0.850). In subgroup analysis of the patients who completed both treatment lines per protocol, the median first-line PFS was 2.1 m for the mFOLFIRI/mFOLFOX7arm versus 8.0 m for the mFOLFOX7/mFOLFIRI arm (p = 0.053), and the median second-line PFS values were 1.2 m versus 5.1 m (p = 0.287). Total PFS and OS were 8.1m and 11.0 m for the mFOLFIRI/mFOLFOX7 group compared with 12.2m and 20.2 m for the mFOLFOX7/mFOLFIRI group (p = 0.008, p = 0.030). Both regimens were well-tolerated with acceptable and manageable toxicities. Hence, there was no significant difference in the PFS or DCR. However, mFOLFOX7 followed by mFOLFIRI might have a better OS. PMID:29228659

Prospective randomized phase II study of FOLFIRI versus FOLFOX7 in advanced gastric adenocarcinoma: a Chinese Western Cooperative Gastrointestinal Oncology Group Study.

PubMed

Li, Qiu; Wen, Feng; Zhou, Chengya; Qiu, Meng; Liu, Jiyan; Chen, Jing; Yi, Cheng; Li, Zhiping; Luo, Deyun; Xu, Feng; Cai, Xiaohong; Bi, Feng

2017-11-17

Until now, no standard chemotherapy has been widely accepted for advanced gastric cancer (GC). The current research aimed to compare folinic acid, fluorouracil with irinotecan (mFOLFIRI) or with oxaliplatin (mFOLFOX7) as first-line treatments in patients with locally advanced GC in an open, randomized, phase II study. Previously untreated metastatic or recurrent GC patients with measurable disease received mFOLFIRI (arm A) or mFOLFOX7 (arm B) every 2 weeks. The defined second-line treatment was mFOLFOX7 for arm A and mFOLFIRI for arm B. Primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), disease control rate (DCR) and toxicity. The evaluable population consisted of 128 patients (54 in arm A; 74 in arm B). Median PFS of arm A was 2.9 months (m) (95% confidence interval, CI , 1.9 to 4.1 m) versus 4.1 m (95% CI , 3.2 to 4.8 m) for arm B ( p = 0.109). Median OS was 9.9 months (95% CI , 6.0 to 13.5 m) for arm A versus 12.0 m for arm B (95% CI , 10.3 to 13.7m; p = 0.431). DCRs for arm A and arm B were 59.3% and 66.3%, respectively ( p = 0.850). In subgroup analysis of the patients who completed both treatment lines per protocol, the median first-line PFS was 2.1 m for the mFOLFIRI/mFOLFOX7arm versus 8.0 m for the mFOLFOX7/mFOLFIRI arm ( p = 0.053), and the median second-line PFS values were 1.2 m versus 5.1 m ( p = 0.287). Total PFS and OS were 8.1m and 11.0 m for the mFOLFIRI/mFOLFOX7 group compared with 12.2m and 20.2 m for the mFOLFOX7/mFOLFIRI group ( p = 0.008, p = 0.030). Both regimens were well-tolerated with acceptable and manageable toxicities. Hence, there was no significant difference in the PFS or DCR. However, mFOLFOX7 followed by mFOLFIRI might have a better OS.

75 FR 39561 - Administrative Guidelines; Subsidy Layering Reviews for Proposed Section 8 Project-Based Voucher...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... review process. The operational support analysis will consider the debt coverage ratio (DCR) and the... performing subsidy layering reviews for project-based voucher HAP contracts for new construction and... construction and rehabilitated housing under the project-based voucher program where the applicable State or...

Jessica Olstad | NREL

Science.gov Websites

effects of feedstocks and catalysts on gasification products. She is currently the lead engineer on the -based liquid products (such as bio-oil) due to the high oxygen content, high viscosity, and fuel. Olstad is very interested in studying the effects of feeding bio-vapors into the DCR system

HgCdTe APD-based linear-mode photon counting components and ladar receivers

NASA Astrophysics Data System (ADS)

Jack, Michael; Wehner, Justin; Edwards, John; Chapman, George; Hall, Donald N. B.; Jacobson, Shane M.

2011-05-01

Linear mode photon counting (LMPC) provides significant advantages in comparison with Geiger Mode (GM) Photon Counting including absence of after-pulsing, nanosecond pulse to pulse temporal resolution and robust operation in the present of high density obscurants or variable reflectivity objects. For this reason Raytheon has developed and previously reported on unique linear mode photon counting components and modules based on combining advanced APDs and advanced high gain circuits. By using HgCdTe APDs we enable Poisson number preserving photon counting. A metric of photon counting technology is dark count rate and detection probability. In this paper we report on a performance breakthrough resulting from improvement in design, process and readout operation enabling >10x reduction in dark counts rate to ~10,000 cps and >104x reduction in surface dark current enabling long 10 ms integration times. Our analysis of key dark current contributors suggest that substantial further reduction in DCR to ~ 1/sec or less can be achieved by optimizing wavelength, operating voltage and temperature.

A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical Trial/Experimental Study.

PubMed

Wang, Lei; Liang, Lijun; Yang, Tao; Qiao, Yun; Xia, Youyou; Liu, Liang; Li, Chao; Lu, Peizhi; Jiang, Xiaodong

2017-12-01

Malignant glioma is the most common primary malignant brain tumor that displays high vascularity, making vascular endothelial growth factor receptors become promising targets. This study was conducted to evaluate the efficacy and safety of apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeted vascular endothelial growth factor receptor 2, combined with irinotecan, in patients with recurrent malignant glioma. Ten patients with recurrent malignant glioma who were experiencing relapse after treatment of temozolomide were enrolled in this study. They received oral apatinib (500 mg qd) in conjunction with irinotecan (340 mg/m or 125 mg/m depending on use of enzyme-inducing antiepileptic drugs) for 6 cycles. After that the patients continued to take apatinib as maintenance. Dosage adjustment occurred in only 3 (30.0%) patients. Among the 10 patients, 9 were available for the efficacy evaluation. There were 5 with partial response, 2 with stable disease and 2 with progressive disease. The objective response rate and the disease control rate (DCR) were 55% (5/9) and 78% (7/9), respectively. The median progress free survival time was 8.3 months. As for safety analysis, the most 3 common adverse events were gastrointestinal reaction (31.8%), hypertension (22.7%), and myelosuppression (18.0%). Apatinib combined with irinotecan seems to be a promising therapeutic option for recurrent malignant glioma patients. Perspective clinical studies with adequate sample size are required to validate our results. NCT02848794 /Ahead-BG306.

A phase II study of sorafenib in recurrent and/or metastatic salivary gland carcinomas: Translational analyses and clinical impact.

PubMed

Locati, L D; Perrone, F; Cortelazzi, B; Bergamini, C; Bossi, P; Civelli, E; Morosi, C; Lo Vullo, S; Imbimbo, M; Quattrone, P; Dagrada, G P; Granata, R; Resteghini, C; Mirabile, A; Alfieri, S; Orlandi, E; Mariani, L; Saibene, G; Pilotti, S; Licitra, L

2016-12-01

Pre-clinical and clinical evidence suggests a rationale for the use of anti-angiogenic agents, including sorafenib, in recurrent and/or metastatic salivary gland carcinomas (RMSGCs). This study evaluates the activity of sorafenib in patients with RMSGCs and also investigates whether the activity of sorafenib could be related to its main tailored targets (i.e. BRAF, vascular endothelial growth factor receptor 2 [VEGFR2], platelet-derived growth factor receptor α [PDGFRα] and β, RET, KIT). Patients received sorafenib at 400 mg BID. The primary end-point was response rate (RR) including complete response or partial response (PR); secondary end-points included RR according to Choi criteria, disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). Thirty-seven patients (19 adenoid cystic cancers, ACC) were enrolled. Six PRs were recorded. RR was 16% (95% confidence interval [CI]: 6-32; 11% in ACC and 22% in non-ACC). Choi criteria could be applied in 30 out of 37 cases with a RR of 50% (95% CI: 31-69%); DCR was 76% (95% CI: 59-88%). Incidence of ≥G3 adverse events was 29.7%. Median PFS and OS for the entire population were 5.9 months and 23.4 months, respectively. Median PFS and OS were 8.9 and 26.4 months for ACC versus 4.2 and 12.3 months for non-ACC patients. All the cases showed expression of PDGFRβ in the stroma and VEGFR2 in endothelial cells; PDGFRα positivity was found in the stroma of four (27%) cases. All except for two cases showed no PDGFRβ, VEGFR2 and PDGFRα expression in the tumour cells. KIT expression was restricted to ACC and a weak RET expression was limited to one adenocarcinoma, not otherwise specified (NOS). No BRAF mutation was found. No correlation was observed between the sorafenib activity and the expression of its markers although all six responders (two ACC, one adenocarcinoma, NOS, one salivary duct cancer [SDC], one high-grade mucoepidermoid [HG-MEC] and one poorly-differentiated cancer) are enriched in the stromal component showing a PDGFRβ immunodecoration. In ACCs, immunohistochemistry revealed MYB protein expression in 15/16 cases (94%) and the MYB-NFIB fusion oncogene was observed in 9/14 (64%). Sorafenib is the first anti-angiogenic agent to demonstrate activity in RMSGC patients, particularly in some histotypes such as HG-MEC, SDC and adenocarcinoma, NOS. The PDGFRβ-positive rich stromal component characterising these histotypes and the lack of correlation between the activity of sorafenib and its targets suggests anti-angiogenic effect as the prevalent mechanism of action of sorafenib in SGCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Digital Curriculum Resources in Mathematics Education: Foundations for Change

ERIC Educational Resources Information Center

Pepin, Birgit; Choppin, Jeffrey; Ruthven, Kenneth; Sinclair, Nathalie

2017-01-01

In this conceptual review paper we draw on recent literature with respect to digital curriculum resources (DCR); we briefly outline and explain selected theoretical frames; and we discuss issues related to the design, and the use (by teachers and students) of digital curricula and e-textbooks in mathematics education. The results of our review…

Deferred Capital Renewal as a Spoiler for Campus Programs

ERIC Educational Resources Information Center

Whitefield, Joe

2010-01-01

For facilities managers, deferred capital renewal (DCR) is the issue that, in many ways, can play the role of spoiler for other programs and initiatives are that important to their campuses. In particular, operations and maintenance programs, campus growth strategies, and even sustainability programs can suffer setbacks caused by the unplanned…

78 FR 58986 - Dry Cargo Residue Discharges in the Great Lakes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-25

...-AA89 Dry Cargo Residue Discharges in the Great Lakes AGENCY: Coast Guard, DHS. ACTION: Notice of... final rule to regulate discharges of dry cargo residue (DCR) in the Great Lakes. The Coast Guard... final rule to regulate discharges of dry cargo residue in the Great Lakes. In August 2008, the Coast...

Comparison of efficacy between buprenorphine and tramadol in the detoxification of opioid (heroin)-dependent subjects.

PubMed

Chawla, Jatinder Mohan; Pal, Hemraj; Lal, Rakesh; Jain, Raka; Schooler, Nina; Balhara, Yatan Pal Singh

2013-01-01

Tramadol is a synthetic opiate and a centrally acting weak m-opioid receptor agonist. The potential advantages of tramadol include ease of administration, low abuse potential, and being nonscheduled. This study compared tramadol and buprenorphine for controlling withdrawal symptoms in patients with opioid dependence syndrome. Consenting male subjects between 20 and 45 years of age who fulfilled the ICD-10-DCR criteria for opiate dependence syndrome were randomly assigned in a double-blind, double-dummy placebo-controlled trial for detoxification. Those with multiple drug dependence, abnormal cardiac, renal and hepatic functions, psychosis, or organic mental illness were excluded. Assessments included Subjective Opiate Withdrawal Scale (SOWS), Objective Opiate Withdrawal Scale (OOWS), Visual Analog Scale (VAS), and Side Effect Check List. Subjects were evaluated daily and study duration was 10 days. Sixty two subjects were enrolled. The mean SOWS and OOWS and VAS were significantly lower in the buprenorphine group on second and third day of detoxification as compared to the tramadol group. Although the retention rate was higher for buprenorphine group throughout the study, when compared with tramadol the difference was not significant on any day. Three subjects in the tramadol group had seizures. Tramadol was found to have limited detoxification efficacy in moderate to severe opioid withdrawal and substantial risk of seizures as compared to buprenorphine. Further studies are warranted to examine its efficacy in mild opioid withdrawal symptoms and its potential use in outpatient settings where its administration advantages may be valuable.

A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma

PubMed Central

Wang, Lei; Liang, Lijun; Yang, Tao; Qiao, Yun; Xia, Youyou; Liu, Liang; Li, Chao; Lu, Peizhi; Jiang, Xiaodong

2017-01-01

Abstract Background: Malignant glioma is the most common primary malignant brain tumor that displays high vascularity, making vascular endothelial growth factor receptors become promising targets. This study was conducted to evaluate the efficacy and safety of apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeted vascular endothelial growth factor receptor 2, combined with irinotecan, in patients with recurrent malignant glioma. Methods: Ten patients with recurrent malignant glioma who were experiencing relapse after treatment of temozolomide were enrolled in this study. They received oral apatinib (500 mg qd) in conjunction with irinotecan (340 mg/m2 or 125 mg/m2 depending on use of enzyme-inducing antiepileptic drugs) for 6 cycles. After that the patients continued to take apatinib as maintenance. Dosage adjustment occurred in only 3 (30.0%) patients. Results: Among the 10 patients, 9 were available for the efficacy evaluation. There were 5 with partial response, 2 with stable disease and 2 with progressive disease. The objective response rate and the disease control rate (DCR) were 55% (5/9) and 78% (7/9), respectively. The median progress free survival time was 8.3 months. As for safety analysis, the most 3 common adverse events were gastrointestinal reaction (31.8%), hypertension (22.7%), and myelosuppression (18.0%). Conclusion: Apatinib combined with irinotecan seems to be a promising therapeutic option for recurrent malignant glioma patients. Perspective clinical studies with adequate sample size are required to validate our results. Trial Registration: NCT02848794 /Ahead–BG306. PMID:29245310

Impact of Substance Use Disorder on Presentation and Short-Term Course of Schizophrenia

PubMed Central

Chakraborty, Rudraprosad; Chatterjee, Arunima; Chaudhury, Suprakash

2014-01-01

The aim of the present study was to compare a cohort of schizophrenia patients with substance use disorder (SUD) with a similar cohort of schizophrenia patients without SUD with regard to sociodemographic variables, clinical variables, psychopathology, anxiety symptoms, depressive symptoms, treatment outcome, and side effect profile of drugs. A total of 143 consecutive inpatients with ICD-10 DCR diagnosis of schizophrenia were included after obtaining informed consent. Patients were evaluated by a semistructured data sheet and Maudsley Addiction Profile. They were then rated by Positive and Negative Symptoms Scale, Calgary Depression Scale, Hamilton Anxiety Rating Scale, and Brief Psychiatric Rating Scale at presentation, three weeks, and six weeks. At three weeks and six weeks, they were also evaluated by UKU Side Effect Rating Scale. Substance abuse was detected in 63.6% schizophrenia patients. Nicotine was the commonest substance followed by cannabis and alcohol. Substance users had longer untreated illness and more depressive symptoms at presentation and six-week follow-up. Dual diagnosis patients had difficulty in abstraction at three and six weeks but not at presentation. Schizophrenia patients with SUD had more depressive symptoms. SUD appeared to mask abstraction difficulties at presentation. Schizophrenia patients with SUD should be carefully assessed for presence of depression. PMID:24839596

[Traumatic Lacrimal Duct Stenosis: Demographics and Success Rate of Surgical Procedures for Secondary Treatment].

PubMed

Alnawaiseh, M; Böhm, M R R; Rosentreter, A; Wieneke, A C; Wirths, G; Merté, R L; Eter, N; Zumhagen, L

2016-06-01

Traumatic lacrimal duct stenosis can be the result of sharp trauma of the eyelid, indirect trauma or surgery in the nasoorbital region, as well as burns, chemotherapy and radiation of the facial region. The aim of the study is to present the demographics, patient satisfaction, and course of different surgical procedures for secondary treatment of traumatic lacrimal duct stenosis. We retrospectively reviewed the medical records of 50 patients who required surgery for traumatic lacrimal duct stenosis from 2009 to 2011 at the University Eye Hospital in Muenster. The evaluation included the following criteria: age, sex, duration of symptoms, complication rate and the rate of recurrence. We systematically evaluated the medical data and asked the patients about the recent symptoms via telephone questionnaire. 60 eyes of 50 patients were included (18 women; 32 men; age: 51.8 ± 17.1 years); 34 eyes (56.7 %) had already had operations of the lacrimal system. The success rate was 58.1 %. The mean postoperative follow-up was 52.3 ± 10.7 months. In 11 cases (18.3 %), a dakryocystorhinostomy (DCR) was necessary. Traumatic lacrimal stenosis is more common in men, and has a poorer prognosis than lacrimal duct stenosis from other causes. Georg Thieme Verlag KG Stuttgart · New York.

The tissue-selecting technique: segmental stapled hemorrhoidopexy.

PubMed

Lin, Hong-Cheng; Lian, Lei; Xie, Shang-Kui; Peng, Hui; Tai, Jian-Dong; Ren, Dong-Lin

2013-11-01

We describe a technique for the management of prolapsing hemorrhoids, with the aim to minimize the risk of anal stricture and rectovaginal fistula and to reduce the impact of the stapling technique on rectal compliance. This modified procedure was successfully applied in China, and preliminary data showed promising outcomes (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A117).

Digital College Readiness: A Multi-Case Study of Early College High School Graduates' Perceptions of the Demands and Opportunities to Learn

ERIC Educational Resources Information Center

Furness, Rachelle K.

2017-01-01

Clarifying the concept of digital college readiness (DCR) can direct pedagogical and policy shifts toward the integration of digital literacies instruction as an essential component of college readiness, especially for educators and researchers in the field of developmental education. Since the 1980s, the demands for digitally mediated literacies…

Biochemical and Structural Characterization of the Human TL1A Ectodomain†¶

PubMed Central

Zhan, Chenyang; Yan, Qingrong; Patskovsky, Yury; Li, Zhenhong; Toro, Rafael; Meyer, Amanda; Cheng, Huiyong; Brenowitz, Michael; Nathenson, Stanley G; Almo, Steven C

2009-01-01

TNF-like 1A (TL1A) is a newly described member of the TNF superfamily that is directly implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease, atherosclerosis and rheumatoid arthritis. We report the crystal structure of the human TL1A extracellular domain at a resolution of 2.5 Å, which reveals a jelly-roll fold typical of the TNF superfamily. This structural information, in combination with complementary mutagenesis and biochemical characterization, provides insights into the binding interface and the specificity of the interactions between TL1A and the DcR3 and DR3 receptors. These studies suggest that the mode of interaction between TL1A and DcR3 differs from other characterized TNF ligand/receptor complexes. In addition, we have generated functional TL1A mutants with altered disulfide bonding capability that exhibit enhanced solution properties, which will facilitate the production of materials for future cell-based and whole animal studies. In summary, these studies provide insights into the structure and function of TL1A and provide the basis for the rational manipulation of its interactions with cognate receptors. PMID:19522538

MicroRNA-dependent regulation of metamorphosis and identification of microRNAs in the red flour beetle, Tribolium castaneum.

PubMed

Wu, Wei; Xiong, Wenfeng; Li, Chengjun; Zhai, Mengfan; Li, Yao; Ma, Fei; Li, Bin

2017-10-01

To date, although some microRNAs (miRNAs) have been discovered in the holometabolism insect Tribolium castaneum, large numbers of miRNAs still require investigation. Knocking down Dicer-1 (Dcr-1) and Argonaute-1 (Ago-1) in late larvae impaired miRNA synthesis, affected the juvenile hormone pathway by up-regulating Methoprene-tolerant (Met) and Krüppel-homolog1 (Kr-h1) transcript levels, and resulted in a series of defects in T. castaneum development and metamorphosis. Thus, high-throughput Illumina/Solexa sequencing was performed with a mixed sample of eight key developmental stages of T. castaneum. In total, 1154 unique miRNAs were discovered containing 274 conserved miRNAs belong to 68 miRNA families, 108 known candidate miRNAs and 772 novel miRNAs. Genome locus analysis showed that miRNA clusters are more abundant in T. castaneum than other species. The results indicated that RNAi of Dcr-1 and Ago-1 in T. castaneum resulted in miRNA-induced metamorphosis defects. Furthermore, large numbers of novel miRNAs were discovered in T. castaneum and localized to T. castaneum genome loci. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic connectivity regression: Determining state-related changes in brain connectivity

PubMed Central

Cribben, Ivor; Haraldsdottir, Ragnheidur; Atlas, Lauren Y.; Wager, Tor D.; Lindquist, Martin A.

2014-01-01

Most statistical analyses of fMRI data assume that the nature, timing and duration of the psychological processes being studied are known. However, often it is hard to specify this information a priori. In this work we introduce a data-driven technique for partitioning the experimental time course into distinct temporal intervals with different multivariate functional connectivity patterns between a set of regions of interest (ROIs). The technique, called Dynamic Connectivity Regression (DCR), detects temporal change points in functional connectivity and estimates a graph, or set of relationships between ROIs, for data in the temporal partition that falls between pairs of change points. Hence, DCR allows for estimation of both the time of change in connectivity and the connectivity graph for each partition, without requiring prior knowledge of the nature of the experimental design. Permutation and bootstrapping methods are used to perform inference on the change points. The method is applied to various simulated data sets as well as to an fMRI data set from a study (N=26) of a state anxiety induction using a socially evaluative threat challenge. The results illustrate the method’s ability to observe how the networks between different brain regions changed with subjects’ emotional state. PMID:22484408

Donor Research in Australia: Challenges and Promise

PubMed Central

Masser, Barbara; Smith, Geoff; Williams, Lisa A.

2014-01-01

Summary Donors are the key to the core business of Blood Collection Agencies (BCAs). However, historically, they have not been a focus of research undertaken by these organizations. This model is now changing, with significant donor research groups established in a number of countries, including Australia. Donor research in the Australian Red Cross Blood Service (Blood Service) is concentrated in the Donor and Community Research (DCR) team. Cognizant of the complex and ever-changing landscape with regard to optimal donor management, the DCR team collaborates with academics located at universities around Australia to coordinate a broad program of research that addresses both short- and-long term challenges to the blood supply. This type of collaboration is not, however, without challenges. Two major collaborative programs of the Blood Service's research, focusing on i) the recruitment and retention of plasmapheresis donors and ii) the role of the emotion pride in donor motivation and return, are showcased to elucidate how the challenges of conducting collaborative BCA research can be met. In so doing, these and the other research programs described herein demonstrate how the Blood Service supports and contributes to research that not only revises operational procedures but also contributes to advances in basic science. PMID:25254025

The combination of decoy receptor 3 and soluble triggering receptor expressed on myeloid cells-1 for the diagnosis of nosocomial bacterial meningitis.

PubMed

Liu, Yong-Juan; Shao, Li-Hua; Zhang, Jian; Fu, Shan-Ji; Wang, Gang; Chen, Feng-Zhe; Zheng, Feng; Ma, Rui-Ping; Liu, Hai-Hong; Dong, Xiao-Meng; Ma, Li-Xian

2015-03-23

Early diagnosis and appropriate antibiotic treatment can significantly reduce mortality of nosocomial bacterial meningitis. However, it is a challenge for clinicians to make an accurate and rapid diagnosis of bacterial meningitis. This study aimed at determining whether combined biomarkers can provide a useful tool for the diagnosis of bacterial meningitis. A retrospective study was carried out. Cerebrospinal fluid (CSF) levels of decoy receptor 3 (DcR3) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) were detected by enzyme-linked immunosorbent assay (ELISA). The patients with bacterial meningitis had significantly elevated levels of the above mentioned biomarkers. The two biomarkers were all risk factors with bacterial meningitis. The biomarkers were constructed into a "bioscore". The discriminative performance of the bioscore was better than that of each biomarker, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.842 (95% confidence intervals (CI) 0.770-0.914; p< 0.001). Combined measurement of CSF DcR3 and sTREM-1 concentrations improved the prediction of nosocomial bacterial meningitis. The combined strategy is of interest and the validation of that improvement needs further studies.

Biochemical and Structural Characterization of the Human TL1A Ectodomain

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

Zhan, C.; Yan, Q; Patskovsky, Y

TNF-like 1A (TL1A) is a newly described member of the TNF superfamily that is directly implicated in the pathogenesis of autoimmune diseases, including inflammatory bowel disease, atherosclerosis, and rheumatoid arthritis. We report the crystal structure of the human TL1A extracellular domain at a resolution of 2.5 {angstrom}, which reveals a jelly-roll fold typical of the TNF superfamily. This structural information, in combination with complementary mutagenesis and biochemical characterization, provides insights into the binding interface and the specificity of the interactions between TL1A and the DcR3 and DR3 receptors. These studies suggest that the mode of interaction between TL1A and DcR3more » differs from other characterized TNF ligand/receptor complexes. In addition, we have generated functional TL1A mutants with altered disulfide bonding capability that exhibit enhanced solution properties, which will facilitate the production of materials for future cell-based and whole animal studies. In summary, these studies provide insights into the structure and function of TL1A and provide the basis for the rational manipulation of its interactions with cognate receptors.« less

Fading-free transmission of 124-Gb/s PDM-DMT signal over 100-km SSMF using digital carrier regeneration.

PubMed

Li, Cai; Hu, Rong; Yang, Qi; Luo, Ming; Li, Wei; Yu, Shaohua

2016-01-25

The coherent reception of intensity modulated signal has been recently widely investigated, in which the signal is recovered by the envelop detection. High linewidth tolerance is achieved with such scheme. However, strong optical carrier exists during the transmission, which degrades the optical power efficiency. In this paper, an efficient modulation scheme for discrete multi-tone (DMT) signal is proposed based on the Mach-Zehnder modulator (MZM). Different from the traditional intensity modulation, the proposed method employs both intensity and phase domain. Thus, the optical carrier power can be greatly reduced by adjusting the bias of MZM around the null point. By employing coherent detection and digital carrier regeneration (DCR), the carrier suppressed DMT signal can be recovered using envelop detection. No carrier frequency or phase estimation is required. Numerical investigations are made to demonstrate the feasibility, in which significant improvements are found for the proposed DCR method, showing great tolerance against laser linewidth and carrier power reduction. Finally, a 124-Gb/s transmission of polarization-division multiplexed DMT (PDM-DMT) signal is demonstrated over 100-km SSMF, with only -8 dB optical carrier to signal power ratio (CSPR).

Groundwater contamination in the Roorkee area, India: 2D joint inversion of radiomagnetotelluric and direct current resistivity data

NASA Astrophysics Data System (ADS)

Yogeshwar, P.; Tezkan, B.; Israil, M.; Candansayar, M. E.

2012-01-01

The impact of sewage irrigation and groundwater contamination were investigated near Roorkee in north India using the Direct Current Resistivity (DCR) method and the Radiomagnetotelluric (RMT) method. Intensive field measurements were carried out in the vicinity of a waste disposal site, which was extensively irrigated with sewage water. For comparison a profile was investigated on a reference site, where no contamination was expected. In addition to conventional 1D and 2D inversion, the measured data sets were interpreted using a 2D joint inversion algorithm. The inversion results from the data obtained from the sewage irrigated site indicate a decrease of resistivity up to 75% in comparison with the reference site. The depth range from 5 to 15 m is identified as a shallow unconfined aquifer and the decreased resistivities are ascribed as the influence of contamination. Furthermore, a systematic increase in the resistivities of the shallow unconfined aquifer is detected as we move away from the waste disposal site. The advantages of both, the DCR and RMT methods, are quantitatively integrated by the 2D joint inversion of both data sets and lead to a joint model, which explains both data sets.

An important discovery on combination of irreversible electroporation and allogeneic natural killer cell immunotherapy for unresectable pancreatic cancer

PubMed Central

Liang, Shuzhen; Wang, Xiaohua; Liang, Yinqing; Zhang, Mingjie; Chen, Jibing; Niu, Lizhi; Xu, Kecheng

2017-01-01

Purpose To study the safety and clinical efficacy on combination of irreversible electroporation and allogeneic natural killer cell therapy for treating Stage III/IV pancreatic cancer, evaluating median progression free survival (PFS), and overall survival (OS). Results Adverse events of all patients were limited to grades 1 and 2, including local (mainly tussis 13.4%, nausea and emesis 7.1%, pain of puncture point 29.6% and duodenum and gastric retention 4.3%) and systemic (mainly fatigue 22.3%, fever 31.6%, and transient reduction of intraoperative blood pressure 25.1% and white cell count reduction 18.3%) reactions, fever was the most frequent. The serum amylase level at 24 h and 7 d after IRE was not significantly changed compared to those before IRE (P > 0.05). CA19–9 value was lower in IRE-NK group than in IRE at 1 month after treatment (P < 0.05). After a median follow-up of 7.4 months (3.6–11.2 months): in stage III group, median PFS was higher in IRE-NK group (9.3 months) than in IRE group (8.1 months, P = 0.0465), median OS was higher in IRE-NK (13.2 months) than in IRE (11.4 months, P = 0.0411), and median PFS was higher in who received multiple NK than single NK (9.8 months vs.8.1 months, P = 0.0423, respectively), median OS who received multiple NK was higher than single NK (13.9 months vs.12.3 months, P = 0.0524, respectively), the RR in IRE-NK (63.2%) was higher than in IRE (50.0%, P < 0.05); in stage IV group, median OS was higher in IRE-NK (9.8 months) than in IRE (8.7 months, P = 0.0397), the DCR in IRE-NK (66.7%) was higher than in IRE (42.9%, P < 0.05). Materials and Methods Between July 2016 and May 2017, we enrolled 71 patients who met the enrollment criteria. The patients were divided into stage III (32 patients, 17 patients received only IRE and 15 patients received IRE-NK (Irreversible electroporation- natural killer): 8 patients underwent a course of NK and 7 patients underwent ≥ 3 courses) and stage IV (39 patients, 22 patients received only IRE and 17 patients received IRE-NK: 9 patients underwent a course of NK and 8 patients underwent ≥ 3 courses). The safety and short-term effects were evaluated firstly, then the median PFS, median OS, response rate (RR) and disease control rate (DCR) were assessed. Conclusions Combination of irreversible electroporation and allogeneic natural killer cell immunotherapy significantly increased median PFS and median OS in stage III pancreatic cancer and extended the median OS of stage IV pancreatic cancer. Multiple allogeneic natural killer cells infusion was associated with better prognosis to stage III pancreatic cancer. PMID:29254205

A Clinical Comparison Study of Attention Deficit/Hyperactivity Disorder (DSM-IV) and Hyperkinetic Disorder (ICD-10) in Indian children and Adolescents

ERIC Educational Resources Information Center

Sitholey, Prabhat; Agarwal, Vivek; Bharti, Vikram

2012-01-01

Aims: To compare the usefulness of DSM IV and ICD-10 DCR criteria in clinic children presenting with the symptoms of inattention and hyperactivity-impulsivity. Methods: 62 children (54 boys and 8 girls) participated in the study. Children were assessed on Kiddie schedule for affective disorders and schizophrenia--present and lifetime version and…

A New Approach to Modeling the Cost of Ownership for Aircraft Systems.

DTIC Science & Technology

1981-08-01

expensive airborne missiles (e.g., Maverick, SRAM ) are funded in separate program elements of their own. If an aircraft system generates requirements for...PNTS b-I p,y,b,u EIR -u p9Y RTOK (FH/MO)QPA pUF PREPGNp ( - DCR) ) BUE b pp PGEN~)~1b-I ~ SER. = SEt. SEF j J,y j CIDM - CIDMP + CIDME + CIDMEI

Surface roughness and packaging tightness affect calcium lactate crystallization on Cheddar cheese.

PubMed

Rajbhandari, P; Kindstedt, P S

2014-01-01

Calcium lactate crystals that sometimes form on Cheddar cheese surfaces are a significant expense to manufacturers. Researchers have identified several postmanufacture conditions such as storage temperature and packaging tightness that contribute to crystal formation. Anecdotal reports suggest that physical characteristics at the cheese surface, such as roughness, cracks, and irregularities, may also affect crystallization. The aim of this study was to evaluate the combined effects of surface roughness and packaging tightness on crystal formation in smoked Cheddar cheese. Four 20-mm-thick cross-section slices were cut perpendicular to the long axis of a retail block (~300g) of smoked Cheddar cheese using a wire cutting device. One cut surface of each slice was lightly etched with a cheese grater to create a rough, grooved surface; the opposite cut surface was left undisturbed (smooth). The 4 slices were vacuum packaged at 1, 10, 50, and 90kPa (very tight, moderately tight, loose, very loose, respectively) and stored at 1°C. Digital images were taken at 1, 4, and 8 wk following the first appearance of crystals. The area occupied by crystals and number of discrete crystal regions (DCR) were quantified by image analysis. The experiment was conducted in triplicate. Effects of storage time, packaging tightness, surface roughness, and their interactions were evaluated by repeated-measures ANOVA. Surface roughness, packaging tightness, storage time, and their 2-way interactions significantly affected crystal area and DCR number. Extremely heavy crystallization occurred on both rough and smooth surfaces when slices were packaged loosely or very loosely and on rough surfaces with moderately tight packaging. In contrast, the combination of rough surface plus very tight packaging resulted in dramatic decreases in crystal area and DCR number. The combination of smooth surface plus very tight packaging virtually eliminated crystal formation, presumably by eliminating available sites for nucleation. Cut-and-wrap operations may significantly influence the crystallization behavior of Cheddar cheeses that are saturated with respect to calcium lactate and thus predisposed to form crystals. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Drug consumption rooms: Comparing times, spaces and actors in issues of social acceptability in French public debate.

PubMed

Jauffret-Roustide, Marie; Cailbault, Isabelle

2018-06-01

In October 2016, the first French drug consumption room (DCR) opened in Paris. We propose to examine the process through which this issue has been framed as a matter of public concern, after being ignored for almost 20 years. Our analysis of the controversy on DCRs investigates how public conversations on harm reduction evolve according to the time period (from the 1990s to the present), scale of discourse (local vs. national), and involved actors (politicians, professionals, local residents, and drug users). Our methodology includes analyses of media content: we reviewed 1735 articles published between 1990 and 2017. Our theoretical approach is in line with the sociology "des épreuves" derived from pragmatic sociology and controversy analysis. This approach goes beyond interactionism by attempting to place situations back into broader sociological realities. We also pay special attention to governance, a political lens that focuses on local aspects of negotiations and on the implication of a variety of actors. While the current debate on DCRs in France draws on constraints and resources already present in the harm reduction debate of the 1980s, it also repositions itself by avoiding moral argumentation and featuring less confrontation in the professional sphere. Today, we can see that the center of this tense debate has shifted from the professional sphere to the political and residential spheres. Most often, residents advance concerns that are not directly related to drug users themselves, but that derive from their apprehension of living in a displaced and stranded neighborhood. The public conversation leaves little room for drug users, even though they are the primary stakeholders of harm reduction and play a crucial role in DCR advocacy. Our work reveals that the controversy about DCR is the product of complex interactions between different kinds of actors harm reduction professionals, political actors at the local and national levels, local residents, and drug users. Comparing different instances of public debate reveals the specific limitations and potentials for change in French drug policy. Copyright © 2018. Published by Elsevier B.V.

High-dose HOOK effect in urinary DcR2 assay in patients with chronic kidney disease.

PubMed

Chen, Jia; Chen, Ke-Hong; Wang, Li-Ming; Zhang, Wei-Wei; Feng, Lei; Dai, Huan-Zi; He, Ya-Ni

2018-06-05

Urinary DcR2 (uDcR2) is a biomarker for the early detection the tubulointerstitial injury (TII) in patients with chronic kidney disease (CKD), but the high-dose hook effect may lead to falsely low or even negative results when using an enzyme-linked immunosorbent assay (ELISA). This study aimed to investigate if the high-dose hook effect exists with ELISA testing, and to uncover a potential approach for reducing this effect. 72 CKD patients were recruited and categorized into four groups based on TII scores. uDcR2 was measured in undiluted and serially diluted (two-, four-, eight- and 16-fold dilutions) urine using an ELISA kit. The results from the assay were normalized to urinary creatinine. We evaluated the correlation between uDcR2/cre levels at different dilutions and renal histological parameters. Receiver operating characteristic (ROC) curves were generated to examine the value of uDcR2/cre for predicting TII. uDcR2/cre levels in the undiluted urine were significantly higher in patients with CKD than those in the control. However, higher TII scores did not yield higher levels of uDcR2/cre in the undiluted urine. After serial dilution, uDcR2/cre levels were highest with the four-fold dilution. A positive correlation was found between uDcR2/cre levels at different dilutions and TII scores, with the highest correlation coefficient and the largest AUC being observed at the four-fold dilution. The high-dose hook effect was apparent during ELISA testing of uDcR2 in CKD patients, yet dilution of the urine samples neutralized this effect. However, the use of a four-fold dilution of urine for uDcR2/cre testing may eliminate the high-dose hook effect and make it possible to effectively monitor the severity of TII in CKD patients. Copyright © 2018. Published by Elsevier Inc.

Skeletal Muscle Metrics on Clinical 18F-FDG PET/CT Predict Health Outcomes in Patients with Sarcoma

PubMed Central

Foster, Brent; Boutin, Robert D.; Lenchik, Leon; Gedeon, David; Liu, Yu; Nittur, Vinay; Badawi, Ramsey D.; Li, Chin-Shang; Canter, Robert J.; Chaudhari, Abhijit J.

