Brain-derived neurotrophic factor Val66Met polymorphism and dexamethasone/CRH test results in depressed patients.

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Schüle, Cornelius; Zill, Peter; Baghai, Thomas C; Eser, Daniela; Zwanzger, Peter; Wenig, Nadine; Rupprecht, Rainer; Bondy, Brigitta

2006-09-01

Data suggest that both neurotrophic and hypothalamic-pituitary-adrenocortical (HPA) systems are involved in the pathophysiology of depression. The aim of the present study was to investigate whether the non-conservative brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has an impact on HPA axis activity in depressed patients. At admission, the dexamethasone/CRH (DEX/CRH) test was performed in 187 drug-free in-patients suffering from major depression or depressed state of bipolar disorder (DSM-IV criteria). Moreover, genotyping of BDNF Val66Met polymorphism was carried out using the fluorescence resonance energy transfer method (FRET). Homozygous carriers of the Met/Met genotype showed a significantly higher HPA axis activity during the DEX/CRH test than patients carrying the Val/Val or Val/Met genotype (ACTH, cortisol). Our results further contribute to the hypothesized association between HPA axis dysregulation and reduced neuroplasticity in depression and are consistent with the assumption that BDNF is a stress-responsive intercellular messenger modifying HPA axis activity.

Gender-specific differences in the incidence of microalbuminuria in metabolic syndrome patients after treatment with fimasartan: The K-MetS study.

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Park, Jeong Bae; Kim, Su-A; Sung, Ki-Chul; Kim, Jang Young

2017-01-01

The effect of resolving metabolic syndrome on target organ damage in hypertensive patients is not well described. We evaluated whether treating metabolic syndrome (MetS) with an angiotensin receptor blocker subsequently reduced microalbuminuria in the K-MetS cohort. Among 10,601 total metabolic syndrome patients, 3,250 (52.2% male, 56.2±10.0 years) with sufficient data on five specific metabolic components were included in this study. Patients were divided into four groups based on MetS status at baseline and 3 months. All patients received an angiotensin receptor blocker, fimasartan, for these 3 months; thereafter, treatment was modified at the discretion of each patient's physician. Microalbuminuria and the albumin/creatine ratio were evaluated as a proxy of organ damage. Blood pressure and waist circumference decreased from baseline to 3 months and 1 year. The average albumin/creatinine ratio significantly improved during the first three months of the study from 36.0±147.4 to 21.0±74.9 mg/g (pTreatment of hypertensive patients for one year with the angiotensin receptor blocker fimasartan significantly reduced the albumin/creatine ratio, irrespective of whether the patient had MetS; however, the albumin/creatinine ratio was significantly higher in patents with persistent or newly developed MetS compared to patients without MetS. Additionally, these findings were more prominent in women than in men.

BDNF-Val66Met-Polymorphism Impact on Cortical Plasticity in Schizophrenia Patients: A Proof-of-Concept Study

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Nitsche, Michael A.; Wobrock, Thomas; Bunse, Tilmann; Rein, Bettina; Herrmann, Maximiliane; Schmitt, Andrea; Nieratschker, Vanessa; Witt, Stephanie H.; Rietschel, Marcella; Falkai, Peter; Hasan, Alkomiet

2015-01-01

Background: Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients. Methods: Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied. Results: Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS. Conclusions: These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory

Phase II and Biomarker Study of the Dual MET/VEGFR2 Inhibitor Foretinib in Patients With Papillary Renal Cell Carcinoma

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Choueiri, Toni K.; Vaishampayan, Ulka; Rosenberg, Jonathan E.; Logan, Theodore F.; Harzstark, Andrea L.; Bukowski, Ronald M.; Rini, Brian I.; Srinivas, Sandy; Stein, Mark N.; Adams, Laurel M.; Ottesen, Lone H.; Laubscher, Kevin H.; Sherman, Laurie; McDermott, David F.; Haas, Naomi B.; Flaherty, Keith T.; Ross, Robert; Eisenberg, Peter; Meltzer, Paul S.; Merino, Maria J.; Bottaro, Donald P.; Linehan, W. Marston; Srinivasan, Ramaprasad

2013-01-01

Purpose Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors. Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). We aimed to evaluate the efficacy and safety of foretinib in patients with PRCC. Patients and Methods Patients were enrolled onto the study in two cohorts with different dosing schedules of foretinib: cohort A, 240 mg once per day on days 1 through 5 every 14 days (intermittent arm); cohort B, 80 mg daily (daily dosing arm). Patients were stratified on the basis of MET pathway activation (germline or somatic MET mutation, MET [7q31] amplification, or gain of chromosome 7). The primary end point was overall response rate (ORR). Results Overall, 74 patients were enrolled, with 37 in each dosing cohort. ORR by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was 13.5%, median progression-free survival was 9.3 months, and median overall survival was not reached. The presence of a germline MET mutation was highly predictive of a response (five of 10 v five of 57 patients with and without germline MET mutations, respectively). The most frequent adverse events of any grade associated with foretinib were fatigue, hypertension, gastrointestinal toxicities, and nonfatal pulmonary emboli. Conclusion Foretinib demonstrated activity in patients with advanced PRCC with a manageable toxicity profile and a high response rate in patients with germline MET mutations. PMID:23213094

The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese heroin-dependent patients.

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Chen, Shiou-Lan; Lee, Sheng-Yu; Chang, Yun-Hsuan; Wang, Tzu-Yun; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2015-02-02

BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of long-term heroin use. Thus, we investigated the relationships between brain-derived neurotrophic factor (BDNF) plasma concentrations and the BDNF Val66Met nucleotide polymorphism (SNP) in heroin-dependent patients. The pretreatment expression levels of plasma BDNF and the BDNF Val66Met SNP in 172 heroin-dependent patients and 102 healthy controls were checked. BDNF levels were significantly lower in patients (F = 52.28, p BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not affect plasma BDNF levels in our participants. In heroin-dependent patients, plasma BDNF levels were negatively correlated with the length of heroin dependency. Long-term (>15 years) users had significantly lower plasma BDNF levels than did short-term (BDNF concentration in habitual heroin users are not affected by BDNF Val66Met gene variants, but by the length of the heroin dependency.

Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer

OpenAIRE

Shitara, Kohei; Kim, Tae Min; Yokota, Tomoya; Goto, Masahiro; Satoh, Taroh; Ahn, Jin-Hee; Kim, Hyo Song; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hamauchi, Satoshi; Kudo, Toshihiro; Doi, Toshihido; Bang, Yung-Jue

2017-01-01

SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260–570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety...

Phase I Trial of Anti-MET Monoclonal Antibody in MET-Overexpressed Refractory Cancer.

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Lee, Jeeyun; Kim, Seung Tae; Park, Sungju; Lee, Sujin; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Ahn, Hongmo; Bok, Haesook; Kim, Kyoung-Mee; Ahn, Myung Ju; Kang, Won Ki; Park, Young Suk

2018-06-01

Samsung Advance Institute of Technology-301 (SAIT301) is a human immunoglobulin G2 antibody that can specifically target mesenchymal epithelial transition factor (c-MET). This novel antibody has higher priority over hepatocyte growth factors when binding to the Sema domain of c-MET and accelerates the internalization and degradation of c-MET, proving its powerful antitumor activities in intra- as well as extracellular areas. SAIT301 was administered intravenously once every 3 weeks in c-MET overexpressed solid tumor patients, focusing on metastatic colorectal cancer (CRC) according to common clinical phase I criteria. Dose escalation was performed according to a modified Fibonacci design, following the conventional 3+3 design. The purpose of this phase I study was to assess the safety profile, to establish the recommended dose for clinical phase II studies and to assess potential anticancer activity of the compound. Sixteen patients with a median age of 56 (range, 39-69) years were enrolled in the study. The most common adverse events were decreased appetite (50.0%), hypophosphatemia, fatigue and dizziness (25.0%, respectively), and diarrhea, blood alkaline phosphatase increased and dyspnea (18.8%, respectively). For tumor response, no patients achieved complete response. One (9.1%) CRC patient had a partial response in the 1.23 mg/kg group, 4 (36.4%) patients achieved stable disease (2 in the 0.41 mg/kg group, 2 in the 1.23 mg/kg group, 0 in the 3.69 mg/kg group, and 1 in the 8.61 mg/kg group). Because of the increase in dose-limiting toxicities (DLTs) at 8.61 mg/kg, the 3.69 mg/kg dose was considered the maximum tolerated dose and selected for further assessment in phase II. We successfully completed a phase I trial with MET antibody in a MET-overexpressed patient population focusing on CRC, and found that the DLTs were alkaline phosphatase elevation or hypophosphatemia. The recommended dose of SAIT301 for phase II is the dose of 3.69 mg/kg. Copyright © 2018

Eligibility of real-world patients with chemo-refractory, K-RAS wild-type, metastatic colorectal cancer for palliative intent regorafenib monotherapy.

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Angeles, Arkhjamil; Hung, Wayne; Cheung, Winson Y

2018-06-23

The CORRECT trial demonstrated survival benefits with regorafenib monotherapy in patients with treatment-refractory, metastatic colorectal cancer (mCRC). However, the trial's stringent eligibility criteria for regorafenib may limit its external validity. We aimed to examine treatment attrition rates and eligibility for regorafenib in routine practice. We identified patients at the British Columbia Cancer Agency diagnosed with mCRC who demonstrated disease progression or intolerable toxicity on 2 or more lines of systemic therapy. During the study timeframe, panitumumab and cetuximab were only used in the chemo-refractory setting. Data on clinicopathologic variables and patient outcomes were ascertained and analyzed. Eligibility was determined using the CORRECT trial criteria. A total of 391 patients were identified, among whom only 39% were eligible for regorafenib: 35% in the panitumumab group and 51% in the cetuximab group. The main reasons for ineligibility in all patients were Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 1 (69%), an elevated total bilirubin (21%), and thromboembolic events in the past 6 months (10%). No difference in eligibility for regorafenib was observed between patients previously receiving panitumumab or cetuximab (P = 0.914; 95% CI 0.550-1.951). Kaplan-Meier analyses showed that regorafenib-eligible compared to regorafenib-ineligible patients had an increased median overall survival of 5.3 versus 2.1 months, respectively (P < 0.001). However, Cox proportional hazard analyses showed that only ECOG PS rather than trial eligibility was correlated with outcomes. The strict eligibility criteria disqualify most patients with treatment-refractory mCRC for regorafenib therapy. Future trials should broaden the eligibility criteria to improve external validity.

Association between COMT Polymorphism Val158Met and Opioid Consumption in Patients with Postoperative Pain: A Meta-Analysis

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Bo Hu

2018-01-01

Full Text Available Background/Aims: Several factors influencing postoperative pain and the effect of opioid analgesics have been investigated on an individual level. The aim of this study was to clarify the impact of catecholamine-O-methyltransferase (COMT gene Val158Met on opioid consumption in postoperative patients. Methods: A systematic review and meta-analysis of the literature up to September 30, 2017, were performed by using PubMed, Cochrane Library, ISI Web of Science, and Chinese National Knowledge Infrastructure (CNKI database. The meta-analysis examined all studies involving the association between genetic polymorphisms of COMT Val158Met and opioid consumption during the acute postoperative period. Results: Of the 153 identified studies, 23 studies were retrieved for systematic review and 10 studies were retrieved for meta-analysis. However, it was impossible to conduct meta-analysis on the association between COMT Val158Met polymorphism and postoperative pain because of heterogeneity of the data. Overall, meta-analysis showed that COMT Val/Met carriers consumed less opioid for analgesia within the first 24 hours after surgery (SMD = 0.14, 95% CI = [0.03, 0.25], P = 0.01 but not within 48 hours (SMD = 0.14, 95% CI = [0.08, 0.36], P = 0.21. There was no significant difference in opioid consumption between Val/ Val and Met/Met patients. Conclusion: Patients with Val/Met but not Met/Met allele variant consumed less opioid, though larger and better-designed studies are required to obtain an exclusive conclusion about the correlation between postoperative pain and COMT Val158Met polymorphism.

Suicide attempt, clinical correlates, and BDNF Val66Met polymorphism in chronic patients with schizophrenia.

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Xia, Haisen; Zhang, Guangya; Du, Xiangdong; Zhang, Yingyang; Yin, Guangzhong; Dai, Jing; He, Man-Xi; Soares, Jair C; Li, Xiaosi; Zhang, Xiang Yang

2018-02-01

Recent evidence suggests the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidal behavior. Because schizophrenia patients usually have high suicide rates and numerous studies have suggested that BDNF may contribute to the psychopathology of schizophrenia, we hypothesized that the functional polymorphism of BDNF (Val66Met) was associated with suicide attempts in patients with schizophrenia in a Chinese Han population. This polymorphism was genotyped in 825 chronic schizophrenia patients with (n = 123) and without (n = 702) suicide attempts and 445 healthy controls without a history of suicide attempts using a case-control design. The schizophrenia symptoms were assessed by the Positive and Negative Syndrome Scale. There were no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls. However, we found the Val allele (p = .023) and the Val/Val genotypes (p = .058) to be associated with a history of suicide attempts. Moreover, some clinical characteristics, including age and cigarettes smoked each day, interacted with the BDNF gene variant and appeared to play an important role in suicide attempts among schizophrenia patients. The BDNF Val66Met polymorphism itself and its interaction with some clinical variables may influence suicide attempts among schizophrenia patients. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

40 CFR 264.555 - Disposal of CAMU-eligible wastes in permitted hazardous waste landfills.

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2010-07-01

... this section are met: (1) The waste meets the definition of CAMU-eligible waste in § 264.552(a)(1) and... remediation. (d) Applicable hazardous waste management requirements in this part, including recordkeeping... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Disposal of CAMU-eligible wastes in...

Eligibility of Metastatic Pancreatic Cancer Patients for First-Line Palliative Intent nab-Paclitaxel Plus Gemcitabine Versus FOLFIRINOX.