2018-01-01

The aim of this study was to determine the association of measures of skeletal muscle determined from 18F-FDG PET/CT with health outcomes in patients with soft-tissue sarcoma. 14 patients (8 women and 6 men; mean age 66.5 years) with sarcoma had PET/CT examinations. On CTs of the abdomen and pelvis, skeletal muscle was segmented, and cross-sectional muscle area, muscle volume, and muscle attenuation were determined. Within the segmented muscle, intramuscular fat area, volume, and density were derived. On PET images, the standardized uptake value (SUV) of muscle was determined. Regression analyses were conducted to determine the association between the imaging measures and health outcomes including overall survival (OS), local recurrence-free survival (LRFS), distant cancer recurrence (DCR), and major surgical complications (MSC). The association between imaging metrics and pre-therapy levels of serum C-reactive protein (CRP), creatinine, hemoglobin, and albumin was determined. Decreased volumetric muscle CT attenuation was associated with increased DCR. Increased PET SUV of muscle was associated with decreased OS and LRFS. Lower muscle SUV was associated with lower serum hemoglobin and albumin. Muscle measurements obtained on routine 18F-FDG PET/CT are associated with outcomes and serum hemoglobin and albumin in patients with sarcoma. PMID:29756042

Skeletal Muscle Metrics on Clinical 18F-FDG PET/CT Predict Health Outcomes in Patients with Sarcoma.

PubMed

Foster, Brent; Boutin, Robert D; Lenchik, Leon; Gedeon, David; Liu, Yu; Nittur, Vinay; Badawi, Ramsey D; Li, Chin-Shang; Canter, Robert J; Chaudhari, Abhijit J

2018-01-01

The aim of this study was to determine the association of measures of skeletal muscle determined from 18 F-FDG PET/CT with health outcomes in patients with soft-tissue sarcoma. 14 patients (8 women and 6 men; mean age 66.5 years) with sarcoma had PET/CT examinations. On CTs of the abdomen and pelvis, skeletal muscle was segmented, and cross-sectional muscle area, muscle volume, and muscle attenuation were determined. Within the segmented muscle, intramuscular fat area, volume, and density were derived. On PET images, the standardized uptake value (SUV) of muscle was determined. Regression analyses were conducted to determine the association between the imaging measures and health outcomes including overall survival (OS), local recurrence-free survival (LRFS), distant cancer recurrence (DCR), and major surgical complications (MSC). The association between imaging metrics and pre-therapy levels of serum C-reactive protein (CRP), creatinine, hemoglobin, and albumin was determined. Decreased volumetric muscle CT attenuation was associated with increased DCR. Increased PET SUV of muscle was associated with decreased OS and LRFS. Lower muscle SUV was associated with lower serum hemoglobin and albumin. Muscle measurements obtained on routine 18 F-FDG PET/CT are associated with outcomes and serum hemoglobin and albumin in patients with sarcoma.

Space Transportation Engine Program (STEP), phase B

NASA Technical Reports Server (NTRS)

1990-01-01

The Space Transportation Engine Program (STEP) Phase 2 effort includes preliminary design and activities plan preparation that will allow smooth and time transition into a Prototype Phase and then into Phases 3, 4, and 5. A Concurrent Engineering approach using Total Quality Management (TQM) techniques, is being applied to define an oxygen-hydrogen engine. The baseline from Phase 1/1' studies was used as a point of departure for trade studies and analyses. Existing STME system models are being enhanced as more detailed module/component characteristics are determined. Preliminary designs for the open expander, closed expander, and gas generator cycles were prepared, and recommendations for cycle selection made at the Design Concept Review (DCR). As a result of July '90 DCR, and information subsequently supplied to the Technical Review Team, a gas generator cycle was selected. Results of the various Advanced Development Programs (ADP's) for the Advanced Launch Systems (ALS) were contributive to this effort. An active vehicle integration effort is supplying the NASA, Air Force, and vehicle contractors with engine parameters and data, and flowing down appropriate vehicle requirements. Engine design and analysis trade studies are being documented in a data base that was developed and is being used to organize information. To date, seventy four trade studies were input to the data base.

Multicenter phase II study of apatinib treatment for metastatic gastric cancer after failure of second-line chemotherapy.

PubMed

Ruan, Hanguang; Dong, Junlin; Zhou, Xueliang; Xiong, Juan; Wang, Hua; Zhong, Xiaoming; Cao, Xiaolong

2017-11-28

Apatinib is a tyrosine kinase inhibitor and vascular endothelial growth factor receptor 2 (VEGFR-2) targeted drug. A phase I clinical trial showed that this agent has antitumor activity in Chinese patients with metastatic gastric cancer (mGC). The aim of this study was to investigate the safety and efficacy of apatinib treatment in patients with mGC. This was an open-label, multicenter, single-arm study involving four institutions in China. We enrolled 42 patients from March 2015 to October 2015 who experienced tumor progression after second-line chemotherapy and had no other treatment options that clearly conferred a survival benefit. Oral apatinib (850 mg daily) was administered within 30 min of eating breakfast, lunch, or dinner on days 1 through 28 of each 4-week cycle. The median progression-free survival (PFS) time and median overall survival (OS) time were 4.0 months (95% CI, 2.85-5.15) and 4.50 months (95% CI, 4.03-4.97), respectively. The disease control rate (DCR) and objective response rate (ORR) were, respectively, 78.57% and 9.52% after 2 cycles and 57.14% and 19.05% after 4 cycles. The main adverse events (AEs) were secondary hypertension, elevated aminotransferase, and hand-foot syndrome, with incidences of 35.71%, 45.24%, and 40.48%, respectively. The most common grade 3 to 4 AEs were secondary hypertension and elevated aminotransferase, with incidences of 7.14% each. Apatinib is effective and safe in heavily pretreated patients with mGC who fail to respond to two or more prior chemotherapy regimens. Toxicities were tolerable or could be clinically managed.

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.

PubMed

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 injection could significantly restore the cellular immunity damaged by platinum-based chemotherapy. It may be an important tumor immune modulator and protector for patients with NSCLC treated with chemotherapy.

Data on the key performance indicators for quality of service of GSM networks in Nigeria.

PubMed

Popoola, Segun I; Atayero, Aderemi A; Faruk, Nasir; Badejo, Joke A

2018-02-01

In this data article, the Key Performance Indicators (KPIs) for Quality of Service (QoS) of Global System for Mobile Communications (GSM) networks in Nigeria are provided and analyzed. The data provided in this paper contain the Call Setup Success Rate (CSSR), Drop Call Rate (DCR), Stand-alone Dedicated Channel (SDCCH) congestion, and Traffic Channel (TCH) congestion for the four GSM network operators in Nigeria (Airtel, Etisalat, Glo, and MTN). These comprehensive data were obtained from the Nigerian Communications Commission (NCC). Significant differences in each of the KPIs for the four quarters of each year were presented based on Analysis of Variance (ANOVA). The values of the KPIs were plotted against the months of the year for better visualization and understanding of data trends across the four quarters. Multiple comparisons of the mean-quarterly differences of the KPIs were also presented using Tukey's Post Hoc test. Public availability and further interpretation and discussion of these useful information will assist the network providers, Nigerian government, local and international regulatory bodies, policy makers, and other stakeholders in ensuring access of people, machines, and things to high quality telecommunications services.

Symptom Severity and Quality of Life Among Long-term Colorectal Cancer Survivors Compared With Matched Control Subjects: A Population-Based Study.

PubMed

Hart, Tae L; Charles, Susan T; Gunaratne, Mekhala; Baxter, Nancy N; Cotterchio, Michelle; Cohen, Zane; Gallinger, Steven

2018-03-01

Data are lacking regarding physical functioning, psychological well-being, and quality of life among colorectal cancer survivors >10 years postdiagnosis. The purpose of this study was to examine self-reported physical functioning, quality of life, and psychological well-being in long-term colorectal cancer survivors compared with age- and sex-matched unaffected control subjects. Participants completed a cross-sectional survey. The colorectal cancer survivors and unaffected control subjects were recruited from the Ontario Familial Colorectal Cancer Registry. A population-based sample of colorectal cancer survivors (N = 296) and their age- and sex-matched unaffected control subjects (N = 255) were included. Survivors were, on average, 15 years postdiagnosis. Quality of life was measured with the Functional Assessment of Cancer Therapy-General scale, bowel dysfunction with the Memorial Sloan-Kettering Cancer Center scale, urinary dysfunction with the International Consultation on Incontinence Questionnaire-Short Form, fatigue with the Functional Assessment of Chronic Illness Therapy-Fatigue scale, and depression with the Center for Epidemiologic Studies-Depression scale. In linear mixed-model analyses adjusting for income, education, race, and comorbid medical conditions, survivors reported good emotional, functional, physical, and overall quality of life, comparable to control subjects. Fatigue and urinary functioning did not differ significantly between survivors and control subjects. Survivors reported significantly higher social quality of life and lower depression compared with unaffected control subjects. The only area where survivors reported significantly worse deficits was in bowel dysfunction, but the magnitude of differences was relatively small. Generalizability is limited by moderately low participation rates. Findings are likely biased toward healthy participants. No baseline assessment was available to examine change in outcomes over time. Long-term colorectal cancer survivors appear to have comparable quality of life and, in some areas, better well-being than their unaffected peers. Bowel dysfunction may continue to be an ongoing issue even 15 years after colorectal cancer diagnosis. Overall quality of life can be expected to be good in this group of older survivors. See Video Abstract at http://links.lww.com/DCR/A476.

The chemical NJ15 affects hypocotyl elongation and shoot gravitropism via cutin polymerization.

PubMed

Jaroensanti-Tanaka, Naiyanate; Miyazaki, Sho; Hosoi, Akito; Tanaka, Keisuke; Ito, Shinsaku; Iuchi, Satoshi; Nakano, Takeshi; Kobayashi, Masatomo; Nakajima, Masatoshi; Asami, Tadao

2018-06-18

We previously found a chemical, designated as NJ15, which inhibited both auxin and brassinosteroid responses in dark-grown Arabidopsis. To study its mode of action, we performed a phenotypic screening of NJ15-low-sensitive lines among mutant pools of Arabidopsis. One line (f127) showed clear NJ15-low-sensitivity in terms of hypocotyl elongation and shoot gravitropism. After further testing, it was determined that DCR, an enzyme involved in cutin polymerization, had lost its function in the mutant, which caused its low sensitivity to NJ15. Fatty acids are the base materials for polymers such as cutin and cuticular wax. We confirmed that NJ15 affects fatty acid biosynthesis, and that it does differently from cafenstrole, a known inhibitor of cuticular wax formation. Based on these results, we propose that the target of NJ15 is likely located within the cutin polymer formation pathway. Caf: cafenstrole; DEG: differentially expressed gene; FDR: false discovery rate; FOX: full length cDNA-overexpressor; VLCFA: very-long-chain fatty acid.

Radiation Hardness of dSiPM Sensors in a Proton Therapy Radiation Environment

NASA Astrophysics Data System (ADS)

Diblen, Faruk; Buitenhuis, Tom; Solf, Torsten; Rodrigues, Pedro; van der Graaf, Emiel; van Goethem, Marc-Jan; Brandenburg, Sytze; Dendooven, Peter

2017-07-01

In vivo verification of dose delivery in proton therapy by means of positron emission tomography (PET) or prompt gamma imaging is mostly based on fast scintillation detectors. The digital silicon photomultiplier (dSiPM) allows excellent scintillation detector timing properties and is thus being considered for such verification methods. We present here the results of the first investigation of radiation damage to dSiPM sensors in a proton therapy radiation environment. Radiation hardness experiments were performed at the AGOR cyclotron facility at the KVI-Center for Advanced Radiation Technology, University of Groningen. A 150-MeV proton beam was fully stopped in a water target. In the first experiment, bare dSiPM sensors were placed at 25 cm from the Bragg peak, perpendicular to the beam direction, a geometry typical for an in situ implementation of a PET or prompt gamma imaging device. In the second experiment, dSiPM-based PET detectors containing lutetium yttrium orthosilicate scintillator crystal arrays were placed at 2 and 4 m from the Bragg peak, perpendicular to the beam direction; resembling an in-room PET implementation. Furthermore, the experimental setup was simulated with a Geant4-based Monte Carlo code in order to determine the angular and energy distributions of the neutrons and to determine the 1-MeV equivalent neutron fluences delivered to the dSiPM sensors. A noticeable increase in dark count rate (DCR) after an irradiation with about 108 1-MeV equivalent neutrons/cm2 agrees with observations by others for analog SiPMs, indicating that the radiation damage occurs in the single photon avalanche diodes and not in the electronics integrated on the sensor chip. It was found that in the in situ location, the DCR becomes too large for successful operation after the equivalent of a few weeks of use in a proton therapy treatment room (about 5 × 1013 protons). For PET detectors in an in-room setup, detector performance was unchanged even after an irradiation equivalent to three years of use in a treatment room (3 × 1015 protons).

Robot-Assisted Ventral Mesh Rectopexy for Rectal Prolapse: A 5-Year Experience at a Tertiary Referral Center.

PubMed

van Iersel, Jan J; Formijne Jonkers, Hendrik A; Paulides, Tim J C; Verheijen, Paul M; Draaisma, Werner A; Consten, Esther C J; Broeders, Ivo A M J

2017-11-01

Laparoscopic ventral mesh rectopexy is being increasingly performed internationally to treat rectal prolapse syndromes. Robotic assistance appears advantageous for this procedure, but literature regarding robot-assisted ventral mesh rectopexy is limited. The primary objective of this study was to assess the safety and effectiveness of robot-assisted ventral mesh rectopexy in the largest consecutive series of patients to date. This study is a retrospective cross-sectional analysis of prospectively collected data. The study was conducted in a tertiary referral center. All of the patients undergoing robot-assisted ventral mesh rectopexy for rectal prolapse syndromes between 2010 and 2015 were evaluated. Preoperative and postoperative (mesh and nonmesh) morbidity and functional outcome were analyzed. The actuarial recurrence rates were calculated using the Kaplan-Meier method. A total of 258 patients underwent robot-assisted ventral mesh rectopexy (mean ± SD follow-up = 23.5 ± 21.8 mo; range, 0.2 - 65.1 mo). There were no conversions and only 5 intraoperative complications (1.9%). Mortality (0.4%) and major (1.9%) and minor (<30 d) early morbidity (7.0%) were acceptably low. Only 1 (1.3%) mesh-related complication (asymptomatic vaginal mesh erosion) was observed. A significant improvement in obstructed defecation (78.6%) and fecal incontinence (63.7%) were achieved for patients (both p < 0.0005). At final follow-up, a new onset of fecal incontinence and obstructed defecation was induced or worsened in 3.9% and 0.4%. The actuarial 5-year external rectal prolapse and internal rectal prolapse recurrence rates were 12.9% and 10.4%. This was a retrospective study including patients with minimal follow-up. No validated scores were used to assess function. The study was monocentric, and there was no control group. Robot-assisted ventral mesh rectopexy is a safe and effective technique to treat rectal prolapse syndromes, providing an acceptable recurrence rate and good symptomatic relief with minimal morbidity. See Video Abstract at http://links.lww.com/DCR/A427.

From Clinical Trials to the Front Line: Vinflunine for Treatment of Urothelial Cell Carcinoma at the National Cancer Institute of Naples.

PubMed

Facchini, Gaetano; Della Pepa, Chiara; Cavaliere, Carla; Cecere, Sabrina C; Di Napoli, Marilena; D'Aniello, Carmine; Crispo, Anna; Iovane, Gelsomina; Maiolino, Piera; Tramontano, Teresa; Piscitelli, Raffaele; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Sorrentino, Domenico; Perdonà, Sisto; Pignata, Sandro

2016-01-01

The efficacy of Vinflunine, after failure of platinum-based chemotherapy in patients with metastatic or recurrent Transitional Cell Cancer of the Urothelial Tract, TCCU, has been demonstrated in an international, randomized, phase III trial comparing Vinflunine plus Best Supportive Care, BSC, with BSC alone. On the basis of that study vinflunine has been approved by the European Medicine Association, EMA, for treatment of TCCU patients after failure of a platinum treatment. However, since data in clinical trials often differ from routine clinical practice due to unselected population and less strict monitoring, "real life" experiences are very helpful to verify the efficacy of a new therapy. This was a spontaneous, observational, retrospective study involving 43 patients with metastatic TCCU treated with vinflunine at our cancer center, data about demographics, disease characteristics, and previous treatments were collected and outcome and toxicities of vinflunine were analyzed. 41 of 43 patients were eligible for RR analysis, the Overall RR was 12%, the Disease Control Rate was 29%; when including only patients treated in II line the DCR rose to 33%; the median PFS and the median OS were 2.2 and 6.9 months, respectively. Our findings were consistent with the outcome data emerged in the phase III randomized trial and in the other observational studies conducted all around Europe in the last 2-3 years. This experience supports the use of vinflunine in patients with advanced TTCU as effective and manageable antineoplastic drug.

Astrometric Detection of Extrasolar Planets: Results of a Feasibility Study with the Palomar 5 Meter Telescope

NASA Technical Reports Server (NTRS)

Pravdo, Steven H.; Shaklan, Stuart B.

1996-01-01

The detection of extrasolar planets around stars like the Sun remains an important goal of astronomy. We present results from Palomar 5 m observations of the open cluster NGC 2420 in which we measure some of the sources of noise that will be present in an astrometric search for extrasolar planets. This is the first time that such a large aperture has been used for high-precision astrometry. We find that the atmospheric noise is 150 micro-arcsec hr(exp 1/2) across a 90 sec field of view and that differential chromatic refraction (DCR) can be calibrated to 128 micro-arcsec for observations within 1 hr of the meridian and 45 deg of zenith. These results confirm that a model for astrometric measurements can be extrapolated to large apertures. We demonstrate, based upon these results, that a large telescope achieves the sensitivity required to perform a statistically significant search for extra solar planets. We describe an astrometric technique to detect planets, the astrometric signals expected, the role of reference stars, and the sources of measurement noise: photometric noise, atmospheric motion between stars, sky background, instrumental noise, and DCR. For the latter, we discuss a method to reduce the noise further to 66 micro-arcsecond for observations within 1 hr of the meridian and 45 deg of zenith. We discuss optimal lists of target stars taken from the latest Gliese & Jahreiss catalog of nearby stars with the largest potential astrometric signals, declination limits for both telescope accessibility and reduced DCR, and galactic latitude limits for a sufficiant number of reference stars. Two samples are described from which one can perform statistically significant searches for gas giant planets around nearby stars. One sample contains 100 "solar class" stars with an average stellar mass of 0.82 solar mass; the other maximizes the number of stars, 574, by searching mainly low-mass M stars. We perform Monte Carlo simulations of the statistical significance of the expected results by using measured and estimated noise quantities. We show the semimajor axis parameter spaces that are searched for each star and how an increase in the length of the observing program expands these spaces. The search over semimajor axis parameter space relates to the theory of gas giant planet formation.

NASA Scientific and Technical Publications: A Catalog of Special Publications, Reference Publications, Conference Publications, and Technical Papers 1991-1992

DTIC Science & Technology

1993-02-01

Scientific and Technical Information EXOBIOLOGY. HEALTH. MICROBIOLOGY . MICROOR- System during September 1990. Subject coverage includes: GANISMS...Houston. TX N91-24731 National Aeronautics and Space Administration. MICROBIOLOGY ON SPACE STATION FREEDOM Washington, DCr DUANE L. PIERSON, ed...and solution INASA-SP-7011(345)) p 37 N91-16547 Beyond the Baseline 1991ý Proceedings of the Space [NASA-TP-3242) p 43 N92-33483 Microbiology on Space

VizieR Online Data Catalog: Li enrichment histories of the thick/thin disc (Fu+, 2018)

NASA Astrophysics Data System (ADS)

Fu, X.; Romano, D.; Bragaglia, A.; Mucciarelli, A.; Lind, K.; Delgado Mena, E.; Sousa, S. G.; Randich, S.; Bressan, A.; Sbordone, L.; Martell, S.; Korn, A. J.; Abia, C.; Smiljanic, R.; Jofre, P.; Pancino, E.; Tautvaisiene, G.; Tang, B.; Lanzafame, A. C.; Magrini, L.; Carraro, G.; Bensby, T.; Damiani, F.; Alfaro, E. J.; Flaccomio, E.; Morbidelli, L.; Zaggia, S.; Lardo, C.; Monaco, L.; Frasca, A.; Donati, P.; Drazdauskas, A.; Chorniy, Y.; Bayo, A.; Kordopatis, G.

2017-11-01

To investigate the Galactic lithium enrichment history we se- lect well-measured main sequence field stars with UVES spectra from the GES iDR4 catalogue. In our selection, 1884 UVES stars are marked as field stars, including those of the Galactic disc and halo designated as MW (GEMW) fields, standard CoRoT (GES D_CR) field, standard radial velocity (GES DRV) field, and stars to the Galactic Bulge direction (GEMWBL). (1 data file).

The effects of Fu Zi on changes in the body heat of dogs.

PubMed

Chen, Tian-Tian; Qi, Chunhua; Guo, Huijun; Cheng, Ziqiang; Zhou, Dong; Liu, Haitao; Liu, Jianzhu

2009-03-01

The aim of the present study was to investigate the effects of Fu Zi on changes in the body heat of dogs. Twelve clinically healthy dogs were divided into two groups: the control group (six dogs) and the experimental group (six dogs). The control group was made to ingest normal saline mixed with canned meat, while the experimental group was made to ingest the Fu Zi solution mixed with canned meat. The infrared thermographic system was used to determine the level of body heat generated by these dogs. These areas include the dorsocranial (DCr), dorsocaudal (DCd), ventrocranial (VCr), and ventrocaudal (VCd) regions at pretreatment and were determined at 10, 20, 30, 50, 90, 120, 240, and 360 minutes after treatment for each of these areas. The results showed a tendency toward increased body heat until 30 minutes after ingestion of the Fu Zi powder mixed with canned meat. The significant differences in the changes of body heat were detected at 360 minutes in the DCd regions, 20 minutes in the VCr regions, and 30 minutes in the VCd regions between the experimental and control groups (p < 0.05). Based from our results, we find that Fu Zi can increase and maintain the dogs' body heat for at least 6 hours.

Surface Alpha Interactions in P-Type Point-Contact HPGe Detectors: Maximizing Sensitivity of 76Ge Neutrinoless Double-Beta Decay Searches

NASA Astrophysics Data System (ADS)

Gruszko, Julieta

Though the existence of neutrino oscillations proves that neutrinos must have non-zero mass, Beyond-the-Standard-Model physics is needed to explain the origins of that mass. One intriguing possibility is that neutrinos are Majorana particles, i.e., they are their own anti-particles. Such a mechanism could naturally explain the observed smallness of the neutrino masses, and would have consequences that go far beyond neutrino physics, with implications for Grand Unification and leptogenesis. If neutrinos are Majorana particles, they could undergo neutrinoless double-beta decay (0nBB), a hypothesized rare decay in which two antineutrinos annihilate one another. This process, if it exists, would be exceedingly rare, with a half-life over 1E25 years. Therefore, searching for it requires experiments with extremely low background rates. One promising technique in the search for 0nBB is the use of P-type point-contact (P-PC) high-purity Germanium (HPGe) detectors enriched in 76Ge, operated in large low-background arrays. This approach is used, with some key differences, by the MAJORANA and GERDA Collaborations. A problematic background in such large granular detector arrays is posed by alpha particles incident on the surfaces of the detectors, often caused by 222Rn contamination of parts or of the detectors themselves. In the MAJORANA DEMONSTRATOR, events have been observed that are consistent with energy-degraded alphas originating near the passivated surface of the detectors, leading to a potential background contribution in the region-of-interest for neutrinoless double-beta decay. However, it is also observed that when energy deposition occurs very close to the passivated surface, high charge trapping occurs along with subsequent slow charge re-release. This leads to both a reduced prompt signal and a measurable change in slope of the tail of a recorded pulse. Here we discuss the characteristics of these events and the development of a filter that can identify the occurrence of this delayed charge recovery (DCR) effect, allowing for the efficient rejection of passivated surface alpha events in analysis. Using a dedicated test-stand called the TUM Upside-down BEGe (TUBE) scanner, we have characterized the response of a P-PC detector like those used in the DEMONSTRATOR to alphas incident on the sensitive surfaces, developing a model for the radial dependence of the energy loss to charge trapping and determining the dominant mechanism behind the delayed charge effect. We have also used these measurements to demonstrate the complementarity of the DCR analysis with the drift-time analysis that is used to identify alpha background candidate events in the GERDA detectors. Using these two methods, we demonstrate the ability to effectively reject all alpha events (to within statistical uncertainty) with only 0.2% bulk event sacrifice. Applying the DCR analysis to the events observed in the MAJORANA DEMONSTRATOR, we find that it reduces the backgrounds in the 0nBB region-of-interest by a factor of 29, increasing the expected experimental sensitivity by a factor of 3 over the lifetime of the DEMONSTRATOR. The results of the dedicated measurements in the TUBE scanner can be used to build a background model for alpha decays in the DEMONSTRATOR; here, we examine two simplified geometric models for the alpha source distribution and find that the observed spectral shape is consistent with alpha events originating in the plastics of the detector units.

From Clinical Trials to the Front Line: Vinflunine for Treatment of Urothelial Cell Carcinoma at the National Cancer Institute of Naples

PubMed Central

Facchini, Gaetano; Della Pepa, Chiara; Cavaliere, Carla; Cecere, Sabrina C.; Di Napoli, Marilena; D'Aniello, Carmine; Crispo, Anna; Iovane, Gelsomina; Maiolino, Piera; Tramontano, Teresa; Piscitelli, Raffaele; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Sorrentino, Domenico; Perdonà, Sisto; Pignata, Sandro

2016-01-01

Background: The efficacy of Vinflunine, after failure of platinum-based chemotherapy in patients with metastatic or recurrent Transitional Cell Cancer of the Urothelial Tract, TCCU, has been demonstrated in an international, randomized, phase III trial comparing Vinflunine plus Best Supportive Care, BSC, with BSC alone. On the basis of that study vinflunine has been approved by the European Medicine Association, EMA, for treatment of TCCU patients after failure of a platinum treatment. However, since data in clinical trials often differ from routine clinical practice due to unselected population and less strict monitoring, “real life” experiences are very helpful to verify the efficacy of a new therapy. Methods: This was a spontaneous, observational, retrospective study involving 43 patients with metastatic TCCU treated with vinflunine at our cancer center, data about demographics, disease characteristics, and previous treatments were collected and outcome and toxicities of vinflunine were analyzed. Results: 41 of 43 patients were eligible for RR analysis, the Overall RR was 12%, the Disease Control Rate was 29%; when including only patients treated in II line the DCR rose to 33%; the median PFS and the median OS were 2.2 and 6.9 months, respectively. Conclusion: Our findings were consistent with the outcome data emerged in the phase III randomized trial and in the other observational studies conducted all around Europe in the last 2–3 years. This experience supports the use of vinflunine in patients with advanced TTCU as effective and manageable antineoplastic drug. PMID:27199753

A preliminary randomised controlled study of short-term Antrodia cinnamomea treatment combined with chemotherapy for patients with advanced cancer.

PubMed

Tsai, Ming-Yen; Hung, Yu-Chiang; Chen, Yen-Hao; Chen, Yung-Hsiang; Huang, Yu-Chuen; Kao, Chao-Wei; Su, Yu-Li; Chiu, Hsien-Hsueh Elley; Rau, Kun-Ming

2016-08-26

Antrodia cinnamomea (AC) is a popular medicinal mushroom in Taiwan that has been widely used for treatment of various cancers. Few clinical studies have reported its application and efficiency in therapeutic chemotherapy strategies. We performed a double-blind, randomized clinical study to investigate whether AC given for 30 days had acceptable safety and efficacy in advanced cancer patients receiving chemotherapy. Patients with advanced and/or metastatic adenocarcinoma, performance status (PS) 0-2, and adequate organ function who had previously been treated with standard chemotherapy were randomly assigned to receive routine chemotherapy regimens with AC (20 ml twice daily) orally for 30 days or placebo. The primary endpoint was 6-month overall survival (OS); the secondary endpoints were disease control rate (DCR), quality of life (QoL), adverse event (AE), and biochemical features within 30 days of treatment. From August 2010 to July 2012, 37 subjects with gastric, lung, liver, breast, and colorectal cancer (17 in the AC group, 20 in the placebo group) were enrolled in the study. Disease progression was the primary cause of death in 4 (33.3 %) AC and 8 (66.7 %) placebo recipients. Mean OSs were 5.4 months for the AC group and 5.0 months for the placebo group (p = 0.340), and the DCRs were 41.2 and 55 %, respectively (p = 0.33). Most hematologic, liver, or kidney functions did not differ significantly between the two groups, but platelet counts were lower in the AC group than in the placebo group (p = 0.02). QoL assessments were similar in the two groups, except that the AC group showed significant improvements in quality of sleep (p = 0.04). Although we found a lower mortality rate and longer mean OS in the AC group than in the control group, A. cinnamomea combined with chemotherapy was not shown to improve the outcome of advanced cancer patients, possibly due to the small sample size. In fact, the combination may present a potential risk of lowered platelet counts. Adequately powered clinical trials will be necessary to address this question. ClinicalTrials.gov NCT01287286 .

A divide-conquer-recombine algorithmic paradigm for large spatiotemporal quantum molecular dynamics simulations

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

Shimojo, Fuyuki; Hattori, Shinnosuke; Department of Physics, Kumamoto University, Kumamoto 860-8555

We introduce an extension of the divide-and-conquer (DC) algorithmic paradigm called divide-conquer-recombine (DCR) to perform large quantum molecular dynamics (QMD) simulations on massively parallel supercomputers, in which interatomic forces are computed quantum mechanically in the framework of density functional theory (DFT). In DCR, the DC phase constructs globally informed, overlapping local-domain solutions, which in the recombine phase are synthesized into a global solution encompassing large spatiotemporal scales. For the DC phase, we design a lean divide-and-conquer (LDC) DFT algorithm, which significantly reduces the prefactor of the O(N) computational cost for N electrons by applying a density-adaptive boundary condition at themore » peripheries of the DC domains. Our globally scalable and locally efficient solver is based on a hybrid real-reciprocal space approach that combines: (1) a highly scalable real-space multigrid to represent the global charge density; and (2) a numerically efficient plane-wave basis for local electronic wave functions and charge density within each domain. Hybrid space-band decomposition is used to implement the LDC-DFT algorithm on parallel computers. A benchmark test on an IBM Blue Gene/Q computer exhibits an isogranular parallel efficiency of 0.984 on 786 432 cores for a 50.3 × 10{sup 6}-atom SiC system. As a test of production runs, LDC-DFT-based QMD simulation involving 16 661 atoms is performed on the Blue Gene/Q to study on-demand production of hydrogen gas from water using LiAl alloy particles. As an example of the recombine phase, LDC-DFT electronic structures are used as a basis set to describe global photoexcitation dynamics with nonadiabatic QMD (NAQMD) and kinetic Monte Carlo (KMC) methods. The NAQMD simulations are based on the linear response time-dependent density functional theory to describe electronic excited states and a surface-hopping approach to describe transitions between the excited states. A series of techniques are employed for efficiently calculating the long-range exact exchange correction and excited-state forces. The NAQMD trajectories are analyzed to extract the rates of various excitonic processes, which are then used in KMC simulation to study the dynamics of the global exciton flow network. This has allowed the study of large-scale photoexcitation dynamics in 6400-atom amorphous molecular solid, reaching the experimental time scales.« less

Clinical efficacy of icotinib in lung cancer patients with different EGFR mutation status: a meta-analysis

PubMed Central

Xu, Ping; Xiang, Da-Xiong; Yang, Rui; Wei, Wei; Qu, Qiang

2017-01-01

Icotinib is a novel and the third listed epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which exerts a good anti-tumor efficacy on non-small cell lung cancer (NSCLC). The efficacy of EGFR-TKIs has been shown to be associated with the EGFR mutation status, especially exon 19 deletion (19Del) and exon 21 L858R mutation. Therefore, a meta-analysis was performed to assess the efficacy of icotinib in NSCLC patients harboring EGFR mutations (19Del or L858R) and wild type (19Del and L858R loci wild type). A total of 24 studies were included for comparing the objective response rate (ORR) in the EGFR wild type and mutant patients treated with icotinib. The ORRs of EGFR mutant patients (19Del or L858R) are better than those of EGFR wild type patients (OR = 7.03(5.09–9.71), P < 0.00001). The pooling ORs from 21 studies on the disease control rate (DCR) in EGFR mutant patients are better than those of EGFR wild type patients (OR = 10.54(5.72–19.43), P < 0.00001). Moreover, the ORRs of EGFR 19Del patients are better than those of EGFR L858R patients after pooling ORs of 12 studies (OR = 2.04(1.12–3.73), P = 0.019). However, there was no significant difference on DCRs of EGFR 19Del patients and those of EGFR L858R patients (OR = 2.01(0.94–4.32), P = 0.072). Our findings indicated that compared with EGFR wild type patients, EGFR mutant patients have better ORRs and DCRs after icotinib treatment; EGFR 19Del patients treated with icotinib have better ORRs than EGFR L858R patients. EGFR mutation status is a useful biomarker for the evaluation of icotinib efficacy in NSCLC patients. PMID:28430623

Clinical efficacy of icotinib in lung cancer patients with different EGFR mutation status: a meta-analysis.

PubMed

Qu, Jian; Wang, Ya-Nan; Xu, Ping; Xiang, Da-Xiong; Yang, Rui; Wei, Wei; Qu, Qiang

2017-05-16

Icotinib is a novel and the third listed epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which exerts a good anti-tumor efficacy on non-small cell lung cancer (NSCLC). The efficacy of EGFR-TKIs has been shown to be associated with the EGFR mutation status, especially exon 19 deletion (19Del) and exon 21 L858R mutation. Therefore, a meta-analysis was performed to assess the efficacy of icotinib in NSCLC patients harboring EGFR mutations (19Del or L858R) and wild type (19Del and L858R loci wild type). A total of 24 studies were included for comparing the objective response rate (ORR) in the EGFR wild type and mutant patients treated with icotinib. The ORRs of EGFR mutant patients (19Del or L858R) are better than those of EGFR wild type patients (OR = 7.03(5.09-9.71), P < 0.00001). The pooling ORs from 21 studies on the disease control rate (DCR) in EGFR mutant patients are better than those of EGFR wild type patients (OR = 10.54(5.72-19.43), P < 0.00001). Moreover, the ORRs of EGFR 19Del patients are better than those of EGFR L858R patients after pooling ORs of 12 studies (OR = 2.04(1.12-3.73), P = 0.019). However, there was no significant difference on DCRs of EGFR 19Del patients and those of EGFR L858R patients (OR = 2.01(0.94-4.32), P = 0.072). Our findings indicated that compared with EGFR wild type patients, EGFR mutant patients have better ORRs and DCRs after icotinib treatment; EGFR 19Del patients treated with icotinib have better ORRs than EGFR L858R patients. EGFR mutation status is a useful biomarker for the evaluation of icotinib efficacy in NSCLC patients.

An optimized low-power voltage controlled oscillator

NASA Astrophysics Data System (ADS)

Shah, Kriyang; Le, Hai Phuong; Singh, Jugdutt

2007-01-01

This paper presents an optimised low-power low-phase-noise Voltage Controlled Oscillator (VCO) for Bluetooth wireless applications. The system level design issues and tradeoffs related to Direct Conversion Receiver (DCR) and Low Intermediate Frequency (IF) architecture for Bluetooth are discussed. Subsequently, for a low IF architecture, the critical VCO performance parameters are derived from system specifications. The VCO presented in the paper is optimised by implementing a novel biasing circuit that employs two current mirrors, one at the top and the other one at the bottom of the cross-coupled complementary VCO, to give the exact replica of the current in both the arms of current mirror circuit. This approach, therefore, significantly reduces the system power consumption as well as improves the system performance. Results show that, the VCO consumes only 281μW of power at 2V supply. Its phase noise performance are -115dBc/Hz, -130dBc/Hz and -141dBc/Hz at the offset frequency of 1MHz, 3MHz and 5MHz respectively. Results indicate that 31% reduction in power consumption is achieved as compared to the traditional VCO design. These characteristics make the designed VCO a better candidate for Bluetooth wireless application where power consumption is the major issue.

Association between BIM deletion polymorphism and clinical outcome of EGFR-mutated NSCLC patient with EGFR-TKI therapy: A meta-analysis.

PubMed

Ma, Ji-Yong; Yan, Hai-Jun; Gu, Wei

2015-01-01

BIM deletion polymorphism was deemed to be associated with downregulation of BIM, resulting in a decreased apoptosis induced by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC). However, accumulating evidences concerning the association between BIM deletion polymorphism and efficacy of EGFR-TKI and survival in EGFR-mutation-driven NSCLC patient reported contradictory results. A meta-analysis was conducted by combing six original eligible studies including 871 NSCLC patients. Our study showed that BIM deletion polymorphism was significantly associated with poor response to EGFR-TKI therapy in mutant EGFRNSCLC patients (P(h) = 0.309, P(z) = 0.001, OR = 0.39, 95% confidence interval (CI) = 0.23-0.67). Disease control rate (DCR) in mutant EGFRNSCLC patient with treatment of EGFR-TKI was significantly decreased in patients with BIM deletion polymorphism comparing to patients harbored BIM wild variant (P(h) = 0.583, P(Z) = 0.007, OR = 0.46, 95%CI = 0.25-0.85). EGFR mutation-derived NSCLC patient carrying BIM deletion polymorphism had a shorter progression-free survival (PFS; P(h) < 0.001, P(z) < 0.001, hazard ratio (HR) = 1.37, 95%CI = 1.09-1.71) and overall survival (OS; P(h) = 0.90, P(z) = 0.003, HR = 1.25, 95%CI = 1.08-1.45), than those harbored BIM wild variant. These results suggested that BIM deletion polymorphism might be a cause that contributes to primary EGFR-TKI resistance, and it could be used as a genetic predictor for EGFR-TKI outcome and an independent prognostic factor of EGFR mutation-driven NSCLC patient.

[Involved-field three-dimensional conformal radiation treatment for stage III non-small-cell lung].