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Peixoto, Renata D; Ho, Maria; Renouf, Daniel J; Lim, Howard J; Gill, Sharlene; Ruan, Jenny Y; Cheung, Winson Y

2017-10-01

The PRODIGE and MPACT trials showed superiority of FOLFIRINOX and nab-paclitaxel plus gemcitabine (NG) over gemcitabine alone, respectively. However, both had strict inclusion criteria. We sought to determine the characteristics of patients with metastatic pancreatic cancer (MPC) which inform the appropriateness of first-line chemotherapy FOLFIRINOX and NG in routine practice. Patients with MPC who initiated palliative chemotherapy with gemcitabine from 2000 to 2011 at the British Columbia Cancer Agency were identified. Clinicopathologic variables and outcomes were retrospectively collected and compared among groups. Eligibility criteria for each regimen were in accordance with the respective pivotal phase III trials. A total of 473 patients were included: 25% of the patients were eligible for FOLFIRINOX versus 45% for NG. Main reasons for FOLFIRINOX ineligibility were Eastern Cooperative Oncology Group (ECOG) performance status (PS)≥2 (56.5%), age older than 75 years (19.0%), and bilirubin>1.5× upper limit of normal (18.6%), whereas those for NG ineligibility were bilirubin > upper limit of normal (24.5%), ECOG PS≥3 (14.6%), and cardiac dysfunction (13.8%). Univariate analyses revealed that FOLFIRINOX and NG-eligible patients had longer median overall survival than their respective ineligible group (8.6 vs. 4.7 mo, Paccounting for ECOG PS in the multivariate model, however, eligibility for either FOLFIRINOX or NG no longer predicted for better overall survival. The majority of patients with MPC are not candidates to either NG or FOLFIRINOX due to restrictive eligibility requirements. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.

The effect of Saccharomyces boulardii in patients eligible for liver transplantation.

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Liboredo, Juliana Costa; Ferrari, Maria de Lourdes Abreu; Vilela, Eduardo Garcia; Lima, Agnaldo Soares; Correia, Maria Isabel Toulson Davisson

2014-09-12

The aim of this study was to evaluate the influence of Saccharomyces boulardii on the intestinal permeability, laboratory parameters and MELD and Child-Pugh severity scores in cirrhotic patients eligible for liver transplantation. Eighteen patients followed in a Transplant Outpatient Clinic were evaluated immediately before the beginning of treatment, after a 30-day period of treatment period with probiotics and at the end of the second study month (after a thirty-day period without probiotics). Fifteen healthy controls also underwent the intestinal permeability test (lactulose/mannitol). Before the probiotic, the median lactulose/ mannitol ratio was greater in the cirrhotic patients (0.0209, range 0.0012-0.1984) compared to the healthy controls (0.0030, range 0.0020-0.0013) (p boulardii, there was no improvement in intestinal permeability or significant differences in the laboratory parameters for the three evaluations. Patients eligible for liver transplants presented with increased intestinal permeability compared to healthy controls. A thirty-day treatment with S. boulardii did not improve this intestinal permeability or the severity scores, nor did it impact the laboratory parameters. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Six habits to enhance MET performance under stress: A discussion paper reviewing team mechanisms for improved patient outcomes.

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Fein, Erich C; Mackie, Benjamin; Chernyak-Hai, Lily; O'Quinn, C Richard V; Ahmed, Ezaz

2016-05-01

Effective team decision making has the potential to improve the quality of health care outcomes. Medical Emergency Teams (METs), a specific type of team led by either critical care nurses or physicians, must respond to and improve the outcomes of deteriorating patients. METs routinely make decisions under conditions of uncertainty and suboptimal care outcomes still occur. In response, the development and use of Shared Mental Models (SMMs), which have been shown to promote higher team performance under stress, may enhance patient outcomes. This discussion paper specifically focuses on the development and use of SMMs in the context of METs. Within this process, the psychological mechanisms promoting enhanced team performance are examined and the utility of this model is discussed through the narrative of six habits applied to MET interactions. A two stage, reciprocal model of both nonanalytic decision making within the acute care environment and analytic decision making during reflective action learning was developed. These habits are explored within the context of a MET, illustrating how applying SMMs and action learning processes may enhance team-based problem solving under stress. Based on this model, we make recommendations to enhance MET decision making under stress. It is suggested that the corresponding habits embedded within this model could be imparted to MET members and tested by health care researchers to assess the efficacy of this integrated decision making approach in respect to enhanced team performance and patient outcomes. Copyright © 2015. Published by Elsevier Ltd.

Pathological upgrading in prostate cancer patients eligible for active surveillance: Does prostate-specific antigen density matter?

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Jin, Byung-Soo; Kang, Seok-Hyun; Kim, Duk-Yoon; Oh, Hoon-Gyu; Kim, Chun-Il; Moon, Gi-Hak; Kwon, Tae-Gyun; Park, Jae-Shin

2015-09-01

To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score≤6, PSA≤10 ng/mL, and ≤2 positive biopsy cores). Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL(2), obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance.

HIV-infected presumptive tuberculosis patients without tuberculosis: How many are eligible for antiretroviral therapy in Karnataka, India?

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Ajay M.V. Kumar

2017-03-01

Full Text Available For certain subgroups within people living with the human immunodeficiency virus (HIV [active tuberculosis (TB, pregnant women, children <5 years old, and serodiscordant couples], the World Health Organization recommends antiretroviral therapy (ART irrespective of CD4 count. Another subgroup which has received increased attention is “HIV-infected presumptive TB patients without TB”. In this study, we assess the proportion of HIV-infected presumptive TB patients eligible for ART in Karnataka State (population 60 million, India. This was a cross-sectional analysis of data of HIV-infected presumptive TB patients diagnosed in May 2015 abstracted from national TB and HIV program records. Of 42,585 presumptive TB patients, 28,964 (68% were tested for HIV and 2262 (8% were HIV positive. Of the latter, 377 (17% had active TB. Of 1885 “presumptive TB patients without active TB”, 1100 (58% were already receiving ART. Of the remaining 785 who were not receiving ART, 617 (79% were assessed for ART eligibility and of those, 548 (89% were eligible for ART. About 90% of “HIV-infected presumptive TB patients without TB” were eligible for ART. This evidence supports a public health approach of starting all “HIV-infected presumptive TB patients without TB” on ART irrespective of CD4 count in line with global thinking about ‘test and treat’.

Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis.

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Rakanović-Todić, Maida; Burnazović-Ristić, Lejla; Ibrulj, Slavka; Mulbegović, Nedžad

2014-05-01

Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of the clinical condition in patients with multiple Sclerosis (MS). The goal of the present research was to evaluate met-enkephalin in vitro effects on the number and type of chromosome aberrations in the peripheral blood lymphocytes of patients with MS. Our research detected disappearance of ring chromosomes and chromosome fragmentations in the cultures of the peripheral blood lymphocytes treated with met-enkephalin (1.2 μg/mL). However, this research did not detect any significant effects of met-enkephalin on the reduction of structural chromosome aberrations and disappearance of dicentric chromosomes. Chromosomes with the greatest percent of inclusion in chromosome aberrations were noted as: chromosome 1, chromosome 2 and chromosome 9. Additionally, we confirmed chromosome 14 as the most frequently included in translocations. Furthermore, met-enkephalin effects on the increase of the numerical aberrations in both concentrations applied were detected. Those findings should be interpreted cautiously and more research in this field should be conducted.

Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis

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Maida Rakanović-Todić

2014-05-01

Full Text Available Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of the clinical condition in patients with multiple Sclerosis (MS. The goal of the present research was to evaluate met-enkephalin in vitro effects on the number and type of chromosome aberrations in the peripheral blood lymphocytes of patients with MS. Our research detected disappearance of ring chromosomes and chromosome fragmentations in the cultures of the peripheral blood lymphocytes treated with met-enkephalin (1.2 μg/mL. However, this research did not detect any significant effects of met-enkephalin on the reduction of structural chromosome aberrations and disappearance of dicentric chromosomes. Chromosomes with the greatest percent of inclusion in chromosome aberrations were noted as: chromosome 1, chromosome 2 and chromosome 9. Additionally, we confirmed chromosome 14 as the most frequently included in translocations. Furthermore, met-enkephalin effects on the increase of the numerical aberrations in both concentrations applied were detected. Those findings should be interpreted cautiously and more research in this field should be conducted. 

High-frequency ultrasound in carpal tunnel syndrome: assessment of patient eligibility for surgical treatment

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Katarzyna Kapuścińska

2015-09-01

Full Text Available Carpal tunnel syndrome (CTS is the most common entrapment neuropathy and a frequent cause of sick leaves because of work-related hand overload. That is why an early diagnosis and adequate treatment (conservative or surgical are essential for optimal patient management. Aim: The aim of the study is to assess the usefulness of high-frequency ultrasound in CTS for the assessment of patient eligibility for surgical treatment. Material and methods: The study involved 62 patients (50 women and 12 men, aged 28–70, mean age 55.2 with scheduled surgeries of CTS on the basis of clinical symptoms, physical examination performed by a neurosurgeon and a positive result of EMG testing. The ultrasound examinations of the wrist were performed in all these patients. On the basis of the collected data, the author has performed multiple analyses to confi rm the usefulness of ultrasound imaging in assessing patient eligibility for surgical treatment of CTS. Results: US examinations showed evidence of median nerve compression at the level of the carpal tunnel in all of the examined patients. This was further confi rmed during surgical procedures. The mean value of the cross-sectional area at the proximal part of the pisiform bone was 17.45 mm2 (min. 12 mm2 , max. 31 mm2 . Nerve hypoechogenicity proximal to the nerve compression site was visible in all 62 patients (100%. Increased nerve vascularity on the transverse section was present in 50 patients (80.65%. Conclusions: Ultrasonography with the use of high-frequency transducers is a valuable diagnostic tool both for assessing patient eligibility for surgical treatment of CTS, and in postoperative assessment of the treatment efficacy.

76 FR 43350 - Notice of Determinations Regarding Eligibility To Apply for Worker Adjustment Assistance and...

Science.gov (United States)

2011-07-20

... Motivation, Inc., Greenville, OH: June 13, 2010. TA-W-80,236; Unimin Corporation, Green Mountain, NC: June 15... the requirements of 246(a)(3)(A)(ii) have not been met for the reasons specified. The Department has... the eligibility criteria for worker adjustment assistance have not been met for the reasons specified...

Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

Science.gov (United States)

Hu, Peizhen; Chung, Leland W K; Berel, Dror; Frierson, Henry F; Yang, Hua; Liu, Chunyan; Wang, Ruoxiang; Li, Qinlong; Rogatko, Andre; Zhau, Haiyen E

2013-01-01

We reported (PLoS One 6 (12):e28670, 2011) that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC) tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE) tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1) expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

Cardiovascular Risk and Statin Eligibility of Young Adults After an MI: Partners YOUNG-MI Registry.

Science.gov (United States)

Singh, Avinainder; Collins, Bradley L; Gupta, Ankur; Fatima, Amber; Qamar, Arman; Biery, David; Baez, Julio; Cawley, Mary; Klein, Josh; Hainer, Jon; Plutzky, Jorge; Cannon, Christopher P; Nasir, Khurram; Di Carli, Marcelo F; Bhatt, Deepak L; Blankstein, Ron

2018-01-23

Despite significant progress in primary prevention, the rate of MI has not declined in young adults. The purpose of this study was to evaluate statin eligibility based on the 2013 American College of Cardiology/American Heart Association guidelines for treatment of blood cholesterol and 2016 U.S. Preventive Services Task Force recommendations for statin use in primary prevention in a cohort of adults who experienced a first-time myocardial infarction (MI) at a young age. The YOUNG-MI registry is a retrospective cohort from 2 large academic centers, which includes patients who experienced an MI at age ≤50 years. Diagnosis of type 1 MI was adjudicated by study physicians. Pooled cohort risk equations were used to estimate atherosclerotic cardiovascular disease risk score based on data available prior to MI or at the time of presentation. Of 1,685 patients meeting inclusion criteria, 210 (12.5%) were on statin therapy prior to MI and were excluded. Among the remaining 1,475 individuals, the median age was 45 years, there were 294 (20%) women, and 846 (57%) had ST-segment elevation MI. At least 1 cardiovascular risk factor was present in 1,225 (83%) patients. The median 10-year atherosclerotic cardiovascular disease risk score of the cohort was 4.8% (interquartile range: 2.8% to 8.0%). Only 724 (49%) and 430 (29%) would have met criteria for statin eligibility per the 2013 American College of Cardiology/American Heart Association guidelines and 2016 U.S. Preventive Services Task Force recommendations, respectively. This finding was even more pronounced in women, in whom 184 (63%) were not eligible for statins by either guideline, compared with 549 (46%) men (p adults who present with an MI at a young age would not have met current guideline-based treatment thresholds for statin therapy prior to their MI. These findings highlight the need for better risk assessment tools among young adults. Copyright © 2018 American College of Cardiology Foundation. Published by

Lipid ratio as a suitable tool to identify individuals with MetS risk: A case- control study.

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Abbasian, Maryam; Delvarianzadeh, Mehri; Ebrahimi, Hossein; Khosravi, Farideh

2017-11-01

This study aimed to compare the serum lipids ratio in staff with and without metabolic syndrome (MetS) who were working in Shahroud University of Medical Sciences. This case-control study was conducted in 2015 on 499 personnel aged 30-60 years old. ATP III criteria were used to diagnose patients with MetS. The data were analyzed by using logistic regression and ROC curve. Mean lipid ratio was higher in individuals having the MetS in both sexes compared with those without. In addition, the mean levels of lipid ratios significantly increased with increasing number of MetS components in both sexes. Also it could be concluded that TG/HDL-C ratio is the best marker for the diagnosis of MetS in men and women. Moreover, the cut-off point for the TG/HDL-C was 2.86 in women and 4.03 in men. It was found that for any unit of increases in the TG/HDL-C, the risk of developing the MetS will increase by 2.12 times. TG/HDL-C ratio is found to be the best clinical marker for the diagnosis of MetS compare with other lipid ratios, therefore it is recommended to be used as a feasible tool to identify individuals with MetS risk. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

The BDNF Val66Met polymorphism has opposite effects on memory circuits of multiple sclerosis patients and controls.

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Francesco Fera

Full Text Available Episodic memory deficits are frequent symptoms in Multiple Sclerosis and have been associated with dysfunctions of the hippocampus, a key region for learning. However, it is unclear whether genetic factors that influence neural plasticity modulate episodic memory in MS. We thus studied how the Brain Derived Neurotrophic Factor Val(66Met genotype, a common polymorphism influencing the hippocampal function in healthy controls, impacted on brain networks underlying episodic memory in patients with Multiple Sclerosis. Functional magnetic resonance imaging was used to assess how the Brain Derived Neurotrophic Factor Val(66Met polymorphism modulated brain regional activity and functional connectivity in 26 cognitively unimpaired Multiple Sclerosis patients and 25 age- and education-matched healthy controls while performing an episodic memory task that included encoding and retrieving visual scenes. We found a highly significant group by genotype interaction in the left posterior hippocampus, bilateral parahippocampus, and left posterior cingulate cortex. In particular, Multiple Sclerosis patients homozygous for the Val(66 allele, relative to Met(66 carriers, showed greater brain responses during both encoding and retrieval while the opposite was true for healthy controls. Furthermore, a robust group by genotype by task interaction was detected for the functional connectivity between the left posterior hippocampus and the ipsilateral posterior cingulate cortex. Here, greater hippocampus-posterior cingulate cortex connectivity was observed in Multiple Sclerosis Met(66 carriers relative to Val(66 homozygous during retrieval (but not encoding while, again, the reverse was true for healthy controls. The Val(66Met polymorphism has opposite effects on hippocampal circuitry underlying episodic memory in Multiple Sclerosis patients and healthy controls. Enhancing the knowledge of how genetic factors influence cognitive functions may improve the clinical

Convergent RANK- and c-Met-mediated signaling components predict survival of patients with prostate cancer: an interracial comparative study.

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Peizhen Hu

Full Text Available We reported (PLoS One 6 (12:e28670, 2011 that the activation of c-Met signaling in RANKL-overexpressing bone metastatic LNCaP cell and xenograft models increased expression of RANK, RANKL, c-Met, and phosphorylated c-Met, and mediated downstream signaling. We confirmed the significance of the RANK-mediated signaling network in castration resistant clinical human prostate cancer (PC tissues. In this report, we used a multispectral quantum dot labeling technique to label six RANK and c-Met convergent signaling pathway mediators simultaneously in formalin fixed paraffin embedded (FFPE tissue specimens, quantify the intensity of each expression at the sub-cellular level, and investigated their potential utility as predictors of patient survival in Caucasian-American, African-American and Chinese men. We found that RANKL and neuropilin-1 (NRP-1 expression predicts survival of Caucasian-Americans with PC. A Gleason score ≥ 8 combined with nuclear p-c-Met expression predicts survival in African-American PC patients. Neuropilin-1, p-NF-κB p65 and VEGF are predictors for the overall survival of Chinese men with PC. These results collectively support interracial differences in cell signaling networks that can predict the survival of PC patients.

Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis

OpenAIRE

Maida Rakanović-Todić; Lejla Burnazović-Ristić; Slavka Ibrulj; Nedžad Mulabegović

2014-01-01

Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of t...

Identifying primary care patients at risk for future diabetes and cardiovascular disease using electronic health records

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Shrader Peter

2009-09-01

Full Text Available Abstract Background Prevention of diabetes and coronary heart disease (CHD is possible but identification of at-risk patients for targeting interventions is a challenge in primary care. Methods We analyzed electronic health record (EHR data for 122,715 patients from 12 primary care practices. We defined patients with risk factor clustering using metabolic syndrome (MetS characteristics defined by NCEP-ATPIII criteria; if missing, we used surrogate characteristics, and validated this approach by directly measuring risk factors in a subset of 154 patients. For subjects with at least 3 of 5 MetS criteria measured at baseline (2003-2004, we defined 3 categories: No MetS (0 criteria; At-risk-for MetS (1-2 criteria; and MetS (≥ 3 criteria. We examined new diabetes and CHD incidence, and resource utilization over the subsequent 3-year period (2005-2007 using age-sex-adjusted regression models to compare outcomes by MetS category. Results After excluding patients with diabetes/CHD at baseline, 78,293 patients were eligible for analysis. EHR-defined MetS had 73% sensitivity and 91% specificity for directly measured MetS. Diabetes incidence was 1.4% in No MetS; 4.0% in At-risk-for MetS; and 11.0% in MetS (p MetS vs No MetS = 6.86 [6.06-7.76]; CHD incidence was 3.2%, 5.3%, and 6.4% respectively (p Conclusion Risk factor clustering in EHR data identifies primary care patients at increased risk for new diabetes, CHD and higher resource utilization.

MET Expression in Primary and Metastatic Clear Cell Renal Cell Carcinoma: Implications of Correlative Biomarker Assessment to MET Pathway Inhibitors

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Brian Shuch

2015-01-01

Full Text Available Aims. Inhibitors of the MET pathway hold promise in the treatment for metastatic kidney cancer. Assessment of predictive biomarkers may be necessary for appropriate patient selection. Understanding MET expression in metastases and the correlation to the primary site is important, as distant tissue is not always available. Methods and Results. MET immunofluorescence was performed using automated quantitative analysis and a tissue microarray containing matched nephrectomy and distant metastatic sites from 34 patients with clear cell renal cell carcinoma. Correlations between MET expressions in matched primary and metastatic sites and the extent of heterogeneity were calculated. The mean expression of MET was not significantly different between primary tumors when compared to metastases (P=0.1. MET expression weakly correlated between primary and matched metastatic sites (R=0.5 and a number of cases exhibited very high levels of discordance between these tumors. Heterogeneity within nephrectomy specimens compared to the paired metastatic tissues was not significantly different (P=0.39. Conclusions. We found that MET expression is not significantly different in primary tumors than metastatic sites and only weakly correlates between matched sites. Moderate concordance of MET expression and significant expression heterogeneity may be a barrier to the development of predictive biomarkers using MET targeting agents.

MET overexpression, gene amplification and relevant clinicopathological features in gastric adenocarcinoma.

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Zhang, Jing; Guo, Lei; Liu, Xiuyun; Li, Wenbin; Ying, Jianming

2017-02-07

This study was conducted to investigate the expression of MET in Chinese gastric adenocarcinoma cohort, the correlation between MET overexpression and clinical pathological features, HER2 expression and MET gene amplification. A total of 816 gastric adenocarcinoma patients were included and MET and HER2 immunohistochemical (IHC) staining were performed. IHC and dual-color silver in situ hybridization analysis were performed in the tissue microarrays, constructed from the 240 patients who were randomly selected. MET overexpression (IHC 3+) was observed in 6.0% (49/816) of the cohort. MET overexpression rate was higher in patients with poor prognostic factors, such as clinical stages III/IV (p =0.012) and pathologic stages T3/T4 (p =0.027). The HER2 overexpression (IHC 3+) rate was 8.8% (72/816) and MET overexpression rate was higher in HER2 positive patients (9.7%, 7/72). A high concordance rate (94.6%) between MET overexpression and gene amplification was demonstrated. Therefore, MET overexpression could serve as a prognostic biomarker and a potential therapeutic target for gastric cancer.

Targeting MET Amplification as a New Oncogenic Driver

International Nuclear Information System (INIS)

Kawakami, Hisato; Okamoto, Isamu; Okamoto, Wataru; Tanizaki, Junko; Nakagawa, Kazuhiko; Nishio, Kazuto

2014-01-01

Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy

Targeting MET Amplification as a New Oncogenic Driver

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Kawakami, Hisato [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Okamoto, Isamu, E-mail: okamotoi@kokyu.med.kyushu-u.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582 (Japan); Okamoto, Wataru [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Division of Transrlational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577 (Japan); Tanizaki, Junko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, HIM223, 450 Brookline Avenue, Boston, MA 02215 (United States); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan)

2014-07-22

Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy.

Predictive factors in patients eligible for pegfilgrastim prophylaxis focusing on RDI using ordered logistic regression analysis.

Science.gov (United States)

Kanbayashi, Yuko; Ishikawa, Takeshi; Kanazawa, Motohiro; Nakajima, Yuki; Kawano, Rumi; Tabuchi, Yusuke; Yoshioka, Tomoko; Ihara, Norihiko; Hosokawa, Toyoshi; Takayama, Koichi; Shikata, Keisuke; Taguchi, Tetsuya

2018-03-16

Although pegfilgrastim prophylaxis is expected to maintain the relative dose intensity (RDI) of chemotherapy and improve safety, information is limited. However, the optimal selection of patients eligible for pegfilgrastim prophylaxis is an important issue from a medical economics viewpoint. Therefore, this retrospective study identified factors that could predict these eligible patients to maintain the RDI. The participants included 166 cancer patients undergoing pegfilgrastim prophylaxis combined with chemotherapy in our outpatient chemotherapy center between March 2015 and April 2017. Variables were extracted from clinical records for regression analysis of factors related to maintenance of the RDI. RDI was classified into four categories: 100% = 0, 85% or predictive factors in patients eligible for pegfilgrastim prophylaxis to maintain the RDI. Threshold measures were examined using a receiver operating characteristic (ROC) analysis curve. Age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.04-1.11; P maintenance. ROC curve analysis of the group that failed to maintain the RDI indicated that the threshold for age was 70 years and above, with a sensitivity of 60.0% and specificity of 80.2% (area under the curve: 0.74). In conclusion, younger age, anemia (less), and administration of pegfilgrastim 24-72 h after chemotherapy were significant factors for RDI maintenance.

c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival.

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Lee, Su Jin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Kim, Seung Tae

2018-03-02

Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features and survival. Primary tumor sites were 67 right-sided colon, 98 left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%) exhibited c-MET overexpression. There was no significant difference in the prevalence of c-MET overexpression according to primary site, histologic differentiation, molecular markers, or metastatic sites. In a comparison of the tumor response to first-line chemotherapy according to the level of c-MET expression, we found no significant difference in either partial response or disease control rate. In the survival analysis, patients with c-MET overexpression had significantly shorter overall survival (39 vs. 27 months; P = .018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7 months; P = .024). c-MET overexpression, which was detected in 39 CRC patients (15.3%) irrespective of primary sites or molecular markers, indicated a poor survival prognosis and predicted shorter PFS during bevacizumab treatment in patients with CRC. Further studies are warranted to elucidate the value of c-MET-targeted therapy in CRC patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Prevalence and clinical association of MET gene overexpression and amplification in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape project.

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Bubendorf, Lukas; Dafni, Urania; Schöbel, Martin; Finn, Stephen P; Tischler, Verena; Sejda, Aleksandra; Marchetti, Antonio; Thunnissen, Erik; Verbeken, Eric K; Warth, Arne; Sansano, Irene; Cheney, Richard; Speel, Ernst Jan M; Nonaka, Daisuke; Monkhorst, Kim; Hager, Henrik; Martorell, Miguel; Savic, Spasenija; Kerr, Keith M; Tan, Qiang; Tsourti, Zoi; Geiger, Thomas R; Kammler, Roswitha; Schulze, Katja; Das-Gupta, Ashis; Shames, David; Peters, Solange; Stahel, Rolf A

2017-09-01

In a well-defined NSCLC cohort of the ETOP Lungscape program, we explored the epidemiology of IHC MET overexpression and amplification, their inter-correlation, and their association to outcome. Resected NSCLC were assessed for MET gene copy number (GCN) and expression using silver in-situ hybridization (SISH) and immunohistochemistry (IHC) on TMAs in a multicenter setting. MET amplification was defined as MET/centromere ratio≥2 (with average MET GCN≥4), high MET GCN as CGN≥5 and MET IHC+ as ≥2+ intensity in ≥50% of tumor cells. A total of 182 MET IHC+ and EGFR/KRAS WT tumors were analyzed for METex14 skipping mutation. MET IHC+ was found in 23.8% of 2432 patients, significantly associated with female gender, small tumor size, and adenocarcinoma histology. We observed a high inter-laboratory variability in IHC and SISH analysis. MET amplification prevailed in 4.6% and MET GCN≥5 in 4.1% of 1572 patients. MET amplification and MET GCN≥5 were not significantly associated with any tumor characteristics or stage. Both were significantly associated with IHC MET positivity (poverexpression, SISH MET amplification or high MET GCN was found with OS, RFS or TTR. MET overexpression is found in 23.8% of surgically resected NSCLC. MET amplification prevails in 4.6% and is associated with MET overexpression. Both have no influence on prognosis. The large inter-laboratory variability in IHC highlights the challenge of MET IHC analysis in routine practice. Copyright © 2017 Elsevier B.V. All rights reserved.

Eligibility for renal denervation

DEFF Research Database (Denmark)

Persu, Alexandre; Jin, Yu; Baelen, Marie

2014-01-01

-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according...... undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility...... (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered....

Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatment Effect in Trials Using Targeted Therapies for Rheumatoid Arthritis

DEFF Research Database (Denmark)

Christensen, Anton Wulf; Tarp, Simon; Furst, Daniel E

2015-01-01

OBJECTIVE: To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs....... Odds ratios (ORs) were calculated from the response rates and compared among the trial eligibility criteria/patient baseline characteristics of interest. Comparisons are presented as the Ratio of Odds Ratios (ROR). RESULTS: Sixty-two trials (19,923 RA patients) were included in the primary analyses...... using ACR20 response. Overall, targeted therapies constituted an effective treatment (OR 3.96 95% confidence interval (CI) 3.41 to 4.60). The majority of the trial eligibility criteria and patient baseline characteristics did not modify treatment effect. The added benefit of targeted therapies was lower...

Eligibility and Predictors for Acute Revascularization Procedures in a Stroke Center.