PubMed

Yu, Jin-Ming; Sun, Xin-Dong; Li, Ming-Huan; Zhang, Jian-Dong; Yao, Chun-Ping; Liu, Sen; Zhang, Zhen

2006-07-01

To investigate the feasibility of involved-field irradiation (IFI ) for stage III non-small cell lung cancer (NSCLC). From September 1997 to November 2001, 200 stage-III NSCLC patients were randomly divided into two groups-- IFI and ENI (elective node irradiation). The IFI group was irradiated by 3DCR to a dose of 68-74 Gy/34-37f/7-9 w including the primary tumor and the lymph nodes of > or = 10 mm in short axis. The ENI group was irradiated to a dose of 60-64 Gy/30-32f/6-7.5 w including the primary tumor, ipsilateral hilum, subcarinal and mediastinal lymph nodes, even the supraclavicular area when the lymph nodes of superior mediastinum were involved. The overall response (CR + PR) rates were 90.0% in IFI group and 79.0% in ENI group. Radiation pneumonitis developed in 29.0% of the patients in ENI group and 17.0% in IFI group (P = 0.04). The 1-year primary tumor failure rate in IFI group (13.0%) was lower than that (23.0%) in ENI group. The 1-year involved nodal failure rate was 20.0% in ENI group and 10.0% in IFI group (P = 0.048). The 1-year elective node failure rate was 16.0% in ENI group versus 21.0% in IFI group (P = 0.39). The 1-, 2-and 3-year overall survival rate was 67.2% , 38.7% , 27.3% , respectively, in IFI group; versus 59.7% , 25.6% , 19.2% in ENI group, with a difference significant in the 2-year overall survival rate between IFI and ENI group (P = 0.048). Involved-field 3D-CRT for stage-III non-small cell lung cancer is well tolerated. It does not increase the rate of lymph node failure in the elective node irradiation field, and may improve the survival due to dose escalation.

The examination of the spread of the leachates coming out of a solid waste disposal area on the ground with geophysical and geochemical methods (Sivas, Turkey)

NASA Astrophysics Data System (ADS)

Özel, Sevda; Yılmaz, Ali; Emin Candansayar, M.

2017-03-01

This study has been conducted in the irregular solid waste disposal area in the city of Sivas. The pollution spread formed by the leachates coming out of the disposal area has been examined with geophysical and geochemical works in this study. For this reason, the spread of the leachate pollution expanding in different geological units at both sides of a creek on the ground has been examined. For this purpose, the pollution spread has been examined with the methods of Direct Current Resistivity (DCR) and Electromagnetic Conductivity (EMC) and soil analyses. In the DCR method, 2D inversion of each sounding-profile datum measured alongside the lines parallel to each other and 3D inversion of the data measured in all the lines have been used in the interpretations. Apparent conductivity map has been attained from EMC measurements. The results of heavy metal analyses in the soil samples taken alongside the Haçin Creek have been assessed with the Spider diagram method. It has been determined that the flow of the leachate from geophysical models is in a SE direction and towards Kızılırmak and it continues vertically deeper than 4 m. In addition, it has been understood that the flow direction of the leachate is inspected by the geological structures. It has been understood from the geochemical results that the pollution in the soil stems from the leachate. In this way, it has been observed that the underground and surface water resources in the territory are under the threat of the pollution occurring due to the leachate.

Evaluation of preventive and therapeutic activity of novel non-steroidal anti-inflammatory drug, CG100649, in colon cancer: Increased expression of TNF-related apoptosis-inducing ligand receptors enhance the apoptotic response to combination treatment with TRAIL.

PubMed

Woo, Jong Kyu; Kang, Ju-Hee; Jang, Yeong-Su; Ro, Seonggu; Cho, Joong Myung; Kim, Hwan-Mook; Lee, Sang-Jin; Oh, Seung Hyun

2015-04-01

Non-steroidal anti-inflammatory drugs (NSAIDs) have been suggested as the potential new class of preventive or therapeutic antitumor agents. The aim of the present study was to evaluate the antitumor activity of the novel NSAID, CG100649. CG100649 is a novel NSAID dual inhibitor for COX-2 and carbonic anhydrase (CA)-I/-II. In the present study, we investigated the alternative mechanism by which CG100649 mediated suppression of the colon cancer growth and development. The anchorage‑dependent and -independent clonogenic assay showed that CG100649 inhibited the clonogenicity of human colon cancer cells. The flow cytometric analysis showed that CG100649 induced the G2/M cell cycle arrest in colon cancer cells. Animal studies showed that CG100649 inhibited the tumor growth in colon cancer xenograft in nude mice. Furthermore, quantitative PCR and FACS analysis demonstrated that CG100649 upregulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors (DR4 and DR5) but decreased the expression of decoy receptors (DcR1 and DcR2) in colon cancer cells. The results showed that CG100649 treatment sensitized TRAIL‑mediated growth suppression and apoptotic cell death. The combination treatment resulted in significant repression of the intestinal polyp formation in APCmin/+ mice. Our data clearly demonstrated that CG100649 contains preventive and therapeutic activity for colon cancer. The present study may be useful for identification of the potential benefit of the NSAID CG100649, for the achievement of a better treatment response in colon cancer.

Functional roles of three cutin biosynthetic acyltransferases in cytokinin responses and skotomorphogenesis.

PubMed

Wu, Lei; Zhou, Zhao-Yang; Zhang, Chun-Guang; Chai, Juan; Zhou, Qin; Wang, Li; Hirnerová, Eva; Mrvková, Michaela; Novák, Ondřej; Guo, Guang-Qin

2015-01-01

Cytokinins (CKs) regulate plant development and growth via a two-component signaling pathway. By forward genetic screening, we isolated an Arabidopsis mutant named grow fast on cytokinins 1 (gfc1), whose seedlings grew larger aerial parts on MS medium with CK. gfc1 is allelic to a previously reported cutin mutant defective in cuticular ridges (dcr). GFC1/DCR encodes a soluble BAHD acyltransferase (a name based on the first four enzymes characterized in this family: Benzylalcohol O-acetyltransferase, Anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase and Deacetylvindoline 4-O-acetyltransferase) with diacylglycerol acyltransferase (DGAT) activity in vitro and is necessary for normal cuticle formation on epidermis in vivo. Here we show that gfc1 was a CK-insensitive mutant, as revealed by its low regeneration frequency in vitro and resistance to CK in adventitious root formation and dark-grown hypocotyl inhibition assays. In addition, gfc1 had de-etiolated phenotypes in darkness and was therefore defective in skotomorphogenesis. The background expression levels of most type-A Arabidopsis Response Regulator (ARR) genes were higher in the gfc1 mutant. The gfc1-associated phenotypes were also observed in the cutin-deficient glycerol-3-phosphate acyltransferase 4/8 (gpat4/8) double mutant [defective in glycerol-3-phosphate (G3P) acyltransferase enzymes GPAT4 and GPAT8, which redundantly catalyze the acylation of G3P by hydroxyl fatty acid (OH-FA)], but not in the cutin-deficient mutant cytochrome p450, family 86, subfamily A, polypeptide 2/aberrant induction of type three 1 (cyp86A2/att1), which affects the biosynthesis of some OH-FAs. Our results indicate that some acyltransferases associated with cutin formation are involved in CK responses and skotomorphogenesis in Arabidopsis.

Functional Roles of Three Cutin Biosynthetic Acyltransferases in Cytokinin Responses and Skotomorphogenesis

PubMed Central

Chai, Juan; Zhou, Qin; Wang, Li; Hirnerová, Eva; Mrvková, Michaela; Novák, Ondřej; Guo, Guang-Qin

2015-01-01

Cytokinins (CKs) regulate plant development and growth via a two-component signaling pathway. By forward genetic screening, we isolated an Arabidopsis mutant named grow fast on cytokinins 1 (gfc1), whose seedlings grew larger aerial parts on MS medium with CK. gfc1 is allelic to a previously reported cutin mutant defective in cuticular ridges (dcr). GFC1/DCR encodes a soluble BAHD acyltransferase (a name based on the first four enzymes characterized in this family: Benzylalcohol O-acetyltransferase, Anthocyanin O-hydroxycinnamoyltransferase, anthranilate N-hydroxycinnamoyl/benzoyltransferase and Deacetylvindoline 4-O-acetyltransferase) with diacylglycerol acyltransferase (DGAT) activity in vitro and is necessary for normal cuticle formation on epidermis in vivo. Here we show that gfc1 was a CK-insensitive mutant, as revealed by its low regeneration frequency in vitro and resistance to CK in adventitious root formation and dark-grown hypocotyl inhibition assays. In addition, gfc1 had de-etiolated phenotypes in darkness and was therefore defective in skotomorphogenesis. The background expression levels of most type-A Arabidopsis Response Regulator (ARR) genes were higher in the gfc1 mutant. The gfc1-associated phenotypes were also observed in the cutin-deficient glycerol-3-phosphate acyltransferase 4/8 (gpat4/8) double mutant [defective in glycerol-3-phosphate (G3P) acyltransferase enzymes GPAT4 and GPAT8, which redundantly catalyze the acylation of G3P by hydroxyl fatty acid (OH-FA)], but not in the cutin-deficient mutant cytochrome p450, family 86, subfamily A, polypeptide 2/aberrant induction of type three 1 (cyp86A2/att1), which affects the biosynthesis of some OH-FAs. Our results indicate that some acyltransferases associated with cutin formation are involved in CK responses and skotomorphogenesis in Arabidopsis. PMID:25803274

Novel Visual Sensor Coverage and Deployment in Time Aware PTZ Wireless Visual Sensor Networks.

PubMed

Yap, Florence G H; Yen, Hong-Hsu

2016-12-30

In this paper, we consider the visual sensor deployment algorithm in Pan-Tilt-Zoom (PTZ) Wireless Visual Sensor Networks (WVSNs). With PTZ capability, a sensor's visual coverage can be extended to reduce the number of visual sensors that need to be deployed. The coverage zone of a visual sensor in PTZ WVSN is composed of two regions, a Direct Coverage Region (DCR) and a PTZ Coverage Region (PTZCR). In the PTZCR, a visual sensor needs a mechanical pan-tilt-zoom operation to cover an object. This mechanical operation can take seconds, so the sensor might not be able to adjust the camera in time to capture the visual data. In this paper, for the first time, we study this PTZ time-aware PTZ WVSN deployment problem. We formulate this PTZ time-aware PTZ WVSN deployment problem as an optimization problem where the objective is to minimize the total visual sensor deployment cost so that each area is either covered in the DCR or in the PTZCR while considering the PTZ time constraint. The proposed Time Aware Coverage Zone (TACZ) model successfully captures the PTZ visual sensor coverage in terms of camera focal range, angle span zone coverage and camera PTZ time. Then a novel heuristic, called Time Aware Deployment with PTZ camera (TADPTZ) algorithm, is proposed to solve the problem. From our computational experiments, we found out that TACZ model outperforms the existing M coverage model under all network scenarios. In addition, as compared to the optimal solutions, the TACZ model is scalable and adaptable to the different PTZ time requirements when deploying large PTZ WVSNs.

Novel Visual Sensor Coverage and Deployment in Time Aware PTZ Wireless Visual Sensor Networks

PubMed Central

Yap, Florence G. H.; Yen, Hong-Hsu

2016-01-01

In this paper, we consider the visual sensor deployment algorithm in Pan-Tilt-Zoom (PTZ) Wireless Visual Sensor Networks (WVSNs). With PTZ capability, a sensor’s visual coverage can be extended to reduce the number of visual sensors that need to be deployed. The coverage zone of a visual sensor in PTZ WVSN is composed of two regions, a Direct Coverage Region (DCR) and a PTZ Coverage Region (PTZCR). In the PTZCR, a visual sensor needs a mechanical pan-tilt-zoom operation to cover an object. This mechanical operation can take seconds, so the sensor might not be able to adjust the camera in time to capture the visual data. In this paper, for the first time, we study this PTZ time-aware PTZ WVSN deployment problem. We formulate this PTZ time-aware PTZ WVSN deployment problem as an optimization problem where the objective is to minimize the total visual sensor deployment cost so that each area is either covered in the DCR or in the PTZCR while considering the PTZ time constraint. The proposed Time Aware Coverage Zone (TACZ) model successfully captures the PTZ visual sensor coverage in terms of camera focal range, angle span zone coverage and camera PTZ time. Then a novel heuristic, called Time Aware Deployment with PTZ camera (TADPTZ) algorithm, is proposed to solve the problem. From our computational experiments, we found out that TACZ model outperforms the existing M coverage model under all network scenarios. In addition, as compared to the optimal solutions, the TACZ model is scalable and adaptable to the different PTZ time requirements when deploying large PTZ WVSNs. PMID:28042829

Videoreflective dacryomeniscometry in normal adults and in patients with functional or primary acquired nasolacrimal duct obstruction.

PubMed

Francis, Ian C; Chan, Derek G; Papalkar, Daya; Papas, Eric B; Stapleton, Fiona

2005-03-01

Videoreflective dacryomeniscometry (VRD) for evaluation of marginal tear film has not been performed in patients with watery eye or in a controlled study. We used VRD to evaluate the height of the central marginal lower lid tear film in normal adults and compared it with two watery-eye groups and a postoperative dacryocystorhinostomy (DCR) group. Case-controlled interventional case series. We evaluated with VRD 20 subjects with normal lacrimal drainage function, 21 patients with primary acquired nasolacrimal duct obstruction (PANDO), 28 patients with functional nasolacrimal duct obstruction (FNLDO), and a postoperative group of 14 patients derived from the previous two pathologic groups. Comparison between the four groups was performed to determine statistically significant differences between tear film height. PANDO and FNLDO groups were shown to have significantly greater median tear meniscus heights ([TMH] PANDO: 620 microm, interquartile range [IQR] 453 microm; FNLDO: 731 microm, IQR 529 microm) than normal subjects (296 microm, IQR 214 microm; P < .001) and postoperative PANDO patients (265 microm, IQR 159 microm). There was no significant difference in TMH between PANDO and FNLDO groups preoperatively (P = .275). There was a reduction in median TMH postoperatively of 355 microm (P = .008) in PANDO and 360 microm (P = .068) in FNLDO. PANDO and FNLDO patients have similar preoperative TMH. In both these groups, TMH is significantly greater than in normal control subjects. Lacrimal drainage surgery substantially reduces TMH as measured using VRD in PANDO.

A Pathway Based Classification Method for Analyzing Gene Expression for Alzheimer's Disease Diagnosis.

PubMed

Voyle, Nicola; Keohane, Aoife; Newhouse, Stephen; Lunnon, Katie; Johnston, Caroline; Soininen, Hilkka; Kloszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Hodges, Angela; Kiddle, Steven; Dobson, Richard Jb

2016-01-01

Recent studies indicate that gene expression levels in blood may be able to differentiate subjects with Alzheimer's disease (AD) from normal elderly controls and mild cognitively impaired (MCI) subjects. However, there is limited replicability at the single marker level. A pathway-based interpretation of gene expression may prove more robust. This study aimed to investigate whether a case/control classification model built on pathway level data was more robust than a gene level model and may consequently perform better in test data. The study used two batches of gene expression data from the AddNeuroMed (ANM) and Dementia Case Registry (DCR) cohorts. Our study used Illumina Human HT-12 Expression BeadChips to collect gene expression from blood samples. Random forest modeling with recursive feature elimination was used to predict case/control status. Age and APOE ɛ4 status were used as covariates for all analysis. Gene and pathway level models performed similarly to each other and to a model based on demographic information only. Any potential increase in concordance from the novel pathway level approach used here has not lead to a greater predictive ability in these datasets. However, we have only tested one method for creating pathway level scores. Further, we have been able to benchmark pathways against genes in datasets that had been extensively harmonized. Further work should focus on the use of alternative methods for creating pathway level scores, in particular those that incorporate pathway topology, and the use of an endophenotype based approach.

Proceedings of the Annual Chemical Defense Bioscience Review (4th) Held at Aberdeen Proving Ground, Maryland on 30 May-1 June 1984

DTIC Science & Technology

1984-06-01

solution of NaIO. The resulting mixture was again separated by HPLC as shown in Figure 8. The new peaks which appear at 53 end 56 min are probably the...separated by HPLC as shown in Figure 10. This Figure shows the locations of the unmodified deoxynucleosides, deoxycytidine (dCR), deoxyguanosine (dGR...was labeled with 3H-DFP as -dTe-scried in the t.ext. 333 HPLC SIZE EXCLUSION CHROMATOGRAPHY PURIFIED AChE 25_ 0 20 -- LU Cco z< C 15 UI E_0 W C&’- Z CU

Assessing Need for Medication-Assisted Treatment for Opiate-Dependent Prison Inmates

PubMed Central

Albizu-García, Carmen E.; Caraballo, José Noel; Caraballo-Correa, Glorimar; Hernández-Viver, Adriana; Román-Badenas, Luis

2012-01-01

Individuals with a history of heroin dependence are overrepresented in American correctional facilities and 75% of inmates with a drug use disorder do not receive treatment during incarceration or after release. Medication-assisted treatment (MAT) with opiate agonists, such as methadone or buprenorphine, constitute standard of care; to guide planning for an expansion of drug treatment services in correctional facilities, a needs assessment was conducted at the Department of Correction and Rehabilitation (DCR) of Puerto Rico (PR). We report on the research process, the findings that informed our recommendations for the PCR to expand MAT for eligible inmates, and lessons learned. PMID:22263714

A Randomized Control Trial of Preoperative Oral Antibiotics as Adjunct Therapy to Systemic Antibiotics for Preventing Surgical Site Infection in Clean Contaminated, Contaminated, and Dirty Type of Colorectal Surgeries.

PubMed

Anjum, Nadeem; Ren, Jianan; Wang, Gefei; Li, Guanwei; Wu, Xiuwen; Dong, Hu; Wu, Qin; Li, Jieshou

2017-12-01

Preoperative bowel preparation with or without oral antibiotics is controversial in terms of postoperative surgical site infections. This study aimed to evaluate the efficacy of oral antibiotics as adjunct therapy to systemic antibiotics with mechanical bowel preparation for preventing surgical site infections in clean contaminated, contaminated, and dirty colorectal procedures. This was a single-center, prospective randomized study. This study was conducted at the General Surgery Department at Jinling Hospital, Nanjing University, China, from July 15, 2014 to January 20, 2016. Patients aged ≥18 years scheduled for abdominal surgery with clean-contaminated, contaminated, and dirty wounds were selected. Patients were randomly assigned to receive preoperative mechanical bowel preparation or mechanical bowel preparation with oral antibiotics. The primary outcome was the rate of surgical site infections. The secondary outcomes were extra-abdominal complications, duration of postoperative ileus, and readmission rate. Ninety-five patients were allocated to each group. Eight and 26 surgical site infections (8.42% vs 27.3 %, p = 0.004) occurred in the mechanical bowel preparation with oral antibiotics and mechanical bowel preparation groups. Thirteen extra-abdominal complications were reported: 6 in the mechanical bowel preparation with oral antibiotics group and 7 in the mechanical bowel preparation group (6.3% vs 7.3%, p = 0.77). Postoperative ileus duration did not differ between groups (p = 0.23). There were 4 readmissions in the mechanical bowel preparation group and none in the mechanical bowel preparation with oral antibiotics group (p = 0.04). On multivariable analysis, blood loss ≥500 mL (OR, 5.1; 95% CI, 1.27-20.4; p = 0.02), ASA score ≥3 (OR, 3.9; 95% CI, 1.2-12.5; p = 0.01), contaminated types (OR, 3.6; 95% CI, 1.5-8.6; p = 0.01), and administration of preoperative oral antibiotics (OR, 0.20; 95% CI, 0.06-0.60; p = 0.005) independently affected the incidence of surgical site infections. This was a single-center study. Preoperative oral antibiotics, as adjunct therapy to systemic antibiotics and mechanical bowel preparation, significantly reduced surgical site infections and minimized the readmission rates in clean contaminated, contaminated, and dirty types of colorectal surgery. See Video Abstract at http://links.lww.com/DCR/A437.

RNAi mediates post-transcriptional repression of gene expression in fission yeast Schizosaccharomyces pombe

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

Smialowska, Agata, E-mail: smialowskaa@gmail.com; School of Life Sciences, Södertörn Högskola, Huddinge 141-89; Djupedal, Ingela

Highlights: • Protein coding genes accumulate anti-sense sRNAs in fission yeast S. pombe. • RNAi represses protein-coding genes in S. pombe. • RNAi-mediated gene repression is post-transcriptional. - Abstract: RNA interference (RNAi) is a gene silencing mechanism conserved from fungi to mammals. Small interfering RNAs are products and mediators of the RNAi pathway and act as specificity factors in recruiting effector complexes. The Schizosaccharomyces pombe genome encodes one of each of the core RNAi proteins, Dicer, Argonaute and RNA-dependent RNA polymerase (dcr1, ago1, rdp1). Even though the function of RNAi in heterochromatin assembly in S. pombe is established, its rolemore » in controlling gene expression is elusive. Here, we report the identification of small RNAs mapped anti-sense to protein coding genes in fission yeast. We demonstrate that these genes are up-regulated at the protein level in RNAi mutants, while their mRNA levels are not significantly changed. We show that the repression by RNAi is not a result of heterochromatin formation. Thus, we conclude that RNAi is involved in post-transcriptional gene silencing in S. pombe.« less

Birth order and post-traumatic stress disorder.

PubMed

Green, Ben; Griffiths, Emily C

2014-01-01

To compare the birth order of patients with post-traumatic stress disorder (PTSD) and adjustment disorder (AD) with population norms. 83 PTSD patients and 104 AD control patients from a psychiatric trauma clinic were diagnosed according to DCR-10 guidelines. A family history was taken as to number of siblings, and their birth order. We compared the distribution of birth order for each patient group against birth order distributions expected by chance for the same years of birth using UK population-level birth order from the Office for National Statistics. Psychiatric patients with PTSD were more likely to be from a large family, specifically to be the fifth child or later (OR 4.78, p < .001) and less likely to be the eldest child (OR .65, p < .001) than the general population in England and Wales. There were no differences for birth order between AD patients and the general population. People with PTSD are more likely to be the youngest children from large families than expected from a random sample of people born in the same years. This association with birth order was not found for another psychiatric diagnosis AD from the same clinic. We discuss possible psychosocial and biological causes, and implications for further research.

Endoscopic placement of Jones lacrimal tubes with the assistance of holmium YAG laser.

PubMed

Boboridis, Kostas G; Downes, Richard N

2005-06-01

The aim of this paper is to highlight the use of the Holmium YAG laser in the endoscopic placement of Lester Jones tubes in patients with a blocked canaliculus or failed lacrimal pump function. Sixteen cases with a non-functional canaliculus were included over a one-year period. Following caruncle excision, a 19 G needle is inserted through the medial canthal tissues into the nasal space. Nasal endoscopy confirms the accurate positioning in relation to the nasal anatomy. With the Holmium YAG laser, a tissue channel is fashioned around the guide needle through the structures of the lateral nasal wall to facilitate an accurate and secure placement of the Jones tube. The endoscopic, laser-assisted placement reduces the operating time to less than 20 minutes, minimizes tissue trauma and does not require the initial surgical steps of an open DCR procedure. There were 14 cases (87.5%) with securely retained tubes and two cases (12.5%) that required tube replacement. The advantage of the procedure is especially great in revision surgery where the ostium is opened through scar tissue. Nasal endoscopy with the assistance of the Holmium YAG laser offers simplicity and precision in the placement of Jones tubes. It minimizes tissue trauma and increases the surgical success rate.

Transection of Nasolacrimal Duct in Endoscopic Medial Maxillectomy: Implication on Epiphora.

PubMed

Imre, Abdulkadir; Imre, Seher Saritepe; Pinar, Ercan; Ozkul, Yilmaz; Songu, Murat; Ece, Ahmet Ata; Aladag, Ibrahim

2015-10-01

Management of the nasolacrimal system is usually recommended during medial maxillectomy via external approach because of reported higher rates of postoperative epiphora. Association of the endoscopic medial maxillectomy (EMM) with epiphora, however, is not clearly stated. In this study, we attempted to evaluate whether patients develop epiphora after simple transection of the nasolacrimal duct during EMM. Medical records of 26 patients who underwent endoscopic tumor resection for inverted papilloma (IP) were retrospectively reviewed. Patients who underwent EMM with nasolacrimal canal transection were included and recalled for lacrimal system evaluation. Twelve patients were eligible for inclusion and fluorescein dye disappearance test (FDDT) was performed for each patient. Patient demographics, tumor data, surgical procedures, and follow-up time were recorded. Of the 12 patients included in the study, 6 underwent canine fossa transantral approach concurrently with EMM. The mean duration of follow-up was 21.1 months (range, 6-84 months). Eight patients were graded as 0, whereas 4 patients were graded as 1 according to FDDT. All test results were interpreted as negative for epiphora. All patients were completely symptom free of epiphora. Epiphora after EMM with nasolacrimal canal transection among patients with sinonasal tumors appears to be uncommon. Therefore, prophylactic concurrent management of nasolacrimal system including stenting, dacryocystorhinostomy (DCR), or postoperative lacrimal lavage are not mandatory for all patients.

Reliable InP-based Geiger-mode avalanche photodiode arrays

NASA Astrophysics Data System (ADS)

Smith, Gary M.; McIntosh, K. Alex; Donnelly, Joseph P.; Funk, Joseph E.; Mahoney, Leonard J.; Verghese, Simon

2009-05-01

Arrays as large as 256 x 64 of single-photon counting avalanche photodiodes have been developed for defense applications in free-space communication and laser radar. Focal plane arrays (FPAs) sensitive to both 1.06 and 1.55 μm wavelength have been fabricated for these applications. At 240 K and 4 V overbias, the dark count rate (DCR) of 15 μm diameter devices is typically 250 Hz for 1.06 μm sensitive APDs and 1 kHz for 1.55 μm APDs. Photon detection efficiencies (PDE) at 4 V overbias are about 45% for both types of APDs. Accounting for microlens losses, the full FPA has a PDE of 30%. The reset time needed for a pixel to avoid afterpulsing at 240 K is about 3-4 μsec. These devices have been used by system groups at Lincoln Laboratory and other defense contractors for building operational systems. For these fielded systems the device reliability is a strong concern. Individual APDs as well as full arrays have been run for over 1000 hrs of accelerated testing to verify their stability. The reliability of these GM-APDs is shown to be under 10 FITs at operating temperatures of 250 K, which also corresponds to an MTTF of 17,100 yrs.

Temperature-Controlled Delivery of Radiofrequency Energy in Fecal Incontinence: A Randomized Sham-Controlled Clinical Trial.

PubMed

Visscher, Arjan P; Lam, Tze J; Meurs-Szojda, Maria M; Felt-Bersma, Richelle J F

2017-08-01

Controlled delivery of radiofrequency energy has been suggested as treatment for fecal incontinence. The aim of this study was to determine whether the clinical response to the radiofrequency energy procedure is superior to sham in patients with fecal incontinence. This was a randomized sham-controlled clinical trial from 2008 to 2015. This study was conducted in an outpatient clinic. Forty patients with fecal incontinence in whom maximal conservative management had failed were randomly assigned to receiving either radiofrequency energy or sham procedure. Fecal incontinence was measured using the Vaizey incontinence score (range, 0-24). The impact of fecal incontinence on quality of life was measured by using the fecal incontinence quality-of-life score (range, 1-4). Measurements were performed at baseline and at 6 months. Anorectal function was evaluated using anal manometry and anorectal endosonography at baseline and at 3 months. At baseline, Vaizey incontinence score was 16.8 (SD 2.9). At t = 6 months, the radiofrequency energy group improved by 2.5 points on the Vaizey incontinence score compared with the sham group (13.2 (SD 3.1), 15.6 (SD 3.3), p = 0.02). The fecal incontinence quality-of-life score at t = 6 months was not statistically different. Anorectal function did not show any alteration. Patients with severe fecal incontinence were included in the study, thus making it difficult to generalize the results. Both radiofrequency energy and sham procedure improved the fecal incontinence score, the radiofrequency energy procedure more than sham. Although statistically significant, the clinical impact for most of the patients was negligible. Therefore, the radiofrequency energy procedure should not be recommended for patients with fecal incontinence until patient-related factors associated with treatment success are known. See Video Abstract at http://links.lww.com/DCR/A373.

Clinical Outcomes of Self-Expandable Metal Stents for Malignant Rectal Obstruction.

PubMed

Lee, Hyun Jung; Hong, Sung Pil; Cheon, Jae Hee; Kim, Tae Il; Kim, Won Ho; Park, Soo Jung

2018-01-01

Self-expandable metal stents are widely used to treat malignant colorectal obstruction. However, data on clinical outcomes of stent placement for rectal obstruction specifically are lacking. We aimed to investigate the clinical outcomes of self-expandable metal stents in malignant rectal obstruction in comparison with those in left colonic obstruction and to identify factors associated with clinical failure and complication. This was a retrospective study. The study was conducted at a tertiary care center. Between January 2005 and December 2013, medical charts of patients who underwent stent placement for malignant rectal or left colonic obstruction were reviewed retrospectively. Study intervention included self-expandable metal stent placement. Technical success, clinical success, and complications were measured. Technical success rates for the 2 study groups (rectum vs left colon, 93.5% vs 93.1%; p = 0.86) did not differ significantly; however, the clinical success rate was lower in patients with rectal obstruction (85.4% vs 92.1%; p = 0.02). In addition, the complication rate was higher in patients with rectal obstruction (37.4% vs 25.1%; p = 0.01). Patients with rectal obstruction showed higher rates of obstruction because of extracolonic malignancy (33.8% vs 15.8%; p < 0.001) and stent use for palliation (78.6% vs 56.3%; p < 0.001). Multivariate analysis indicated obstruction attributed to extracolonic malignancy and covered stent usage to be independent risk factors for clinical failure. Factors predictive of complications in the palliative group were total obstruction, obstruction because of extracolonic malignancy, and covered stent usage. This was a retrospective, single-center study. The efficacy and safety of stent placement for malignant rectal obstruction were comparable with those for left colonic obstruction. However, obstruction attributed to extracolonic malignancy, use of covered stents, and total obstruction negatively impacted clinical outcomes of self-expandable metal stent placement and must be considered by endoscopists. See Video Abstract at http://links.lww.com/DCR/A417.

Effect of mitomycin-C on contraction and migration of human nasal mucosa fibroblasts: implications in dacryocystorhinostomy.

PubMed

Kumar, Vinay; Ali, Mohammad Javed; Ramachandran, Charanya

2015-09-01

To determine the effect of mitomycin-C (MMC) on the contraction and migration of human nasal mucosal fibroblasts (HNMFs) in vitro in order to identify the least concentration of MMC required to prevent cicatrix development following dacryocystorhinostomy (DCR). Primary cultures of HNMFs were established from nasal mucosal tissues of patients undergoing DCR. Myofibroblast transformation of HNMFs was induced using transforming growth factor-β (TGF-β1) and confirmed by immunostaining for α-smooth muscle actin (α-SMA). Collagen gel contraction assay was employed to study contraction in the presence or absence of TGF-β1 (5 and 10 ng/mL) and MMC (0.2 and 0.4 mg/mL). Scratch wound assay was employed to determine the influence of MMC treatment on cell migration. Quantification of gel contraction and wound closure was done using Image J software. α-SMA expression increased with TGF-β1 treatment in a time- and dose-dependent manner indicating myofibroblast transformation of HNMFs. MMC inhibited TGF-β1- induced collagen gel contraction in a dose-dependent manner (0.4 mg/mL>0.2 mg/mL). Further, there was a decrease in the migration of MMC-treated HNMFs, resulting in delayed wound closure that corroborated with the loss of actin stress fibres. MMC successfully inhibited TGF-β1-induced myofibroblast transformation, collagen gel contraction and significantly reduced the migration of HNMFs to cover the wound even at a low concentration of 0.2 mg/mL. This study provides evidence that low concentration and short duration of MMC treatment is efficient in reducing increased contraction and migration of HMNFs in response to injury. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Investigation of the Comparative Effects of Red and Infrared Laser Therapy on Skeletal Muscle Repair in Diabetic Rats.

PubMed

Assis, Lívia; Manis, Camila; Fernandes, Kelly Rossetti; Cabral, Daniel; Magri, Angela; Veronez, Suellen; Renno, Ana Claudia Muniz

2016-07-01

The aim of this study was to evaluate the in vivo response of 2 different laser wavelengths (red and infrared) on skeletal muscle repair process in diabetic rats. Forty Wistar rats were randomly divided into 4 experimental groups: basal control-nondiabetic and muscle-injured animals without treatment (BC); diabetic muscle-injured without treatment (DC); diabetic muscle-injured, treated with red laser (DCR) and infrared laser (DCIR). The injured region was irradiated daily for 7 consecutive days, starting immediately after the injury using a red (660 nm) and an infrared (808 nm) laser. The histological results demonstrated in both treated groups (red and infrared wavelengths) a modulation of the inflammatory process and a better tissue organization located in the site of the injury. However, only infrared light significantly reduced the injured area and increased MyoD and myogenin protein expression. Moreover, both red and infrared light increased the expression of the proangiogenic vascular endothelial growth factor and reduced the cyclooxygenase 2 protein expression. These results suggest that low-level laser therapy was efficient in promoting skeletal muscle repair in diabetic rats. However, the effect of infrared wavelength was more pronounced by reducing the area of the injury and modulating the expression proteins related to the repair.

SiPMs characterization and selection for the DUNE far detector photon detection system

NASA Astrophysics Data System (ADS)

Sun, Y.; Maricic, J.

2016-01-01

The Deep Underground Neutrino Experiment (DUNE) together with the Long Baseline Neutrino Facility (LBNF) hosted at the Fermilab will provide a unique, world-leading program for the exploration of key questions at the forefront of neutrino physics and astrophysics. CP violation in neutrino flavor mixing is one of its most important potential discoveries. Additionally, the experiment will determine the neutrino mass hierarchy and precisely measure the neutrino mixing parameters which may potentially reveal new fundamental symmetries of nature. Moreover, the DUNE is also designed for the observation of nucleon decay and supernova burst neutrinos. The photon detection (PD) system in the DUNE far detector provides trigger for cosmic backgrounds, enhances supernova burst trigger efficiency and improves the energy resolution of the detector. The DUNE adopts the technology of liquid argon time projection chamber (LArTPC) that requires the PD sensors, silicon photomultipliers (SiPM), to be carefully chosen to not only work properly in LAr temperature, but also meet certain specifications for the life of the experiment. A comprehensive testing of SiPMs in cryostat is necessary since the datasheet provided by the manufactures in the market does not cover this temperature regime. This paper gives the detailed characterization results of SenSL C-Series 60035 SiPMs, including gain, dark count rate (DCR), cross-talk and after-pulse rate. Characteristic studies on SiPMs from other vendors are also discussed in order to avoid any potential problems associated with using a single source. Moreover, the results of the ongoing mechanical durability tests are shown for the current candidate, SenSL B/C-Series 60035 SiPMs.

A Randomized Trial Comparing Stapled Rectal Mucosectomy Versus Open and Semiclosed Hemorrhoidectomy.

PubMed

Ripetti, Valter; La Vaccara, Vincenzo; Greco, Santi; Arullani, Augusto

2015-11-01

Different results have been reported concerning the postoperative outcomes of different surgical approaches for hemorrhoids. We aimed to determine the postoperative outcome following 3 main surgical techniques. A prospective, randomized trial was designed with 180 patients in 3 arms of 60 patients each. The study was conducted from April 1999 to January 2007 at the University Hospital "Campus Bio-Medico di Roma." All of the patients who were referred for hemorrhoid surgery were enrolled according to inclusion and exclusion criteria (ISRCTN12040297). Treatments according to the open, semiclosed, and stapled techniques were compared. Sample size was calculated to determine a difference in terms of the intensity of postoperative pain at the first week and the days required for return to work activity. After 1 week, patients who underwent semiclosed hemorrhoidectomy reported significantly less pain (p < 0.01) and a significant decrease in analgesic intake from the third postoperative day (p < 0.01) than after the other 2 techniques. The patients resumed work ≈11 days after semiclosed and stapled techniques (11.8 and 11.6 days), which was earlier compared with 21.3 days in the open group (p < 0.05). The high number of patients excluded might be considered a limitation of the study, but our selection criteria including patients living within 50 km of the hospital allowed for a low rate (9.4%) of patients lost to follow-up. This study found an earlier resumption of work and less pain in patients who underwent the stapled and semiclosed procedures rather than open, which was associated with more complications, particularly because of a higher rate of stenosis (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A196).

Timed‑flat infusion of 5‑fluorouracil with docetaxel and oxaliplatin as first‑line treatment of gastroesophageal adenocarcinoma: A single institution experience with the FD/FOx regimen.

PubMed

Cortellini, Alessio; Cannita, Katia; Parisi, Alessandro; Venditti, Olga; Lanfiuti Baldi, Paola; De Berardis, Berardo; Vicentini, Roberto; Vicentini, Vincenzo; Verna, Lucilla; Porzio, Giampiero; Ficorella, Corrado

2018-06-06

To date, there is no consensus regarding first‑line chemotherapy for patients with HER2‑negative, locally advanced/metastatic gastric cancer (a/m GC). In the present study we reported a retrospective case‑series of patients treated with a weekly regimen containing timed‑flat infusion of 5‑fluorouracil (TFI/5‑FU), docetaxel and oxaliplatin. From June 2007 to July 2017, 32 consecutive a/m GC patients were treated with first‑line standard (st) or modulated (mod) 'FD/FOx' regimen: Weekly 12 h (from 10.00 p.m. to 10.00 a.m.) TFI/5‑FU for two consecutive nights at 900 mg/m2/day, associated to weekly alternating docetaxel, 50 mg/m2 and oxaliplatin, 80 mg/m2. The median age of the patients was 60 years and their Eastern Cooperative Oncology Group‑performance status (ECOG‑PS) was as follows: i) ECOG‑PS 0/1, (n=28, 87.5%); and ii) ECOG‑PS 2 (n=4, 12.5%). Patient activity, efficacy and safety data were collected and subgroup analyses were conducted among patients treated with st and mod FD/FOx. In the intention‑to‑treat (ITT) analysis, the objective response rate (ORR) was 75% (95% CI, 53‑90) and the disease control rate (DCR) was 87.5% (95% CI, 67.6‑97.3). After a median follow‑up of 16 months, median progression‑free survival (PFS) and median overall survival (OS) were 14.0 and 19.0 months, respectively. The received dose‑intensities were ~80% of the standard doses for each agent. The most relevant treatment‑related grade 3 adverse events were: Neutropenia (40.6%), asthenia (18.7%) and diarrhea (18.7%). The only treatment‑related grade 4 adverse event was neutropenia (9.3%). No febrile neutropenia was observed and none of the patients died as a result of adverse events. FD/FOx regimen appeared to be a feasible option as a first‑line treatment of a/m GC patients, especially in case of high‑tumor burden, with the need of rapid tumor shrinkage and disease‑related symptoms palliation.