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Vanacker, Peter; Lambrou, Dimitris; Eskandari, Ashraf; Mosimann, Pascal J; Maghraoui, Ali; Michel, Patrik

2016-07-01

Endovascular treatment (EVT) is a new standard of care for selected, large vessel occlusive strokes. We aimed to determine frequency of potentially eligible patients for intravenous thrombolysis (IVT) and EVT in comprehensive stroke centers. In addition, predictors of EVT eligibility were derived. Patients from a stroke center-based registry (2003-2014), admitted within 24 hours of last proof of usual health, were selected if they had all data to determine IVT and EVT eligibility according to American Heart Association/American Stroke Association (AHA/ASA) guidelines (class I-IIa recommendations). Moreover, less restrictive criteria adapted from randomized controlled trials and clinical practice were tested. Maximum onset-to-door time windows for IVT eligibility were 3.5 hours (allowing door-to-needle delay of ≤60 minutes) and 4.5 hours for EVT eligibility (door-to-groin delay ≤90 minutes). Demographic and clinical information were used in logistic regression analysis to derive variables associated with EVT eligibility. A total of 2704 patients with acute ischemic stroke were included, of which 26.8% were transfers. Of all patients with stroke arriving at our comprehensive stroke center, a total proportion of 12.4% patients was eligible for IVT. Frequency of EVT eligibility differed between AHA/ASA guidelines and less restrictive approach: 2.9% versus 4.9%, respectively, of all patients with acute ischemic stroke and 10.5% versus 17.7%, respectively, of all patients arriving within <6 hours. Predictors for AHA-EVT eligibility were younger, shorter onset-to-admission delays, higher National Institutes of Health Stroke Scale (NIHSS), decreased vigilance, hemineglect, absent cerebellar signs, atrial fibrillation, smoking, and decreasing glucose levels (area under the curve=0.86). Of patients arriving within 6 hours at a comprehensive stroke center, 10.5% are EVT eligible according to AHA/ASA criteria, 17.7% according to criteria resembling randomized controlled

Factors associated with loss to clinic among HIV patients not yet known to be eligible for antiretroviral therapy (ART) in Mozambique

Science.gov (United States)

Pati, Rituparna; Lahuerta, Maria; Elul, Batya; Okamura, Mie; Alvim, Maria Fernanda; Schackman, Bruce; Bang, Heejung; Fernandes, Rufino; Assan, Americo; Lima, Josue; Nash, Denis

2013-01-01

Introduction Retention in HIV care prior to ART initiation is generally felt to be suboptimal, but has not been well-characterized. Methods We examined data on 37,352 adult pre-ART patients (ART ineligible or unknown eligibility) who enrolled in care during 2005–2008 with >1 clinical visit at 23 clinics in Mozambique. We defined loss to clinic (LTC) as >12 months since the last visit among those not known to have died/transferred. Cox proportional-hazards models were used to examine factors associated with LTC, accounting for clustering within sites. Results Of 37,352 pre-ART patients, 61% had a CD4 count within three months of enrolment (median CD4: 452, IQR: 345–611). 17,598 (47.1%) were ART ineligible and 19,754 (52.9%) were of unknown eligibility status at enrolment because of missing information on CD4 count and/or WHO stage. Kaplan-Meier estimates for LTC at 12 months were 41% (95% CI: 40.2–41.8) and 48% (95% CI: 47.2–48.8), respectively. Factors associated with LTC among ART ineligible patients included male sex (AHRmen_vs_non-pregnant women: 1.5; 95% CI: 1.4–1.6) and being pregnant at enrolment (AHRpregnant_vs_non-pregnant women: 1.3; 95% CI: 1.1–1.5). Older age, more education, higher weight and more advanced WHO stage at enrolment were independently associated with lower risks of LTC. Similar findings were observed among patients whose ART eligibility status was unknown at enrolment. Conclusions Substantial LTC occurred prior to ART initiation among patients not yet known to be eligible for ART, including nearly half of patients without documented ART eligibility assessment. Interventions are needed to target pre-ART patients who may be at higher risk for LTC, including pregnant women and patients with less advanced HIV disease. PMID:23755857

PHA665752, a small-molecule inhibitor of c-Met, inhibits hepatocyte growth factor-stimulated migration and proliferation of c-Met-positive neuroblastoma cells

International Nuclear Information System (INIS)

Crosswell, Hal E; Dasgupta, Anindya; Alvarado, Carlos S; Watt, Tanya; Christensen, James G; De, Pradip; Durden, Donald L; Findley, Harry W

2009-01-01

c-Met is a tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF), and both c-Met and its ligand are expressed in a variety of tissues. C-Met/HGF/SF signaling is essential for normal embryogenesis, organogenesis, and tissue regeneration. Abnormal c-Met/HGF/SF signaling has been demonstrated in different tumors and linked to aggressive and metastatic tumor phenotypes. In vitro and in vivo studies have demonstrated inhibition of c-Met/HGF/SF signaling by the small-molecule inhibitor PHA665752. This study investigated c-Met and HGF expression in two neuroblastoma (NBL) cell lines and tumor tissue from patients with NBL, as well as the effects of PHA665752 on growth and motility of NBL cell lines. The effect of the tumor suppressor protein PTEN on migration and proliferation of tumor cells treated with PHA665752 was also evaluated. Expression of c-Met and HGF in NBL cell lines SH-EP and SH-SY5Y and primary tumor tissue was assessed by immunohistochemistry and quantitative RT-PCR. The effect of PHA665752 on c-Met/HGF signaling involved in NBL cell proliferation and migration was evaluated in c-Met-positive cells and c-Met-transfected cells. The transwell chemotaxis assay and the MTT assay were used to measure migration and proliferation/cell-survival of tumor cells, respectively. The PPAR-γ agonist rosiglitazone was used to assess the effect of PTEN on PHA665752-induced inhibition of NBL cell proliferation/cell-survival and migration High c-Met expression was detected in SH-EP cells and primary tumors from patients with advanced-stage disease. C-Met/HGF signaling induced both migration and proliferation of SH-EP cells. Migration and proliferation/cell-survival were inhibited by PHA665752 in a dose-dependent manner. We also found that induced overexpression of PTEN following treatment with rosiglitazone significantly enhanced the inhibitory effect of PHA665752 on NBL-cell migration and proliferation. c-Met is highly expressed in most tumors from

COMT Val158Met, but not BDNF Val66Met, is associated with white matter abnormalities of the temporal lobe in patients with first-episode, treatment-naïve major depressive disorder: a diffusion tensor imaging study

Directory of Open Access Journals (Sweden)

Hayashi K

2014-06-01

Full Text Available Kenji Hayashi,1 Reiji Yoshimura,1 Shingo Kakeda,2 Taro Kishi,3 Osamu Abe,4 Wakako Umene-Nakano,1 Asuka Katsuki,1 Hikaru Hori,1 Atsuko Ikenouchi-Sugita,1 Keita Watanabe,2 Satoru Ide,2 Issei Ueda,2 Junji Moriya,2 Nakao Iwata,3 Yukunori Korogi,2 Marek Kubicki,5 Jun Nakamura1 1Department of Psychiatry, 2Department of Radiology, University of Occupational and Environmental Health, Kitakyushu, Japan; 3Department of Psychiatry, Fujita Health University, Toyoake, Japan; 4Department of Radiology, Nihon University School of Medicine, Tokyo, Japan; 5Psychiatry Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Abstract: We investigated the association between the Val158Met polymorphism of the catechol-O-methyltransferase (COMT gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF gene, and white matter changes in patients with major depressive disorder (MDD and healthy subjects using diffusion tensor imaging (DTI. We studied 30 patients with MDD (17 males and 13 females, with mean age ± standard deviation [SD] =44±12 years and 30 sex- and age-matched healthy controls (17 males and 13 females, aged 44±13 years. Using DTI analysis with a tract-based spatial statistics (TBSS approach, we investigated the differences in fractional anisotropy, radial diffusivity, and axial diffusivity distribution among the three groups (patients with the COMT gene Val158Met, those with the BDNF gene Val66Met, and the healthy subjects. In a voxel-wise-based group comparison, we found significant decreases in fractional anisotropy and axial diffusivity within the temporal lobe white matter in the Met-carriers with MDD compared with the controls (P<0.05. No correlations in fractional anisotropy, axial diffusivity, or radial diffusivity were observed between the MDD patients and the controls, either among those with the BDNF Val/Val genotype or among the BDNF Met-carriers. These results suggest an association

MET amplification, expression, and exon 14 mutations in colorectal adenocarcinoma.

Science.gov (United States)

Zhang, Meng; Li, Guichao; Sun, Xiangjie; Ni, Shujuan; Tan, Cong; Xu, Midie; Huang, Dan; Ren, Fei; Li, Dawei; Wei, Ping; Du, Xiang

2018-04-08

MET amplification, expression, and splice mutations at exon 14 result in dysregulation of the MET signaling pathway. The aim of this study was to identify the relationship between MET amplification, protein or mRNA expression, and mutations in colorectal cancer (CRC). MET immunohistochemistry (IHC) was used for MET protein expression analysis and fluorescence in situ hybridization (FISH) was used for MET amplification detection. Both analyses were performed in tissue microarrays (TMA) containing 294 of colorectal adenocarcinoma tissue samples and 131 samples of adjacent normal epithelial tissue. MET mRNA expression was examined by real-time quantitative polymerase chain reaction (qRT-PCR) in 72 fresh colorectal adenocarcinoma tissue samples and adjacent normal colon tissue. PCR sequencing was performed to screen for MET exon 14 splice mutations in 59 fresh CRC tissue samples. Our results showed that MET protein expression was higher in colorectal tumor tissue than in adjacent normal intestinal epithelium. Positive MET protein expression was associated with significantly poorer overall survival (OS) and disease-free survival (DFS). Multivariate analysis revealed that positive MET protein expression was an independent risk factor for DFS, but not for OS. MET mRNA expression was upregulated in tumor tissues compared with the adjacent normal tissues. The incidence of MET amplification was 4.4%. None of the patients was positive for MET mutation. Collectively, MET was overexpressed in colorectal adenocarcinoma, and its positive protein expression predicted a poorer outcome in CRC patients. Furthermore, according to our results, MET amplification and 14 exon mutation are extremely rare events in colorectal adenocarcinoma. Copyright © 2018. Published by Elsevier Inc.

The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus.

Science.gov (United States)

Zhuang, Langen; Li, Ming; Yu, Changhua; Li, Can; Zhao, Mingming; Lu, Ming; Zheng, Taishan; Zhang, Rong; Zhao, Weijing; Bao, Yuqian; Xiang, Kunsan; Jia, Weiping; Wang, Niansong; Liu, Limei

2014-02-01

The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case-control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.

MetHumi - Humidity Device for Mars MetNet Lander

Science.gov (United States)

Genzer, Maria; Polkko, Jouni; Harri, Ari-Matti; Schmidt, Walter; Leinonen, Jussi; Mäkinen, Teemu; Haukka, Harri

2010-05-01

MetNet Mars Mission focused for Martian atmospheric science is based on a new semihard landing vehicle called the MetNet Lander (MNL). The MNL will have a versatile science payload focused on the atmospheric science of Mars. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. MetHumi is the humidity sensor of MetNet Lander designed to work on Martian surface. It is based on Humicap® technology developed by Vaisala, Inc. MetHumi is a capacitive type of sensing device where an active polymer film changes capacitance as function of relative humidity. One MetHumi device package consists of one humidity transducer including three Humicap® sensor heads, an accurate temperature sensor head (Thermocap® by Vaisala, Inc.) and constant reference channels. MetHumi is very small, lightweighed and has low power consumption. It weighs only about 15 g without wires, and consumes 15 mW of power. MetHumi can make meaningful relative humidity measurements in range of 0 - 100%RH down to -70°C ambient temperature, but it survives even -135°C ambient temperature.

Met kerse op met -konstruksies 1 : 'n Verwysingspuntperspektief ...

African Journals Online (AJOL)

Met kerse op met-konstruksies1: 'n Verwysingspuntperspektief. Johanna Messerschmidt, Luna Bergh. Abstract. This article analyses the usage of the Afrikaans preposition met ('with'). The analysis is done within the framework of Cognitive Linguistics and more specifically within the model proposed by Langacker (1993) ...

Induction regimens for transplant-eligible patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials

Directory of Open Access Journals (Sweden)

Zeng ZH

2017-07-01

Full Text Available Zi-Hang Zeng,1,2 Jia-Feng Chen,1,2 Yi-Xuan Li,1,2 Ran Zhang,1,2 Ling-Fei Xiao,1,2 Xiang-Yu Meng1,2 1Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, 2Department of Evidence-Based Medicine and Clinical Epidemiology, Second Clinical College of Wuhan University, Wuhan, People’s Republic of China Objective: The aim of this study was to compare the early efficacy and survivals of induction regimens for transplant-eligible patients with untreated multiple myeloma. Materials and methods: A comprehensive literature search in electronic databases was conducted for relevant randomized controlled trials (RCTs. Eligible studies were selected according to the predefined selection criteria, before they were evaluated for methodological quality. Basic characteristics and data for network meta-analysis (NMA were extracted from included trials and pooled in our meta-analysis. The end points were the overall response rate (ORR, progression-free survival (PFS, and overall survival (OS. Results: A total of 14 RCTs that included 4,763 patients were analyzed. The post-induction ORR was higher with bortezomib plus thalidomide plus dexamethasone (VTD regimens, and VTD was better than the majority of other regimens. For OS, VTD plus cyclophosphamide (VTDC regimens showed potential superiority over other regimens, but the difference was not statistically significant. The PFS was longer with thalidomide plus doxorubicin plus dexamethasone (TAD regimens for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM. Conclusion: The NMA demonstrated that the VTD, VTDC, and TAD regimens are most beneficial in terms of ORR, OS, and PFS for transplant-eligible patients with NDMM, respectively. Keywords: multiple myeloma, newly diagnosed, transplant-eligible, induction therapies, network meta-analysis

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment | Division of Cancer Prevention

Science.gov (United States)

This randomized phase IIb trial studies how well ACTOplus met XR works in treating in patients with stage I-IV oral cavity or oropharynx cancer that are undergoing definitive treatment. Chemoprevention is the use of drugs to keep oral cavity or oropharynx cancer from forming or coming back. The use of ACTOplus met XR may slow disease progression in patients with oral cavity or

Depression, 5HTTLPR and BDNF Val66Met polymorphisms, and plasma BDNF levels in hemodialysis patients with chronic renal failure