Quantitative Reactivity Scales for Dynamic Covalent and Systems Chemistry.

PubMed

Zhou, Yuntao; Li, Lijie; Ye, Hebo; Zhang, Ling; You, Lei

2016-01-13

Dynamic covalent chemistry (DCC) has become a powerful tool for the creation of molecular assemblies and complex systems in chemistry and materials science. Herein we developed for the first time quantitative reactivity scales capable of correlation and prediction of the equilibrium of dynamic covalent reactions (DCRs). The reference reactions are based upon universal DCRs between imines, one of the most utilized structural motifs in DCC, and a series of O-, N-, and S- mononucleophiles. Aromatic imines derived from pyridine-2-carboxyaldehyde exhibit capability for controlling the equilibrium through distinct substituent effects. Electron-donating groups (EDGs) stabilize the imine through quinoidal resonance, while electron-withdrawing groups (EWGs) stabilize the adduct by enhancing intramolecular hydrogen bonding, resulting in curvature in Hammett analysis. Notably, unique nonlinearity induced by both EDGs and EWGs emerged in Hammett plot when cyclic secondary amines were used. This is the first time such a behavior is observed in a thermodynamically controlled system, to the best of our knowledge. Unified quantitative reactivity scales were proposed for DCC and defined by the correlation log K = S(N) (R(N) + R(E)). Nucleophilicity parameters (R(N) and S(N)) and electrophilicity parameters (R(E)) were then developed from DCRs discovered. Furthermore, the predictive power of those parameters was verified by successful correlation of other DCRs, validating our reactivity scales as a general and useful tool for the evaluation and modeling of DCRs. The reactivity parameters proposed here should be complementary to well-established kinetics based parameters and find applications in many aspects, such as DCR discovery, bioconjugation, and catalysis.

Impact of the Agulhas Return Current on the glacial Subantarctic region in the South Indian Ocean

NASA Astrophysics Data System (ADS)

Ikehara, M.; Crosta, X.; Manoj, M. C.

2017-12-01

The Southern Ocean has played an important role in the evolution of the global climate system. The Southern Ocean circulation is dominated by the Antarctic Circumpolar Current (ACC), the world's longest and largest current system. Sea ice coverage on sea surface strongly affects the climate of the Southern Hemisphere through its impacts on the energy and gas budget, on the atmospheric circulation, on the hydrological cycle, and on the biological productivity. The Agulhas Return Current (ARC) originates from the Agulhas Current, the major western boundary current in the Indian Ocean, and transports heat from subtropical to subantarctic region. It's thought that the Agulhas leakage from the Indian Ocean to the Atlantic was reduced for the last glacial due to a northward shift of the westerlies and ACC, however, there are still unknown yet how the ARC was responded to the reduced Agulhas leakage. A piston core DCR-1PC was collected from the Del Caño Rise (46°S, 44°E, 2632m), Indian sector of the Southern Ocean. Core site located in the Subantarctic region between the Subtropical Front (STF) and Subantarctic Front (SAF). Age model of the core was established by radiocarbon dating of planktic foraminifer Globorotalia bulloides and oxygen isotope stratigraphy of benthic foraminifers Cibicidoides wuellerstorfi and Melonis bareelanus. Sediment of DCR-1PC show the cyclic changes of diatom/carbonate ooze sedimentation corresponding to Southern Ocean fronts' migrations on glacial-interglacial timescales. Records of ice-rafted debris (IRD) and oxygen isotope in planktic foraminfer G. bulloides suggest that the melting of sea ice was significantly increased during the last glacial maximum (LGM) in the Subantarctic surface water. Diatom assemblage based summer SST also shows the relative warmer condition in the Subantarctic during the LGM. These results might be explained by the strong influence of the Agulhas Return Current during the LGM in the Subantarctic. The reduced Agulhas leakage due to a northward shift of the westerlies and ACC impacted significantly on sea ice melting in the glacial Subantarctic region in the South Indian Ocean.

Magnetic resonance imaging in the pre-operative evaluation of obstructive epiphora: true-FISP and VIBE vs gadolinium.

PubMed

Somma, Francesco; d'Agostino, Vincenzo; Tortora, Fabio; Serra, Nicola; Sorrentino, Gerardo; Piscitelli, Valeria; Somma, Andrea; Gamerra, Mario

2017-02-01

To assess unenhanced magnetic resonance imaging (MRI) in the preoperative evaluation of obstructive epiphora in patients undergoing dacryocystorhinostomy (DCR) and in particular, to evaluate the efficacy of this technique in the detection of the exact level of obstruction occurring in the naso-lachrymal duct (NLD). The correct identification and characterization of the NLD and its obstructions lead to a more effective surgery, preventing recurrent dacryocystitis after the surgical treatment. From January 2009 to December 2014, 127 obstructive epiphoras were diagnosed and treated in 127 patients (35 M, 92 F; mean age 60.7 ± 7.48 years, range 42-75 years) with endoscopic DCR, in a IRB-approved protocol. To precisely define the morphology of the NLD and the site of obstruction, some of these patients (67/127) underwent unenhanced 1.5-T MR with TrueFISP and VIBE sequences, while the remaining (60/127) underwent Gadolinium-enhanced 1.5-T MR. Afterwards, surgery checked the real site of obstruction in both groups of patients (enhanced and unenhanced MR), with surgical outcomes matched with previous MR reports. In all cases, unenhanced MRI was able to detect the exact site of obstruction along the NLD, allowing a correct planning of surgical endoscopic procedures. On the contrary, enhanced MRI wrongly diagnosed six patients with proximal stenosis (6/60, 10.0%) as intermediate NLD obstruction. Unenhanced MRI was found to be more accurate than enhanced MRI with a statistical significant difference (p value = 0.0256) and obviously cheaper and easier to perform. All imaging reports were verified with surgery. The correct identification of the level of obstruction allowed successful surgery in around 73% (93/127) of patients, who had no recurrence during 6-month follow-up. In patients with epiphora, unenhanced MR showed to be highly reliable and even more effective than enhanced MR in the preoperative characterization of NLD stenosis, with no need of performing complex, time-wasting and expensive procedures for the administration of topical contrast media.

What Is the Risk of Anastomotic Leak After Repeat Intestinal Resection in Patients With Crohn's Disease?

PubMed

Johnston, W Forrest; Stafford, Caitlin; Francone, Todd D; Read, Thomas E; Marcello, Peter W; Roberts, Patricia L; Ricciardi, Rocco

2017-12-01

Approximately half of Crohn's patients require intestinal resection, and many need repeat resections. The purpose of this study was to evaluate the increased risk of clinical anastomotic leak in patients with a history of previous intestinal resection undergoing repeat resection with anastomosis for Crohn's disease. This was a retrospective analysis of prospectively collected departmental data with 100% capture. The study was conducted at the department of colorectal surgery in a tertiary care teaching hospital between July 2007 and March 2016. A cohort of consecutive patients with Crohn's disease who were treated with intestinal resection and anastomosis, excluding patients with proximal fecal diversion, were included. The cohort was divided into 2 groups, those with no previous resection compared with those with previous resection. Clinical anastomotic leak within 30 days of surgery was measured. Of the 206 patients who met criteria, 83 patients had previous intestinal resection (40%). The 2 groups were similar in terms of patient factors, immune-suppressing medication use, and procedural factors. Overall, 20 clinical anastomotic leaks were identified (10% leak rate). There were 6 leaks (5%) detected in patients with no previous intestinal resection and 14 leaks (17%) detected in patients with a history of previous intestinal resection (p < 0.005). The OR of anastomotic leak in patients with Crohn's disease with previous resection compared with no previous resection was 3.5 (95% CI, 1.3-9.4). Patients with 1 previous resection (n = 53) had a leak rate of 13%, whereas patients with ≥2 previous resections (n = 30) had a leak rate of 23%. The number of previous resections correlated with increasing risk for clinical anastomotic leak (correlation coefficient = 0.998). This was a retrospective study with limited data to perform a multivariate analysis. Repeat intestinal resection in patients with Crohn's disease is associated with an increased rate of anastomotic leakage when compared with initial resection despite similar patient, medication, and procedural factors. See Video Abstract at http://links.lww.com/DCR/A459.

Efficacy and safety of Everolimus and Exemestane in hormone-receptor positive (HR+) human-epidermal-growth-factor negative (HER2-) advanced breast cancer patients: New insights beyond clinical trials. The EVA study.

PubMed

Cazzaniga, M E; Airoldi, M; Arcangeli, V; Artale, S; Atzori, F; Ballerio, A; Bianchi, G V; Blasi, L; Campidoglio, S; Ciccarese, M; Cursano, M C; Piezzo, M; Fabi, A; Ferrari, L; Ferzi, A; Ficorella, C; Frassoldati, A; Fumagalli, A; Garrone, O; Gebbia, V; Generali, D; La Verde, N; Maur, M; Michelotti, A; Moretti, G; Musolino, A; Palumbo, R; Pistelli, M; Porpiglia, M; Sartori, D; Scavelli, C; Schirone, A; Turletti, A; Valerio, M R; Vici, P; Zambelli, A; Clivio, L; Torri, V

2017-10-01

The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33-83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1-7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4-58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%). The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Appendectomy and Risk of Subsequent Diverticular Disease Requiring Hospitalization: A Population-Based Case-Control Study.

PubMed

Sköldberg, Filip; Olén, Ola; Ekbom, Anders; Schmidt, Peter T

2018-07-01

Appendicitis and acute diverticulitis share clinical features and are both influenced by genetic and environmental factors. Appendectomy has been positively associated with diverticular disease in hospital-based case-control studies. The aim of the present study was to investigate, in a population-based setting, whether appendectomy, with or without appendicitis, is associated with an altered risk of hospitalization with diverticular disease. This was a population-based case-control study. The study was based on national healthcare and population registers. We studied 41,988 individuals hospitalized between 2000 and 2010 with a first-time diagnosis of colonic diverticular disease and 413,115 matched control subjects. The association between appendectomy with or without appendicitis and diverticular disease was investigated by conditional logistic regression, including a model adjusting for hospital use. A total of 2813 cases (6.7%) and 19,037 controls (4.6%) had a previous record of appendectomy (appendectomy with acute appendicitis: adjusted OR = 1.31 (95% CI, 1.24-1.39); without appendicitis: adjusted OR = 1.30 (95% CI, 1.23-1.38)). Appendectomy was most strongly associated with an increased risk of diverticular disease within 1 year (with appendicitis: adjusted OR = 2.26 (95% CI, 1.61-3.16); without appendicitis: adjusted OR = 3.98 (95% CI, 2.71-5.83)), but the association was still present ≥20 years after appendectomy (with appendicitis: adjusted OR = 1.22 (95% CI, 1.12-1.32); without appendicitis: adjusted OR = 1.19 (95% CI, 1.10-1.28)). Detailed clinical information on the cases was not available. There were unmeasured potential confounders, such as smoking and dietary factors. The findings are consistent with a hypothesis of appendectomy causing an increased risk of diverticular disease, for example, by affecting the mucosal immune system or the gut microbiome. However, several other mechanisms may contribute to, or account for, the positive association, including a propensity for abdominal pain increasing the risk of both the exposure and the outcome. See Video Abstract at http://links.lww.com/DCR/A604.

Effectiveness of Liposomal Bupivacaine in Colorectal Surgery: A Pragmatic Nonsponsored Prospective Randomized Double Blinded Trial in a Community Hospital.

PubMed

Knudson, Rachel A; Dunlavy, Paul W; Franko, Jan; Raman, Shankar R; Kraemer, Soren R

2016-09-01

Prior industry conducted studies have shown that long acting liposomal bupivacaine injection improves pain control postoperatively. To evaluate whether liposomal bupivacaine reduced the use of postoperative opioid (http://links.lww.com/DCR/A253) pain medication as compared to standard bupivacaine following colorectal surgery. A double blinded, prospective, randomized controlled trial comparing liposomal bupivacaine versus standard bupivacaine in patients undergoing elective colon resection. Community hospital with general surgery residency program with all cases performed by colorectal surgeons. Fifty-seven patients were randomized and reported as intention-to-treat analysis with 6 protocol violations. Sensitivity analysis excluding these 6 patients demonstrated no change in study results or conclusion. Mean age was 67 ± 2 years and 56% were male. There were 36 patients who underwent minimally invasive surgery, and 21 patients had an open colon resection. Experimental arm received liposomal bupivacaine while control arm received standard bupivacaine. Primary outcome measure was intravenous hydromorphone equivalent used via PCA during first 48 hours after operation. There was no significant difference between the two groups in the amount of opioid used orally or intravenously in the postoperative period. The primary outcome measure was PCA hydromorphone consumption during first two postoperative days after operation (hydromorphone equivalent use in standard bupivacaine group 11.3 ± 8.9 mg versus 13.3 ± 11.9 mg in liposomal bupivacaine group, p = 0.58 Mann-Whitney test). Small pragmatic trials typically remain underpowered for secondary analyses. A larger study could help to further delineate other outcomes that are impacted by postoperative pain. Liposomal bupivacaine did not change the amount of opioid used postoperatively. Based on our study, liposomal bupivacaine does not provide any added benefit over conventional bupivacaine after colon resection. (ClinicalTrials.gov: NCT02052557).

An investigation into the psychobiology of social phobia: personality domains and serotonergic function.

PubMed

Chatterjee, S; Sunitha, T A; Velayudhan, A; Khanna, S

1997-06-01

The aim of the present study was to explore a psychobiological perspective in the aetiology of social phobia. The emphasis was on serotonergic function and personality. A total of 20 social phobics according to ICD-10 DCR criteria were assessed with the Schedule for Clinical Assessment in Neuropsychiatry and the International Personality Disorder Examination. They were compared with an age-matched normal population with regard to scores on the Fear of Negative Evaluation Scale, the Social Avoidance and Distress Scale, the Temperament and Character Inventory, and platelet 5HT2 receptor function. Other Axis-I disorders and cluster C personality disorders were frequently encountered. The social phobia group was characterized by high levels of harm avoidance, and low levels of novelty seeking, co-operativeness and self-directedness. Platelet 5HT2 receptor density did not differentiate between the groups, but was associated with severity of social phobia. An integrated psychobiological model is presented.

Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial.

PubMed

Clement, P M; Gauler, T; Machiels, J P; Haddad, R I; Fayette, J; Licitra, L F; Tahara, M; Cohen, E E W; Cupissol, D; Grau, J J; Guigay, J; Caponigro, F; de Castro, G; de Souza Viana, L; Keilholz, U; Del Campo, J M; Cong, X J; Ehrnrooth, E; Vermorken, J B

2016-08-01

In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years. Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed. Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups. Advancing age (≥65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients. NCT01345682 (ClinicalTrials.gov). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Subtotal colectomy in severe ulcerative and Crohn's colitis: what benefit does the laparoscopic approach confer?

PubMed

Messenger, David E; Mihailovic, Dana; MacRae, Helen M; O'Connor, Brenda I; Victor, J Charles; McLeod, Robin S

2014-12-01

Comparative outcome data for laparoscopic and open subtotal colectomy in IBD are lacking and often difficult to interpret owing to low case volumes, heterogeneity in case mix, and variation in laparoscopic technique. This study aimed to determine the safety of laparoscopic subtotal colectomy in severe colitis and to determine whether the laparoscopic approach improved short-term outcomes in comparison with the open approach. This was a retrospective cohort study using data from a prospectively maintained clinical database. This study was conducted at a single center, Mount Sinai Hospital, Toronto. All patients undergoing subtotal colectomy for either ulcerative or Crohn's colitis between 2000 and 2011 were included. A standardized operative technique was used for both laparoscopic and open subtotal colectomies. Cases performed by non-laparoscopic surgeons were excluded. Perioperative outcome measures were operative duration, estimated blood loss, total morphine requirement, and length of postoperative stay. Postoperative outcome measures were the rates of minor and major complications. Laparoscopic subtotal colectomies were performed in 131 of 290 cases (45.2%). Nine patients required conversion to an open procedure (6.9%). The uptake of laparoscopic subtotal colectomy increased from 10.2% in 2000/2001 to 71.7% in 2010/2011. Regression analysis with propensity-score adjustment for operative approach revealed that the operative duration was 25.5 minutes longer in laparoscopic cases (95% CI 12.3-38.6; p < 0.001), but that patients experienced fewer minor complications (OR 0.47; 95% CI 0.23-0.96; p = 0.04) and required less morphine (adjusted difference, -72.8 mg; 95% CI 4.9-141; p = 0.04). The inherent selection bias of this retrospective cohort study may not be accounted for by multivariate analysis with propensity-score adjustment. Laparoscopic subtotal colectomy is safe and may reduce the rate of minor postoperative complications. The increase in operative duration reflects the technical demands associated with this procedure (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A160).

Value of FDG-PET/CT Volumetry After Chemoradiotherapy in Rectal Cancer.

PubMed

Okuno, Takayuki; Kawai, Kazushige; Koyama, Keitaro; Takahashi, Miwako; Ishihara, Soichiro; Momose, Toshimitsu; Morikawa, Teppei; Fukayama, Masashi; Watanabe, Toshiaki

2018-03-01

Neoadjuvant chemoradiotherapy followed by an optimal surgery is the standard treatment for patients with locally advanced rectal cancer. FDG-PET/CT is commonly used as the modality for assessing the effect of chemoradiotherapy. The purpose of this study was to investigate whether PET/CT-based volumetry could contribute to the prediction of pathological complete response or prognosis after neoadjuvant chemoradiotherapy. This was a retrospective cohort study. This study was conducted at a single research center. Ninety-one consecutive patients with locally advanced rectal cancer were enrolled between January 2005 and December 2015. Patients underwent PET/CT before and after neoadjuvant chemoradiotherapy. Maximum standardized uptake value and total lesion glycolysis on PET/CT before and after neoadjuvant chemoradiotherapy were calculated using isocontour methods. Correlations between these variables and clinicopathological factors and prognosis were assessed. PET/CT-associated variables before chemoradiotherapy were not correlated with either clinicopathological factors or prognosis. Maximum standardized uptake value was associated with pathological complete response, but total lesion glycolysis was not. Maximum standardized uptake value correlated with ypT, whereas total lesion glycolysis correlated with both ypT and ypN. High total lesion glycolysis was associated with a considerably poorer prognosis; the 5-year recurrence rate was 65% and the 5-year mortality rate 42%, whereas in lesions with low total lesion glycolysis, these were 6% and 2%. On multivariate analysis, high total lesion glycolysis was an independent risk factor for recurrence (HR = 4.718; p = 0.04). The gain in fluoro-2-deoxy-D-glucose uptake may differ between scanners, thus the general applicability of this threshold should be validated. In patients with locally advanced rectal cancer, high total lesion glycolysis after neoadjuvant chemoradiotherapy is strongly associated with a worse prognosis. Total lesion glycolysis after chemoradiotherapy may be a promising preoperative predictor of recurrence and death. See Video Abstract at http://links.lww.com/DCR/A464.

Hyaline cartilage calcification of the first metatarsophalangeal joint is associated with osteoarthritis but independent of age and BMI.

PubMed

Hubert, Jan; Hawellek, Thelonius; Hischke, Sandra; Bertrand, Jessica; Krause, Matthias; Püschel, Klaus; Rüther, Wolfgang; Niemeier, Andreas

2016-11-15

Hyaline cartilage calcification (CC) is associated with osteoarthritis (OA) in hip and knee joints. The first metatarsophalangeal joint (1 st MTPJ) is frequently affected by OA, but it is unclear if CC occurs in the 1 st MTPJ. The aim of the present study was to analyze the prevalence of CC of the 1 st MTPJ in the general population by high-resolution digital contact radiography (DCR) and to determine its association with histological OA severity, age and body mass index (BMI). 168 metatarsal heads of 84 donors (n = 47 male, n = 37 female; mean age 62.73 years, SD ±18.8, range 20-93) were analyzed by DCR for the presence of CC. Histological OA grade (hOA) by OARSI was analyzed in the central load-bearing zone of the first metatarsal head (1 st MH). Structural equation modeling (SEM) was performed to analyze the interrelationship between CC, hOA, age and BMI. The prevalence of CC of 1 st MH was 48.8 % (41/84) (95 %-CI [37.7 %, 60.0 %]), independent of the affected side (p = 0.42), gender (p = 0.41) and BMI (p = 0.51). The mean amount of CC of one MH correlated significantly with that of the contralateral side (r s  = 0.4, 95 %-CI [0.26, 0.52], p < 0.001). The mean amount of CC (in % of total cartilage area) of the MH correlated significantly with the severity of hOA (r s  = 0.51, 95 %-CI [0.32, 0.65], p < 0.001). SEM revealed significant associations between CC and hOA (r = 0.74, p < 0.001) and between hOA and age (β = 0.62, p = 0.001), but not between CC and age (p = 0.15). There was no significant influence of BMI on either CC (p = 0.37) or hOA (p = 0.16). The observation that CC of the 1 st MH is significantly associated with the severity of OA but independent of age and BMI, suggests an intimate relationship between CC and the pathogenesis of OA, the exact nature of which will have to be explored by future studies.

Delineation of a quick clay zone at Smørgrav, Norway, with electromagnetic methods under geotechnical constraints

NASA Astrophysics Data System (ADS)

Kalscheuer, Thomas; Bastani, Mehrdad; Donohue, Shane; Persson, Lena; Aspmo Pfaffhuber, Andreas; Reiser, Fabienne; Ren, Zhengyong

2013-05-01

In many coastal areas of North America and Scandinavia, post-glacial clay sediments have emerged above sea level due to iso-static uplift. These clays are often destabilised by fresh water leaching and transformed to so-called quick clays as at the investigated area at Smørgrav, Norway. Slight mechanical disturbances of these materials may trigger landslides. Since the leaching increases the electrical resistivity of quick clay as compared to normal marine clay, the application of electromagnetic (EM) methods is of particular interest in the study of quick clay structures. For the first time, single and joint inversions of direct-current resistivity (DCR), radiomagnetotelluric (RMT) and controlled-source audiomagnetotelluric (CSAMT) data were applied to delineate a zone of quick clay. The resulting 2-D models of electrical resistivity correlate excellently with previously published data from a ground conductivity metre and resistivity logs from two resistivity cone penetration tests (RCPT) into marine clay and quick clay. The RCPT log into the central part of the quick clay identifies the electrical resistivity of the quick clay structure to lie between 10 and 80 Ω m. In combination with the 2-D inversion models, it becomes possible to delineate the vertical and horizontal extent of the quick clay zone. As compared to the inversions of single data sets, the joint inversion model exhibits sharper resistivity contrasts and its resistivity values are more characteristic of the expected geology. In our preferred joint inversion model, there is a clear demarcation between dry soil, marine clay, quick clay and bedrock, which consists of alum shale and limestone.

ELRIS2D: A MATLAB Package for the 2D Inversion of DC Resistivity/IP Data

NASA Astrophysics Data System (ADS)

Akca, Irfan

2016-04-01

ELRIS2D is an open source code written in MATLAB for the two-dimensional inversion of direct current resistivity (DCR) and time domain induced polarization (IP) data. The user interface of the program is designed for functionality and ease of use. All available settings of the program can be reached from the main window. The subsurface is discre-tized using a hybrid mesh generated by the combination of structured and unstructured meshes, which reduces the computational cost of the whole inversion procedure. The inversion routine is based on the smoothness constrained least squares method. In order to verify the program, responses of two test models and field data sets were inverted. The models inverted from the synthetic data sets are consistent with the original test models in both DC resistivity and IP cases. A field data set acquired in an archaeological site is also used for the verification of outcomes of the program in comparison with the excavation results.

Two classes of silencing RNAs move between C. elegans tissues

PubMed Central

Jose, Antony M; Garcia, Giancarlo A; Hunter, Craig P

2011-01-01

Summary Organism-wide RNA interference (RNAi) is due to the transport of mobile silencing RNA throughout the organism but the identities of these mobile RNA species in animals are unknown. Here we present genetic evidence that both the initial double-stranded RNA (dsRNA), which triggers RNAi, and at least one dsRNA intermediate produced during RNAi can act as or generate mobile silencing RNA in Caenorhabditis elegans. This dsRNA intermediate requires the long dsRNA-binding protein RDE-4, the endonuclease DCR-1, which cleaves long dsRNA into double-stranded short-interfering RNA (ds-siRNA), and the putative nucleotidyltransferase MUT-2 (RDE-3). However, single-stranded siRNA and downstream secondary siRNA produced upon amplification by the RNA-dependent RNA Polymerase RRF-1 do not generate mobile silencing RNA. Restricting inter-tissue transport to long dsRNA and directly processed siRNA intermediates rather than amplified siRNA may serve to modulate the extent of systemic silencing in proportion to available dsRNA. PMID:21984186

A pilot study of nimotuzumab combined with cisplatin and 5-FU in patients with advanced esophageal squamous cell carcinoma

PubMed Central

Ling, Yang; Chen, Jia; Tao, Min; Chu, Xiaoyuan; Zhang, Xizhi

2012-01-01

Objective To observe the short-term effect and adverse reaction of Nimotuzumab in combination with chemotherapy on advanced esophageal squamous cell carcinoma (ESCC). Method 19 patients were treated with the following protocol: Nimotuzumab 400mg/time/week in the 1st week, 200mg/time/week from the 2nd to 8th week, intravenous drip (IVD); Cisplatin 80 mg/m2, IVD, 4 weeks a cycle and repeated again; 5-FU 750 mg/m2, continuous 24-hours pump-in × 5 days, 4 weeks a cycle and repeated again. Result 16 of all 19 patients can be evaluated. After treatment, RP is 42.1% (95% CI, 19.9-64.3%) and DCR is 68.4%; the main side effects include arrest of bone marrow, gastrointestinal reactions, asthenia, etc. Conclusion Nimotuzumab in combination with cisplatin/5-FU regimens in patients with advanced ESCC is safe and effective, which deserves a further expanded sample research. PMID:22295168

Have we progressed in the surgical literature? Thirty-year trends in clinical studies in 3 surgical journals.

PubMed

Shawhan, Robert R; Hatch, Quinton M; Bingham, Jason R; Nelson, Daniel W; Fitzpatrick, Emile B; McLeod, Robin; Johnson, Eric K; Maykel, Justin A; Steele, Scott R

2015-01-01

We practice in an era of evidence-based medicine. In 1993, Solomon and McLeod published an article examining study designs in 3 surgical journals from 1980 and 1990. The purpose of this study was to evaluate subsequent 30-year trends in the quality of selected literature. All of the articles from Diseases of the Colon & Rectum, Surgery, and the British Journal of Surgery during 2000 and 2010 were classified by study design. Nonclinical studies were substratified by animal/laboratory, surgical technique, editorial/review, or miscellaneous articles. Clinical articles were categorized as case or comparative studies, further categorized by study design, and rated on a 10-point scale to determine strength. We compared interobserver reliability using a random sample. This study was conducted at 3 North American medical centers. Patients described in the scope of the literature were included in this study. Frequency, type, and strength of study design were measured. We evaluated 1911 articles (967 clinical; 17% comparative). There was a significant increase in multicenter clinical studies (from 12% to 27%; p < 0.0001) and mean study population (from 326 to 6775; p < 0.05). Studies using administrative data increased from 14% to 43% (p < 0.0001). Case reports decreased from 16% to 7% of all clinical studies (p < 0.001), whereas the percentage of comparative studies increased from 14% to 21% (p = 0.001). The percentage of randomized controlled trials did not increase significantly (8.5% in 2000; 10.0% in 2010; p = 0.44). The mean 10-point score for comparative studies was 6.7 for both years (p = 0.50). There was good interobserver agreement in the classification of studies (κ = 0.70) and moderate agreement in scoring comparative studies (κ = 0.47). This descriptive study cannot fully account for the reasons behind the identified differences. Comparative and multicenter studies, mean study population, and the use of administrative data increased from 2000 to 2010. This suggests that increased use of administrative databases has allowed larger populations of patients from more institutions to be studied and may be more generalizable. Researchers should strive toward improving the level of evidence (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A167).

Differences and similarities of risk factors for suicidal ideation and attempts among patients with depressive or bipolar disorders.

PubMed

Aaltonen, Kari; Näätänen, Petri; Heikkinen, Martti; Koivisto, Maaria; Baryshnikov, Ilya; Karpov, Boris; Oksanen, Jorma; Melartin, Tarja; Suominen, Kirsi; Joffe, Grigori; Paunio, Tiina; Isometsä, Erkki

2016-03-15

Substantial literature exists on risk factors for suicidal behaviour. However, their comparative strength, independence and specificity for either suicidal ideation or suicide attempt(s) remain unclear. The Helsinki University Psychiatric Consortium (HUPC) Study surveyed 287 psychiatric care patients with ICD-10-DCR depressive or bipolar disorders about lifetime suicidal behaviour, developmental history and attachment style, personality and psychological traits, current and lifetime symptom profiles, and life events. Psychiatric records were used to confirm diagnosis and complement information on suicide attempts. Multinomial regression models predicting lifetime suicidal ideation and single or repeated suicide attempts were generated. Overall, 21.6% patients had no lifetime suicidal behaviour, 33.8% had lifetime suicide ideation without attempts, and 17.1% had a single and 27.5% repeated suicide attempts. In univariate analyses, lifetime suicidal behaviour was associated with numerous factors. In multivariate models, suicidal ideation was independently predicted by younger age, severe depressive disorder, bipolar disorder type II/nos, hopelessness, and childhood physical abuse. Repeated suicide attempts were independently predicted by younger age, female sex, severe depressive disorder with or without psychotic symptoms, bipolar disorder type II/nos, alcohol use disorder, borderline personality disorder traits, and childhood physical abuse. Cross-sectional and retrospective study design, utilization of clinical diagnoses, and relatively low response rate. Risk factors for suicidal ideation and attempts may diverge both qualitatively and in terms of dose response. When effects of risk factors from multiple domains are concurrently examined, proximal clinical characteristics remain the most robust. All risk factors cluster into the group of repeated attempters. Copyright © 2015 Elsevier B.V. All rights reserved.

Survival Benefit of Japanese Extended Lymphadenectomy for Clinically Node-Negative and Node-Positive Colorectal Cancers.

PubMed

Ouchi, Akira; Komori, Koji; Kimura, Kenya; Kinoshita, Takashi; Shimizu, Yasuhiro; Nagino, Masato

2018-02-01

The impact of extended lymphadenectomy for colorectal cancer is still not sufficiently clear. The aim of the present study was to evaluate the survival benefit of extended lymphadenectomy compared with nonextended lymphadenectomy for clinically node-negative and node-positive colorectal cancers. The present study was a retrospective cohort study that used prospectively collected data and a propensity score matching method. The present study was conducted at a single specialized colorectal surgery department. Of the 1314 patients who underwent radical resection with nonextended or extended lymphadenectomy between 1988 and 2007, we included 711 and 603 patients in the cN0 and cN1/2 series. Propensity score matching was applied, and 141 and 63 pairs were extracted from the cN0 and cN1/2 series. Disease-free survival, cancer-specific survival, and overall survival of the 2 groups were calculated and compared. In the cN0 series, no differences were observed in the long-term outcomes between the nonextended and extended groups. In the cN1/2 series, the disease-free survival, cancer-specific survival and overall survival were significantly higher (log rank, p = 0.04, p = 0.02, and p = 0.01, respectively), and the frequency of local recurrence was significantly lower (p = 0.04) in the extended group. The present study was limited by its nonrandomized retrospective design. Extended lymphadenectomy demonstrated a good inhibitory effect on the local recurrence rate and led to improved disease-free survival, cancer-specific survival, and overall survival of patients in the cN1/2 series. See Video Abstract at http://links.lww.com/DCR/A517.

An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2 tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin lymphoma.

PubMed

Li, Ling; Xiao, Sa; Zhang, Lei; Li, Xin; Fu, Xiaorui; Wang, Xinhua; Wu, Jingjing; Sun, Zhenchang; Zhang, Xudong; Chang, Yu; Nan, Feifei; Yan, Jiaqin; Li, Zhaoming; Shi, Mengyuan; Young, Ken H; Zhang, Mingzhi

2018-03-23

Apatinib, a novel small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, have shown remarkable efficacy in many solid cancers. But evidence of antitumor activity in patients with lymphoma is still limited. We conducted an open-label, single-armed, exploratory study in relapse or refractory non-Hodgkin lymphoma patients for the efficacy and safety of apatinib. Patients with relapse or refractory non-Hodgkin patients meet the criteria were eligible for enrollment. Treatment comprised of oral apatinib 500 mg once daily with 21 days as a treatment cycle. The primary end point was response rate. Secondary end points included progression-free survival (PFS) and overall survival (OS). Between February 2016 and December 2016, 21 patients were enrolled. The ORR (CR plus PR) was 47.6% (10 of 21 patients) included 9.5% CRs and 38.1% PRs. 23.8% patients achieved stable disease made the DCR 71.4% (15/21). The median OS was 7.3 months (95% CI, 7.1 to 7.9) and the median PFS was 7.1 months (95% CI, 4.2 to 7.3). Most patients suffered from grade 1 to grade 2 treatment-related adverse events and the most common nonhematologic adverse events were proteinuria (47.6%), hypertension (42.9%) and hand-foot syndrome (33.3%), respectively. In our study, the results we presented showed apatinib might have a rapid, safe and high efficacy on relapsed or refractory non-Hodgkin lymphoma patients. Based on the data more clinic trials are expected to be taken to identification the efficacy of apatinib on lymphoma further.

Role of transfused red blood cells for shock and coagulopathy within remote damage control resuscitation.

PubMed

Spinella, Philip C; Doctor, Allan

2014-05-01

The philosophy of damage control resuscitation (DCR) and remote damage control resuscitation (RDCR) can be summarized by stating that the goal is to prevent death from hemorrhagic shock by "staying out of trouble instead of getting out of trouble." In other words, it is preferred to arrest the progression of shock, rather than also having to reverse this condition after significant tissue damage and organ injury cascades are established. Moreover, to prevent death from exsanguination, a balanced approach to the treatment of both shock and coagulopathy is required. This was military doctrine during World War II, but seemed to be forgotten during the last half of the 20th century. Damage control resuscitation and RDCR have revitalized the approach, but there is still more to learn about the most effective and safe resuscitative strategies to simultaneously treat shock and hemorrhage. Current data suggest that our preconceived notions regarding the efficacy of standard issue red blood cells (RBCs) during the hours after transfusion may be false. Standard issue RBCs may not increase oxygen delivery and may in fact decrease it by disturbing control of regional blood flow distribution (impaired nitric oxide processing) and failing to release oxygen, even when perfusing hypoxic tissue (abnormal oxygen affinity). Standard issue RBCs may assist with hemostasis but appear to have competing effects on thrombin generation and platelet function. If standard issue or RBCs of increased storage age are not optimal, then are there alternatives that will allow for an efficacious and safe treatment of shock while also supporting hemostasis? Studies are required to determine if fresh RBCs less than 7 to 10 days provide an outcome advantage. A resurgence in the study of whole blood stored at 4°C for up to 10 days also holds promise. Two randomized controlled trials in humans have indicated that following transfusion with either whole blood stored at 4°C or platelets stored at 4°C there was less clinical bleeding than when blood was reconstituted with components or when platelets were stored at 22°C. Early reversal of shock is essential to prevent exacerbation of coagulopathy and progression of cell death cascades in patients with severe traumatic injuries. Red blood cell storage solutions have evolved to accommodate the needs of non-critically ill patients yet may not be optimal for patients in hemorrhagic shock. Continued focus on the recognition and treatment of shock is essential for continued improvement in outcomes for patients who require damage control resuscitation and RDCR.

Clinical validation of a highly sensitive assay to detect EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma.

PubMed

Li, Yuping; Xu, Hanyan; Su, Shanshan; Ye, Junru; Chen, Junjie; Jin, Xuru; Lin, Quan; Zhang, Dongqing; Ye, Caier; Chen, Chengshui

2017-01-01

Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive epidermal growth factor receptor (EGFR) mutations detection in lung cancer patients, but the existing methods have limitations in sensitivity or in availability. In this study, we evaluated the performance of a novel assay called ADx-SuperARMS in detecting EGFR mutations in plasma cell-free DNA from patients with advanced lung adenocarcinoma. A total of 109 patients with metastatic advanced adenocarcinoma were recruited who provided both blood samples and matched tumor tissue samples. EGFR mutation status in plasma samples were tested with ADx-SuperARMS EGFR assay and tumor tissue samples were tested with ADx-ARMS EGFR assay. The clinical sensitivity, specificity, positive prediction value (PPV), and negative prediction value (NPV) of ADx-SuperARMS EGFR assay were calculated by using EGFR mutation status in tumor tissue as standard reference. A receiver operating characteristic (ROC) analysis was implemented and an area under the curve (AUC) was calculated to evaluate sensitivity and specificity of exon 19 deletion (E19Del) and L858R mutation detection. The objective response rate (ORR) were calculated according to the EGFR mutation status determined by ADx-superARMS as well. 0.2% analytical sensitivity and 100% specificity of the ADx-SuperARMS EGFR assays for EGFR E19Del, L858R, and T790M mutants were confirmed by using a series of diluted cell line DNA. In the clinical study, EGFR mutations were detected in 45.9% (50/109) of the plasma samples and in 56.9% (62/109) of the matched tumor tissue samples. The sensitivity, specificity, PPV and NPV of the ADx-SuperARMS EGFR assay for plasma EGFR mutation detection were 82.0% (50/61), 100% (48/48), 100% (50/50), and 81.4% (48/59), respectively. In ROC analysis, ADx-SuperARMS achieved sensitivity and specificity of 88% and 99% in E19Dels as well as sensitivity and specificity of 89% and 100% in L858R, respectively. Among the 35 patients who were plasma EGFR mutation positive and treated with first generation of EGFR-tyrosine kinase inhibitors (TKIs), 23 (65.7%) achieved partial response, 11 (31.4%) sustained disease, and 1 (2.9%) progressive disease. The ORR and disease control rate (DCR) were 65.7% and 97.1%, respectively. ADx-SuperARMS EGFR assay is likely to be a highly sensitive and specific method to noninvasively detect plasma EGFR mutations of patients with advanced lung adenocarcinoma. The EGFR mutations detected by ADx-SuperARMS EGFR assay could predict the efficacy of the treatment with first generation of EGFR-TKIs. Hence, EGFR blood testing with ADx-SuperARMS could address the unmet clinical needs.

Tailored Treatment Strategy for Locally Advanced Rectal Carcinoma Based on the Tumor Response to Induction Chemotherapy: Preliminary Results of the French Phase II Multicenter GRECCAR4 Trial.

PubMed

Rouanet, Philippe; Rullier, Eric; Lelong, Bernard; Maingon, Philippe; Tuech, Jean-Jacques; Pezet, Denis; Castan, Florence; Nougaret, Stéphanie

2017-07-01

Preoperative radiochemotherapy and total mesorectal excision are the standard-of-care for locally advanced rectal carcinoma, but some patients could be over- or undertreated. This study aimed to assess the feasibility of radiochemotherapy tailored based on the tumor response to induction chemotherapy (FOLFIRINOX) to obtain a minimum R0 resection rate of 90% in the 4 arms of the study. This study is a multicenter randomized trial (NCT01333709). This study was conducted at 16 French cancer specialty centers. Two hundred six patients with locally advanced rectal carcinoma were enrolled between 2011 and 2014. Good responders (≥75% tumor volume reduction) were randomly assigned to immediate surgery (arm A) or standard radiochemotherapy (Cap 50: 50 Gy irradiation and 1600 mg/m oral capecitabine daily) plus surgery (arm B). Poor responders were randomly assigned to Cap 50 (arm C) or intensive radiochemotherapy (Cap 60, 60 Gy irradiation, arm D) before surgery. The primary end point was a R0 resection rate (circumferential resection margin >1 mm). The experimental strategies were to be considered effective if at least 28 successes (R0 resection) among 31 patients in each arm of stratum I and 34 successes among 40 patients in each arm of stratum II were reported (Simon 2-stage design). After induction treatment (good compliance), 194 patients were classified as good (n = 30, 15%) or poor (n = 164, 85%) responders who were included in arms A and B (16 and 14 patients) and arms C and D (113 and 51 patients). The trial was prematurely stopped because of low accrual in arms A and B and recruitment completion in arms C and D. Data from 133 randomly assigned patients were analyzed: 11, 19, 52, and 51 patients in arms A, B, C, and D. Good responders had smaller tumors than poor responders (23 cm vs 45 cm; p < 0.001). The surgical procedure was similar among groups. The R0 resection rates [90% CI] were 100% [70-100], 100% [85-100], 83% [72-91], and 88% [77-95]. Among the first 40 patients, 34 successes were reported in arms C and D (85% R0 resection rate). The circumferential resection margin ≤1 rates were 0%, 0%, 12%, and 5% in arms A, B, C, and D. The rate of transformation from positive to negative circumferential resection margin was 93%. There was low accrual in arms A and B. Tailoring preoperative radiochemotherapy based on the induction treatment response appears safe for poor responders and promising for good responders. Long-term clinical results are needed to confirm its efficacy. See Video Abstract at http://links.lww.com/DCR/A359.

[A three-year follow-up study on the transfer of mild cognitive impairment to Alzheimer's disease among the elderly in Taiyuan city].

PubMed

Wang, Yan-ping; Zhai, Jing-bo; Zhu, Fang; Zhang, Wen-wen; Yang, Xiao-juan; Qu, Cheng-yi

2011-02-01

To explore the incidence rate of people with mild cognitive impairment (MCI) which transferred to Alzheimer's disease (AD) and to study the related influencing factors. 600 MCI aged people were experienced screening test which was conducted by WHO-BCA, MMSE and DCR. A three-year follow-up study was conducted to get the information on the aged people with MCI. Data related to demography, behavior, chronic diseases and perception of the elderly with MCI were collected through face to face interview. Characteristics of the elderly with MCI aged people were tested by 16PF. The content of Apoe was tested by PCR. People with NC were investigated by telephone to get the progression and the time to AD. Methodologies on statistics were log-rank test and Cox proportional hazards regression model. The incidence rate of MCI to AD was 6.53% person-years. The incidence rate of the normal people to AD was 1.24% person-years. The hazard of MCI to AD was 5.27 times (95%CI: 3.01 - 9.82) of the normal people to AD. The result of Cox proportional hazards regression model displayed that:older age (RR = 3.14, 95%CI: 2.98 - 7.46), hypertension (RR = 3.28, 95%CI: 3.02 - 8.48), hyperlipemia (RR = 2.22, 95%CI: 1.29 - 3.82), diabetes (RR = 4.87, 95%CI: 2.56 - 9.25), lack of sports (RR = 2.02, 95%CI: 1.29-3.14), anxiety (RR = 4.46, 95%CI: 3.07 - 8.14), dread fullness (RR = 4.08, 95%CI: 3.52 - 5.25), loneliness (RR = 1.89, 95%CI: 1.13 - 3.16), characteristics of anxiety (RR = 5.07, 95%CI: 2.56 - 10.04, introvert characteristics (RR = 2.05, 95%CI: 1.33 - 3.15) and ApoE4 (RR = 1.73, 95%CI: 1.15 - 2.63) were the risk factors of MCI to AD. Higher education (RR = 0.29, 95%CI: 0.07 - 0.43), intellectual work (RR = 0.14, 95%CI: 0.05 - 0.32), often reading books (RR = 0.30, 95%CI: 0.15 - 0.58), often taking part in recreational activities (RR = 0.41, 95%CI: 0.23 - 0.75) seemed to be the protective of MCI to AD. The rate of the elderly with MCI that developing to AD was high, suggesting further study on the cognitive situation among the MCI aged people should be carried out.

Accuracy of CT enterography and magnetic resonance enterography imaging to detect lesions preoperatively in patients undergoing surgery for Crohn's disease.

PubMed

Seastedt, Kenneth P; Trencheva, Koiana; Michelassi, Fabrizio; Alsaleh, Doaa; Milsom, Jeffrey W; Sonoda, Toyooki; Lee, Sang W; Nandakumar, Govind

2014-12-01

CT enterography and magnetic resonance enterography have emerged as first-line imaging technologies for the evaluation of the gastrointestinal tract in Crohn's disease. The purpose of this work was to evaluate the accuracy of these imaging modalities to identify Crohn's disease lesions preoperatively. This was a retrospective chart review. The study was conducted at a single institution. Seventy-six patients with Crohn's disease with preoperative CT enterography and/or magnetic resonance enterography were included in the study. The number of stenoses, fistulas, and abscesses on CT enterography and/or magnetic resonance enterography before surgery were compared with operative findings. Forty patients (53%) were women, 46 (60%) underwent surgery for recurrent Crohn's disease, and 46 (57%) had previous abdominal surgery. Thirty-six (47%) had a preoperative CT enterography and 43 (57%) had a preoperative magnetic resonance enterography. CT enterography sensitivity was 75% for stenosis and 50% for fistula. MRE sensitivity was 68% for stenosis and 60% for fistula. The negative predictive values of CT enterography and magnetic resonance enterography for stenosis were very low (54% and 65%) and were 85% and 81% for fistula. CT enterography had 76% accuracy for stenosis and 79% for fistula; magnetic resonance enterography had 78% accuracy for stenosis and 85% for fistula. Both were accurate for abscess. False-negative rates for CT enterography were 50% for fistula and 25% for stenosis. False-negative rates for magnetic resonance enterography were 40% for fistula and 32% for stenosis. Unexpected intraoperative findings led to modification of the planned surgical procedure in 20 patients (26%). This study was limited by its small sample size, its retrospective nature, and that some studies were performed at outside institutions. CT enterography and magnetic resonance enterography in patients with Crohn's disease were accurate for the identification of abscesses but not for fistulas or stenoses. Surgeons should search for additional lesions intraoperatively. Patients should be appropriately counseled regarding the need for unexpected interventions (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A162).

Colorectal Cancer Safety Net: Is It Catching Patients Appropriately?

PubMed

Althans, Alison R; Brady, Justin T; Times, Melissa L; Keller, Deborah S; Harvey, Alexis R; Kelly, Molly E; Patel, Nilam D; Steele, Scott R

2018-01-01

Disparities in access to colorectal cancer care are multifactorial and are affected by socioeconomic elements. Uninsured and Medicaid patients present with advanced stage disease and have worse outcomes compared with similar privately insured patients. Safety net hospitals are a major care provider to this vulnerable population. Few studies have evaluated outcomes for safety net hospitals compared with private institutions in colorectal cancer. The purpose of this study was to compare demographics, screening rates, presentation stage, and survival rates between a safety net hospital and a tertiary care center. Comparative review of patients at 2 institutions in the same metropolitan area were conducted. The study included colorectal cancer care delivered either at 1 safety net hospital or 1 private tertiary care center in the same city from 2010 to 2016. A total of 350 patients with colorectal cancer from each hospital were evaluated. Overall survival across hospital systems was measured. The safety net hospital had significantly more uninsured and Medicaid patients (46% vs 13%; p < 0.001) and a significantly lower median household income than the tertiary care center ($39,299 vs $49,741; p < 0.0001). At initial presentation, a similar percentage of patients at each hospital presented with stage IV disease (26% vs 20%; p = 0.06). For those undergoing resection, final pathologic stage distribution was similar across groups (p = 0.10). After a comparable median follow-up period (26.6 mo for safety net hospital vs 29.2 mo for tertiary care center), log-rank test for overall survival favored the safety net hospital (p = 0.05); disease-free survival was similar between hospitals (p = 0.40). This was a retrospective review, reporting from medical charts. Our results support the value of safety net hospitals for providing quality colorectal cancer care, with survival and recurrence outcomes equivalent or improved compared with a local tertiary care center. Because safety net hospitals can provide equivalent outcomes despite socioeconomic inequalities and financial constraints, emphasis should be focused on ensuring that adequate funding for these institutions continues. See Video Abstract at http://links.lww.com/DCR/A454.

Ensuring Safe Exploration: Ares Launch Vehicle Integrated Vehicle Ground Vibration Testing

NASA Technical Reports Server (NTRS)

Tuma, M. L.; Chenevert, D. J.

2009-01-01

Ground vibration testing has been an integral tool for developing new launch vehicles throughout the space age. Several launch vehicles have been lost due to problems that would have been detected by early vibration testing, including Ariane 5, Delta III, and Falcon 1. NASA will leverage experience and testing hardware developed during the Saturn and Shuttle programs to perform ground vibration testing (GVT) on the Ares I crew launch vehicle and Ares V cargo launch vehicle stacks. NASA performed dynamic vehicle testing (DVT) for Saturn and mated vehicle ground vibration testing (MVGVT) for Shuttle at the Dynamic Test Stand (Test Stand 4550) at Marshall Space Flight Center (MSFC) in Huntsville, Alabama, and is now modifying that facility to support Ares I integrated vehicle ground vibration testing (IVGVT) beginning in 2012. The Ares IVGVT schedule shows most of its work being completed between 2010 and 2014. Integrated 2nd Stage Ares IVGVT will begin in 2012 and IVGVT of the entire Ares launch stack will begin in 2013. The IVGVT data is needed for the human-rated Orion launch vehicle's Design Certification Review (DCR) in early 2015. During the Apollo program, GVT detected several serious design concerns, which NASA was able to address before Saturn V flew, eliminating costly failures and potential losses of mission or crew. During the late 1970s, Test Stand 4550 was modified to support the four-body structure of the Space Shuttle. Vibration testing confirmed that the vehicle's mode shapes and frequencies were better than analytical models suggested, however, the testing also identified challenges with the rate gyro assemblies, which could have created flight instability and possibly resulted in loss of the vehicle. Today, NASA has begun modifying Test Stand 4550 to accommodate Ares I, including removing platforms needed for Shuttle testing and upgrading the dynamic test facilities to characterize the mode shapes and resonant frequencies of the vehicle. The IVGVT team expects to collect important information about the new launch vehicles, greatly increasing astronaut safety as NASA prepares to explore the Moon and beyond.

Role of permissive hypotension, hypertonic resuscitation and the global increased permeability syndrome in patients with severe hemorrhage: adjuncts to damage control resuscitation to prevent intra-abdominal hypertension.

PubMed

Duchesne, Juan C; Kaplan, Lewis J; Balogh, Zsolt J; Malbrain, Manu L N G

2015-01-01

Secondary intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are closely related to fluid resuscitation. IAH causes major deterioration of the cardiac function by affecting preload, contractility and afterload. The aim of this review is to discuss the different interactions between IAH, ACS and resuscitation, and to explore a new hypothesis with regard to damage control resuscitation, permissive hypotension and global increased permeability syndrome. Review of the relevant literature via PubMed search. The recognition of the association between the development of ACS and resuscitation urged the need for new approach in traumatic shock management. Over a decade after wide spread application of damage control surgery damage control resuscitation was developed. DCR differs from previous resuscitation approaches by attempting an earlier and more aggressive correction of coagulopathy, as well as metabolic derangements like acidosis and hypothermia, often referred to as the 'deadly triad' or the 'bloody vicious cycle'. Permissive hypotension involves keeping the blood pressure low enough to avoid exacerbating uncontrolled haemorrhage while maintaining perfusion to vital end organs. The potential detrimental mechanisms of early, aggressive crystalloid resuscitation have been described. Limitation of fluid intake by using colloids, hypertonic saline (HTS) or hyperoncotic albumin solutions have been associated with favourable effects. HTS allows not only for rapid restoration of circulating intravascular volume with less administered fluid, but also attenuates post-injury oedema at the microcirculatory level and may improve microvascular perfusion. Capillary leak represents the maladaptive, often excessive, and undesirable loss of fluid and electrolytes with or without protein into the interstitium that generates oedema. The global increased permeability syndrome (GIPS) has been articulated in patients with persistent systemic inflammation failing to curtail transcapillary albumin leakage and resulting in increasingly positive net fluid balances. GIPS may represent a third hit after the initial insult and the ischaemia reperfusion injury. Novel markers like the capillary leak index, extravascular lung water and pulmonary permeability index may help the clinician in guiding appropriate fluid management. Capillary leak is an inflammatory condition with diverse triggers that results from a common pathway that includes ischaemia-reperfusion, toxic oxygen metabolite generation, cell wall and enzyme injury leading to a loss of capillary endothelial barrier function. Fluid overload should be avoided in this setting.

Abnormal early dynamic individual patterns of functional networks in low gamma band for depression recognition.

PubMed

Bi, Kun; Chattun, Mahammad Ridwan; Liu, Xiaoxue; Wang, Qiang; Tian, Shui; Zhang, Siqi; Lu, Qing; Yao, Zhijian

2018-06-13

The functional networks are associated with emotional processing in depression. The mapping of dynamic spatio-temporal brain networks is used to explore individual performance during early negative emotional processing. However, the dysfunctions of functional networks in low gamma band and their discriminative potentialities during early period of emotional face processing remain to be explored. Functional brain networks were constructed from the MEG recordings of 54 depressed patients and 54 controls in low gamma band (30-48 Hz). Dynamic connectivity regression (DCR) algorithm analyzed the individual change points of time series in response to emotional stimuli and constructed individualized spatio-temporal patterns. The nodal characteristics of patterns were calculated and fed into support vector machine (SVM). Performance of the classification algorithm in low gamma band was validated by dynamic topological characteristics of individual patterns in comparison to alpha and beta band. The best discrimination accuracy of individual spatio-temporal patterns was 91.01% in low gamma band. Individual temporal patterns had better results compared to group-averaged temporal patterns in all bands. The most important discriminative networks included affective network (AN) and fronto-parietal network (FPN) in low gamma band. The sample size is relatively small. High gamma band was not considered. The abnormal dynamic functional networks in low gamma band during early emotion processing enabled depression recognition. The individual information processing is crucial in the discovery of abnormal spatio-temporal patterns in depression during early negative emotional processing. Individual spatio-temporal patterns may reflect the real dynamic function of subjects while group-averaged data may neglect some individual information. Copyright © 2018. Published by Elsevier B.V.

OUR EXPERIENCES WITH ERLOTINIB IN SECOND AND THIRD LINE TREATMENT PATIENTS WITH ADVANCED STAGE IIIB/ IV NON-SMALL CELL LUNG CANCER

PubMed Central

Mehić, Bakir; Stanetić, Mirko; Tinjić, Ljuljeta; Smoljanović, Vlatka

2008-01-01

HeadHER1/EGFR is known to play a pivotal role in tumorigenesis and is overexpressed in up to 80% of NSCLCs. The study of an Expanded Access Clinical Program of Erlotinib in NSCLC is a phase IV openlabel, non-randomized, multicenter trial in patients with advanced (inoperable stage IIIb/IV) NSCLC who were eligible for treatment with erlotinib but had no access to trial participation. Patients for the study from Bosnia and Herzegovina (B&H) were selected from two Clinical centres (Sarajevo and Banja Luka). The aim of study was to evaluated efficacy and tolerability of erlotinib monotherapy in this setting. All patients who received at least one dose of erlotinib and data were entered in the database as of the CRF cut-off date of 14th May 2008 were included in analysis of data (n = 19). This population is defined as the Intent to Treat (ITT) population and includes all patients who had at least one dose of erlotinib regardless of whether major protocol violations were incurred. The findings are consistent with the results of the randomized, placebo-controlled BR.21 study. Indicating that erlotinib is an effective option for patients with advanced NSCLC who are unsuitable for, or who have previously failed standard chemotherapy. In B&H group of patients DCR was almost 84%, and PFS was approximately 24,7 weeks (compared with 44% and 9,7 weeks for erlotinib reported in phase III). Almost three quarter of the patients received erlotinib as their second line of therapy. Overall, erlotinib was well tolerated; there were no patients who withdrew due to a treatment-related AE (mainly rash) and there were few dose reductions. 24% of patients experienced an SAE (most commonly gastrointestinal (GI) disorders). PMID:19125714

Measuring In-Hospital Recovery After Colorectal Surgery Within a Well-Established Enhanced Recovery Pathway: A Comparison Between Hospital Length of Stay and Time to Readiness for Discharge.

PubMed

Balvardi, Saba; Pecorelli, Nicolò; Castelino, Tanya; Niculiseanu, Petru; Liberman, A Sender; Charlebois, Patrick; Stein, Barry; Carli, Franco; Mayo, Nancy E; Feldman, Liane S; Fiore, Julio F

2018-05-15

Hospital length of stay is often used as a measure of in-hospital recovery but may be confounded by organizational factors. Time to readiness for discharge may provide a superior index of recovery. The purpose of this study was to contribute evidence for the construct validity of time to readiness for discharge and length of stay as measures of in-hospital recovery after colorectal surgery in the context of a well-established enhanced recovery pathway. This was an observational validation study designed according to the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. The study was conducted at a university-affiliated tertiary hospital. A total of 100 consecutive patients undergoing elective colorectal resection (mean age = 65 y; 57% men; 81% laparoscopic) who participated in a randomized controlled trial were included. We tested a priori hypotheses that length of stay and time-to-readiness for discharge are longer in patients undergoing open surgery, with lower physical status, with severe comorbidities, with postoperative complications, undergoing rectal surgery, who are older (≥75 y), who have a new stoma, and who have inflammatory bowel disease. Median time-to-readiness for discharge and length of stay were both 3 days. For both measures, 6 of 8 construct validity hypotheses were supported (hypotheses 1 and 4-8). The use of secondary data from a randomized controlled trial (risk of selection bias) was a limitation. Results may not be generalizable to institutions where patient care is not equally structured. This study contributes evidence to the construct validity of time-to-readiness for discharge and length of stay as measures of in-hospital recovery within enhanced recovery pathways. Our findings suggest that length of stay can be a less resource-intensive and equally construct-valid index of in-hospital recovery compared with time-to-readiness for discharge. Enhanced recovery pathways may decrease process-of-care variances that impact length of stay, allowing more timely discharge once discharge criteria are achieved. See Video Abstract at http://links.lww.com/DCR/A564.

Diode laser-assisted endoscopic dacryocystorhinostomy: a comparison of three different combinations of adjunctive procedures.

PubMed

Dogan, Remzi; Meric, Aysenur; Ozsütcü, Mustafa; Yenigun, Alper

2013-08-01

Chronic dacryocystitis is a frequently encountered condition which can be corrected by dacryocystorhinostomy. Today, the diode laser is increasingly put to use in such corrective operations. This study aims to answer the questions of which adjunctive procedures and which combinations of such procedures are necessary and effective in securing more successful outcomes in diode laser dacryocystorhinostomy. This prospective randomized study included eighty patients (13 male, 67 female) who underwent dacryocystorhinostomy in our hospital during the 2 year period of January 2009-January 2011. The patients were selected consecutively and were randomly allocated to three groups. Group 1 (30): diode laser + mitomycin C + silicone intubation; Group 2 (27): diode laser + silicone intubation; Group 3 (23): diode laser + mitomycin C. All patients were evaluated postoperatively on day 1, week 1, and on the 1st, 3rd, 6th, 12th, 18th, and 24th months. The postoperative evaluation consisted of preoperative and postoperative ostium measurements, recording postoperative complications, and calculating and comparing success rates and operative times. The mean ages of the patients were 63.4 for Group 1, 60.7 for Group 2, and 61.8 for Group 3. No statistically significant difference was found among the groups regarding pre- and postoperative ostium measurements. The success rates were 84.3, 80, and 76.9 % for Groups 1, 2, and 3, respectively. Complications noted in Group 1 were restenosis (3), premature silicone tube loss (1), development of granulation tissue (3), synechia (2), infection (2), and hemorrhage (3). Those for Group 2 were restenosis (5), premature tube loss (2), granulation (8), synechia (6), infection (3), and hemorrhage (4). Group 3 had 6 cases with stenosis, 5 with granulation, 3 with infection, 6 with synechia, and 5 with hemorrhage. The operative times of the groups were 25.5, 15.3, and 18.1 min, respectively, for Group 1, 2, and 3. All three groups had statistically significant differences regarding the duration of surgery, with p < 0.001, p < 0.001, and p = 0.002 for Group 1 and 2, Group 1 and 3, and Group 2 and 3, respectively. Our study showed that when diode laser DCR was combined with bicanalicular silicone intubation and intraoperative mitomycin C application, those adjunctive procedures, while increasing operative time, enhanced the success rate and diminished complications as compared to diode laser plus intubation and/or diode laser plus mitomycin C.

Transcriptome Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection

PubMed Central

Kolliopoulou, Anna; Van Nieuwerburgh, Filip; Stravopodis, Dimitrios J.; Deforce, Dieter; Swevers, Luc; Smagghe, Guy

2015-01-01

Many insects can be persistently infected with viruses but do not show any obvious adverse effects with respect to physiology, development or reproduction. Here, Bombyx mori strain Daizo, persistently infected with cytoplasmic polyhedrosis virus (BmCPV), was used to study the host’s transcriptional response after pathogenic infection with the same virus in midgut tissue of larvae persistently and pathogenically infected as 2nd and 4th instars. Next generation sequencing revealed that from 13,769 expressed genes, 167 were upregulated and 141 downregulated in both larval instars following pathogenic infection. Several genes that could possibly be involved in B. mori immune response against BmCPV or that may be induced by the virus in order to increase infectivity were identified, whereas classification of differentially expressed transcripts (confirmed by qRT-PCR) resulted in gene categories related to physical barriers, immune responses, proteolytic / metabolic enzymes, heat-shock proteins, hormonal signaling and uncharacterized proteins. Comparison of our data with the available literature (pathogenic infection of persistently vs. non-persistently infected larvae) unveiled various similarities of response in both cases, which suggests that pre-existing persistent infection does not affect in a major way the transcriptome response against pathogenic infection. To investigate the possible host’s RNAi response against BmCPV challenge, the differential expression of RNAi-related genes and the accumulation of viral small RNAs (vsRNAs) were studied. During pathogenic infection, siRNA-like traces like the 2-fold up-regulation of the core RNAi genes Ago-2 and Dcr-2 as well as a peak of 20 nt small RNAs were observed. Interestingly, vsRNAs of the same size were detected at lower rates in persistently infected larvae. Collectively, our data provide an initial assessment of the relative significance of persistent infection of silkworm larvae on the host response following pathogenic infection with CPV, while they also highlight the relative importance of RNAi as an antiviral mechanism. PMID:25816294

Risk Factors Associated With Circumferential Resection Margin Positivity in Rectal Cancer: A Binational Registry Study.

PubMed

Warrier, Satish K; Kong, Joseph Cherng; Guerra, Glen R; Chittleborough, Timothy J; Naik, Arun; Ramsay, Robert G; Lynch, A Craig; Heriot, Alexander G

2018-04-01

Rectal cancer outcomes have improved with the adoption of a multidisciplinary model of care. However, there is a spectrum of quality when viewed from a national perspective, as highlighted by the Consortium for Optimizing the Treatment of Rectal Cancer data on rectal cancer care in the United States. The aim of this study was to assess and identify predictors of circumferential resection margin involvement for rectal cancer across Australasia. A retrospective study from a prospectively maintained binational colorectal cancer database was interrogated. This study is based on a binational colorectal cancer audit database. Clinical information on all consecutive resected rectal cancer cases recorded in the registry from 2007 to 2016 was retrieved, collated, and analyzed. The primary outcome measure was positive circumferential resection margin, measured as a resection margin ≤1 mm. A total of 3367 patients were included, with 261 (7.5%) having a positive circumferential resection margin. After adjusting for hospital and surgeon volume, hierarchical logistic regression analysis identified a 6-variable model encompassing the independent predictors, including urgent operation, abdominoperineal resection, open technique, low rectal cancer, T3 to T4, and N1 to N2. The accuracy of the model was 92.3%, with an receiver operating characteristic of 0.783 (p < 0.0001). The quantitative risk associated with circumferential resection margin positivity ranged from <1% (no risk factors) to 43% (6 risk factors). This study was limited by the lack of recorded long-term outcomes associated with circumferential resection margin positivity. The rate of circumferential resection margin involvement in patients undergoing rectal cancer resection in Australasia is low and is influenced by a number of factors. Risk stratification of outcome is important with the increasing demand for publicly accessible quality data. See Video Abstract at http://links.lww.com/DCR/A512.

Salvage Surgery for Locoregional Failure in Anal Squamous Cell Carcinoma.

PubMed

Guerra, Glen R; Kong, Joseph C; Bernardi, Maria-Pia; Ramsay, Robert G; Phillips, Wayne A; Warrier, Satish K; Lynch, A Craig; Ngan, Samuel Y; Heriot, Alexander G

2018-02-01

Anal squamous cell carcinoma is a rare cancer with a high cure rate, making research into the treatment of locoregional failure difficult. The purpose of this study was to examine factors related to local treatment failure and determine the outcomes of patients undergoing local salvage resection. This was a retrospective cohort study. This study was conducted at a quaternary referral center. Patients with anal squamous cell carcinoma treated with chemoradiotherapy between January 1983 and December 2015 were included. The influence of patient-, tumor-, and treatment-related factors on the primary outcome measures of locoregional failure, overall survival, and disease-free survival were investigated. Of 467 patients with anal squamous cell carcinoma, 63 experienced locoregional failure with 41 undergoing salvage resection. Twenty-seven patients (38%) had persistent disease and 36 (62%) developed locoregional recurrence. Multivariate analysis identified tumor stage (HR, 3.16; p < 0.002) as an independent predictor of locoregional failure. Thirty abdominoperineal resections and 11 pelvic exenterations were undertaken with no surgical mortality. At a median follow-up of 20 months (range, 4-150 months), 5-year overall and disease-free survival for the salvage cohort was 51% and 47%. Margin positivity was an independent predictor for relapse post-salvage surgery on multivariate analysis (HR, 20.1; p = 0.027). Nineteen patients (48%) developed further relapse, which included all 10 patients with a positive resection margin, 3 of whom underwent re-resection. Of the 19 patients with relapse, 3 remain alive and 2 have persistent disease. Limitations include the retrospective nature of the database, the prolonged time period of the study, and episodes of incomplete data. Advanced T stage is an independent predictor of local failure in anal squamous cell carcinoma. Most patients can be salvaged, with a positive resection margin being a strong predictor of further relapse and poor outcome. See Video Abstract at http://links.lww.com/DCR/A515.

Abdominal- versus thigh-based reconstruction of perineal defects in patients with cancer.

PubMed

Pang, John; Broyles, Justin M; Berli, Jens; Buretta, Kate; Shridharani, Sachin M; Rochlin, Danielle H; Efron, Jonathan E; Sacks, Justin M

2014-06-01

An abdominoperineal resection is an invasive procedure that leaves the patient with vast pelvic dead space. Traditionally, the vertical rectus abdominus myocutaneous flap is used to reconstruct these defects. Oftentimes, this flap cannot be used because of multiple ostomy placements or previous abdominal surgery. The anterolateral thigh flap can be used; however, the efficacy of this flap has been questioned. We report a single surgeon's experience with perineal reconstruction in patients with cancer with the use of either the vertical rectus abdominus myocutaneous flap or the anterolateral thigh flap to demonstrate acceptable outcomes with either repair modality. From 2010 to 2012, 19 consecutive patients with perineal defects secondary to cancer underwent flap reconstruction. A retrospective chart review of prospectively entered data was conducted to determine the frequency of short-term and long-term complications. This study was conducted at an academic, tertiary-care cancer center. Patients in the study were patients with cancer who were receiving perineal reconstruction. Interventions were surgical and included either abdomen- or thigh-based reconstruction. The main outcome measures included infection, flap failure, length of stay, and time to radiotherapy. Of the 19 patients included in our study, 10 underwent anterolateral thigh flaps and 9 underwent vertical rectus abdominus myocutaneous flaps for reconstruction. There were no significant differences in demographics between groups (p > 0.05). Surgical outcomes and complications demonstrated no significant differences in the rate of infection, hematoma, bleeding, or necrosis. The mean length of stay after reconstruction was 9.7 ± 3.4 days (± SD) in the anterolateral thigh flap group and 13.4 ± 7.7 days in the vertical rectus abdominus myocutaneous flap group (p > 0.05). The limitations of this study include a relatively small sample size and retrospective evaluation. This study suggests that the anterolateral thigh flap is an acceptable alternative to the vertical rectus abdominus myocutaneous flap for perineal reconstruction (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A134).

Osthole induces human nasopharyngeal cancer cells apoptosis through Fas-Fas ligand and mitochondrial pathway.

PubMed

Liu, Pei-Ying; Chang, Dun-Cheng; Lo, Yu-Sheng; Hsi, Yi-Ting; Lin, Chia-Chieh; Chuang, Yi-Ching; Lin, Shu-Hui; Hsieh, Ming-Ju; Chen, Mu-Kuan

2018-04-01

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. The present study investigated the activity of osthole in suppressing NPC along with the underlying mechanism. Cell growth inhibition was measured using the MTT assay. Apoptosis was detected through 4',6-diamidino-2-phenylindole staining and flow cytometry. Western blotting was used to identify the signaling pathway. Osthole markedly inhibited cell proliferation and induced apoptosis in the NPC cell line. Western blotting results revealed the increased activation of caspases 3, 8, and 9 and poly (ADP-ribose) polymerase. Osthole treatment significantly reduced the expression of the antiapoptotic protein Bcl-2 and increased the expression of the proapoptotic proteins Bax, Bak, BimL, BimS, and t-Bid. Osthole treatment also increased the expression of Fas, FADD, TNF-R1, TNF-R2, DcR2, RIP, and DR5. In addition, osthole treatment significantly increased the expression levels of phosphorylated ERK1/2 and JNK1/2. These results suggested that osthole exerts cytotoxic effects on NPC cell lines mainly through apoptosis mediated by the Fas-Fas ligand and mitochondrial pathway. Osthole could be a potential anticancer agent for NPC. © 2018 Wiley Periodicals, Inc.

Feasibility of an advanced thrust termination assembly for a solid propellant rocket motor

NASA Technical Reports Server (NTRS)

1975-01-01

A total of 68 quench tests were conducted in a vented bomb assembly (VBA). Designed to simulate full-scale motor operating conditions, this laboratory apparatus uses a 2-inch-diameter, end-burning propellant charge and an insulated disc of consolidated hydrated aluminum sulfate along with the explosive charge necessary to disperse the salt and inject it onto the burning surface. The VBA was constructed to permit variation of motor design parameters of interest; i.e., weight of salt per unit burning surface area, weight of explosive per unit weight of salt, distance from salt surface to burning surface, incidence angle of salt injection, chamber pressure, and burn time. Completely satisfactory salt quenching, without re-ignition, occurred in only two VBA tests. These were accomplished with a quench charge ratio (QCR) of 0.023 lb salt per square inch of burning surface at dispersing charge ratios (DCR) of 13 and 28 lb of salt per lb of explosive. Candidate materials for insulating salt charges from the rocket combustion environment were evaluated in firings of 5-inch-diameter, uncured end-burner motors. A pressed, alumina ceramic fiber material was selected for further evaluation and use in the final demonstration motor.

Deletion of the rbo Gene Increases the Oxygen Sensitivity of the Sulfate-Reducing Bacterium Desulfovibrio vulgaris Hildenborough

PubMed Central

Voordouw, Johanna K.; Voordouw, Gerrit

1998-01-01

The rbo gene of Desulfovibrio vulgaris Hildenborough encodes rubredoxin oxidoreductase (Rbo), a 14-kDa iron sulfur protein; forms an operon with the gene for rubredoxin; and is preceded by the gene for the oxygen-sensing protein DcrA. We have deleted the rbo gene from D. vulgaris with the sacB mutagenesis procedure developed previously (R. Fu and G. Voordouw, Microbiology 143:1815–1826, 1997). The absence of the rbo-gene in the resulting mutant, D. vulgaris L2, was confirmed by PCR and protein blotting with Rbo-specific polyclonal antibodies. D. vulgaris L2 grows like the wild type under anaerobic conditions. Exposure to air for 24 h caused a 100-fold drop in CFU of L2 relative to the wild type. The lag times of liquid cultures of inocula exposed to air were on average also greater for L2 than for the wild type. These results demonstrate that Rbo, which is not homologous with superoxide dismutase or catalase, acts as an oxygen defense protein in the anaerobic, sulfate-reducing bacterium D. vulgaris Hildenborough and likely also in other sulfate-reducing bacteria and anaerobic archaea in which it has been found. PMID:9687445

Matter density perturbation and power spectrum in running vacuum model

NASA Astrophysics Data System (ADS)

Geng, Chao-Qiang; Lee, Chung-Chi

2017-01-01

We investigate the matter density perturbation δm and power spectrum P(k) in the running vacuum model, with the cosmological constant being a function of the Hubble parameter, given by Λ = Λ0 + 6σHH0 + 3νH2, in which the linear and quadratic terms of H would originate from the QCD vacuum condensation and cosmological renormalization group, respectively. Taking the dark energy perturbation into consideration, we derive the evolution equation for δm and find a specific scale dcr = 2π/kcr, which divides the evolution of the universe into the sub-interaction and super-interaction regimes, corresponding to k ≪ kcr and k ≫ kcr, respectively. For the former, the evolution of δm has the same behaviour as that in the Λ cold dark model, while for the latter, the growth of δm is frozen (greatly enhanced) when ν + σ > (<)0 due to the couplings between radiation, matter and dark energy. It is clear that the observational data rule out the cases with ν < 0 and ν + σ < 0, while the allowed window for the model parameters is extremely narrow with ν , |σ | ≲ O(10^{-7}).

First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5-fluorouracil (DCF) plus panitumumab in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction: final results and biomarker analysis from an Italian oncology group for clinical research (GOIRC) phase II study.

PubMed

Tomasello, Gianluca; Valeri, Nicola; Ghidini, Michele; Smyth, Elizabeth C; Liguigli, Wanda; Toppo, Laura; Mattioli, Rodolfo; Curti, Alessandra; Hahne, Jens C; Negri, Federica M; Panni, Stefano; Ratti, Margherita; Lazzarelli, Silvia; Gerevini, Fabiana; Colombi, Chiara; Panni, Andrea; Rovatti, Massimo; Treccani, Leonardo; Martinotti, Mario; Passalacqua, Rodolfo

2017-12-19

Survival for patients with advanced gastroesophageal cancer (AGC) using standard treatment regimens is poor. EGFR overexpression is common in AGC and associated with poor prognosis. We hypothesized that increasing the dose intensity of chemotherapy and adding panitumumab could improve efficacy. HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d 1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1-2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c.i. on d 1-2, q15 d, plus pegfilgrastim 6 mg on d 3. Patients with disease control after 4 cycles received panitumumab until progression. From 05/2010 to 01/2014, 52 patients (75% male; median age 64.5 y; metastatic 90%, locally advanced 10%; 96% adenocarcinoma; 25% GEJ) were recruited. Three CR, 29 PR, 10 SD and 8 PD were observed, for an ORR by ITT (primary endpoint) of 62% (95% CI, 48%-75%) and a DCR of 81%. Median TTP was 4.9 months (95% CI, 4.2-7.0) and mOS 10 months (95% CI, 8.2- 13.5). Most frequent G3-4 toxicities: leucopenia (29%), asthenia (27%), skin rash (25%), neutropenia (19%), anorexia (17%), febrile neutropenia (13%), and diarrhea (15%). EGFR expression tested both with dd-PCR and FISH was not associated with any significant clinical benefit from treatment. Dose-dense DCF plus panitumumab is an active regimen. However, the toxicity profile of this limits further development. Further research on predictive biomarkers for treatment efficacy in AGC is required.Clinical trial information: 2009-016962-10.