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Wang LJ

2014-07-01

Full Text Available Liang-Jen Wang,1,* Chih-Ken Chen,2,3,* Heng-Jung Hsu,3,4 I-Wen Wu,3,4 Chiao-Yin Sun,3,4 Chin-Chan Lee3,41Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Psychiatry, Chang Gung Memorial Hospital, Keelung, Taiwan; 3Chang Gung University School of Medicine, Taoyuan, Taiwan; 4Department of Nephrology, Chang Gung Memorial Hospital, Keelung, Taiwan *LJW and CKC are joint first authors and contributed equally to this manuscriptObjective: Depression is the most prevalent comorbid psychiatric disease among hemodialysis patients with end-stage renal disease. This cross-sectional study investigated whether depression in hemodialysis patients is associated with the polymorphism of the 5' flanking transcriptional region (5-HTTLPR of the serotonin transporter gene, the valine (Val-to-methionine (Met substitution at codon 66 (Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF gene, or plasma BDNF levels.Methods: A total of 188 participants (mean age: 58.5±14.0 years; 89 men and 99 women receiving hemodialysis at the Chang Gung Memorial Hospital were recruited. The diagnosis of major depressive disorder (MDD was confirmed using the Chinese version of the Mini International Neuropsychiatric Interview. The genotypes of 5-HTTLPR and BDNF Val66Met were conducted using polymerase chain reactions plus restriction fragment length polymorphism analysis. The plasma BDNF levels were measured using an enzyme-linked immunosorbent assay kit.Results: Forty-five (23.9% patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR criteria for a MDD. There were no significant effects of the 5-HTTLPR or BDNF Val66Met gene polymorphism on MDD among the hemodialysis patients. The plasma BDNF levels correlated significantly with age (P=0.003 and sex (P=0.047 but not with depression, the genotypes of 5

MetBaro - Pressure Device for Mars MetNet Lander

Science.gov (United States)

Haukka, Harri; Polkko, Jouni; Harri, Ari-Matti; Schmidt, Walter; Leinonen, Jussi; Genzer, Maria; Mäkinen, Teemu

2010-05-01

MetNet Mars Mission focused for Martian atmospheric science is based on a new semihard landing vehicle called the MetNet Lander (MNL). The MNL will have a versatile science payload focused on the atmospheric science of Mars. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. MetBaro is the pressure sensor of MetNet Lander designed to work on Martian surface. It is based on Barocap® technology developed by Vaisala, Inc. MetBaro is a capacitive type of sensing device where capasitor plates are moved by ambient pressure. MetBaro device consists of two pressure transducers including a total of 4 Barocap® sensor heads of high-stability and high-resolution types. The long-term stability of MetBaro is in order of 20…50 µBar and resolution a few µBar. MetBaro is small, lightweighed and has low power consumption. It weighs about 50g without wires and controlling FPGA, and consumes 15 mW of power. A similar device has successfully flown in Phoenix mission, where it performed months of measurements on Martian ground. Another device is also part of the Mars Science Laboratory REMS instrument (to be launched in 2011).

34 CFR 377.31 - What information must a grantee provide to eligible clients?

Science.gov (United States)

2010-07-01

... clients? 377.31 Section 377.31 Education Regulations of the Offices of the Department of Education... PROJECTS TO INCREASE CLIENT CHOICE PROGRAM What Post-Award Conditions Must Be Met by a Grantee? § 377.31 What information must a grantee provide to eligible clients? Each grantee shall advise all clients and...

MetBaro - Pressure Instrument for Mars MetNet Lander

Science.gov (United States)

Polkko, J.; Haukka, H.; Harri, A.-M.; Schmidt, W.; Leinonen, J.; Mäkinen, T.

2009-04-01

THE METNET MISSION FOCUSED ON THE Martian atmospheric science is based on a new semihard landing vehicle called the MetNet Lander (MNL). The MNL will have a versatile science payload focused on the atmospheric science of Mars. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. MetBaro is the pressure instrument of MetNet Lander designed to work on Martian surface. It is based on Barocap® technology developed by Vaisala, Inc. MetBaro is a capacitic type of sensing device where capasitor plates are moved by ambient pressure. MetBaro device consists of two pressure transducers including a total of 6 Barocap® sensor heads of high-stability and high-resolution types. The long-term stability of MetBaro is in order of 20…50 µBar and resolution a few µBar. MetBaro is small, lightweighed and has low power consumption. It weighs about 50g without wires and controlling FPGA, and consumes 15 mW of power. A similar device has successfully flown in Phoenix mission, where it performed months of measurements on Martian ground. Another device is also part of the Mars Science Laboratory REMS instrument (to be launched in 2011).

Effective implementation of novel MET pharmacodynamic assays in translational studies.

Science.gov (United States)

Srivastava, Apurva K; Navas, Tony; Herrick, William G; Hollingshead, Melinda G; Bottaro, Donald P; Doroshow, James H; Parchment, Ralph E

2017-01-01

MET tyrosine kinase (TK) dysregulation is significantly implicated in many types of cancer. Despite over 20 years of drug development to target MET in cancers, a pure anti-MET therapeutic has not yet received market approval. The failure of two recently concluded phase III trials point to a major weakness in biomarker strategies to identify patients who will benefit most from MET therapies. The capability to interrogate oncogenic mutations in MET via circulating tumor DNA (ctDNA) provides an important advancement in identification and stratification of patients for MET therapy. However, a wide range in type and frequency of these mutations suggest there is a need to carefully link these mutations to MET dysregulation, at least in proof-of-concept studies. In this review, we elaborate how we can utilize recently developed and validated pharmacodynamic biomarkers of MET not only to show target engagement, but more importantly to quantitatively measure MET dysregulation in tumor tissues. The MET assay endpoints provide evidence of both canonical and non-canonical MET signaling, can be used as "effect markers" to define biologically effective doses (BEDs) for molecularly targeted drugs, confirm mechanism-of-action in testing combination of drugs, and establish whether a diagnostic test is reporting MET dysregulation. We have established standard operating procedures for tumor biopsy collections to control pre-analytical variables that have produced valid results in proof-of-concept studies. The reagents and procedures are made available to the research community for potential implementation on multiple platforms such as ELISA, quantitative immunofluorescence assay (qIFA), and immuno-MRM assays.

Differences in MetS marker prevalence between black African and ...

African Journals Online (AJOL)

Multiple linear regression analysis, independent of covariates, showed that the albumin:creatinine ratio is explained only by glucose in Africans. Conclusion: African women, as a group, present with few MetS risk factors, and glucose is associated with renal function risk in Africans. Keywords: MetS, metabolic syndrome, ...

COMT (Val158Met and BDNF (Val66Met Genes Polymorphism in Schizophrenia: A Case-Control Report

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ramin saravani

2017-10-01

Full Text Available Objective: The effects of human brain-derived neurotropic factor (BDNF Val66Met (G>A and the human Catechol-O-methylTransferase (COMT Val158Met (G>A polymorphisms on Schizophrenia (SCZ risk were evaluated.Methods: This case control study included 92 SCZ patients and 92 healthy controls (HCs. Genotyping of both variants were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR.Results: The findings showed that BDNF Val66Met (G>A variant increased the risk of SCZ (OR=2.008 95%CI=1.008-4.00, P=0.047, GA vs. GG, OR=3.876 95%CI=1.001-14.925, P=0.049. AA vs. GG, OR=2.272. 95%CI=1.204-4.347, P=0.011, GA+AA vs. GG, OR=2.22 95%CI=1.29-3.82. P=0.005, A vs. G. COMT Val158Met (G>A polymorphism was not associated with the risk/protective of SCZ.Conclusion: The results proposed that BDNF Val66Met (G>A polymorphism may increase the risk of SCZ development and did not support an association between COMT Val158Met (G>A variant and risk/protective of SCZ. Further studies and different ethnicities are recommended to confirm the findings.

Cathecol-O-methyl transferase Val158Met genotype is not a risk factor for conversion disorder.

Science.gov (United States)

Armagan, E; Almacıoglu, M L; Yakut, T; Köse, A; Karkucak, M; Köksal, O; Görükmez, O

2013-03-19

Alterations in catechol-O-methyltransferase (COMT) activity are involved in various types of neurological disorders. We examined a possible association between the COMT Val158Met polymorphism and conversion disorder in a study of 48 patients with conversion disorder and 48 control patients. In the conversion disorder group, 31 patients were Val/Met heterozygotes, 15 patients were Val/Val homozygotes and 2 patients were Met/Met homozygotes. In the control group, 32 patients were Val/Met heterozygotes and 16 patients were Val/Val homozygotes. There was no significant difference between the groups. We conclude that the COMT Val158Met genotype is quite common in Turkey and that it is not a risk factor for conversion disorder in the Turkish population.

The efficacy of 12 weeks non-surgical treatment for patients not eligible for total knee replacement

DEFF Research Database (Denmark)

Skou, Søren Thorgaard; Rasmussen, Sten; Laursen, Mogens Berg

2015-01-01

OBJECTIVE: To compare the efficacy of a 12-week non-surgical treatment program with usual care in patients with knee osteoarthritis (OA) not eligible for total knee replacement (TKR). METHOD: This two-arm parallel group assessor-blinded randomized controlled trial (RCT) included 100 adults from...... secondary care with knee OA, confirmed by radiography (Kellgren-Lawrence grade ≥1), but not eligible for a TKR. The 12-week non-surgical treatment program consisted of individualized progressed neuromuscular exercise, patient education, insoles, dietary advice and prescription of pain medication...... if indicated, while usual care comprised two leaflets with information and advice on knee OA and recommended treatments. The primary outcome was the change from baseline to 12 months in the Knee injury and Osteoarthritis Outcome Score (KOOS)4 defined as the average score for the KOOS subscales of pain...

MET gene exon 14 deletion created using the CRISPR/Cas9 system enhances cellular growth and sensitivity to a MET inhibitor.

Science.gov (United States)

Togashi, Yosuke; Mizuuchi, Hiroshi; Tomida, Shuta; Terashima, Masato; Hayashi, Hidetoshi; Nishio, Kazuto; Mitsudomi, Tetsuya

2015-12-01

MET splice site mutations resulting in an exon 14 deletion have been reported to be present in about 3% of all lung adenocarcinomas. Patients with lung adenocarcinoma and a MET splice site mutation who have responded to MET inhibitors have been reported. The CRISPR/Cas9 system is a recently developed genome-engineering tool that can easily and rapidly cause small insertions or deletions. We created an in vitro model for MET exon 14 deletion using the CRISPR/Cas9 system and the HEK293 cell line. The phenotype, which included MET inhibitor sensitivity, was then investigated in vitro. Additionally, MET splice site mutations were analyzed in several cancers included in The Cancer Genome Atlas (TCGA) dataset. An HEK293 cell line with a MET exon 14 deletion was easily and rapidly created; this cell line had a higher MET protein expression level, enhanced MET phosphorylation, and prolonged MET activation. In addition, a direct comparison of phenotypes using this system demonstrated enhanced cellular growth, colony formation, and MET inhibitor sensitivity. In the TCGA dataset, lung adenocarcinomas had the highest incidence of MET exon 14 deletions, while other cancers rarely carried such mutations. Approximately 10% of the lung adenocarcinoma samples without any of driver gene alterations carried the MET exon 14 deletion. These findings suggested that this system may be useful for experiments requiring the creation of specific mutations, and the present experimental findings encourage the development of MET-targeted therapy against lung cancer carrying the MET exon 14 deletion. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

11C-MET PET/MRI for detection of recurrent glioma.

Science.gov (United States)

Deuschl, C; Kirchner, J; Poeppel, T D; Schaarschmidt, B; Kebir, S; El Hindy, N; Hense, J; Quick, H H; Glas, M; Herrmann, K; Umutlu, L; Moenninghoff, C; Radbruch, A; Forsting, M; Schlamann, M

2018-04-01

Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid 11 C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid 11 C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid 11 C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. Hybrid 11 C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for 11 C-MET PET (96.77% and 73.68%), and for hybrid 11 C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid 11 C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing 11 C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). This feasibility study showed that hybrid PET/MRI might strengthen

EEG alpha power as an intermediate measure between brain-derived neurotrophic factor Val66Met and depression severity in patients with major depressive disorder.

Science.gov (United States)

Zoon, Harriët F A; Veth, C P M; Arns, Martijn; Drinkenburg, W H I M; Talloen, Willem; Peeters, Pieter J; Kenemans, J L

2013-06-01

Major depressive disorder has a large impact on patients and society and is projected to be the second greatest global burden of disease by 2020. The brain-derived neurotrophic factor (BDNF) gene is considered to be one of the important factors in the etiology of major depressive disorder. In a recent study, alpha power was found to mediate between BDNF Met and subclinical depressed mood. The current study looked at a population of patients with major depressive disorder (N = 107) to examine the association between the BDNF Val66Met polymorphism, resting state EEG alpha power, and depression severity. For this purpose, repeated-measures analysis of variance, partial correlation, and multiple linear models were used. Results indicated a negative association between parietal-occipital alpha power in the eyes open resting state and depression severity. In addition, Met/Met patients showed lower global absolute alpha power in the eyes closed condition compared with Val-carriers. These findings are in accordance with the previously uncovered pathway between BDNF Val66Met, resting state EEG alpha power, and depression severity. Additional research is needed for the clarification of this tentative pathway and its implication in personalized treatment of major depressive disorder.

Therapy of Patients with Malignant Glioma with Targeted A-Radionuclide Therapy Using 213Bi-DOTA-[Thi8, Met (Oo)11]-Substanz P

International Nuclear Information System (INIS)

Forrer, F.; Mueller-Brand, J.; Cordier, D.; Merlo, A.; Morgenstern, A.; Bruchertseifer, F.; Maecke, H.R.