First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5-fluorouracil (DCF) plus panitumumab in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction: final results and biomarker analysis from an Italian oncology group for clinical research (GOIRC) phase II study

PubMed Central

Tomasello, Gianluca; Valeri, Nicola; Ghidini, Michele; Smyth, Elizabeth C.; Liguigli, Wanda; Toppo, Laura; Mattioli, Rodolfo; Curti, Alessandra; Hahne, Jens C.; Negri, Federica M.; Panni, Stefano; Ratti, Margherita; Lazzarelli, Silvia; Gerevini, Fabiana; Colombi, Chiara; Panni, Andrea; Rovatti, Massimo; Treccani, Leonardo; Martinotti, Mario; Passalacqua, Rodolfo

2017-01-01

Background Survival for patients with advanced gastroesophageal cancer (AGC) using standard treatment regimens is poor. EGFR overexpression is common in AGC and associated with poor prognosis. We hypothesized that increasing the dose intensity of chemotherapy and adding panitumumab could improve efficacy. Methods HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d 1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1-2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c.i. on d 1-2, q15 d, plus pegfilgrastim 6 mg on d 3. Patients with disease control after 4 cycles received panitumumab until progression. Results From 05/2010 to 01/2014, 52 patients (75% male; median age 64.5 y; metastatic 90%, locally advanced 10%; 96% adenocarcinoma; 25% GEJ) were recruited. Three CR, 29 PR, 10 SD and 8 PD were observed, for an ORR by ITT (primary endpoint) of 62% (95% CI, 48%-75%) and a DCR of 81%. Median TTP was 4.9 months (95% CI, 4.2-7.0) and mOS 10 months (95% CI, 8.2- 13.5). Most frequent G3-4 toxicities: leucopenia (29%), asthenia (27%), skin rash (25%), neutropenia (19%), anorexia (17%), febrile neutropenia (13%), and diarrhea (15%). EGFR expression tested both with dd-PCR and FISH was not associated with any significant clinical benefit from treatment. Conclusions Dose-dense DCF plus panitumumab is an active regimen. However, the toxicity profile of this limits further development. Further research on predictive biomarkers for treatment efficacy in AGC is required. Clinical trial information: 2009-016962-10. PMID:29340092

Quality of Life in Rectal Cancer Patients After Chemoradiation: Watch-and-Wait Policy Versus Standard Resection - A Matched-Controlled Study.

PubMed

Hupkens, Britt J P; Martens, Milou H; Stoot, Jan H; Berbee, Maaike; Melenhorst, Jarno; Beets-Tan, Regina G; Beets, Geerard L; Breukink, Stéphanie O

2017-10-01

Fifteen to twenty percent of patients with locally advanced rectal cancer have a clinical complete response after chemoradiation therapy. These patients can be offered nonoperative organ-preserving treatment, the so-called watch-and-wait policy. The main goal of this watch-and-wait policy is an anticipated improved quality of life and functional outcome in comparison with a total mesorectal excision, while maintaining a good oncological outcome. The aim of this study was to compare the quality of life of watch-and-wait patients with a matched-controlled group of patients who underwent chemoradiation and surgery (total mesorectal excision group). This was a matched controlled study. This study was conducted at multiple centers. The study population consisted of 2 groups: 41 patients after a watch-and-wait policy and 41 matched patients after chemoradiation and surgery. Patients were matched on sex, age, tumor stage, and tumor height. All patients were disease free at the moment of recruitment after a minimal follow-up of 2 years. Quality of life was measured by validated questionnaires covering general quality of life (Short Form 36, European Organization for Research and Treatment of Cancer QLQ-C30), disease-specific total mesorectal excision (European Organization for Research and Treatment of Cancer QLQ-CR38), defecation problems (Vaizey and low anterior resection syndrome scores), sexual problems (International Index of Erectile Function and Female Sexual Function Index), and urinary dysfunction (International Prostate Symptom Score). The watch-and-wait group showed better physical and cognitive function, better physical and emotional roles, and better global health status compared with the total mesorectal excision group. The watch-and-wait patients showed fewer problems with defecation and sexual and urinary tract function. This study only focused on watch-and-wait patients who achieved a sustained complete response for 2 years. In addition, this is a study with a limited number of patients and with quality-of-life measurements on nonpredefined and variable intervals after surgery. After a successful watch-and-wait approach, the quality of life was better than after chemoradiation and surgery on several domains. However, chemoradiation therapy on its own is not without long-term side effects, because one-third of the watch-and-wait patients experienced major low anterior resection syndrome symptoms, compared with 66.7% of the patients in the total mesorectal excision group. See Video Abstract at http://links.lww.com/DCR/A395.

Is the Distance Worth It? Patients With Rectal Cancer Traveling to High-Volume Centers Experience Improved Outcomes.

PubMed

Xu, Zhaomin; Becerra, Adan Z; Justiniano, Carla F; Boodry, Courtney I; Aquina, Christopher T; Swanger, Alex A; Temple, Larissa K; Fleming, Fergal J

2017-12-01

It is unclear whether traveling long distances to high-volume centers would compensate for travel burden among patients undergoing rectal cancer resection. The purpose of this study was to determine whether operative volume outweighs the advantages of being treated locally by comparing the outcomes of patients with rectal cancer treated at local, low-volume centers versus far, high-volume centers. This was a population-based study. The National Cancer Database was queried for patients with rectal cancer. Patients with stage II or III rectal cancer who underwent surgical resection between 2006 and 2012 were included. The outcomes of interest were margins, lymph node yield, receipt of neoadjuvant chemoradiation, adjuvant chemotherapy, readmission within 30 days, 30-day and 90-day mortality, and 5-year overall survival. A total of 18,605 patients met inclusion criteria; 2067 patients were in the long-distance/high-volume group and 1362 in the short-distance/low-volume group. The median travel distance was 62.6 miles for the long-distance/high-volume group and 2.3 miles for the short-distance/low-volume group. Patients who were younger, white, privately insured, and stage III were more likely to have traveled to a high-volume center. When controlled for patient factors, stage, and hospital factors, patients in the short-distance/low-volume group had lower odds of a lymph node yield ≥12 (OR = 0.51) and neoadjuvant chemoradiation (OR = 0.67) and higher 30-day (OR = 3.38) and 90-day mortality (OR = 2.07) compared with those in the long-distance/high-volume group. The short-distance/low-volume group had a 34% high risk of overall mortality at 5 years compared with the long-distance/high-volume group. We lacked data regarding patient and physician decision making and surgeon-specific factors. Our results indicate that when controlled for patient, tumor, and hospital factors, patients who traveled a long distance to a high-volume center had improved lymph node yield, neoadjuvant chemoradiation receipt, and 30- and 90-day mortality compared with those who traveled a short distance to a low-volume center. They also had improved 5-year survival. See Video Abstract at http://links.lww.com/DCR/A446.

Prehospital Medicine and the Future Will ECMO Ever Play a Role?

PubMed

Macku, David; Hedvicak, Pavel; Quinn, John; Bencko, Vladimir

Due to the hybrid warfare currently experienced by multiple NATO coalition and NATO partner nations, the tactical combat casualty care (TCCC) paradigm is greatly challenged. One of the major challenges to TCCC is the ad hoc extension phase in resource-poor environments, referred to as prolonged field care (PFC) and forward resuscitative care (FRC). The nuanced clinical skills with limited resources required by warfighters and auxiliary health care professionals to mitigate death on the battlefield and prevent morbidity and mortality in the PFC phase represent a balance that is still under review. The aim of our article is to describe the connection between extracorporeal membrane oxygenation (ECMO) or the extracorporeal life support (ECLS) treatment and its possible improvement in prehospital trauma care, at a Role 1 or 2 facility and, more provocatively, in the PFC phase of care in the future through innovative technology and how it connects with FRC. We report and describe here the primary components of ECMO/ECLS and present the main concept of a human extracorporeal circulation cocoon as a transitional living form for the cardiopulmonary stabilization of wounded combatants on the battlefield and their transportation to higher echelons of care and treatment facilities (to include damage control resuscitation [DCR] and damage control surgery [DCS]). As clinical governance, these matters would fall within the remit of the Committee on Surgical Combat Casualty Care (CoSCCC) and the Committee on Enroute Combat Casualty Care (CoERCCC), and it is within this framework that we propose this concept piece of ECMO in the prehospital space. We caution that this report is a proposed innovation to TCCC but also serves to push the envelope of the PFC and FRC paradigm. What we propose will not change the practice this year, but as ECMO technology progresses, it may change our practice within the next decade. We conclude with proposed novel future research to save life on the battlefield with ECMO as a major challenge and one worth the focus of further research. Medicine is controversial and constantly changing; for those who work in prehospital and battlefield medicine, change is the only constant on which we rely, and without provocative discussion that makes our systems and practice more robust, we will fail. 2018.

Double-spiral magnetic structure of the Fe/Cr multilayer revealed by nuclear resonance reflectivity

NASA Astrophysics Data System (ADS)

Andreeva, M. A.; Baulin, R. A.; Chumakov, A. I.; Rüffer, R.; Smirnov, G. V.; Babanov, Y. A.; Devyaterikov, D. I.; Milyaev, M. A.; Ponomarev, D. A.; Romashev, L. N.; Ustinov, V. V.

2018-01-01

We have studied the magnetization depth profiles in a [57Fe (dFe) /Cr (dCr) ]30 multilayer with ultrathin Fe layers and nominal thickness of the chromium spacers dCr≈2.0 nm using nuclear resonance scattering of synchrotron radiation. The presence of a broad pure-magnetic half-order (1/2) Bragg reflection has been detected at zero external field. The joint fit of the reflectivity curves and Mössbauer spectra of reflectivity measured near the critical angle and at the "magnetic" peak reveals that the magnetic structure of the multilayer is formed by two spirals, one in the odd and another one in the even iron layers, with the opposite signs of rotation. The double-spiral structure starts from the surface with the almost-antiferromagnetic alignment of the adjacent Fe layers. The rotation of the two spirals leads to nearly ferromagnetic alignment of the two magnetic subsystems at some depth, where the sudden turn of the magnetic vectors by ˜180∘ (spin flop) appears, and both spirals start to rotate in opposite directions. The observation of this unusual double-spiral magnetic structure suggests that the unique properties of giant magnetoresistance devices can be further tailored using ultrathin magnetic layers.

GTSF-1 is required for formation of a functional RNA-dependent RNA Polymerase complex in Caenorhabditis elegans.

PubMed

Almeida, Miguel Vasconcelos; Dietz, Sabrina; Redl, Stefan; Karaulanov, Emil; Hildebrandt, Andrea; Renz, Christian; Ulrich, Helle D; König, Julian; Butter, Falk; Ketting, René F

2018-05-16

Argonaute proteins and their associated small RNAs (sRNAs) are evolutionarily conserved regulators of gene expression. Gametocyte-specific factor 1 (Gtsf1) proteins, characterized by two tandem CHHC zinc fingers and an unstructured C-terminal tail, are conserved in animals and have been shown to interact with Piwi clade Argonautes, thereby assisting their activity. We identified the Caenorhabditis elegans Gtsf1 homolog, named it gtsf-1 and characterized it in the context of the sRNA pathways of C. elegans We report that GTSF-1 is not required for Piwi-mediated gene silencing. Instead, gtsf-1 mutants show a striking depletion of 26G-RNAs, a class of endogenous sRNAs, fully phenocopying rrf-3 mutants. We show, both in vivo and in vitro , that GTSF-1 interacts with RRF-3 via its CHHC zinc fingers. Furthermore, we demonstrate that GTSF-1 is required for the assembly of a larger RRF-3 and DCR-1-containing complex (ERIC), thereby allowing for 26G-RNA generation. We propose that GTSF-1 homologs may act to drive the assembly of larger complexes that act in sRNA production and/or in imposing sRNA-mediated silencing activities. © 2018 The Authors.

Mucinous Histology Signifies Poor Oncologic Outcome in Young Patients With Colorectal Cancer.

PubMed

Soliman, Basem G; Karagkounis, Georgios; Church, James M; Plesec, Thomas; Kalady, Matthew F

2018-05-01

The incidence of colorectal cancer in the young (under age 40) is increasing, and this population has worse oncologic outcomes. Mucinous histology is a potential prognostic factor in colorectal cancer, but has not been evaluated specifically in young patients. The objective of the study was to determine factors associated with poor outcome in young patients with colorectal cancer (≤40 years) and to determine relationships between mucinous histology and oncologic outcomes in this population. This is a retrospective study. Patients from a single-institution tertiary care center were studied. A total of 224 patients with colorectal cancer under 40 years of age diagnosed between 1990 and 2010 were included (mean age, 34.7 years; 51.3% female). 34 patients (15.2%) had mucinous histology. There were no interventions. Oncologic outcomes were analyzed according to the presence of mucinous histology. The mucinous and nonmucin colorectal cancer study populations were statistically similar in age, sex, tumor location, pathological stage, differentiation, and adjuvant chemotherapy use. Five-year disease-free survival was 29.1% versus 71.3% (p < 0.0001) and 5-year overall survival was 54.7% versus 80.3% (p < 0.0001) for mucinous and nonmucinous patients, respectively. Mucinous colorectal cancers recurred earlier at a median time of 36.4 months versus 94.2 months for nonmucin colorectal cancers (p < 0.001). On multivariate analysis, pathological stage (stage II HR, 3.61; 95% CI, 1.37-9.50; stage III HR, 5.27; 95% CI, 2.12-12.33), positive margins (HR, 1.95; 95% CI, 1.12-3.23), angiolymphatic invasion (HR, 2.15; 95% CI, 1.26-3.97), and mucinous histology (HR, 2.36; 95% CI, 1.44-3.96) were independently associated with worse disease-free and overall survival. This is a retrospective study without genetic information. Mucinous histology is a negative prognostic factor in young patients with colorectal cancer. This is associated with early and high recurrence rates, despite use of standard neoadjuvant and adjuvant regimens. Physicians need to be aware of this association and potentially explore novel treatment options. See Video Abstract at http://links.lww.com/DCR/A575.

Racial and Socioeconomic Differences Manifest in Process Measure Adherence for Enhanced Recovery After Surgery Pathway.

PubMed

Leeds, Ira L; Alimi, Yewande; Hobson, Deborah R; Efron, Jonathan E; Wick, Elizabeth C; Haut, Elliott R; Johnston, Fabian M

2017-10-01

Adherence to care processes and surgical outcomes varies by population subgroups for the same procedure. Enhanced recovery after surgery pathways are intended to standardize care, but their effect on process adherence and outcomes for population subgroups is unknown. This study aims to demonstrate the association between recovery pathway implementation, process measures, and short-term surgical outcomes by population subgroup. This study is a pre- and post-quality improvement implementation cohort study. This study was conducted at a tertiary academic medical center. A modified colorectal enhanced recovery after surgery pathway was implemented. Patients were included who had elective colon and rectal resections before (2013) and following (2014-2016) recovery pathway implementation. Thirty-day outcomes by race and socioeconomic status were analyzed using a difference-in-difference approach with correlation to process adherence. We identified 639 cases (199 preimplementation, 440 postimplementation). In these cases, 75.2% of the patients were white, and 91.7% had a high socioeconomic status. Groups were similar in terms of other preoperative characteristics. Following pathway implementation, median lengths of stay improved in all subgroups (-1.0 days overall, p ≤ 0.001), but with no statistical difference by race or socioeconomic status (p = 0.89 and p = 0.29). Complication rates in both racial and socioeconomic groups were no different (26.4% vs 28.8%, p = 0.73; 27.3% vs 25.0%, p = 0.86) and remained unchanged with implementation (p = 0.93, p = 0.84). By race, overall adherence was 31.7% in white patients and 26.5% in nonwhite patients (p = 0.32). Although stratification by socioeconomic status demonstrated decreased overall adherence in the low-status group (31.8% vs 17.1%, p = 0.05), white patients were more likely to have regional pain therapy (57.1% vs 44.1%, p = 0.02) with a similar trend seen with socioeconomic status. Data were collected primarily for quality improvement purposes. Differences in outcomes by race and socioeconomic status did not arise following implementation of an enhanced recovery pathway. Differences in process measures by population subgroups highlight differences in care that require further investigation. See Video Abstract at http://links.lww.com/DCR/A386.

Predicting Survival After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Appendix Adenocarcinoma.

PubMed

Aziz, Omer; Jaradat, Ihab; Chakrabarty, Bipasha; Selvasekar, Chelliah R; Fulford, Paul E; Saunders, Mark P; Renehan, Andrew G; Wilson, Malcolm S; O'Dwyer, Sarah T

2018-05-15

Appendix adenocarcinomas are rare tumors with propensity for peritoneal metastasis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an established treatment with curative intent, but, to date, studies reporting survival have been heterogeneous with regard to their patient groups (including other tumor types), interventions (not all patients receiving intraperitoneal chemotherapy), and follow-up (varying surveillance protocols). The aim of this study is to quantify the impact of this intervention on survival in a homogeneous group of patients with appendix adenocarcinoma receiving standardized treatment and follow-up, and to determine the impact of prognostic indicators on survival. This is a retrospective analysis of a prospective database at a national peritoneal tumor center where all patients had their appendix pathology reviewed and management planned by a specialized peritoneal tumor multidisciplinary team. Data were extracted on prognostic indicators including peritoneal cancer index, completeness of cytoreduction score, preoperative tumor markers, and histological features. Overall and disease event-free survival from the date of intervention were evaluated using Kaplan Meier curves and univariate Cox proportional hazards regression analysis. A total of 65 patients underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for appendix adenocarcinoma between 2005 and 2015. Median follow-up was 44.3 months. The overall survival was 55.5% and disease event-free survival was 36.1% (5-year rate). Peritoneal Cancer Index <7, complete cytoreduction score of 0, and preoperative CEA of <6 were all associated with significantly higher overall and disease event-free survival. CA19-9 <38 and CA125 <31 were not associated with a significantly higher overall or disease event-free survival. The sample size was limited because of the rarity of this tumor type. This study quantifies the impact of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy on overall and disease event-free survival for appendix adenocarcinoma, identifying key prognostic indicators that may guide treatment. It supports the referral of these rare tumors to specialist centers with appropriate expertise for initial management and follow-up. See Video Abstract at http://www.links.lww.com/DCR/A595.

Greatest Challenges of Rectal Cancer Survivors: Results of a Population-Based Survey.

PubMed

McMullen, Carmit K; Bulkley, Joanna E; Altschuler, Andrea; Wendel, Christopher S; Grant, Marcia; Hornbrook, Mark C; Sun, Virginia; Krouse, Robert S

2016-11-01

Eliciting the priorities of cancer survivors is essential to address the specific needs of cancer survivor subgroups. The purpose of this study was to describe the greatest challenges related to treatment for long-term rectal cancer survivors. This was an observational study with a cross-sectional survey. The study included members of Kaiser Permanente Northern California and Northwest health plans. A survey was mailed to long-term (≥5 years postdiagnosis) survivors of rectal cancer who had an anastomosis, temporary ostomy, or permanent ostomy. The main outcome was measured with an open-ended question about the greatest challenge related to cancer surgery. We categorized responses using a grounded theory approach with double coding for reliability. Bonferroni-adjusted χ values were used to assess differences in the proportions of subgroups who mentioned challenges within each response category. The survey completion rate was 61% (577/953); 76% (440/577) of participants responded to the greatest challenge question. The greatest challenges for respondents were bowel/ostomy management (reported by 44%), negative psychosocial effects (37%), late effects of treatment (21%), comorbidities and aging (13%), postoperative recovery (5%), and negative healthcare experiences (5%). Survivors with temporary ostomy or anastomosis were more likely than survivors with permanent ostomy to report late effects (p < 0.0001 and p = 0.01). Survivors with anastomosis were less likely than survivors with permanent ostomy to report negative psychosocial impacts (p = 0.0001). Generalizability is restricted by the lack of ethnically and racially diverse, uninsured (non-Medicare-eligible population), and non-English-speaking participants. Because the survey was cross-sectional and included respondents at different times since diagnosis, we could not adequately address changes in the greatest challenges over time. Our results reveal the need for bowel/ostomy management, psychosocial services, and surveillance for late effects in survivorship and supportive care services for all survivors of rectal cancer, regardless of ostomy status. The perspective of long-term survivors with anastomosis reveals challenges that may not be anticipated during decision making for treatment (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A254).

Rapid control and feedback rates enhance neuroprosthetic control

PubMed Central

Shanechi, Maryam M.; Orsborn, Amy L.; Moorman, Helene G.; Gowda, Suraj; Dangi, Siddharth; Carmena, Jose M.

2017-01-01

Brain-machine interfaces (BMI) create novel sensorimotor pathways for action. Much as the sensorimotor apparatus shapes natural motor control, the BMI pathway characteristics may also influence neuroprosthetic control. Here, we explore the influence of control and feedback rates, where control rate indicates how often motor commands are sent from the brain to the prosthetic, and feedback rate indicates how often visual feedback of the prosthetic is provided to the subject. We developed a new BMI that allows arbitrarily fast control and feedback rates, and used it to dissociate the effects of each rate in two monkeys. Increasing the control rate significantly improved control even when feedback rate was unchanged. Increasing the feedback rate further facilitated control. We also show that our high-rate BMI significantly outperformed state-of-the-art methods due to higher control and feedback rates, combined with a different point process mathematical encoding model. Our BMI paradigm can dissect the contribution of different elements in the sensorimotor pathway, providing a unique tool for studying neuroprosthetic control mechanisms. PMID:28059065

Rapid control and feedback rates enhance neuroprosthetic control

NASA Astrophysics Data System (ADS)

Shanechi, Maryam M.; Orsborn, Amy L.; Moorman, Helene G.; Gowda, Suraj; Dangi, Siddharth; Carmena, Jose M.

2017-01-01

Brain-machine interfaces (BMI) create novel sensorimotor pathways for action. Much as the sensorimotor apparatus shapes natural motor control, the BMI pathway characteristics may also influence neuroprosthetic control. Here, we explore the influence of control and feedback rates, where control rate indicates how often motor commands are sent from the brain to the prosthetic, and feedback rate indicates how often visual feedback of the prosthetic is provided to the subject. We developed a new BMI that allows arbitrarily fast control and feedback rates, and used it to dissociate the effects of each rate in two monkeys. Increasing the control rate significantly improved control even when feedback rate was unchanged. Increasing the feedback rate further facilitated control. We also show that our high-rate BMI significantly outperformed state-of-the-art methods due to higher control and feedback rates, combined with a different point process mathematical encoding model. Our BMI paradigm can dissect the contribution of different elements in the sensorimotor pathway, providing a unique tool for studying neuroprosthetic control mechanisms.

Reporting of Cardiovascular Medical Device Adverse Events to Pharmaceuticals and Medical Devices Agency, Japan☆

PubMed Central

Handa, Nobuhiro; Ishii, Kensuke; Matsui, Yutaka; Ando, Yuki

2015-01-01

Background Marketing authorization holders (MAHs) are obligated to report adverse events (AEs) within 15 days (some cases 30 days) to the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan. Methods To analyze the timeliness of AE reporting to the PMDA, 6610 reports for five categories of cardiovascular devices were retrieved. Two durations were calculated: (1) time from the date the AE occurred to that when the MAH captured it (DOC: days); and (2) time from the date of MAH capture to that of MAH report (DCR: days). Number of DOC > 15 days (DOC15) and delayed reports (DCR > 15 or 30 days) were also calculated. Results AEs included 9.2% deaths and 7.5% non-recoveries. DOC15 and delayed reports were 51.0% and 10.9%, respectively. By multivariate analysis, DOC15 was associated with foreign AE, device category, MAH, patient outcome, event category, and AE that had to be reported within 15 or 30 days (AE15/30). Delayed report was associated with device category, MAH, patient outcome, event category, and AE15/30. Comments Although Japanese MAHs complied with the obligation to report AEs, they often failed to share AEs with healthcare providers. Registry may be a potential solution, although the cooperation of healthcare providers to input data is essential. PMID:26501120

Transcriptional silencing of a transgene by RNAi in the soma of C. elegans.

PubMed

Grishok, Alla; Sinskey, Jina L; Sharp, Phillip A

2005-03-15

The silencing of transgene expression at the level of transcription in the soma of Caenorhabditis elegans through an RNAi-dependent pathway has not been previously characterized. Most gene silencing due to RNAi in C. elegans occurs at the post-transcriptional level. We observed transcriptional silencing when worms containing the elt-2::gfp/LacZ transgene were fed RNA produced from the commonly used L4440 vector. The transgene and the vector share plasmid backbone sequences. This transgene silencing depends on multiple RNAi pathway genes, including dcr-1, rde-1, rde-4, and rrf-1. Unlike post-transcriptional gene silencing in worms, elt-2::gfp/LacZ silencing is dependent on the PAZ-PIWI protein Alg-1 and on the HP1 homolog Hpl-2. The latter is a chromatin silencing factor, and expression of the transgene is inhibited at the level of intron-containing precursor mRNA. This inhibition is accompanied by a decrease in the acetylation of histones associated with the transgene. This transcriptional silencing in the soma can be distinguished from transgene silencing in the germline by its inability to be transmitted across generations and its dependence on the rde-1 gene. We therefore define this type of silencing as RNAi-induced Transcriptional Gene Silencing (RNAi-TGS). Additional chromatin-modifying components affecting RNAi-TGS were identified in a candidate RNAi screen.

Testing of DLR C/C-SiC for HIFiRE 8 Scramjet Combustor

NASA Technical Reports Server (NTRS)

Glass, David E.; Capriotti, Diego P.; Reimer, Thomas; Kutemeyer, Marius; Smart, Michael

2013-01-01

Ceramic Matrix Composites (CMCs) have been proposed for hot structures in scramjet combustors. Previous studies have calculated significant weight savings by utilizing CMCs (active and passive) versus actively cooled metallic scramjet structures. Both a C/C and a C/C-SiC material system fabricated by DLR (Stuttgart, Germany) are being considered for use in a passively cooled combustor design for HIFiRE 8, a joint Australia / AFRL hypersonic flight program, expected to fly at Mach 7 for approximately 30 sec, at a dynamic pressure of 55 kPa. Flat panels of the DLR C/C and the C/C-SiC were tested in the NASA Langley Direct Connect Rig (DCR) at Mach 5 and Mach 6 enthalpy for several minutes. Gaseous hydrogen fuel was used to fuel the scramjet combustor. The test panels were instrumented with embedded Type K and Type S thermocouples. Zirconia felt insulation was used in some of the tests to increase the surface temperature of the C/C-SiC panel for approximately 350degF. The final C/C-SiC panel was tested for 3 cycles totaling over 135 sec at Mach 6 enthalpy. Slightly more erosion was observed on the C/C panel than the C/C-SiC panels, but both material systems demonstrated acceptable recession performance for the HIFiRE 8 flight.

Efficacy of ranitidine in olanzapine-induced weight gain: a dose-response study.

PubMed

Mehta, Varun S; Ram, Daya

2016-12-01

Weight gain has long been recognized as a side-effect of atypical antipsychotic drugs. Numerous new approaches have been tried for prevention of weight gain, the H2 blockers being one of them. The study was conducted with the aim to evaluate the efficacy of ranitidine in olanzapine-induced weight gain at two fixed doses of 150 and 300 mg day -1 . Seventy-five inpatients with an ICD-10-DCR diagnosis of schizophrenia as their first episode were randomized into three groups of 25 patients each, receiving 150 mg day -1 ranitidine, 300 mg day -1 ranitidine and third group receiving only olanzapine. Their weight and body mass index (BMI) were measured at baseline and at intervals of 4 and 8 weeks. All patients were comparable with respect to their weight and BMI at baseline. When a change in the weight and BMI was assessed at 4 and 8 weeks from baseline, no significant difference was observed between the three groups. Ranitidine at doses of 150 and 300 mg day -1 when combined with olanzapine was ineffective in attenuating olanzapine-induced weight gain. The likely reasons could be the use of low doses for a shorter period of time, or mechanisms other than H2 receptors might play an important role in weight gain. © 2014 Wiley Publishing Asia Pty Ltd.

RNAi drives nonreciprocal translocations at eroding chromosome ends to establish telomere-free linear chromosomes.

PubMed

Begnis, Martina; Apte, Manasi S; Masuda, Hirohisa; Jain, Devanshi; Wheeler, David Lee; Cooper, Julia Promisel

2018-04-01

The identification of telomerase-negative HAATI (heterochromatin amplification-mediated and telomerase-independent) cells, in which telomeres are superseded by nontelomeric heterochromatin tracts, challenged the idea that canonical telomeres are essential for chromosome linearity and raised crucial questions as to how such tracts translocate to eroding chromosome ends and confer end protection. Here we show that HAATI arises when telomere loss triggers a newly recognized illegitimate translocation pathway that requires RNAi factors. While RNAi is necessary for the translocation events that mobilize ribosomal DNA (rDNA) tracts to all chromosome ends (forming "HAATI rDNA " chromosomes), it is dispensable for HAATI rDNA maintenance. Surprisingly, Dicer (Dcr1) plays a separate, RNAi-independent role in preventing formation of the rare HAATI subtype in which a different repetitive element (the subtelomeric element) replaces telomeres. Using genetics and fusions between shelterin components and rDNA-binding proteins, we mapped the mechanism by which rDNA loci engage crucial end protection factors-despite the absence of telomere repeats-and secure end protection. Sequence analysis of HAATI rDNA genomes allowed us to propose RNA and DNA polymerase template-switching models for the mechanism of RNAi-triggered rDNA translocations. Collectively, our results reveal unforeseen roles for noncoding RNAs (ncRNAs) in assembling a telomere-free chromosome end protection device. © 2018 Begnis et al.; Published by Cold Spring Harbor Laboratory Press.

Analysis of risk factors for schizophrenia with two different case definitions: a nationwide register-based external validation study.

PubMed

Sørensen, Holger J; Larsen, Janne T; Mors, Ole; Nordentoft, Merete; Mortensen, Preben B; Petersen, Liselotte

2015-03-01

Different case definitions of schizophrenia have been used in register based research. However, no previous study has externally validated two different case definitions of schizophrenia against a wide range of risk factors for schizophrenia. We investigated hazard ratios (HRs) for a wide range of risk factors for ICD-10 DCR schizophrenia using a nationwide Danish sample of 2,772,144 residents born in 1955-1997. We compared one contact only (OCO) (the case definition of schizophrenia used in Danish register based studies) with two or more contacts (TMC) (a case definition of at least 2 inpatient contacts with schizophrenia). During the follow-up, the OCO definition included 15,074 and the TMC 7562 cases; i.e. half as many. The TMC case definition appeared to select for a worse illness course. A wide range of risk factors were uniformly associated with both case definitions and only slightly higher risk estimates were found for the TMC definition. Choosing at least 2 inpatient contacts with schizophrenia (TMC) instead of the currently used case definition would result in almost similar risk estimates for many well-established risk factors. However, this would also introduce selection and include considerably fewer cases and reduce power of e.g. genetic studies based on register-diagnosed cases only. Copyright © 2015 Elsevier B.V. All rights reserved.

Status of NASA's Space Launch System

NASA Technical Reports Server (NTRS)

Honeycutt, John; Lyles, Garry

2016-01-01

NASA's Space Launch System (SLS) continued to make significant progress in 2015 and 2016, completing hardware and testing that brings NASA closer to a new era of deep space exploration. Programmatically, SLS completed Critical Design Review (CDR) in 2015. A team of independent reviewers concluded that the vehicle design is technically and programmatically ready to move to Design Certification Review (DCR) and launch readiness in 2018. Just five years after program start, every major element has amassed development and flight hardware and completed key tests that will lead to an accelerated pace of manufacturing and testing in 2016 and 2017. Key to SLS' rapid progress has been the use of existing technologies adapted to the new launch vehicle. The existing fleet of RS-25 engines is undergoing adaptation tests to prove it can meet SLS requirements and environments with minimal change. The four-segment shuttle-era booster has been modified and updated with a fifth propellant segment, new insulation, and new avionics. The Interim Cryogenic Upper Stage is a modified version of an existing upper stage. The first Block I SLS configuration will launch a minimum of 70 metric tons (t) of payload to low Earth orbit (LEO). The vehicle architecture has a clear evolutionary path to more than 100t and, ultimately, to 130t. Among the program's major 2015-2016 accomplishments were two booster qualification hotfire tests, a series of RS-25 adaptation hotfire tests, manufacturing of most of the major components for both core stage test articles and first flight tank, delivery of the Pegasus core stage barge, and the upper stage simulator. Renovations to the B-2 test stand for stage green run testing was completed at NASA Stennis Space Center. This year will see the completion of welding for all qualification and flight EM-1 core stage components and testing of flight avionics, completion of core stage structural test stands, casting of the EM-1 solid rocket motors, additional testing of RS-25 engines and flight engine controllers This paper will discuss these and other technical and programmatic successes and challenges over the past year and provide a preview of work ahead before the first flight of this new capability.

Preferential effects of low volume versus high volume replacement with crystalloid fluid in a hemorrhagic shock model in pigs.

PubMed

Ponschab, Martin; Schöchl, Herbert; Keibl, Claudia; Fischer, Henrik; Redl, Heinz; Schlimp, Christoph J

2015-10-06

Fluid resuscitation is a core stone of hemorrhagic shock therapy, and crystalloid fluids seem to be associated with lower mortality compared to colloids. However, as redistribution starts within minutes, it has been suggested to replace blood loss with a minimum of a three-fold amount of crystalloids. The hypothesis was that in comparison to high volume (HV), a lower crystalloid volume (LV) achieves a favorable coagulation profile and exerts sufficient haemodynamics in the acute phase of resuscitation. In 24 anaesthetized pigs, controlled arterial blood loss of 50 % of the estimated blood volume was either (n = 12) replaced with a LV (one-fold) or a HV (three-fold) volume of a balanced, acetated crystalloid solution at room temperature. Hemodynamic parameters, dilution effects and coagulation profile by standard coagulation tests and thromboelastometry at baseline and after resuscitation were determined in both groups. LV resuscitation increased MAP significantly less compared to the HV, 61 ± 7 vs. 82 ± 14 mmHg (p < 0.001) respectively, with no difference between lactate and base excess between groups. Haematocrit after fluid replacement was 0.20 vs. 0.16 (LV vs. HV, p < 0.001), suggesting a grade of blood dilution of 32 vs. 42 % (p < 0.001) compared to baseline values. Compared to LV, HV resulted in decreased core temperature (37.5 ± 0.2 vs. 36.0 ± 0.6 °C, p < 0.001), lower platelet count (318 ± 77 vs. 231 ± 53 K/μL, p < 0.01) and lower plasma fibrinogen levels (205 ± 19 vs. 168 ± 24 mg/dL, p < 0.001). Thromboelastometric measurements showed a significant impairment on viscoelastic clot properties following HV group. While prothrombin time index decreased significantly more in the HV group, activated partial thromboplastin time did not differ between both groups. HV did not result in hyperchloraemic acidosis. Coagulation parameters represented by plasma fibrinogen and ROTEM parameters were also less impaired with LV. With regrad to hematocrit, 60 % of LV remained intracascular , while in HV only 30 % remained in circulation within the first hour of administration. In the acute setting of 50 % controlled blood loss, a one fold LV crystalloid replacement strategy is sufficient to adequately raise blood pressure up to a mean arterial pressure >50 mm Hg. The concept of damage control resuscitation (DCR) with permissive hypotension may be better met by using LV as compared to a three fold HV resuscitation strategy. High volume administration of an acetated balanced crystalloid does not lead to hyperchloraemic acidosis, but may negatively influence clinical parameters, such as higher blood pressure, lower body temperature and impaired coagulation parameters, which could potentially increase bleeding after trauma. Replacement of acute blood loss with just an equal amount of an acetated balanced crystalloid appears to be the preferential treatment strategy in the acute phase after controlled bleeding.

Impact of Release Rates on the Effectiveness of Augmentative Biological Control Agents

PubMed Central

Crowder, David W.

2007-01-01

To access the effect of augmentative biological control agents, 31 articles were reviewed that investigated the impact of release rates of 35 augmentative biological control agents on the control of 42 arthropod pests. In 64% of the cases, the release rate of the biological control agent did not significantly affect the density or mortality of the pest insect. Results where similar when parasitoidsor predators were utilized as the natural enemy. Within any order of natural enemy, there were more cases where release rates did not affect augmentative biological control than cases where release rates were significant. There were more cases in which release rates did not affect augmentative biological control when pests were from the orders Hemiptera, Acari, or Diptera, but not with pests from the order Lepidoptera. In most cases, there was an optimal release rate that produced effective control of a pest species. This was especially true when predators were used as a biological control agent. Increasing the release rate above the optimal rate did not improve control of the pest and thus would be economically detrimental. Lower release rates were of ten optimal when biological control was used in conjunction with insecticides. In many cases, the timing and method of biological control applications were more significant factors impacting the effectiveness of biological control than the release rate. Additional factors that may limit the relative impact of release rates include natural enemy fecundity, establishment rates, prey availability, dispersal, and cannibalism. PMID:20307240

Treatment Failure With Rhythm and Rate Control Strategies in Patients With Atrial Fibrillation and Congestive Heart Failure: An AF-CHF Substudy.