2009-01-01

The prognosis of patients with malignant glioma is very poor. New therapy options are mandatory. Substance P is the main ligand of neurokinin type 1 (NK-1) receptors, which are consistently over-expressed in malignant gliomas and surrounding tumor vessels. Administration of 90 Y-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P was shown to be feasible and safe. However, in critically located tumors, the mean tissue range of 5 mm of 90 Y may lead to unacceptable damage of adjacent, functional critical areas of the brain. We report a phase I study with locally administered 213 Bi labeled DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P in patients with malignant glioma. By using a direct, intratumoral injection, the problem of the short physical half life of Bismuth-213 can be circumvent. To date, 5 patients with malignant glioma (2 Grade IV, 1 Grade III and 2 grade II) without previous treatment were included. One to three catheter systems were placed stereotactically into the tumor. After a diagnostic injection with 111 In-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P and subsequent dosimetry, totally 30 to 138 mCi of 213 Bi-DOTA-[Thi8, Met (O o ) 11 ]-Substanz P was injected intratumorally performing 3 to 4 applications over 2 days. SPECT/CT was used to assess the biodistribution. Follow up was performed clinically and with morphological imaging. Targeted radiopeptide therapy using 213 Bi-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P was very well tolerated by all patients. No additional neurological deficit was observed. Repetitive imaging is suggestive of progressive radiation-induced necrosis, which was validated by subsequent resection of the tumors. Time to progression was found to be 11 and 14 months respectively in patients with grade IV glioma. No progression is found after 18 to 23 months in patients with grade II or III glioma. We conclude that targeted loco-regional radiotherapy using 213 Bi-DOTA-[Thi 8 , Met (O o ) 11 ]-Substanz P represents an innovative and effective

Preproghrelin Leu72Met polymorphism in Chinese subjects with coronary artery disease and controls.

Science.gov (United States)

Tang, Na-Ping; Wang, Lian-Sheng; Yang, Li; Gu, Hai-Juan; Zhu, Huai-Jun; Zhou, Bo; Sun, Qing-Min; Cong, Ri-Hong; Wang, Bin

2008-01-01

Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to exert a protective effect against atherosclerosis. The Leu72Met (+408C>A) polymorphic variant of the preproghrelin, the gene for the ghrelin precursor, has been linked to obesity, diabetes and metabolic syndrome. However, it is unclear whether this polymorphism is associated with coronary artery disease (CAD). We conducted a case-control study with 317 CAD patients and 323 controls to investigate the potential association of the Leu72Met polymorphism with the occurrence of CAD and CAD-related phenotypes in Chinese population. No significant difference in the Leu72Met genotype frequency was observed between CAD patients and controls (P=NS). The Leu72Met polymorphism was not associated with hypertension, diabetes, dyslipidemia, the number of diseased vessels, plasma total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol or fasting glucose levels in CAD patients. However, among CAD patients, those with variant genotypes (Leu72Met and Met72Met) had lower BMI (24.4+/-0.3 kg/m(2)) than Leu72Leu carriers (25.4+/-0.2 kg/m(2), adjusted P=0.033). Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with CAD in Chinese population. However, the Leu72Met variant is associated with BMI among CAD patients.

c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target.

Science.gov (United States)

Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo J A; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

2015-06-03

c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients' clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression.

La metáfora del pasado en la narrativa de Vincenzo Consolo

Directory of Open Access Journals (Sweden)

Carolina Martín López

2015-06-01

Full Text Available El artículo plantea una lectura de la narrativa de Vincenzo Consolo a través de la dialéctica que la metáfora del pasado histórico, literario y lingüístico entabla en el tejido intertextual de su escritura. Los periodos históricos que Consolo elige como fondo y escenario por el que transcurren las vicisitudes y experiencias de sus personajes han sido de crucial importancia en la historia nacional italiana y, precisamente por ello, son altamente recurrentes como representación del presente al que alude el autor. Para expresar la concepción del mundo en que vivimos y su posible actuación en él es asimismo imprescindible para Consolo la exigencia de la metáfora topográfica, de la metáfora del nostos (de la cita constante del viaje de regreso narrado en la Odisea y la recuperación de términos lingüísticos del pasado capaces de contrarrestar la vacuidad terminológica de los medios de comunicación de masas.

Eligibility audits for the randomized neuropathic bone pain trial (TROG 96.05)

International Nuclear Information System (INIS)

Roos, D.E.; Turner, S.L.

2000-01-01

In February 1996 the Trans-Tasman Radiation Oncology Group (TROG) initiated a two-arm, multicentre, prospective randomized trial on radiotherapy for neuropathic pain due to bone metastases (TROG 96.05). This trial compares the response to a single 8-Gy fraction with 20 Gy in five fractions. The accrual target is 270 patients. In order to evaluate compliance with eligibility criteria after approximately 1 year of accrual, an independent audit of the first 42 randomized patients was commissioned. This found that only one of these patients did not have genuine neuropathic pain, but that this patient and seven others (19%) had infringements of other eligibility/exclusion criteria for the trial. Accordingly it was decided to continue the full audit up to 90 patients. This detected no further patients without genuine neuropathic pain, and found only one other eligibility infringement (1/48; 2%). It is concluded that this quality assurance (QA) measure undertaken early in the trial led to significantly improved clinician awareness of, and compliance with, eligibility/exclusion criteria. It also enabled an accurate comparison of outcome data for all randomized versus all eligible patients at the time of the preplanned first interim analysis at 90 patients. In view of the excellent compliance demonstrated in the second audit, a one-in-five sampling is proposed for future audits from centres that have already accrued at least five consecutive eligible patients. This is consistent with TROG QA guidelines now operational. Copyright (2000) Blackwell Science Pty Ltd

Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

Science.gov (United States)

Perez-Rodriguez, M Mercedes; New, Antonia S; Goldstein, Kim E; Rosell, Daniel; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David; Siever, Larry J; Hazlett, Erin A

2017-05-30

A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype. Copyright © 2017. Published by Elsevier B.V.

{sup 11}C-MET PET/MRI for detection of recurrent glioma

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Deuschl, C. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Kirchner, J.; Schaarschmidt, B. [University Duesseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Duesseldorf (Germany); Poeppel, T.D.; Herrmann, K. [University Hospital Essen, Clinic for Nuclear Medicine, Essen (Germany); Kebir, S.; Glas, M. [University Hospital Essen, Division of Clinical Neurooncology, Department of Neurology, Essen (Germany); El Hindy, N. [University Hospital Essen, Department of Neurosurgery, Essen (Germany); Hense, J. [University Hospital Essen, Department of Medical Oncology, West German Cancer Center, Essen (Germany); Quick, H.H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); Umutlu, L.; Moenninghoff, C.; Radbruch, A.; Forsting, M. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Schlamann, M. [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Hospital Cologne, Department of Diagnostic and Interventional Radiology, Cologne (Germany)

2018-04-15

Radiological assessment of brain tumors is widely based on the Radiology Assessment of Neuro-Oncology (RANO) criteria that consider non-specific T1 and T2 weighted images. Limitation of the RANO criteria is that they do not include metabolic imaging techniques that have been reported to be helpful to differentiate treatment related changes from true tumor progression. In the current study, we assessed if the combined use of MRI and PET with hybrid {sup 11}C-MET PET/MRI can improve diagnostic accuracy and diagnostic confidence of the readers to differentiate treatment related changes from true progression in recurrent glioma. Fifty consecutive patients with histopathologically proven glioma were prospectively enrolled for a hybrid {sup 11}C-MET PET/MRI to differentiate recurrent glioma from treatment induced changes. Sole MRI data were analyzed based on RANO. Sole PET data and in a third evaluation hybrid {sup 11}C-MET-PET/MRI data were assessed for metabolic respectively metabolic and morphologic glioma recurrence. Diagnostic performance and diagnostic confidence of the reader were calculated for the different modalities, and the McNemar test and Mann-Whitney U Test were applied for statistical analysis. Hybrid {sup 11}C-MET PET/MRI was successfully performed in all 50 patients. Glioma recurrence was diagnosed in 35 of the 50 patients (70%). Sensitivity and specificity were calculated for MRI (86.11% and 71.43%), for {sup 11}C-MET PET (96.77% and 73.68%), and for hybrid {sup 11}C-MET-PET/MRI (97.14% and 93.33%). For diagnostic accuracy hybrid {sup 11}C-MET-PET/MRI (96%) showed significantly higher values than MRI alone (82%), whereas no significant difference was found for 11C-MET PET (88%). Furthermore, by rating on a five-point Likert scale significantly higher scores were found for diagnostic confidence when comparing {sup 11}C-MET PET/MRI (4.26 ± 0,777) to either PET alone (3.44 ± 0.705) or MRI alone (3.56 ± 0.733). This feasibility study showed that hybrid

MET and Small-Cell Lung Cancer

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Francesco Gelsomino

2014-10-01

Full Text Available Small-cell lung cancer (SCLC is one of the most aggressive lung tumors. The majority of patients with SCLC are diagnosed at an advanced stage. This tumor type is highly sensitive to chemo-radiation treatment, with very high response rates, but invariably relapses. At this time, treatment options are still limited and the prognosis of these patients is poor. A better knowledge of the molecular biology of SCLC allowed us to identify potential druggable targets. Among these, the MET/HGF axis seems to be one of the most aberrant signaling pathways involved in SCLC invasiveness and progression. In this review, we describe briefly all recent literature on the different molecular profiling in SCLC; in particular, we discuss the specific alterations involving c-MET gene and their implications as a potential target in SCLC.

Avoiding preoperative breast MRI when conventional imaging is sufficient to stage patients eligible for breast conserving therapy

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Pengel, Kenneth E., E-mail: k.pengel@nki.nl [Department of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Loo, Claudette E. [Department of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Wesseling, Jelle [Department of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Pijnappel, Ruud M. [Department of Radiology/Image Sciences Institute, University Medical Center Utrecht Heidelberglaan 100, 3584 CX Utrecht (Netherlands); Rutgers, Emiel J.Th. [Department of Surgical Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Gilhuijs, Kenneth G.A. [Department of Radiology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam (Netherlands); Department of Radiology/Image Sciences Institute, University Medical Center Utrecht Heidelberglaan 100, 3584 CX Utrecht (Netherlands)

2014-02-15

Aim: To determine when preoperative breast MRI will not be more informative than available breast imaging and can be omitted in patients eligible for breast conserving therapy (BCT). Methods: We performed an MRI in 685 consecutive patients with 692 invasive breast tumors and eligible for BCT based on conventional imaging and clinical examination. We explored associations between patient, tumor, and conventional imaging characteristics and similarity with MRI findings. Receiver operating characteristic (ROC) analysis was employed to compute the area under the curve (AUC). Results: MRI and conventional breast imaging were similar in 585 of the 692 tumors (85%). At univariate analysis, age (p < 0.001), negative preoperative lymph node status (p = 0.011), comparable tumor diameter at mammography and at ultrasound (p = 0.001), negative HER2 status (p = 0.044), and absence of invasive lobular cancer (p = 0.005) were significantly associated with this similarity. At multivariate analysis, these factors, except HER2 status, retained significant associations. The AUC was 0.68. Conclusions: It is feasible to identify a subgroup of patients prior to preoperative breast MRI, who will most likely show similar results on conventional imaging as on MRI. These findings enable formulation of a practical consensus guideline to determine in which patients a preoperative breast MRI can be omitted.

Avoiding preoperative breast MRI when conventional imaging is sufficient to stage patients eligible for breast conserving therapy

International Nuclear Information System (INIS)

Pengel, Kenneth E.; Loo, Claudette E.; Wesseling, Jelle; Pijnappel, Ruud M.; Rutgers, Emiel J.Th.; Gilhuijs, Kenneth G.A.

2014-01-01

Aim: To determine when preoperative breast MRI will not be more informative than available breast imaging and can be omitted in patients eligible for breast conserving therapy (BCT). Methods: We performed an MRI in 685 consecutive patients with 692 invasive breast tumors and eligible for BCT based on conventional imaging and clinical examination. We explored associations between patient, tumor, and conventional imaging characteristics and similarity with MRI findings. Receiver operating characteristic (ROC) analysis was employed to compute the area under the curve (AUC). Results: MRI and conventional breast imaging were similar in 585 of the 692 tumors (85%). At univariate analysis, age (p < 0.001), negative preoperative lymph node status (p = 0.011), comparable tumor diameter at mammography and at ultrasound (p = 0.001), negative HER2 status (p = 0.044), and absence of invasive lobular cancer (p = 0.005) were significantly associated with this similarity. At multivariate analysis, these factors, except HER2 status, retained significant associations. The AUC was 0.68. Conclusions: It is feasible to identify a subgroup of patients prior to preoperative breast MRI, who will most likely show similar results on conventional imaging as on MRI. These findings enable formulation of a practical consensus guideline to determine in which patients a preoperative breast MRI can be omitted

Evaluation of Patient Assistance Program Eligibility and Availability for Top 200 Brand Name and Generic Drugs in the United States

Directory of Open Access Journals (Sweden)

Chin-Fun Chu

2012-01-01

Full Text Available One strategy to encourage uninsured and underinsured patients' compliance with medication regimen is to refer them to pharmaceutical industry-sponsored patient assistance programs (PAPs. In order to receive the requested medications, patients should be qualified based on the program eligibility requirements. The purpose of this study was to examine PAP eligibility criteria for the most commonly dispensed prescriptions in the United States. We identified 136 unique chemical entities in the Top 200 drug list and 111 (82% of these pharmaceutical products were offered by PAPs. Among the available medications, 69 (62% were brand name; 29 (26% were generic, and 13 (12% had both brand name/generic forms. In terms of the availability of types of drugs (brand name vs. generic provided by PAPs, differences in PAP eligibility requirements were found for citizenship (p < 0.001, permanent residency (p < 0.001, and prescription drug coverage (p< 0.001, but not for income limits (p= 0.051. Overall, PAPs could help low-income patients to obtain necessary medications; however, U.S. citizenship/permanent residency and restriction on prescription coverage are more likely to be required for brand name drugs rather than for generics. PAPs also provide some options for the underinsured and those with private insurance or Medicare Part D plan that offers inadequate prescription coverage.   Type: Original Research

Body mass index was associated with upstaging and upgrading in patients with low-risk prostate cancer who met the inclusion criteria for active surveillance.

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de Cobelli, Ottavio; Terracciano, Daniela; Tagliabue, Elena; Raimondi, Sara; Galasso, Giacomo; Cioffi, Antonio; Cordima, Giovanni; Musi, Gennaro; Damiano, Rocco; Cantiello, Francesco; Detti, Serena; Victor Matei, Deliu; Bottero, Danilo; Renne, Giuseppe; Ferro, Matteo

2015-05-01

Obesity is associated with an increased risk of high-grade prostate cancer (PCa). The effect of body mass index (BMI) as a predictor of progression in men with low-risk PCa has been only poorly assessed. In this study, we evaluated the association of BMI with progression in patients with low-risk PCa who met the inclusion criteria for the active surveillance (AS) protocol. We assessed 311 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level pT2) and upgraded (Gleason score ≥ 7; primary Gleason pattern 4) disease. Seminal vesicle invasion, positive lymph nodes, and tumor volume ≥ 0.5 ml were also recorded. We found that high BMI was significantly associated with upgrading, upstaging, and seminal vesicle invasion, whereas it was not associated with positive lymph nodes or large tumor volume. At multivariate analysis, 1 unit increase of BMI significantly increased the risk of upgrading, upstaging, seminal vesicle invasion, and any outcome by 21%, 23%, 27%, and 20%, respectively. The differences between areas under the receiver operating characteristics curves comparing models with and without BMI were statistically significant for upgrading (P = 0.0002), upstaging (P = 0.0007), and any outcome (P = 0.0001). BMI should be a selection criterion for inclusion of patients with low-risk PCa in AS programs. Our results support the idea that obesity is associated with worse prognosis and suggest that a close AS program is an appropriate treatment option for obese subjects. Copyright © 2015 Elsevier Inc. All rights reserved.

c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target

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Ozawa, Yohei; Nakamura, Yasuhiro; Fujishima, Fumiyoshi; Felizola, Saulo JA; Takeda, Kenichiro; Okamoto, Hiroshi; Ito, Ken; Ishida, Hirotaka; Konno, Takuro; Kamei, Takashi; Miyata, Go; Ohuchi, Noriaki; Sasano, Hironobu

2015-01-01

c-Met is widely known as a poor prognostic factor in various human malignancies. Previous studies have suggested the involvement of c-Met and/or its ligand, hepatocyte growth factor (HGF), in esophageal squamous cell carcinoma (ESCC), but the correlation between c-Met status and clinical outcome remains unclear. Furthermore, the identification of a novel molecular therapeutic target might potentially help improve the clinical outcome of ESCC patients. The expression of c-Met and HGF was immunohistochemically assessed in 104 surgically obtained tissue specimens. The correlation between c-Met/HGF expression and patients’ clinicopathological features, including survival, was evaluated. We also investigated changes in cell functions and protein expression of c-Met and its downstream signaling pathway components under treatments with HGF and/or c-Met inhibitor in ESCC cell lines. Elevated expression of c-Met was significantly correlated with tumor depth and pathological stage. Patients with high c-Met expression had significantly worse survival. In addition, multivariate analysis identified the high expression of c-Met as an independent prognostic factor. Treatment with c-Met inhibitor under HGF stimulation significantly inhibited the invasive capacity of an ESCC cell line with elevated c-Met mRNA expression. Moreover, c-Met and its downstream signaling inactivation was also detected after treatment with c-Met inhibitor. The results of our study identified c-Met expression as an independent prognostic factor in ESCC patients and demonstrated that c-Met could be a potential molecular therapeutic target for the treatment of ESCC with elevated c-Met expression. The online version of this article (doi:10.1186/s12885-015-1450-3) contains supplementary material, which is available to authorized users

The EGFR/ErbB3 Pathway Acts as a Compensatory Survival Mechanism upon c-Met Inhibition in Human c-Met+ Hepatocellular Carcinoma.

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Steven N Steinway

Full Text Available c-Met, a high-affinity receptor for Hepatocyte Growth Factor (HGF, plays a critical role in tumor growth, invasion, and metastasis. Hepatocellular carcinoma (HCC patients with activated HGF/c-Met signaling have a significantly worse prognosis. Targeted therapies using c-Met tyrosine kinase inhibitors are currently in clinical trials for HCC, although receptor tyrosine kinase inhibition in other cancers has demonstrated early success. Unfortunately, therapeutic effect is frequently not durable due to acquired resistance.We utilized the human MHCC97-H c-Met positive (c-Met+ HCC cell line to explore the compensatory survival mechanisms that are acquired after c-Met inhibition. MHCC97-H cells with stable c-Met knockdown (MHCC97-H c-Met KD cells were generated using a c-Met shRNA vector with puromycin selection and stably transfected scrambled shRNA as a control. Gene expression profiling was conducted, and protein expression was analyzed to characterize MHCC97-H cells after blockade of the c-Met oncogene. A high-throughput siRNA screen was performed to find putative compensatory survival proteins, which could drive HCC growth in the absence of c-Met. Findings from this screen were validated through subsequent analyses.We have previously demonstrated that treatment of MHCC97-H cells with a c-Met inhibitor, PHA665752, results in stasis of tumor growth in vivo. MHCC97-H c-Met KD cells demonstrate slower growth kinetics, similar to c-Met inhibitor treated tumors. Using gene expression profiling and siRNA screening against 873 kinases and phosphatases, we identified ErbB3 and TGF-α as compensatory survival factors that are upregulated after c-Met inhibition. Suppressing these factors in c-Met KD MHCC97-H cells suppresses tumor growth in vitro. In addition, we found that the PI3K/Akt signaling pathway serves as a negative feedback signal responsible for the ErbB3 upregulation after c-Met inhibition. Furthermore, in vitro studies demonstrate that

c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma.

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Granito, Alessandro; Guidetti, Elena; Gramantieri, Laura

2015-01-01

c-MET is the membrane receptor for hepatocyte growth factor (HGF), also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC). In particular, c-MET amplification is a rare event, accounting for 4%-5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC.

The Data Gap in the EHR for Clinical Research Eligibility Screening.

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Butler, Alex; Wei, Wei; Yuan, Chi; Kang, Tian; Si, Yuqi; Weng, Chunhua

2018-01-01

Much effort has been devoted to leverage EHR data for matching patients into clinical trials. However, EHRs may not contain all important data elements for clinical research eligibility screening. To better design research-friendly EHRs, an important step is to identify data elements frequently used for eligibility screening but not yet available in EHRs. This study fills this knowledge gap. Using the Alzheimer's disease domain as an example, we performed text mining on the eligibility criteria text in Clinicaltrials.gov to identify frequently used eligibility criteria concepts. We compared them to the EHR data elements of a cohort of Alzheimer's Disease patients to assess the data gap by usingthe OMOP Common Data Model to standardize the representations for both criteria concepts and EHR data elements. We identified the most common SNOMED CT concepts used in Alzheimer 's Disease trials, andfound 40% of common eligibility criteria concepts were not even defined in the concept space in the EHR dataset for a cohort of Alzheimer 'sDisease patients, indicating a significant data gap may impede EHR-based eligibility screening. The results of this study can be useful for designing targeted research data collection forms to help fill the data gap in the EHR.

Eligibility for Renal Denervation: Anatomical Classification and Results in Essential Resistant Hypertension

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Okada, Takuya, E-mail: okabone@gmail.com; Pellerin, Olivier [Georges Pompidou European Hospital, Department of Cardiovascular and Interventional Radiology, Assistance Publique des Hôpitaux de Paris (France); Savard, Sébastien [Georges Pompidou European Hospital, Department of Hypertension, Assistance Publique des Hôpitaux de Paris (France); Curis, Emmanuel; Monge, Matthieu [INSERM, Clinical Investigation Center 9201 (France); Frank, Michael; Bobrie, Guillaume [Georges Pompidou European Hospital, Department of Hypertension, Assistance Publique des Hôpitaux de Paris (France); Yamaguchi, Masato; Sugimoto, Koji [Kobe University Hospital, Department of Radiology and Center for Endovascular Therapy (Japan); Plouin, Pierre-François; Azizi, Michel [Georges Pompidou European Hospital, Department of Hypertension, Assistance Publique des Hôpitaux de Paris (France); Sapoval, Marc [Georges Pompidou European Hospital, Department of Cardiovascular and Interventional Radiology, Assistance Publique des Hôpitaux de Paris (France)

2015-02-15

PurposeTo classify the renal artery (RA) anatomy based on specific requirements for endovascular renal artery denervation (RDN) in patients with drug-resistant hypertension (RH).Materials and MethodsThe RA anatomy of 122 consecutive RH patients was evaluated by computed tomography angiography and classified as two types: A (main RA ≥20 mm in length and ≥4.0 mm in diameter) or B (main RA <20 mm in length or main RA <4.0 mm in diameter). The A type included three subtypes: A1 (without accessory RAs), A2 (with accessory RAs <3.0 mm in diameter), and A3 (with accessory RAs ≥3.0 mm in diameter]. A1 and A2 types were eligible for RDN with the Simplicity Flex catheter. Type B included twi subtypes based on the main RA length and diameter. Patients were accordingly classified into three eligibility categories: complete (CE; both RAs were eligible), partial (PE; one eligible RA), and noneligibility (NE; no eligible RA).ResultsBilateral A1 type was the most prevalent and was observed in 48.4 % of the patients followed by the A1/A2 type (18 %). CE, PE, and NE were observed in 69.7, 22.9, and 7.4 % of patients, respectively. The prevalence of accessory RAs was 41 %.ConclusionsOf RH patients, 30.3 % were not eligible for bilateral RDN with the current Simplicity Flex catheter. This classification provides the basis for standardized reporting to allow for pooling of results of larger patient cohorts in the future.

Eligibility for Renal Denervation: Anatomical Classification and Results in Essential Resistant Hypertension

International Nuclear Information System (INIS)

Okada, Takuya; Pellerin, Olivier; Savard, Sébastien; Curis, Emmanuel; Monge, Matthieu; Frank, Michael; Bobrie, Guillaume; Yamaguchi, Masato; Sugimoto, Koji; Plouin, Pierre-François; Azizi, Michel; Sapoval, Marc

2015-01-01

PurposeTo classify the renal artery (RA) anatomy based on specific requirements for endovascular renal artery denervation (RDN) in patients with drug-resistant hypertension (RH).Materials and MethodsThe RA anatomy of 122 consecutive RH patients was evaluated by computed tomography angiography and classified as two types: A (main RA ≥20 mm in length and ≥4.0 mm in diameter) or B (main RA <20 mm in length or main RA <4.0 mm in diameter). The A type included three subtypes: A1 (without accessory RAs), A2 (with accessory RAs <3.0 mm in diameter), and A3 (with accessory RAs ≥3.0 mm in diameter]. A1 and A2 types were eligible for RDN with the Simplicity Flex catheter. Type B included twi subtypes based on the main RA length and diameter. Patients were accordingly classified into three eligibility categories: complete (CE; both RAs were eligible), partial (PE; one eligible RA), and noneligibility (NE; no eligible RA).ResultsBilateral A1 type was the most prevalent and was observed in 48.4 % of the patients followed by the A1/A2 type (18 %). CE, PE, and NE were observed in 69.7, 22.9, and 7.4 % of patients, respectively. The prevalence of accessory RAs was 41 %.ConclusionsOf RH patients, 30.3 % were not eligible for bilateral RDN with the current Simplicity Flex catheter. This classification provides the basis for standardized reporting to allow for pooling of results of larger patient cohorts in the future

Expression of the c-Met oncogene by tumor cells predicts a favorable outcome in classical Hodgkin's lymphoma.

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Xu, Chuanhui; Plattel, Wouter; van den Berg, Anke; Rüther, Nele; Huang, Xin; Wang, Miao; de Jong, Debora; Vos, Hans; van Imhoff, Gustaaf; Viardot, Andreas; Möller, Peter; Poppema, Sibrand; Diepstra, Arjan; Visser, Lydia

2012-04-01

The c-Met signaling pathway regulates a variety of biological processes, including proliferation, survival and migration. Deregulated c-Met activation has been implicated in the pathogenesis and prognosis of many human malignancies. We studied the function and prognostic significance of c-Met and hepatocyte growth factor protein expression in patients with classical Hodgkin's lymphoma. Expression of c-Met and its ligand, hepatocyte growth factor, were determined by immunohistochemistry. Prognostic values were defined in cohorts of German and Dutch patients with classical Hodgkin's lymphoma. Functional studies were performed on Hodgkin's lymphoma cell lines. Expression of c-Met was detected in the tumor cells of 52% (80/153) of the patients and expression of its ligand, hepatocyte growth factor, in 8% (10/121) of the patients. c-Met expression correlated with a 5-year freedom from tumor progression of 94%, whereas lack of expression correlated with a 5-year freedom from tumor progression of 73% (Pfreedom from tumor progression. In functional studies activation with hepatocyte growth factor did not affect cell growth, while the c-Met inhibitor SU11274 suppressed cell growth by inducing G2/M cell cycle arrest. Although functional studies showed an oncogenic role of the hepatocyte growth factor/c-Met signaling pathway in cell cycle progression, expression of c-Met in tumor cells from patients with classical Hodgkin's lymphoma strongly correlated with a favorable prognosis in two independent cohorts.

Evaluation of Patient Assistance Program Eligibility and Availability for Top 200 Brand Name and Generic Drugs in the United States

Directory of Open Access Journals (Sweden)

Chin-Fun Chu

2012-01-01

Full Text Available One strategy to encourage uninsured and underinsured patients’ compliance with medication regimen is to refer them to pharmaceutical industry–sponsored patient assistance programs (PAPs. In order to receive the requested medications, patients should be qualified based on the program eligibility requirements. The purpose of this study was to examine PAP eligibility criteria for the most commonly dispensed prescriptions in the United States. We identified 136 unique chemical entities in the Top 200 drug list and 111 (82% of these pharmaceutical products were offered by PAPs. Among the available medications, 69 (62% were brand name; 29 (26% were generic, and 13 (12% had both brand name/generic forms. In terms of the availability of types of drugs (brand name vs. generic provided by PAPs, differences in PAP eligibility requirements were found for citizenship (p < 0.001, permanent residency (p < 0.001, and prescription drug coverage (p< 0.001, but not for income limits (p= 0.051. Overall, PAPs could help low-income patients to obtain necessary medications; however, U.S. citizenship/permanent residency and restriction on prescription coverage are more likely to be required for brand name drugs rather than for generics. PAPs also provide some options for the underinsured and those with private insurance or Medicare Part D plan that offers inadequate prescription coverage.