PubMed

Dyrda, Katia; Roy, Denis; Leduc, Hugues; Talajic, Mario; Stevenson, Lynne Warner; Guerra, Peter G; Andrade, Jason; Dubuc, Marc; Macle, Laurent; Thibault, Bernard; Rivard, Lena; Khairy, Paul

2015-12-01

Rate and rhythm control strategies for atrial fibrillation (AF) are not always effective or well tolerated in patients with congestive heart failure (CHF). We assessed reasons for treatment failure, associated characteristics, and effects on survival. A total of 1,376 patients enrolled in the AF-CHF trial were followed for 37  ±  19 months, 206 (15.0%) of whom failed initial therapy leading to crossover. Rhythm control was abandoned more frequently than rate control (21.0% vs. 9.1%, P < 0.0001). Crossovers from rhythm to rate control were driven by inefficacy, whereas worsening heart failure was the most common reason to crossover from rate to rhythm control. In multivariate analyses, failure of rhythm control was associated with female sex, higher serum creatinine, functional class III or IV symptoms, lack of digoxin, and oral anticoagulation. Factors independently associated with failure of rate control were paroxysmal (vs. persistent) AF, statin therapy, and presence of an implantable cardioverter-defibrillator. Crossovers were not associated with cardiovascular mortality (hazard ratio [HR] 1.11 from rhythm to rate control; 95% confidence interval [95% CI, 0.73-1.73]; P = 0.6069; HR 1.29 from rate to rhythm control; 95% CI, 0.73-2.25; P = 0.3793) or all-cause mortality (HR 1.16 from rhythm to rate control, 95% CI [0.79-1.72], P = 0.4444; HR 1.15 from rate to rhythm control, 95% [0.69, 1.91], P = 0.5873). Rhythm control is abandoned more frequently than rate control in patients with AF and CHF. The most common reasons for treatment failure are inefficacy for rhythm control and worsening heart failure for rate control. Changing strategies does not impact survival. © 2015 Wiley Periodicals, Inc.

Effectiveness of a community-based intervention for people with schizophrenia and their caregivers in India (COPSI): a randomised controlled trial.

PubMed

Chatterjee, Sudipto; Naik, Smita; John, Sujit; Dabholkar, Hamid; Balaji, Madhumitha; Koschorke, Mirja; Varghese, Mathew; Thara, Rangaswamy; Weiss, Helen A; Williams, Paul; McCrone, Paul; Patel, Vikram; Thornicroft, Graham

2014-04-19

Observational evidence suggests that community-based services for people with schizophrenia can be successfully provided by community health workers, when supervised by specialists, in low-income and middle-income countries. We did the COmmunity care for People with Schizophrenia in India (COPSI) trial to compare the effectiveness of a collaborative community-based care intervention with standard facility-based care. We did a multicentre, parallel-group, randomised controlled trial at three sites in India between Jan 1, 2009 and Dec 31, 2010. Patients aged 16-60 years with a primary diagnosis of schizophrenia according to the tenth edition of the International Classification of Diseases, Diagnostic Criteria for Research (ICD-10-DCR) were randomly assigned (2:1), via a computer-generated randomisation list with block sizes of three, six, or nine, to receive either collaborative community-based care plus facility-based care or facility-based care alone. Randomisation was stratified by study site. Outcome assessors were masked to group allocation. The primary outcome was a change in symptoms and disabilities over 12 months, as measured by the positive and negative syndrome scale (PANSS) and the Indian disability evaluation and assessment scale (IDEAS). Analysis was by modified intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 56877013. 187 participants were randomised to the collaborative community-based care plus facility-based care group and 95 were randomised to the facility-based care alone group; 253 (90%) participants completed follow-up to month 12. At 12 months, total PANSS and IDEAS scores were lower in patients in the intervention group than in those in the control group (PANSS adjusted mean difference -3.75, 95% CI -7.92 to 0.42; p=0.08; IDEAS -0.95, -1.68 to -0.23; p=0.01). However, no difference was shown in the proportion of participants who had a reduction of more than 20% in overall symptoms (PANSS 85 [51%] in the intervention group vs 44 [51%] in the control group; p=0.89; IDEAS 75 [48%] vs 28 [35%]). We noted a significant reduction in symptom and disability outcomes at the rural Tamil Nadu site (-9.29, -15.41 to -3.17; p=0.003). Two patients (one in each group) died by suicide during the study, and two patients died because of complications of a road traffic accident and pre-existing cardiac disease. 18 (73%) patients (17 in the intervention group) were admitted to hospital during the course of the trial, of whom seven were admitted because of physical health problems, such as acute gastritis and vomiting, road accident, high fever, or cardiovascular disease. The collaborative community-based care plus facility-based care intervention is modestly more effective than facility-based care, especially for reducing disability and symptoms of psychosis. Our results show that the study intervention is best implemented as an initial service in settings where services are scarce, for example in rural areas. Wellcome Trust. Copyright © 2014 Chatterjee et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd. All rights reserved.

Does Mckuer's Law Hold for Heart Rate Control via Biofeedback Display?

NASA Technical Reports Server (NTRS)

Courter, B. J.; Jex, H. R.

1984-01-01

Some persons can control their pulse rate with the aid of a biofeedback display. If the biofeedback display is modified to show the error between a command pulse-rate and the measured rate, a compensatory (error correcting) heart rate tracking control loop can be created. The dynamic response characteristics of this control loop when subjected to step and quasi-random disturbances were measured. The control loop includes a beat-to-beat cardiotachmeter differenced with a forcing function from a quasi-random input generator; the resulting error pulse-rate is displayed as feedback. The subject acts to null the displayed pulse-rate error, thereby closing a compensatory control loop. McRuer's Law should hold for this case. A few subjects already skilled in voluntary pulse-rate control were tested for heart-rate control response. Control-law properties are derived, such as: crossover frequency, stability margins, and closed-loop bandwidth. These are evaluated for a range of forcing functions and for step as well as random disturbances.

Development of digital flow control system for multi-channel variable-rate sprayers

USDA-ARS?s Scientific Manuscript database

Precision modulation of nozzle flow rates is a critical step for variable-rate spray applications in orchards and ornamental nurseries. An automatic flow rate control system activated with microprocessors and pulse width modulation (PWM) controlled solenoid valves was developed to control flow rates...

A packet-based dual-rate PID control strategy for a slow-rate sensing Networked Control System.

PubMed

Cuenca, A; Alcaina, J; Salt, J; Casanova, V; Pizá, R

2018-05-01

This paper introduces a packet-based dual-rate control strategy to face time-varying network-induced delays, packet dropouts and packet disorder in a Networked Control System. Slow-rate sensing enables to achieve energy saving and to avoid packet disorder. Fast-rate actuation makes reaching the desired control performance possible. The dual-rate PID controller is split into two parts: a slow-rate PI controller located at the remote side (with no permanent communication to the plant) and a fast-rate PD controller located at the local side. The remote side also includes a prediction stage in order to generate the packet of future, estimated slow-rate control actions. These actions are sent to the local side and converted to fast-rate ones to be used when a packet does not arrive at this side due to the network-induced delay or due to occurring dropouts. The proposed control solution is able to approximately reach the nominal (no-delay, no-dropout) performance despite the existence of time-varying delays and packet dropouts. Control system stability is ensured in terms of probabilistic Linear Matrix Inequalities (LMIs). Via real-time control for a Cartesian robot, results clearly reveal the superiority of the control solution compared to a previous proposal by authors. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Rate vs. rhythm control and adverse outcomes among European patients with atrial fibrillation.

PubMed

Purmah, Yanish; Proietti, Marco; Laroche, Cecilé; Mazurek, Michal; Tahmatzidis, Dimitrios; Boriani, Giuseppe; Novo, Salvatore; Lip, Gregory Y H

2018-02-01

The impact of rate and rhythm control strategies on outcomes in patients with atrial fibrillation (AF) remains controversial. Our aims were: to report use of rate and rhythm control strategies in European patients from the EURObservational Research Program AF General Pilot Registry. Secondly, to evaluate outcomes according to assigned strategies. Use of pure rate and rhythm control agents was described according to European regions. 1-year follow-up data were reported. Among rate control strategies, beta-blockers were the most commonly used drug. Proportions of patients assigned to rhythm control varied greatly between countries, and amiodarone was the most used rhythm control drug. Of the original 3119 patients, 1036 (33.2%) were assigned to rate control only and 355 (11.4%) to rhythm control only. Patients assigned to a rate control strategy were older (P < 0.0001) and more likely female (P = 0.0266). Patients assigned to a rate control strategy had higher rates for any thrombo-embolic event (P = 0.0245), cardiovascular death (P = 0.0437), and all-cause death (P < 0.0001). Kaplan-Meier analysis showed that rate control strategy was associated with a higher risk for all-cause death (P < 0.001). On Cox regression analysis, rate control strategy was independently associated with all-cause death (P = 0.0256). A propensity matched analysis only found a trend for the association between rate control and all-cause death (P = 0.0664). In a European AF patients' cohort, a pure rate control strategy was associated with a higher risk for adverse events at 1-year follow-up, and partially adjusted analysis suggested that rate control independently increased the risk for all-cause death. A fully adjusted propensity score matched analysis found that this association was no longer statistically significant, suggesting an important role of comorbidities in determining the higher risk for all-cause death. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Real-time motion-based H.263+ frame rate control

NASA Astrophysics Data System (ADS)

Song, Hwangjun; Kim, JongWon; Kuo, C.-C. Jay

1998-12-01

Most existing H.263+ rate control algorithms, e.g. the one adopted in the test model of the near-term (TMN8), focus on the macroblock layer rate control and low latency under the assumptions of with a constant frame rate and through a constant bit rate (CBR) channel. These algorithms do not accommodate the transmission bandwidth fluctuation efficiently, and the resulting video quality can be degraded. In this work, we propose a new H.263+ rate control scheme which supports the variable bit rate (VBR) channel through the adjustment of the encoding frame rate and quantization parameter. A fast algorithm for the encoding frame rate control based on the inherent motion information within a sliding window in the underlying video is developed to efficiently pursue a good tradeoff between spatial and temporal quality. The proposed rate control algorithm also takes the time-varying bandwidth characteristic of the Internet into account and is able to accommodate the change accordingly. Experimental results are provided to demonstrate the superior performance of the proposed scheme.

Drug use in business bathrooms: An exploratory study of manager encounters in New York City

PubMed Central

Wolfson-Stofko, Brett; Bennett, Alex S.; Elliott, Luther; Curtis, Ric

2017-01-01

Background Though public bathroom drug injection has been documented from the perspective of people who inject drugs, no research has explored the experiences of the business managers who oversee their business bathrooms and respond to drug use. These managers, by default, are first-responders in the event of a drug overdose and thus of intrinsic interest during the current epidemic of opioid-related overdoses in the United States. This exploratory study assists in elucidating the experiences that New York City business managers have with people who inject drugs, their paraphernalia, and their overdoses. Methods A survey instrument was designed to collect data on manager encounters with drug use occurring in their business bathrooms. Recruitment was guided by convenience and purposive approaches. Results More than half of managers interviewed (58%, n = 50/86) encountered drug use in their business bathrooms, more than a third (34%) of these managers also found syringes, and the vast majority (90%) of managers had received no overdose recognition or naloxone training. Seven managers encountered unresponsive individuals who required emergency assistance. Conclusion The results from this study underscore the need for additional research on the experiences that community stakeholders have with public injection as well as educational outreach efforts among business managers. This research also suggests that there is need for a national dialogue about potential interventions, including expanded overdose recognition and naloxone training and supervised injection facilities (SIF)/drug consumption rooms (DCR), that could reduce public injection and its associated health risks. PMID:27768996

Molecular requirements for RNA-induced silencing complex assembly in the Drosophila RNA interference pathway.

PubMed

Pham, John W; Sontheimer, Erik J

2005-11-25

Complexes in the Drosophila RNA-induced silencing complex (RISC) assembly pathway can be resolved using native gel electrophoresis, revealing an initiator called R1, an intermediate called R2, and an effector called R3 (now referred to as holo-RISC). Here we show that R1 forms when the Dicer-2/R2D2 heterodimer binds short interfering RNA (siRNA) duplexes. The heterodimer alone can initiate RISC assembly, indicating that other factors are dispensable for initiation. During assembly, R2 requires Argonaute 2 to convert into holo-RISC. This requirement is reminiscent of the RISC-loading complex, which also requires Argonaute 2 for assembly into RISC. We have compared R2 to the RISC-loading complex and show that the two complexes are similar in their sensitivities to ATP and to chemical modifications on siRNA duplexes, indicating that they are likely to be identical. We have examined the requirements for RISC formation and show that the siRNA 5'-termini are repeatedly monitored during RISC assembly, first by the Dcr-2/R2D2 heterodimer and again after R2 formation, before siRNA unwinding. The 2'-position of the 5'-terminal nucleotide also affects RISC assembly, because an siRNA strand bearing a 2'-deoxyribose at this position can inhibit the cognate strand from entering holo-RISC; in contrast, the 2'-deoxyribose-modified strand has enhanced activity in the RNA interference pathway.

Detection of Ophiocordyceps sinensis and Its Common Adulterates Using Species-Specific Primers

PubMed Central

Liu, Yang; Wang, Xiao-yue; Gao, Zi-tong; Han, Jian-ping; Xiang, Li

2017-01-01

Ophiocordyceps sinensis is a fungus that infects Hepialidae caterpillars, mummifying the larvae and producing characteristic fruiting bodies (stromata) that are processed into one of the most valued traditional Chinese medicines (TCM). The product commands a very high price due to a high demand but a very limited supply. Adulteration with other fungi is a common problem and there is a need to test preparation for the presence of the correct fungus. In the current study, a PCR-based approach for the identification of O. sinensis based on a segment of the internal transcribed spacer (ITS) region was developed. The segments is 146-bp in size and is likely to be amplified even in materials where processing led to DNA fragmentation. Primer development was based on the alignment of sequence data generated from a total of 89 samples of O. sinensis and potential adulterants as well as sequences date from 41 Ophiocordyceps species and 26 Cordyceps species available in GenBank. Tests with primer pair, DCF4/DCR4, demonstrated generation of an amplicon from DNA extracted from O. sinensis stromata, but not from extracts derived from adulterants. Species-specific primer pairs were also developed and tested for detection of the common adulterants, Cordyceps gunnii, Cordyceps cicadae, Cordyceps militaris, Cordyceps liangshanensis and Ophiocordyceps nutans. The collection of primers developed in the present study will be useful for the authentication of preparation claiming to only contain O. sinensis and for the detection of fungi used as adulterants in these preparations. PMID:28680424

Mediating role of borderline personality disorder traits in the effects of childhood maltreatment on suicidal behaviour among mood disorder patients.

PubMed

Aaltonen, K I; Rosenström, T; Baryshnikov, I; Karpov, B; Melartin, T; Suominen, K; Heikkinen, M; Näätänen, P; Koivisto, M; Joffe, G; Isometsä, E

2017-07-01

Substantial evidence supports an association between childhood maltreatment and suicidal behaviour. However, few studies have examined factors mediating this relationship among patients with unipolar or bipolar mood disorders. Depressive disorder and bipolar disorder (ICD-10-DCR) patients (n=287) from the Helsinki University Psychiatric Consortium (HUPC) Study were surveyed on self-reported childhood experiences, current depressive symptoms, borderline personality disorder traits, and lifetime suicidal behaviour. Psychiatric records served to complement the information on suicide attempts. We examined by formal mediation analyses whether (1) the effect of childhood maltreatment on suicidal behaviour is mediated through borderline personality disorder traits and (2) the mediation effect differs between lifetime suicidal ideation and lifetime suicide attempts. The impact of childhood maltreatment in multivariate models on either lifetime suicidal ideation or lifetime suicide attempts showed comparable total effects. In formal mediation analyses, borderline personality disorder traits mediated all of the total effect of childhood maltreatment on lifetime suicide attempts, but only one fifth of the total effect on lifetime suicidal ideation. The mediation effect was stronger for lifetime suicide attempts than for lifetime suicidal ideation (P=0.002) and independent of current depressive symptoms. The mechanisms of the effect of childhood maltreatment on suicidal ideation versus suicide attempts may diverge among psychiatric patients with mood disorders. Borderline personality disorder traits may contribute to these mechanisms, although the influence appears considerably stronger for suicide attempts than for suicidal ideation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Acquired hypermethylation of the P16INK4A promoter in abdominal paraganglioma: relation to adverse tumor phenotype and predisposing mutation

PubMed Central

Kiss, Nimrod B; Muth, Andreas; Andreasson, Adam; Juhlin, C Christofer; Geli, Janos; Bäckdahl, Martin; Höög, Anders; Wängberg, Bo; Nilsson, Ola; Ahlman, Håkan; Larsson, Catharina

2013-01-01

Recurrent alterations in promoter methylation of tumor suppressor genes (TSGs) and LINE1 (L1RE1) repeat elements were previously reported in pheochromocytoma and abdominal paraganglioma. This study was undertaken to explore CpG methylation abnormalities in an extended tumor panel and assess possible relationships between metastatic disease and mutation status. CpG methylation was quantified by bisulfite pyrosequencing for selected TSG promoters and LINE1 repeats. Methylation indices above normal reference were observed for DCR2 (TNFRSF10D), CDH1, P16 (CDKN2A), RARB, and RASSF1A. Z-scores for overall TSG, and individual TSG methylation levels, but not LINE1, were significantly correlated with metastatic disease, paraganglioma, disease predisposition, or outcome. Most strikingly, P16 hypermethylation was strongly associated with SDHB mutation as opposed to RET/MEN2, VHL/VHL, or NF1-related disease. Parallel analyses of constitutional, tumor, and metastasis DNA implicate an order of events where constitutional SDHB mutations are followed by TSG hypermethylation and 1p loss in primary tumors, later transferred to metastatic tissue. In the combined material, P16 hypermethylation was prevalent in SDHB-mutated samples and was associated with short disease-related survival. The findings verify the previously reported importance of P16 and other TSG hypermethylation in an independent tumor series. Furthermore, a constitutional SDHB mutation is proposed to predispose for an epigenetic tumor phenotype occurring before the emanation of clinically recognized malignancy. PMID:23154831

Response rates in case-control studies of cancer by era of fieldwork and by characteristics of study design.

PubMed

Xu, Mengting; Richardson, Lesley; Campbell, Sally; Pintos, Javier; Siemiatycki, Jack

2018-04-09

The purpose of this study was to describe time trends in response rates in case-control studies of cancer and identify study design factors that influence response rate. We reviewed 370 case-control studies of cancer published in 12 journals during indicator years in each of the last four decades. We estimated time trends of response rates and reasons for nonresponse in each of the following types of study subjects: cases, medical source controls, and population controls. We also estimated response rates according to characteristics of study context. Median response rates among cases and population controls were between 75% and 80% in the 1970s. Between 1971 and 2010, study response rates declined by 0.31% per year for cases and 0.78% for population controls. Only a minority of studies reported reasons for nonparticipation; subject refusal was the most common reported reason. Studies conducted in North America had lower median response rates than studies conducted in Europe. In-person and telephone interviews elicited higher response rates than mail questionnaires. Response rates from case-control studies of cancer have declined, and this could threaten the validity of results derived from these studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Is rhythm-control superior to rate-control in patients with atrial fibrillation and diastolic heart failure?

PubMed

Kong, Melissa H; Shaw, Linda K; O'Connor, Christopher; Califf, Robert M; Blazing, Michael A; Al-Khatib, Sana M

2010-07-01

Although no clinical trial data exist on the optimal management of atrial fibrillation (AF) in patients with diastolic heart failure, it has been hypothesized that rhythm-control is more advantageous than rate-control due to the dependence of these patients' left ventricular filling on atrial contraction. We aimed to determine whether patients with AF and heart failure with preserved ejection fraction (EF) survive longer with rhythm versus rate-control strategy. The Duke Cardiovascular Disease Database was queried to identify patients with EF > 50%, heart failure symptoms and AF between January 1,1995 and June 30, 2005. We compared baseline characteristics and survival of patients managed with rate- versus rhythm-control strategies. Using a 60-day landmark view, Kaplan-Meier curves were generated and results were adjusted for baseline differences using Cox proportional hazards modeling. Three hundred eighty-two patients met the inclusion criteria (285 treated with rate-control and 97 treated with rhythm-control). The 1-, 3-, and 5-year survival rates were 93.2%, 69.3%, and 56.8%, respectively in rate-controlled patients and 94.8%, 78.0%, and 59.9%, respectively in rhythm-controlled patients (P > 0.10). After adjustments for baseline differences, no significant difference in mortality was detected (hazard ratio for rhythm-control vs rate-control = 0.696, 95% CI 0.453-1.07, P = 0.098). Based on our observational data, rhythm-control seems to offer no survival advantage over rate-control in patients with heart failure and preserved EF. Randomized clinical trials are needed to verify these findings and examine the effect of each strategy on stroke risk, heart failure decompensation, and quality of life.

A Comparative study between MPC and PI controller to control vacuum distillation unit for producing LVGO, MVGO, and HVGO

NASA Astrophysics Data System (ADS)

Wahid, A.; Prasetyo, A. P.

2018-03-01

This study describes the selection of controllers in the vacuum distillation unit (VDU) between a model predictive control (MPC) and a proportional-integral (PI) controller by comparing the integral square error (ISE) values. Design of VDU in this simulation is based on modified Metso Automation Inc. scheme. Controlled variables in this study are feed flow rate, feed temperature, top stage pressure, condenser level, bottom stage temperature, LVGO (light vacuum gas oil), MVGO (medium vacuum gas oil), and HVGO (heavy vacuum gas oil) flow rate. As a result, control performance improvements occurred as using MPC compared to PI controllers, when testing a set-point change, of feed flow rate control, feed temperature, top-stage pressure, bottom-stage temperature and flow rate of LVGO, MVGO, and HVGO, respectively, 36%, 6%, 92%, 53%, 90%, 96% and 88%. Only on condenser level control PI performs much better than the MPC. So PI controller is used for level condenser control. While for the test of disturbance rejection, by changing feed flow rate by 10%, there is improvement of control performance using MPC compared to PI controller on feed temperature control, top-stage pressure, bottom-stage temperature and flow rate LVGO, MVGO and HVGO 0.3%, 0.7%, 14%, 2.7%, 10.6% and 4.3%, respectively.

Asymptotic sideslip angle and yaw rate decoupling control in four-wheel steering vehicles

NASA Astrophysics Data System (ADS)

Marino, Riccardo; Scalzi, Stefano

2010-09-01

This paper shows that, for a four-wheel steering vehicle, a proportional-integral (PI) active front steering control and a PI active rear steering control from the yaw rate error together with an additive feedforward reference signal for the vehicle sideslip angle can asymptotically decouple the lateral velocity and the yaw rate dynamics; that is the control can set arbitrary steady state values for lateral speed and yaw rate at any longitudinal speed. Moreover, the PI controls can suppress oscillatory behaviours by assigning real stable eigenvalues to a widely used linearised model of the vehicle steering dynamics for any value of longitudinal speed in understeering vehicles. In particular, the four PI control parameters are explicitly expressed in terms of the three real eigenvalues to be assigned. No lateral acceleration and no lateral speed measurements are required. The controlled system maintains the well-known advantages of both front and rear active steering controls: higher controllability, enlarged bandwidth for the yaw rate dynamics, suppressed resonances, new stable cornering manoeuvres and improved manoeuvrability. In particular, zero lateral speed may be asymptotically achieved while controlling the yaw rate: in this case comfort is improved since the phase lag between lateral acceleration and yaw rate is reduced. Also zero yaw rate can be asymptotically achieved: in this case additional stable manoeuvres are obtained in obstacle avoidance. Several simulations, including step references and moose tests, are carried out on a standard small SUV CarSim model to explore the robustness with respect to unmodelled effects such as combined lateral and longitudinal tyre forces, pitch, roll and driver dynamics. The simulations confirm the decoupling between the lateral velocity and the yaw rate and show the advantages obtained by the proposed control: reduced lateral speed or reduced yaw rate, suppressed oscillations and new stable manoeuvres.

Characteristics of an aerosol photometer while automatically controlling chamber dilution-air flow rate.

PubMed

O'Shaughnessy, P T; Hemenway, D R

2000-10-01

Trials were conducted to determine those factors that affect the accuracy of a direct-reading aerosol photometer when automatically controlling airflow rate within an exposure chamber to regulate airborne dust concentrations. Photometer response was affected by a shift in the aerosol size distribution caused by changes in chamber flow rate. In addition to a dilution effect, flow rate also determined the relative amount of aerosol lost to sedimentation within the chamber. Additional calculations were added to a computer control algorithm to compensate for these effects when attempting to automatically regulate flow based on a proportional-integral-derivative (PID) feedback control algorithm. A comparison between PID-controlled trials and those performed with a constant generator output rate and dilution-air flow rate demonstrated that there was no significant decrease in photometer accuracy despite the many changes in flow rate produced when using PID control. Likewise, the PID-controlled trials produced chamber aerosol concentrations within 1% of a desired level.

Bonding Pictures: Affective Ratings Are Specifically Associated to Loneliness But Not to Empathy

PubMed Central

Silva, Heraldo D.; Campagnoli, Rafaela R.; Mota, Bruna Eugênia F.; Araújo, Cássia Regina V.; Álvares, Roberta Sônia R.; Mocaiber, Izabela; Rocha-Rego, Vanessa; Volchan, Eliane; Souza, Gabriela G. L.

2017-01-01

Responding to pro-social cues plays an important adaptive role in humans. Our aims were (i) to create a catalog of bonding and matched-control pictures to compare the emotional reports of valence and arousal with the International Affective Picture System (IAPS) pictures; (ii) to verify sex influence on the valence and arousal of bonding and matched-control pictures; (iii) to investigate if empathy and loneliness traits exert a specific influence on emotional reports for the bonding pictures. To provide a finer tool for social interaction studies, the present work defined two new sets of pictures consisting of “interacting dyads” (Bonding: N = 70) and matched controls “non-interacting dyads” (Controls: N = 70). The dyads could be either a child and an adult, or two children. Participants (N = 283, 182 women) were divided in 10 groups for the experimental sessions. The task was to rate the hedonic valence and emotional arousal of bonding and controls; and of pleasant, neutral, and unpleasant pictures from the IAPS. Effects of social-related traits, empathy and loneliness, on affective ratings were tested. Participants rated bonding pictures as more pleasant and arousing than control ones. Ratings did not differentiate bonding from IAPS pleasant pictures. Control pictures showed lower ratings than pleasant but higher ratings than neutral IAPS pictures. Women rated bonding and control pictures as more positive than men. There was no sex difference for arousal ratings. High empathic participants rated bonding and control pictures higher than low empathic participants. Also, they rated pleasant IAPS pictures more positive and arousing; and unpleasant pictures more negative and arousing than the less empathic ones. Loneliness trait, on the other hand, affected very specifically the ratings of bonding pictures; lonelier participants rated them less pleasant and less arousing than less lonely. Loneliness trait did not modulate ratings of other categories. In conclusion, high empathy seems related to emotional strength in general, while high loneliness seems to weaken the engagement in social interaction cues. PMID:28740473

Bonding Pictures: Affective Ratings Are Specifically Associated to Loneliness But Not to Empathy.

PubMed

Silva, Heraldo D; Campagnoli, Rafaela R; Mota, Bruna Eugênia F; Araújo, Cássia Regina V; Álvares, Roberta Sônia R; Mocaiber, Izabela; Rocha-Rego, Vanessa; Volchan, Eliane; Souza, Gabriela G L

2017-01-01

Responding to pro-social cues plays an important adaptive role in humans. Our aims were (i) to create a catalog of bonding and matched-control pictures to compare the emotional reports of valence and arousal with the International Affective Picture System (IAPS) pictures; (ii) to verify sex influence on the valence and arousal of bonding and matched-control pictures; (iii) to investigate if empathy and loneliness traits exert a specific influence on emotional reports for the bonding pictures. To provide a finer tool for social interaction studies, the present work defined two new sets of pictures consisting of "interacting dyads" (Bonding: N = 70) and matched controls "non-interacting dyads" (Controls: N = 70). The dyads could be either a child and an adult, or two children. Participants ( N = 283, 182 women) were divided in 10 groups for the experimental sessions. The task was to rate the hedonic valence and emotional arousal of bonding and controls; and of pleasant, neutral, and unpleasant pictures from the IAPS. Effects of social-related traits, empathy and loneliness, on affective ratings were tested. Participants rated bonding pictures as more pleasant and arousing than control ones. Ratings did not differentiate bonding from IAPS pleasant pictures. Control pictures showed lower ratings than pleasant but higher ratings than neutral IAPS pictures. Women rated bonding and control pictures as more positive than men. There was no sex difference for arousal ratings. High empathic participants rated bonding and control pictures higher than low empathic participants. Also, they rated pleasant IAPS pictures more positive and arousing; and unpleasant pictures more negative and arousing than the less empathic ones. Loneliness trait, on the other hand, affected very specifically the ratings of bonding pictures; lonelier participants rated them less pleasant and less arousing than less lonely. Loneliness trait did not modulate ratings of other categories. In conclusion, high empathy seems related to emotional strength in general, while high loneliness seems to weaken the engagement in social interaction cues.

Control-Structure Ratings on the Fox River at McHenry and Algonquin, Illinois

USGS Publications Warehouse

Straub, Timothy D.; Johnson, Gary P.; Hortness, Jon E.; Parker, Joseph R.

2009-01-01

The Illinois Department of Natural Resources-Office of Water Resources operates control structures on a reach of the Fox River in northeastern Illinois between McHenry and Algonquin. The structures maintain water levels in the river for flood-control and recreational purposes. This report documents flow ratings for hinged-crest gates, a broad-crested weir, sluice gates, and an ogee spillway on the control structures at McHenry and Algonquin. The ratings were determined by measuring headwater and tailwater stage along with streamflow at a wide range of flows at different gate openings. Standard control-structure rating techniques were used to rate each control structure. The control structures at McHenry consist of a 221-feet(ft)-long broad-crested weir, a 4-ft-wide fish ladder, a 50-ft-wide hinged-crest gate, five 13.75-ft-wide sluice gates, and a navigational lock. Sixty measurements were used to rate the McHenry structures. The control structures at Algonquin consist of a 242-ft-long ogee spillway and a 50-ft-wide hinged-crest gate. Forty-one measurements were used to rate the Algonquin control structures.

[Effect of comprehensive control in demonstration plots of parasitic diseases in Guizhou Province].

PubMed

Ai-Ya, Zhu; An-Mei, Li; Guang-Chu, Lin; Jian-Jun, Xu; Liang-Xian, Sun

2011-10-01

To evaluate the effect of comprehensive control in demonstration plots of parasitic diseases in Guizhou Province. The data of parasitic disease control in demonstration plots from 2006 to 2009 were collected and analyzed, including deworming, water and latrines renovation, health education, survey on infections in crowd, etc. After 3 years comprehensive control, the infection rates of soil-transmitted nematodes among people reduced from 30.25% to 8.37%, with the reduction rate of 72.32%. The infection rates of Ascaris lumbricoides, hookworm and Trichuris trichiura reduced from 26.88%, 2.86% and 4.13% to 7.43%, 0.09% and 1.13%, respectively. The awareness rate of health knowledge among residents increased from 44.18% to 93.64%, with an increasing rate of 111.94%. The coverage rate of non-hazardous sanitary latrines was 81.29%. The beneficial rate of the water renovation reached 96.31%. The comprehensive control strategies mainly based on health education and infectious source control correspond to the reality of rural parasitic disease control nowadays. The comprehensive control model integrating government leadership, department cooperation and social concern is useful for parasitic disease control and should be popularized.

An electronic flow control system for a variable-rate tree sprayer

USDA-ARS?s Scientific Manuscript database

Precise modulation of nozzle flow rates is a critical measure to achieve variable-rate spray applications. An electronic flow rate control system accommodating with microprocessors and pulse width modulation (PWM) controlled solenoid valves was designed to manipulate the output of spray nozzles inde...

Optimal False Discovery Rate Control for Dependent Data

PubMed Central

Xie, Jichun; Cai, T. Tony; Maris, John; Li, Hongzhe

2013-01-01

This paper considers the problem of optimal false discovery rate control when the test statistics are dependent. An optimal joint oracle procedure, which minimizes the false non-discovery rate subject to a constraint on the false discovery rate is developed. A data-driven marginal plug-in procedure is then proposed to approximate the optimal joint procedure for multivariate normal data. It is shown that the marginal procedure is asymptotically optimal for multivariate normal data with a short-range dependent covariance structure. Numerical results show that the marginal procedure controls false discovery rate and leads to a smaller false non-discovery rate than several commonly used p-value based false discovery rate controlling methods. The procedure is illustrated by an application to a genome-wide association study of neuroblastoma and it identifies a few more genetic variants that are potentially associated with neuroblastoma than several p-value-based false discovery rate controlling procedures. PMID:23378870

Effect of Drag Reducing Polymer and Suspended Solid on the Rate of Diffusion Controlled Corrosion in 90° Copper Elbow

NASA Astrophysics Data System (ADS)

Fouad, Mohamed Ahmed; Zewail, Taghreed Mohamed; Amine, Nieven Kamal Abbes

2017-06-01

Rate of diffusion controlled corrosion in 90° Copper Elbow acidified dichromate has been investigated in relation to the following parameters: effect of solution velocity in the absence and presence of drag- reducing polymer on the rate of diffusion controlled corrosion, and effect of the presence of suspended solids on the rate of diffusion controlled corrosion. It was found that the presence of drag reducing polymer inhibited the rate of mass transfer, while the presence of suspended solid increased significantly the rate of mass transfer.

Modeling the rate-controlled sorption of hexavalent chromium

USGS Publications Warehouse

Grove, D.B.; Stollenwerk, K.G.

1985-01-01

Sorption of chromium VI on the iron-oxide- and hydroxide-coated surface of alluvial material was numerically simulated with rate-controlled reactions. Reaction kinetics and diffusional processes, in the form of film, pore, and particle diffusion, were simulated and compared with experimental results. The use of empirically calculated rate coefficients for diffusion through the reacting surface was found to simulate experimental data; pore or particle diffusion is believed to be a possible rate-controlling mechanism. The use of rate equations to predict conservative transport and rate- and local-equilibrium-controlled reactions was shown to be feasible.

Control of parallel manipulators using force feedback

NASA Technical Reports Server (NTRS)

Nanua, Prabjot

1994-01-01

Two control schemes are compared for parallel robotic mechanisms actuated by hydraulic cylinders. One scheme, the 'rate based scheme', uses the position and rate information only for feedback. The second scheme, the 'force based scheme' feeds back the force information also. The force control scheme is shown to improve the response over the rate control one. It is a simple constant gain control scheme better suited to parallel mechanisms. The force control scheme can be easily modified for the dynamic forces on the end effector. This paper presents the results of a computer simulation of both the rate and force control schemes. The gains in the force based scheme can be individually adjusted in all three directions, whereas the adjustment in just one direction of the rate based scheme directly affects the other two directions.

Effect on Longitudinal Stability and Control Characteristics of a Boeing B-29 Airplane of Variations in Stick-Force and Control-Rate Characteristics Obtained Through Use of a Booster in the Elevator-Control System

NASA Technical Reports Server (NTRS)

Mathews, Charles W; Talmage, Donald B; Whitten, James B

1952-01-01

A longitudinal stability and control characteristics of a Boeing B-29 airplane have been measured with a booster incorporated in the elevator-control system. Tests were made to determine the effects on the handling qualities of the test airplane of variations in the pilot's control-force gradients as well as the effects of variations in the maximum rate of control motion supplied by the booster. The results of the control-rate investigation indicate that large airplanes may have satisfactory handling qualities with the booster adjusted to give much lower rates of control motion than those normally used by pilots.

A comparison of position and rate control for telemanipulations with consideration of manipulator system dynamics

NASA Technical Reports Server (NTRS)

Kim, Won S.; Tendick, Frank; Stark, Lawrence W.; Ellis, Stephen R.

1987-01-01

Position and rate control are the two common manual control modes in teleoperations. Human operator performance using the two modes is evaluated and compared. Simulated three-axis pick-and-place operations are used as the primary task for evaluation. First, ideal position and rate control are compared by considering several factors, such as joystick gain, joystick type, display mode, task, and manipulator work space size. Then the effects of the manipulator system dynamics are investigated by varying the natural frequency and speed limit. Experimental results show that ideal position control is superior to ideal rate control, regardless of joystick type or display mode, when the manipulation work space is small or comparable to the human operator's control space. Results also show that when the manipulator system is slow, the superiority of position control disappears. Position control is recommended for small-work-space telemanipulation tasks, while rate control is recommended for slow wide-work-space telemanipulation tasks.

Guanosine 3'-diphosphate 5'-diphosphate is not required for growth rate-dependent control of rRNA synthesis in Escherichia coli.

PubMed Central

Gaal, T; Gourse, R L

1990-01-01

rRNA synthesis in Escherichia coli is subject to at least two regulation systems, growth rate-dependent control and stringent control. The inverse correlation between rRNA synthesis rates and guanosine 3'-diphosphate 5'-diphosphate (ppGpp) levels under various physiological conditions has led to the supposition that ppGpp is the mediator of both control mechanisms by inhibiting transcription from rrn P1 promoters. Recently, relA- spoT- strains have been constructed in which both ppGpp synthesis pathways most likely have been removed (M. Cashel, personal communication). We have confirmed that such strains produce no detectable ppGpp and therefore offer a direct means for testing the involvement of ppGpp in the regulation of rRNA synthesis in vivo. Stringent control was determined by measurement of rRNA synthesis after amino acid starvation, while growth rate control was determined by measurement of rRNA synthesis under different nutritional conditions. As expected, the relA- spoT- strain is relaxed for stringent control. However, growth rate-dependent regulation is unimpaired. These results indicate that growth rate regulation can occur in the absence of ppGpp and imply that ppGpp is not the mediator, or at least is not the sole mediator, of growth rate-dependent control. Therefore, growth rate-dependent control and stringent control may utilize different mechanisms for regulating stable RNA synthesis. PMID:2196571

[Evaluation on effectiveness of comprehensive control model for soil-transmitted nematodiasis].

PubMed

Hong-Chun, Tian; Meng, Tang; Hong, Xie; Han-Gang, Li; Xiao-Ke, Zhou; Chang-Hua, Liu; De-Fu, Zheng; Zhong-Jiu, Tang; Ming-Hui, Li; Cheng-Yu, Wu; Yi-Zhu, Ren

2011-10-01

To evaluate the effect of a comprehensive control model for soil-transmitted nematodiasis. Danling County was selected as a demonstration county carrying out the comprehensive prevention model centering on health education, nematode deworming, and drinking water and lavatories changing. On the other side, Hejiang was selected as a control. The effects were evaluated by comparing some indicators such as the infection rates of soil-transmitted nematodiasis and so on. The infection rates of soil-transmitted nematodiasis declined obviously from 2006 to 2009 in the demonstration county. The infection rates of Ascaris lumbricoides, hookworms, Trichiuris trichiura decreased by 91.14%, 81.65% and 65.77%. In the control county, those rates did not have downward tendency. In 2006, those rates in the demonstration county were higher than those in the control, but in 2009 those rates in the demonstration county were lower than those in the control. Through the three-year comprehensive prevention, the infection rates of soil-transmitted nematodiasis declined obviously in the demonstration county. The epidemic situation of soil-transmitted nematodiasis could be controlled effectively by the comprehensive prevention model.

Telerobotic control of a dextrous manipulator using master and six-DOF hand-controllers for space assembly and servicing tasks

NASA Technical Reports Server (NTRS)

O'Hara, John M.

1987-01-01

Two studies were conducted evaluating methods of controlling a telerobot; bilateral force reflecting master controllers and proportional rate six degrees of freedom (DOF) hand controllers. The first study compared the controllers on performance of single manipulator arm tasks, a peg-in-the-hole task, and simulated satellite orbital replacement unit changeout. The second study, a Space Station truss assembly task, required simultaneous operation of both manipulator arms (all 12 DOFs) and complex multiaxis slave arm movements. Task times were significantly longer and fewer errors were committed with the hand controllers. The hand controllers were also rated significantly higher in cognitive and manual control workload on the two-arm task. The master controllers were rated significantly higher in physical workload. There were no significant differences in ratings of manipulator control quality.

Closed-Loop Control of Chemical Injection Rate for a Direct Nozzle Injection System.

PubMed

Cai, Xiang; Walgenbach, Martin; Doerpmond, Malte; Schulze Lammers, Peter; Sun, Yurui

2016-01-20

To realize site-specific and variable-rate application of agricultural pesticides, accurately metering and controlling the chemical injection rate is necessary. This study presents a prototype of a direct nozzle injection system (DNIS) by which chemical concentration transport lag was greatly reduced. In this system, a rapid-reacting solenoid valve (RRV) was utilized for injecting chemicals, driven by a pulse-width modulation (PWM) signal at 100 Hz, so with varying pulse width the chemical injection rate could be adjusted. Meanwhile, a closed-loop control strategy, proportional-integral-derivative (PID) method, was applied for metering and stabilizing the chemical injection rate. In order to measure chemical flow rates and input them into the controller as a feedback in real-time, a thermodynamic flowmeter that was independent of chemical viscosity was used. Laboratory tests were conducted to assess the performance of DNIS and PID control strategy. Due to the nonlinear input-output characteristics of the RRV, a two-phase PID control process obtained better effects as compared with single PID control strategy. Test results also indicated that the set-point chemical flow rate could be achieved within less than 4 s, and the output stability was improved compared to the case without control strategy.

Impact of treatment crossovers on clinical outcomes in the rate and rhythm control strategies for atrial fibrillation: Insights from the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial.

PubMed

Maan, Abhishek; Zhang, Zheng; Qin, Ziling; Wang, Yanbing; Dudley, Samuel; Dabhadakar, Kaustubh; Refaat, Marwan; Mansour, Moussa; Ruskin, Jeremy N; Heist, E Kevin

2017-07-01

We investigated the rates and reasons for crossover to alternative treatment strategies and its impact on mortality in patients who were enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. Over a mean follow-up period of 3.5 years, 842 patients underwent crossover to the alternative treatment arms in AFFIRM. The rate of crossover from rhythm to rate control (594/2,033, 29.2%) was more frequent than the rate of crossover from rate to rhythm control (248/2,027, 12.2%, P < 0.0001). The leading reasons for crossover from rhythm to rate control were failure to achieve or maintain sinus rhythm (272/594, 45.8%) and intolerable adverse effects (122/594, 20.5%). In comparison, the major reasons for crossover from rate to rhythm control were failure to control atrial fibrillation symptoms (159/248, 64.1%) and intolerable adverse effects (9/248, 3.6%). This difference in crossover pattern was statistically significant (P < 0.0001). There was a significantly decreased risk of all-cause mortality (adjusted HR: 0.61, 95% CI: 0.48-0.78, P < 0.0001) and cardiac mortality (adjusted hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.43-0.88, P = 0.008) in the subgroup of patients who crossed over from rhythm to rate control as compared to those who continued in rhythm control. There was a nonsignificant trend toward decreased all-cause (adjusted HR: 0.76, 95% CI: 0.53-1.10, P = 0.14) and cardiac mortality (adjusted HR: 0.70, 95% CI: 0.42-1.18, P = 0.18) in patients who crossed over from rate to rhythm control as compared to those who continued rate control. © 2017 Wiley Periodicals, Inc.

Deletion of the distal Tnfsf11 RL-D2 enhancer that contributes to PTH-mediated RANKL expression in osteoblast lineage cells results in a high bone mass phenotype in mice

PubMed Central

Onal, M.; St John, H.C.; Danielson, A.L.; Pike, J.W.

2016-01-01

Receptor activator of nuclear factor-κB ligand (RANKL) is a TNF-like cytokine that is necessary for osteoclast formation and survival. Elevated RANKL synthesis is associated with both increased osteoclast number and bone resorption. Earlier studies identified an enhancer 76 kb upstream of the Tnfsf11 transcriptional start site (TSS) termed RL-D5 or the distal control region (DCR) that modulates RANKL expression in response to PTH, 1,25(OH)2D3, and an array of cytokines. Mice lacking RL-D5 exhibit high bone mass associated with decreased RANKL expression in bone, spleen, and thymus. In addition to RL-D5, genome-wide studies have identified 9 additional Tnfsf11 enhancers residing upstream of the gene’s TSS, which provide RANKL cell type-specificity and responsiveness to local and systemic factors. ChIP-chip analysis has revealed inducible VDR and CREB binding at an enhancer termed RL-D2 23 kb upstream of the Tnfsf11 TSS in osteoblastic ST2 cells. Herein, we use ChIP-seq analysis to confirm this finding and delete this enhancer from the mouse genome to determine its physiological role in vivo. RL-D2−/− primary stromal cells showed decreased RANKL-induction by both forskolin and 1,25(OH)2D3 ex vivo. Consistent with this, the PTH induction of RANKL expression was significantly blunted in RL-D2−/− mice in vivo. In contrast, lack of RL-D2 had no effect on 1,25(OH)2D3 induction of RANKL in vivo. Similar to the results seen in RL-D5−/− mice, lack of RL-D2 led to decreased skeletal RANKL expression, resulting in decreased osteoclast numbers and a progressive increase in bone mineral density. Lack of RL-D2 increased cancellous bone mass in femur and spine, but did not alter femoral cortical bone thickness. These results highlight the role of distal enhancers in the regulation of RANKL expression by PTH and perhaps 1,25(OH)2D3, and suggest that the RL-D2 and RL-D5 enhancers contribute in either an additive or synergistic manner to regulate bone remodeling. PMID:26332516

Elective Stoma Reversal Has a Higher Incidence of Postoperative Clostridium Difficile Infection Compared With Elective Colectomy: An Analysis Using the American College of Surgeons National Surgical Quality Improvement Program and Targeted Colectomy Databases.

PubMed

Skancke, Matthew; Vaziri, Khashayar; Umapathi, Bindu; Amdur, Richard; Radomski, Michal; Obias, Vincent

2018-05-01

Clostridium difficile infection is caused by the proliferation of a gram-positive anaerobic bacteria after medical or surgical intervention and can result in toxic complications, emergent surgery, and death. This analysis evaluates the incidence of C difficile infection in elective restoration of intestinal continuity compared with elective colon resection. This was a retrospective database review of the 2015 American College of Surgeons National Surgical Quality Improvement Project and targeted colectomy database. The intervention cohort was defined as the primary Current Procedural Terminology codes for ileostomy/colostomy reversal (44227, 44620, 44625, and 44626) and International Classification of Diseases codes for ileostomy/colostomy status (VV44.2, VV44.3, VV55.2, VV55.3, Z93.2, Z93.3, Z43.3, and Z43.2). A total of 2235 patients underwent elective stoma reversal compared with 10403 patients who underwent elective colon resection. Multivariate regression modeling of the impact of stoma reversal on postoperative C difficile infection risk was used as the study intervention. The incidence of C difficile infection in the 30 days after surgery was measured. The incidence of C difficile infection in the 30-day postoperative period was significantly higher (3.04% vs 1.25%; p < 0.001) in patients undergoing stoma reversal. After controlling for differences in cohorts, regression analysis suggested that stoma reversal (OR = 2.701 (95% CI, 1.966-3.711); p < 0.001), smoking (OR = 1.520 (95% CI, 1.063-2.174); p = 0.022), steroids (OR = 1.677 (95% CI, 1.005-2.779); p = 0.048), and disseminated cancer (OR = 2.312 (95% CI, 1.437-3.719); p = 0.001) were associated with C difficile infection incidence in the 30-day postoperative period. The study was limited because it was a retrospective database review with observational bias. Patients who undergo elective stoma reversal have a higher incidence of postoperative C difficile infection compared with patients who undergo an elective colectomy. Given the impact of postoperative C difficile infection, a heightened sense of suspicion should be given to symptomatic patients after stoma reversal. See at Video Abstract at http://links.lww.com/DCR/A553.

Kinematic equations for resolved-rate control of an industrial robot arm

NASA Technical Reports Server (NTRS)

Barker, L. K.

1983-01-01

An operator can use kinematic, resolved-rate equations to dynamically control a robot arm by watching its response to commanded inputs. Known resolved-rate equations for the control of a particular six-degree-of-freedom industrial robot arm and proceeds to simplify the equations for faster computations are derived. Methods for controlling the robot arm in regions which normally cause mathematical singularities in the resolved-rate equations are discussed.

Enhanced erythrocyte aggregation in type 2 diabetes with late complications.

PubMed

Demiroglu, H; Gürlek, A; Barişta, I

1999-01-01

We investigated whether erythrocyte aggregation (EA) is enhanced in type 2 diabetic patients who have developed microvascular or macrovascular complications. EA rates at high and low shear rates were analysed in 141 patients with type 2 diabetes who were further divided into 4 subgroups according to the status of diabetic complications and degree of metabolic control. Groups 1 (n = 43) and 2 (n = 23) consisted of well-controlled patients without and with clinically evident late complications, while groups 3 (n = 33) and 4 (n = 42) represented poorly controlled patients without and with these complications, respectively. 124 healthy subjects served as the control group. Mean EA rate was comparable between control subjects and group 1 both at high (2.05 +/- 0.03 vs. 2.14 +/- 0.07, respectively) and low (6.96 +/- 0.02 vs. 7.04 +/- 0.06, respectively) shear rates. Mean EA rate was also comparable between groups 2 and 4 at high (2.76 +/- 0.09 vs. 2.94 +/- 0.07, respectively) and low (8.18 +/- 0.13 vs. 8.41 +/- 0.1, respectively) shear rates. However, EA at both shear rates in groups 2 and 4 were significantly higher than control subjects, group 1 (p < 0.0001) and group 3 (high shear rate EA: 2.76 +/- 0.09 and low shear rate EA: 7.48 +/- 0.07 (p < 0.01). In group 3, EA rates were significantly higher than control subjects and group 1 (p < 0.05) at both shear rates. No significant correlation was found between EA at high and low shear rates and fibrinogen levels in diabetic subgroups and control subjects. The data suggest that patients with type 2 diabetes who had developed clinically evident late complications have enhanced EA regardless of the degree of metabolic control. Whether enhanced EA is a primary phenomenon contributing to the development of these complications or it occurs secondary to their development remains to be clarified.

Fault-Tolerant and Reconfigurable Control of Unmanned Aerial Vehicles (UAVs)

DTIC Science & Technology

2008-02-29

forces and moments are expressed as functions of angle of attack, sideslip angle, angular rates, and control surface deflection. L, M, and N are...invertible. As for matrix B, the control surfaces of the reusable launch vehicle are designed to control each axes angular rate of aircraft...literature as being invertible. As for matrix B, the control surfaces of the UAV are designed to control angular rate along each axis of the aircraft

Behavioral Treatment of Pseudobulbar Affect: A Case Report.

PubMed

Perotti, Laurence P; Cummings, Latiba D; Mercado, Janyna

2016-04-01

To determine if it is possible to successfully treat pseudobulbar affect (PBA) using a behavioral approach. Two experiments were conducted, each a double reversal design with the same single subject in both. The first experiment tested the hypothesis that the rate of PBA could be controlled by manipulation of its consequences. The second experiment tested the hypothesis that use of a self-control procedure would control the rate of PBA. Rate of PBA could not be controlled by consequence manipulation, but rate of PBA could be controlled through use of a self-control procedure. Pending confirmatory research, behavioral interventions utilizing self-control procedures should be considered in patients with PBA. © 2016 Wiley Periodicals, Inc.

[Effect of two-level community-based health education pattern on schistosomiasis control].

PubMed

Xia, Zhang; He-Hua, Hu; Xiong, Liu; Hua-Ming, Zhang; Shi-Hao, He; Chuan-Yun, Xiao; Rong, Tian; Wei-Rong, Zhang; Cai-Xia, Cui; Xiao-Hong, Wen; Jun, Liu; Li-Ying, Yang; Mei, Chen; Chun-Li, Cao; Shi-Zhu, Li

2016-06-24

To implement a two-level community-based health education pattern of schistosomiasis in residents of endemic areas in marshland and lake regions, so as to explore the suitable pattern of health education under hypo-endemic situation. Two schistosomiasis endemic villages in Jiangling County, Hubei Province were collected as study areas, and among which, one village was treated as an intervention group, where the two-level community-based health education pattern as well as regular control measures was implemented; the other village was a control group, where only regular control measures were implemented. The awareness rates on schistosomiasis control, the rates of correct behavior and the compliance rates of examination, treatment and chemotherapy of the two groups before and after the intervention were compared. According to the results of the baseline survey in 2014, the awareness rates of schistosomiasis control of the intervention and control groups were 84.00% and 77.45%, respectively, the correct rates of behavior of the two groups were 72.00% and 63.73%, respectively, and the compliance rates of the treatment were 80.36% and 82.28%, respectively, there were no statistically significant differences between all the above rates of the two groups (all P > 0.05). After the intervention of the two-level community-based health education, the correct rates of behavior, and the compliance rates of examination and chemotherapy of the two groups were 92.31% and 80.37%, 95.11% and 82.55%, 84.13% and 63.64%, respectively, and the differences between all the rates above of the two groups were statistically significant (all P < 0.05). When compared to those before intervention, the growing rates of the compliance rates of examination, treatment and chemotherapy of the intervention group were 20.97%, 15.33% and 23.29%, respectively, while those of control group were 14.27%, 4.17%, -3.77%, respectively, the growing rates of the intervention groups were higher than those of the control groups. Through the two-level community-based pattern of health education, the compliance rates of examination and treatment of the residents have improved, and therefore, the pattern is suitable for popularization and application in marshland and lake regions.

[Effect of jian-gan-le on advanced schistosomiasis].

PubMed

He, Zheng-Wen; Wang, You-Bin; Huang, Wen-Jun

2011-06-01

A total of 80 cases of advanced schistosomiasis were selected and divided into an experiment group and a control group, 40 cases each group, by the random sampling method. The patients in the experiment group were administered with Jian-gan-le, and the patients in the control group received compound purple granules. In the experiment group, the curative rate was 25.0%, the improving rate was 70.0%, the inefficacy rate was 5%, and the efficiency rate was 95.0%. In the control group, the curative rate was 12.5%, the improving rate was 75%, the inefficacy rate was 12.5%. There was no statistic difference between the 2 groups (P all > 0.05). The expense was cheaper in the experiment group than in the control group.

[Effect of control program of human intestinal parasitic diseases in Nanping City].

PubMed

Ming-Ying, Zhuo; Zhi-Ping, Zhang; Hong-Mei, Zhu; Hui, Zhang; Jia-Mei, Huang; Hui, Wen; Han-Guo, Xie

2016-01-22

To understand the epidemic status of human intestinal parasitic diseases and evaluate the effect of the control program in Nanping City, so as to provide an evidence for improving the disease control. The villages were selected by the stratified cluster sampling method and the residents in these villages were surveyed for human intestinal parasitic diseases, and kindergartens were also selected and the children in these kindergartens were surveyed for Enterobius vermicularis infection. In 2007, before the control program, 9 851 residents of Nanping City were surveyed, with the parasitic infection rate of 9.10% (896 infection cases), and the infection rate of E. vermicularis of children was 18.56% (328/1 767). From 2011 to 2014, when the control program was performed, 4 679 residents were surveyed, with the infection rate of 4.06% (190 infection cases), and the infection rate of E. vermicularis of children was 3.87% (33/853). After the control program was launched, the infection rates of human intestinal parasites were decreased. The overall parasitic infection rate and hookworm infection rate showed increasing trends by age ( χ 2 = 49.03 and 53.58 respectively, both P < 0.01). The infection situation of human intestinal parasites is decreased after the implementation of the control program but the infection rate is still at a high level, and the control work should be strengthened.

Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection for circumferential mixed hemorrhoids.

PubMed

Lu, Ming; Shi, Guang-Ying; Wang, Guo-Qiang; Wu, Yan; Liu, Yang; Wen, Hao

2013-08-14

To identify a more effective treatment protocol for circumferential mixed hemorrhoids. A total of 192 patients with circumferential mixed hemorrhoids were randomized into the treatment group, where they underwent Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection, or the control group, where traditional external dissection and internal ligation were performed. Postoperative recovery and complications were monitored. The time to wound healing was 12.96 ± 2.25 d in the treatment group shorter than 19.58 ± 2.71 d in the control group. Slight pain rate was 58.3% in the treatment group higher than 22.9% in the control group; moderate pain rate was 33.3% in the treatment group lower than 56.3% in the control group severe pain rate was 8.4% in the treatment group lower than 20.8% in the control group. No edema rate was 70.8% in the treatment group higher than 43.8% in the control group; mild local edema rate was 26% in the treatment group lower than 39.6% in the control group obvious local edema was 3.03% in the treatment group lower than 16.7% in the control group. No stenosis rate was 85.4% in the treatment group higher than 63.5% in the control group; moderate stenosis rate was 14.6% in the treatment group Lower than 27.1% in the control group severe anal stenosis rate was 0% in the treatment group lower than 9.4% in the control group. Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection is the optimal treatment for circumferential mixed hemorrhoids and can be widely applied in clinical settings.

Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection for circumferential mixed hemorrhoids

PubMed Central

Lu, Ming; Shi, Guang-Ying; Wang, Guo-Qiang; Wu, Yan; Liu, Yang; Wen, Hao

2013-01-01

AIM: To identify a more effective treatment protocol for circumferential mixed hemorrhoids. METHODS: A total of 192 patients with circumferential mixed hemorrhoids were randomized into the treatment group, where they underwent Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection, or the control group, where traditional external dissection and internal ligation were performed. Postoperative recovery and complications were monitored. RESULTS: The time to wound healing was 12.96 ± 2.25 d in the treatment group shorter than 19.58 ± 2.71 d in the control group. Slight pain rate was 58.3% in the treatment group higher than 22.9% in the control group; moderate pain rate was 33.3% in the treatment group lower than 56.3% in the control group severe pain rate was 8.4% in the treatment group lower than 20.8% in the control group. No edema rate was 70.8% in the treatment group higher than 43.8% in the control group; mild local edema rate was 26% in the treatment group lower than 39.6% in the control group obvious local edema was 3.03% in the treatment group lower than 16.7% in the control group. No stenosis rate was 85.4% in the treatment group higher than 63.5% in the control group; moderate stenosis rate was 14.6% in the treatment group Lower than 27.1% in the control group severe anal stenosis rate was 0% in the treatment group lower than 9.4% in the control group. CONCLUSION: Milligan-Morgan hemorrhoidectomy with anal cushion suspension and partial internal sphincter resection is the optimal treatment for circumferential mixed hemorrhoids and can be widely applied in clinical settings. PMID:23946609

Choice and Outcomes of Rate Control versus Rhythm Control in Elderly Patients with Atrial Fibrillation: A Report from the REPOSI Study.

PubMed

Paciullo, Francesco; Proietti, Marco; Bianconi, Vanessa; Nobili, Alessandro; Pirro, Matteo; Mannucci, Pier Mannuccio; Lip, Gregory Y H; Lupattelli, Graziana

2018-04-01

Among rate-control or rhythm-control strategies, there is conflicting evidence as to which is the best management approach for non-valvular atrial fibrillation (AF) in elderly patients. We performed an ancillary analysis from the 'Registro Politerapie SIMI' study, enrolling elderly inpatients from internal medicine and geriatric wards. We considered patients enrolled from 2008 to 2014 with an AF diagnosis at admission, treated with a rate-control-only or rhythm-control-only strategy. Among 1114 patients, 241 (21.6%) were managed with observation only and 122 (11%) were managed with both the rate- and rhythm-control approaches. Of the remaining 751 patients, 626 (83.4%) were managed with a rate-control-only strategy and 125 (16.6%) were managed with a rhythm-control-only strategy. Rate-control-managed patients were older (p = 0.002), had a higher Short Blessed Test (SBT; p = 0.022) and a lower Barthel Index (p = 0.047). Polypharmacy (p = 0.001), heart failure (p = 0.005) and diabetes (p = 0.016) were more prevalent among these patients. Median CHA 2 DS 2 -VASc score was higher among rate-control-managed patients (p = 0.001). SBT [odds ratio (OR) 0.97, 95% confidence interval (CI) 0.94-1.00, p = 0.037], diabetes (OR 0.48, 95% CI 0.26-0.87, p = 0.016) and polypharmacy (OR 0.58, 95% CI 0.34-0.99, p = 0.045) were negatively associated with a rhythm-control strategy. At follow-up, no difference was found between rate- and rhythm-control strategies for cardiovascular (CV) and all-cause deaths (6.1 vs. 5.6%, p = 0.89; and 15.9 vs. 14.1%, p = 0.70, respectively). A rate-control strategy is the most widely used among elderly AF patients with multiple comorbidities and polypharmacy. No differences were evident in CV death and all-cause death at follow-up.

40 CFR 63.3511 - What reports must I submit?

Code of Federal Regulations, 2013 CFR

2013-07-01

... report the beginning and ending dates you used each option. (v) If you used the emission rate without add-on controls or the emission rate with add-on controls compliance option (§ 63.3491(b) or (c)), the... the reporting period. If you used the emission rate with add-on controls option or the control...

40 CFR 63.3511 - What reports must I submit?

Code of Federal Regulations, 2011 CFR

2011-07-01

... report the beginning and ending dates you used each option. (v) If you used the emission rate without add-on controls or the emission rate with add-on controls compliance option (§ 63.3491(b) or (c)), the... the reporting period. If you used the emission rate with add-on controls option or the control...

Closed-Loop Control of Chemical Injection Rate for a Direct Nozzle Injection System

PubMed Central

Cai, Xiang; Walgenbach, Martin; Doerpmond, Malte; Schulze Lammers, Peter; Sun, Yurui

2016-01-01

To realize site-specific and variable-rate application of agricultural pesticides, accurately metering and controlling the chemical injection rate is necessary. This study presents a prototype of a direct nozzle injection system (DNIS) by which chemical concentration transport lag was greatly reduced. In this system, a rapid-reacting solenoid valve (RRV) was utilized for injecting chemicals, driven by a pulse-width modulation (PWM) signal at 100 Hz, so with varying pulse width the chemical injection rate could be adjusted. Meanwhile, a closed-loop control strategy, proportional-integral-derivative (PID) method, was applied for metering and stabilizing the chemical injection rate. In order to measure chemical flow rates and input them into the controller as a feedback in real-time, a thermodynamic flowmeter that was independent of chemical viscosity was used. Laboratory tests were conducted to assess the performance of DNIS and PID control strategy. Due to the nonlinear input–output characteristics of the RRV, a two-phase PID control process obtained better effects as compared with single PID control strategy. Test results also indicated that the set-point chemical flow rate could be achieved within less than 4 s, and the output stability was improved compared to the case without control strategy. PMID:26805833

Local position control: A new concept for control of manipulators

NASA Technical Reports Server (NTRS)

Kelly, Frederick A.

1988-01-01

Resolved motion rate control is currently one of the most frequently used methods of manipulator control. It is currently used in the Space Shuttle remote manipulator system (RMS) and in prosthetic devices. Position control is predominately used in locating the end-effector of an industrial manipulator along a path with prescribed timing. In industrial applications, resolved motion rate control is inappropriate since position error accumulates. This is due to velocity being the control variable. In some applications this property is an advantage rather than a disadvantage. It may be more important for motion to end as soon as the input command is removed rather than reduce the position error to zero. Local position control is a new concept for manipulator control which retains the important properties of resolved motion rate control, but reduces the drift. Local position control can be considered to be a generalization of resolved position and resolved rate control. It places both control schemes on a common mathematical basis.

Drug use in business bathrooms: An exploratory study of manager encounters in New York City.

PubMed

Wolfson-Stofko, Brett; Bennett, Alex S; Elliott, Luther; Curtis, Ric

2017-01-01

Though public bathroom drug injection has been documented from the perspective of people who inject drugs, no research has explored the experiences of the business managers who oversee their business bathrooms and respond to drug use. These managers, by default, are first-responders in the event of a drug overdose and thus of intrinsic interest during the current epidemic of opioid-related overdoses in the United States. This exploratory study assists in elucidating the experiences that New York City business managers have with people who inject drugs, their paraphernalia, and their overdoses. A survey instrument was designed to collect data on manager encounters with drug use occurring in their business bathrooms. Recruitment was guided by convenience and purposive approaches. More than half of managers interviewed (58%, n=50/86) encountered drug use in their business bathrooms, more than a third (34%) of these managers also found syringes, and the vast majority (90%) of managers had received no overdose recognition or naloxone training. Seven managers encountered unresponsive individuals who required emergency assistance. The results from this study underscore the need for additional research on the experiences that community stakeholders have with public injection as well as educational outreach efforts among business managers. This research also suggests that there is need for a national dialogue about potential interventions, including expanded overdose recognition and naloxone training and supervised injection facilities (SIF)/drug consumption rooms (DCR), that could reduce public injection and its associated health risks. Copyright © 2016 Elsevier B.V. All rights reserved.

Forward surgery.

PubMed

Clasper, J C; Midwinter, M J

2007-09-01

Deployment of Forward Surgery is a balance of risk and benefit. The resources will clearly be less than at a more major facility and so care may be compromised. Equally the tactical situation may be non-permissive and limb and life saving intervention required before the movement is possible. However, in order to provide satisfactory care at a forward location sufficient resources to deliver the full requirements of DCR & DCS must be met, which would limit manoeuvrability. This would include large volumes of blood and blood products, critical care and experienced personnel. The later will need to be some of the most senior medical staff as the decision to not operate, if intervention is unnecessary as the patient could wait or intervention would be futile, is one that requires experience. The deployment of these personnel would need to be balanced with the depletion of the experience from the major facility. Forward surgery may be appropriate in the build up phase, establishing a first surgical foot print to develop into a more capable facility (26) or wind down as the major facility is dismantled to be relocated at an alternative location. Ultimately the deployment of forward surgery hinges on the tactical assessment and the ability to evacuate casualties in a timely fashion to the best equipped and resourced facility possible. This decision must be informed by the limitations this may impose on the management of the majority casualties who do not require forward surgery. Forward surgery should only be deployed as part of an overall trauma system with continuous assessment of outcomes. The goal remains "the right patient, right place at the right time".

Radiation-Induced Loss of Salivary Gland Function Is Driven by Cellular Senescence and Prevented by IL6 Modulation.

PubMed

Marmary, Yitzhak; Adar, Revital; Gaska, Svetlana; Wygoda, Annette; Maly, Alexander; Cohen, Jonathan; Eliashar, Ron; Mizrachi, Lina; Orfaig-Geva, Carmit; Baum, Bruce J; Rose-John, Stefan; Galun, Eithan; Axelrod, Jonathan H

2016-03-01

Head and neck cancer patients treated by radiation commonly suffer from a devastating side effect known as dry-mouth syndrome, which results from the irreversible loss of salivary gland function via mechanisms that are not completely understood. In this study, we used a mouse model of radiation-induced salivary hypofunction to investigate the outcomes of DNA damage in the head and neck region. We demonstrate that the loss of salivary function was closely accompanied by cellular senescence, as evidenced by a persistent DNA damage response (γH2AX and 53BP1) and the expression of senescence-associated markers (SA-βgal, p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6). Notably, profound apoptosis or necrosis was not observed in irradiated regions. Signs of cellular senescence were also apparent in irradiated salivary glands surgically resected from human patients who underwent radiotherapy. Importantly, using IL6 knockout mice, we found that sustained expression of IL6 in the salivary gland long after initiation of radiation-induced DNA damage was required for both senescence and hypofunction. Additionally, we demonstrate that IL6 pretreatment prevented both senescence and salivary gland hypofunction via a mechanism involving enhanced DNA damage repair. Collectively, these results indicate that cellular senescence is a fundamental mechanism driving radiation-induced damage in the salivary gland and suggest that IL6 pretreatment may represent a promising therapeutic strategy to preserve salivary gland function in head and neck cancer patients undergoing radiotherapy. ©2016 American Association for Cancer Research.

Characteristics of Health Care Practices and Systems That Excel in Hypertension Control.

PubMed

Young, An; Ritchey, Matthew D; George, Mary G; Hannan, Judy; Wright, Janet

2018-06-07

Approximately 1 in 3 US adults has hypertension, but only half have their blood pressure controlled. We identified characteristics of health care practices and systems (hereinafter practices) effective in achieving control rates at or above 70% by using data collected via applications submitted from April through June 2017 for consideration in the Million Hearts Hypertension Control Challenge. We included 96 practices serving 635,000 patients with hypertension across 34 US states in the analysis. Mean hypertension control rate was 77.1%; 27.1% of practices had a control rate of 80% or greater. Although many practices served large populations with multiple risk factors for uncontrolled hypertension, high control rates were achieved with implementation of evidenced-based strategies.

A comparison between computer-controlled and set work rate exercise based on target heart rate

NASA Technical Reports Server (NTRS)

Pratt, Wanda M.; Siconolfi, Steven F.; Webster, Laurie; Hayes, Judith C.; Mazzocca, Augustus D.; Harris, Bernard A., Jr.

1991-01-01

Two methods are compared for observing the heart rate (HR), metabolic equivalents, and time in target HR zone (defined as the target HR + or - 5 bpm) during 20 min of exercise at a prescribed intensity of the maximum working capacity. In one method, called set-work rate exercise, the information from a graded exercise test is used to select a target HR and to calculate a corresponding constant work rate that should induce the desired HR. In the other method, the work rate is controlled by a computer algorithm to achieve and maintain a prescribed target HR. It is shown that computer-controlled exercise is an effective alternative to the traditional set work rate exercise, particularly when tight control of cardiovascular responses is necessary.

Effect of Flow Rate Controller on Liquid Steel Flow in Continuous Casting Mold using Numerical Modeling

NASA Astrophysics Data System (ADS)

Gursoy, Kadir Ali; Yavuz, Mehmet Metin

2014-11-01

In continuous casting operation of steel, the flow through tundish to the mold can be controlled by different flow rate control systems including stopper rod and slide-gate. Ladle changes in continuous casting machines result in liquid steel level changes in tundishes. During this transient event of production, the flow rate controller opening is increased to reduce the pressure drop across the opening which helps to keep the mass flow rate at the desired level for the reduced liquid steel level in tundish. In the present study, computational fluid dynamic (CFD) models are developed to investigate the effect of flow rate controller on mold flow structure, and particularly to understand the effect of flow controller opening on meniscus flow. First, a detailed validation of the CFD models is conducted using available experimental data and the performances of different turbulence models are compared. Then, the constant throughput casting operations for different flow rate controller openings are simulated to quantify the opening effect on meniscus region. The results indicate that the meniscus velocities are significantly affected by the flow rate controller and its opening level. The steady state operations, specified as constant throughput casting, do not provide the same mold flow if the controller opening is altered. Thus, for quality and castability purposes, adjusting the flow controller opening to obtain the fixed mold flow structure is proposed. Supported by Middle East Technical University (METU) BAP (Scientific Research Projects) Coordination.

Statistical process control charts for monitoring military injuries.

PubMed

Schuh, Anna; Canham-Chervak, Michelle; Jones, Bruce H

2017-12-01

An essential aspect of an injury prevention process is surveillance, which quantifies and documents injury rates in populations of interest and enables monitoring of injury frequencies, rates and trends. To drive progress towards injury reduction goals, additional tools are needed. Statistical process control charts, a methodology that has not been previously applied to Army injury monitoring, capitalise on existing medical surveillance data to provide information to leadership about injury trends necessary for prevention planning and evaluation. Statistical process control Shewhart u-charts were created for 49 US Army installations using quarterly injury medical encounter rates, 2007-2015, for active duty soldiers obtained from the Defense Medical Surveillance System. Injuries were defined according to established military injury surveillance recommendations. Charts display control limits three standard deviations (SDs) above and below an installation-specific historical average rate determined using 28 data points, 2007-2013. Charts are available in Army strategic management dashboards. From 2007 to 2015, Army injury rates ranged from 1254 to 1494 unique injuries per 1000 person-years. Installation injury rates ranged from 610 to 2312 injuries per 1000 person-years. Control charts identified four installations with injury rates exceeding the upper control limits at least once during 2014-2015, rates at three installations exceeded the lower control limit at least once and 42 installations had rates that fluctuated around the historical mean. Control charts can be used to drive progress towards injury reduction goals by indicating statistically significant increases and decreases in injury rates. Future applications to military subpopulations, other health outcome metrics and chart enhancements are suggested. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Rates of retinal nerve fibre layer thickness change in glaucoma patients and control subjects

PubMed Central

O'Leary, N; Artes, P H; Hutchison, D M; Nicolela, M T; Chauhan, B C

2012-01-01

Purpose To examine the rates of retinal nerve fibre layer thickness (RNFLT) change in glaucoma patients and healthy, age-similar control subjects with three techniques: scanning laser polarimetry with variable corneal compensation (VCC) and enhanced corneal compensation (ECC), and time-domain optical coherence tomography (OCT). Methods Sixty-one patients and thirty-three controls were examined with each technique and with standard automated perimetry (SAP) every 6 months. Rates of global RNFLT change and SAP mean deviation (MD) change were estimated with linear mixed-effects models. Results The median (interquartile range) baseline age was 64.4 (58.2, 71.0) years for patients and 62.4 (56.3, 70.1) years for controls (P=0.56). There was a median of seven examinations over 3.1 years for patients and six examinations in 3.0 years for controls. Baseline visual field MD and RNFLT for all imaging modalities were significantly lower (P<0.01) in patients compared with controls. Rates of RNFLT change were not significantly different between patients and controls (P≥0.19). Mean rates of VCC-measured RNFLT change were −0.18 and −0.37 μm per year in patients and controls, whereas the respective figures for ECC and OCT were −0.13 and −0.31 μm per year, and 0.04 and 0.61 μm per year. Mean rates of MD change were −0.20 and 0.03 dB per year in patients and controls, respectively (P=0.01). Conclusion Rates of RNFLT change in glaucoma patients were not statistically different from control subjects for any modality. A significantly negative rate of MD change in patients suggests a genuine, continued deterioration in these patients not reflected by RNFLT changes. PMID:23079756

Enhancing vehicle cornering limit through sideslip and yaw rate control

NASA Astrophysics Data System (ADS)

Lu, Qian; Gentile, Pierangelo; Tota, Antonio; Sorniotti, Aldo; Gruber, Patrick; Costamagna, Fabio; De Smet, Jasper

2016-06-01

Fully electric vehicles with individually controlled drivetrains can provide a high degree of drivability and vehicle safety, all while increasing the cornering limit and the 'fun-to-drive' aspect. This paper investigates a new approach on how sideslip control can be integrated into a continuously active yaw rate controller to extend the limit of stable vehicle cornering and to allow sustained high values of sideslip angle. The controllability-related limitations of integrated yaw rate and sideslip control, together with its potential benefits, are discussed through the tools of multi-variable feedback control theory and non-linear phase-plane analysis. Two examples of integrated yaw rate and sideslip control systems are presented and their effectiveness is experimentally evaluated and demonstrated on a four-wheel-drive fully electric vehicle prototype. Results show that the integrated control system allows safe operation at the vehicle cornering limit at a specified sideslip angle independent of the tire-road friction conditions.

Power flow controller with a fractionally rated back-to-back converter

DOEpatents

Divan, Deepakraj M.; Kandula, Rajendra Prasad; Prasai, Anish

2016-03-08

A power flow controller with a fractionally rated back-to-back (BTB) converter is provided. The power flow controller provide dynamic control of both active and reactive power of a power system. The power flow controller inserts a voltage with controllable magnitude and phase between two AC sources at the same frequency; thereby effecting control of active and reactive power flows between the two AC sources. A transformer may be augmented with a fractionally rated bi-directional Back to Back (BTB) converter. The fractionally rated BTB converter comprises a transformer side converter (TSC), a direct-current (DC) link, and a line side converter (LSC). By controlling the switches of the BTB converter, the effective phase angle between the two AC source voltages may be regulated, and the amplitude of the voltage inserted by the power flow controller may be adjusted with respect to the AC source voltages.

On Optimizing H. 264/AVC Rate Control by Improving R-D Model and Incorporating HVS Characteristics

NASA Astrophysics Data System (ADS)

Zhu, Zhongjie; Wang, Yuer; Bai, Yongqiang; Jiang, Gangyi

2010-12-01

The state-of-the-art JVT-G012 rate control algorithm of H.264 is improved from two aspects. First, the quadratic rate-distortion (R-D) model is modified based on both empirical observations and theoretical analysis. Second, based on the existing physiological and psychological research findings of human vision, the rate control algorithm is optimized by incorporating the main characteristics of the human visual system (HVS) such as contrast sensitivity, multichannel theory, and masking effect. Experiments are conducted, and experimental results show that the improved algorithm can simultaneously enhance the overall subjective visual quality and improve the rate control precision effectively.