An Interindividual Comparison of O-(2- [18F]Fluoroethyl)-L-Tyrosine (FET)– and L-[Methyl-11C]Methionine (MET)–PET in Patients With Brain Gliomas and Metastases

International Nuclear Information System (INIS)

Grosu, Anca-Ligia; Astner, Sabrina T.; Riedel, Eva; Nieder, Carsten; Wiedenmann, Nicole; Heinemann, Felix; Schwaiger, Markus

2011-01-01

Purpose: L-[methyl- 11 C]methionine (MET)–positron emission tomography (PET) has a high sensitivity and specificity for imaging of gliomas and metastatic brain tumors. The short half-life of 11 C (20 minutes) limits the use of MET-PET to institutions with onsite cyclotron. O-(2- [ 18 F]fluoroethyl)-L-tyrosine (FET) is labeled with 18 F (half-life, 120 minutes) and could be used much more broadly. This study compares the uptake of FET and MET in gliomas and metastases, as well as treatment-induced changes. Furthermore, it evaluates the gross tumor volume (GTV) of gliomas defined on PET and magnetic resonance imaging (MRI). Methods and Materials: We examined 42 patients with pretreated gliomas (29 patients) or brain metastases (13 patients) prospectively by FET- and MET-PET on the same day. Uptake of FET and MET was quantified by standardized uptake values. Imaging contrast was assessed by calculating lesion–to–gray matter ratios. Tumor extension was quantified by contouring GTV in 17 patients with brain gliomas. Gross tumor volume on PET was compared with GTV on MRI. Sensitivity and specificity of MET- and FET-PET for differentiation of viable tumor from benign changes were evaluated by comparing the PET result with histology or clinical follow-up. Results: There was a strong linear correlation between standardized uptake values calculated for both tracers in cortex and lesions: r = 0.78 (p = 0.001) and r = 0.84 (p 18 F]fluoroethyl)-L-tyrosine–PET and MET-PET provide comparable diagnostic information on gliomas and brain metastases. Like MET-PET, FET-PET can be used for differentiation of residual or recurrent tumor from treatment-related changes/pseudoprogression, as well as for delineation of gliomas.

Medical Emergency Team: How do we play when we stay? Characterization of MET actions at the scene.

Science.gov (United States)

Silva, Raquel; Saraiva, Manuel; Cardoso, Teresa; Aragão, Irene C

2016-03-22

The creation, implementation and effectiveness of a medical emergency team (MET) in every hospital is encourage and supported by international bodies of quality certification. Issues such as what is the best composition of the team or the interventions performed by the MET at the scene and the immediate outcomes of the patients after MET intervention have not yet been sufficiently explored. The purpose of the study is to characterize MET actions at the scene and the immediate patient outcome. Retrospective cohort study, at a tertiary care, university-affiliated, 600-bed hospital, in the north of Portugal, over two years. There were 511 MET activations: 389 (76%) were for inpatients. MET activation rate was 8.6/1,000 inpatients. The main criteria for activation were airway threatening in 143 (36.8%), concern of medical staff in 121 (31.1%) and decrease in GCS > 2 in 98 (25.2%) patients; MET calls for cardiac arrest occurred in 68 patients (17.5%). The median (IQR) time the team stayed at the scene was 35 (20-50) minutes. At the scene, the most frequent actions were related to airway and ventilation, namely oxygen administration in 145 (37.3%); in circulation, fluid were administered in 158 (40.6%); overall medication was administered in 185 (47.5%) patients. End-of-life decisions were part of the MET actions in 94 (24.1%) patients. At the end of MET intervention, 73 (18.7%) patients died at the scene, 190 (60.7%) stayed on the ward and the remaining 123 patients were transferred to an increased level of care. Crude hospital mortality rate was 4.1% in the 3 years previously to MET implementation and 3.6% in the following 3 years (p residence. The team stayed on site for half an hour and during that time most of the actions were simple and nurse-driven, but in one third of all activations medical actions were taken, and in a forth (24%) end-of-life decisions made, reinforcing the inclusion of a doctor in the MET. A significant decrease in overall hospital

Eligibility for interventions, co-occurrence and risk factors for unhealthy behaviours in patients consulting for routine primary care: results from the Pre-Empt study.

Science.gov (United States)

Randell, Elizabeth; Pickles, Timothy; Simpson, Sharon A; Spanou, Clio; McCambridge, Jim; Hood, Kerenza; Butler, Christopher C

2015-10-09

Smoking, excessive drinking, lack of exercise and a poor diet remain key causes of premature morbidity and mortality globally, yet it is not clear what proportion of patients attending for routine primary care are eligible for interventions about these behaviours, the extent to which they co-occur within individuals, and which individuals are at greatest risk for multiple unhealthy behaviours. The aim of the trial was to examine 'intervention eligibility' and co-occurrence of the 'big four' risky health behaviours - lack of exercise, smoking, an unhealthy diet and excessive drinking - in a primary care population. Data were collected from adult patients consulting routinely in general practice across South Wales as part of the Pre-Empt study; a cluster randomised controlled trial. After giving consent, participants completed screening instruments, which included the following to assess eligibility for an intervention based on set thresholds: AUDIT-C (for alcohol), HSI (for smoking), IPAQ (for exercise) and a subset of DINE (for diet). The intervention following screening was based on which combination of risky behaviours the patient had. Descriptive statistics, χ2 tests for association and ordinal regressions were undertaken. Two thousand sixty seven patients were screened: mean age of 48.6 years, 61.9 % female and 42.8 % in a managerial or professional occupation. In terms of numbers of risky behaviours screened eligible for, two was the most common (43.6 %), with diet and exercise (27.2 %) being the most common combination. Insufficient exercise was the most common single risky behaviour (12.0 %). 21.8 % of patients would have been eligible for an intervention for three behaviours and 5.9 % for all four behaviours. Just 4.5 % of patients did not identify any risky behaviours. Women, older age groups and those in managerial or professional occupations were more likely to exhibit all four risky behaviours. Very few patients consulting for routine primary care

Gezondheidsrisico's in verband met het werken met Pentachloorfenol : een onderzoek

NARCIS (Netherlands)

Geuskens, R.B.M.; Nossent, S.M.; Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A.; Zielhuis, R.l.

1989-01-01

De gezondheidsrisico's i.v.m. het werken met pentachloorfenol (PCP) wordt geevalueerd. Het gebruik van PCP in Nederlandse arbeidssituaties neemt sterk af en is beperkt tot de formulering van emeltenkorrels en de, met name preventieve, houtverduurzaming. De totale risicopopulatie is niet omvangrijk

Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

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Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

2006-07-01

Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

Brain-derived neurotrophic factor gene val66met polymorphism and executive functioning in patients with bipolar disorder Polimorfismo do gene do fator neurotrófico derivado do cérebro val66met e função executiva em pacientes com transtorno bipolar

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Juliana Fernandes Tramontina

2009-06-01

Full Text Available OBJECTIVE: In the present study, we investigate the association between the val66met polymorphism of the brain-derived neurotrophic factor (BNDF and the performance on the Wisconsin Card Sorting Test in a sample of Caucasian Brazilian patients with bipolar disorder. METHOD: Sixty-four patients with bipolar disorder were assessed and their performance on the Wisconsin Card Sorting Test was compared with the allele frequency and genotype of the val66met polymorphism of the brain-derived neurotrophic factor. RESULTS: The percentage of non-perseverative errors was significantly higher among patients with the val/val genotype. There was no association between (BNDF genotype frequency and other Wisconsin Card Sorting Test domains. CONCLUSION: Our results did not replicate previous descriptions of an association between a worse cognitive performance and the presence of the met allele of the val66met brain-derived neurotrophic factor gene polymorphism.OBJETIVO: O presente estudo tem por objetivo investigar a associação entre o polimorfismo val66met do gene do fator neurotrófico derivado do cérebro (BDNF e o desempenho cognitivo no Teste Wisconsin de Classificação de Cartas em uma amostra de pacientes bipolares brasileiros caucasianos. MÉTODO: Sessenta e quatro pacientes com transtorno bipolar foram avaliados em relação a sua cognição por meio do Teste Wisconsin de Classificação de Cartas que foi comparada com a freqüência alélica e genotípica do polimorfismo val66met do gene do fator neurotrófico derivado do cérebro. RESULTADOS: O percentual de erros não-perseverativos foi significativamente maior nos indivíduos com genótipo val/val. Não foi encontrada diferença significativa entre a freqüência genotípica do polimorfismo do BDNF e os outros domínios do Teste Wisconsin de Classificação de Cartas. CONCLUSÃO: O estudo do polimorfismo val66met em relação ao desempenho executivo em pacientes bipolares caucasianos de uma

Partial revascularization plus medical treatment versus medical treatment alone in patients with multivessel coronary artery disease not eligible for CABG

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M. Sadaka

2013-06-01

Conclusion: In patients with MVD who were not eligible for CABG; IR plus OMT was not superior to OMT alone in improving the 1year clinical outcomes except the improvement in the level of angina class, which could be the adopted strategy to improve the quality of life in such patients but with close follow up.

Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical cancer.

Science.gov (United States)

Boromand, Nadia; Hasanzadeh, Malihe; ShahidSales, Soodabeh; Farazestanian, Marjaneh; Gharib, Masoumeh; Fiuji, Hamid; Behboodi, Negin; Ghobadi, Niloofar; Hassanian, Seyed Mahdi; Ferns, Gordon A; Avan, Amir

2018-06-01

Aberrant activation of the HGF/c-Met signalling pathway is reported to be associated with cell proliferation, progression, and metastasis features of several tumor types, including cervical cancer, suggesting that it may be of potential value as a novel therapeutic target. Furthermore, HPV-positive patients had a higher serum level of HGF or c-Met protein, compared with HPV-negative patients. c-Met or HGF overexpression in lesions of cervical cancer is reported to be related to a poorer prognosis, and hence this may be of value as a prognostic and predictive biomarker. Several approaches have been developed for targeting HGF and/or c-Met. One of these is crizotinib (a dual c-Met/ALK inhibitor). This has been approved by FDA for the treatment of lung-cancer. Further investigations are required to evaluate and optimize the use of c-Met inhibitors in cervical cancer or parallel targeting signalling pathway associated/activated via MET/HGF pathway. The main aim of current review was to give an overview of the potential of the c-Met/HGF pathway as a prognostic, or predictive biomarker in cervical cancer. © 2017 Wiley Periodicals, Inc.

Do Lung Cancer Eligibility Criteria Align with Risk among Blacks and Hispanics?

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Kevin Fiscella

Full Text Available Black patients have higher lung cancer risk despite lower pack years of smoking. We assessed lung cancer risk by race, ethnicity, and sex among a nationally representative population eligible for lung cancer screening based on Medicare criteria.We used data from the National Health and Nutrition Examination Survey, 2007-2012 to assess lung cancer risk by sex, race and ethnicity among persons satisfying Medicare age and pack-year smoking eligibility criteria for lung cancer screening. We assessed Medicare eligibility based on age (55-77 years and pack-years (≥ 30. We assessed 6-year lung cancer risk using a risk prediction model from Prostate, Lung, Colorectal and Ovarian Cancer Screening trial that was modified in 2012 (PLCOm2012. We compared the proportions of eligible persons by sex, race and ethnicity using Medicare criteria with a risk cut-point that was adjusted to achieve comparable total number of persons eligible for screening.Among the 29.7 million persons aged 55-77 years who ever smoked, we found that 7.3 million (24.5% were eligible for lung cancer screening under Medicare criteria. Among those eligible, Blacks had statistically significant higher (4.4% and Hispanics lower lung cancer risk (1.2% than non-Hispanic Whites (3.2%. At a cut-point of 2.12% risk for lung screening eligibility, the percentage of Blacks and Hispanics showed statistically significant changes. Blacks eligible rose by 48% and Hispanics eligible declined by 63%. Black men and Hispanic women were affected the most. There was little change in eligibility among Whites.Medicare eligibility criteria for lung cancer screening do not align with estimated risk for lung cancer among Blacks and Hispanics. Data are urgently needed to determine whether use of risk-based eligibility screening improves lung cancer outcomes among minority patients.

Catechol-O-methyltransferase val158met polymorphism predicts placebo effect in irritable bowel syndrome.

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Kathryn T Hall

Full Text Available Identifying patients who are potential placebo responders has major implications for clinical practice and trial design. Catechol-O-methyltransferase (COMT, an important enzyme in dopamine catabolism plays a key role in processes associated with the placebo effect such as reward, pain, memory and learning. We hypothesized that the COMT functional val158met polymorphism, was a predictor of placebo effects and tested our hypothesis in a subset of 104 patients from a previously reported randomized controlled trial in irritable bowel syndrome (IBS. The three treatment arms from this study were: no-treatment ("waitlist", placebo treatment alone ("limited" and, placebo treatment "augmented" with a supportive patient-health care provider interaction. The primary outcome measure was change from baseline in IBS-Symptom Severity Scale (IBS-SSS after three weeks of treatment. In a regression model, the number of methionine alleles in COMT val158met was linearly related to placebo response as measured by changes in IBS-SSS (p = .035. The strongest placebo response occurred in met/met homozygotes treated in the augmented placebo arm. A smaller met/met associated effect was observed with limited placebo treatment and there was no effect in the waitlist control. These data support our hypothesis that the COMT val158met polymorphism is a potential biomarker of placebo response.

Genomic profiling of a Hepatocyte growth factor-dependent signature for MET-targeted therapy in glioblastoma.

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Johnson, Jennifer; Ascierto, Maria Libera; Mittal, Sandeep; Newsome, David; Kang, Liang; Briggs, Michael; Tanner, Kirk; Marincola, Francesco M; Berens, Michael E; Vande Woude, George F; Xie, Qian

2015-09-17

Constitutive MET signaling promotes invasiveness in most primary and recurrent GBM. However, deployment of available MET-targeting agents is confounded by lack of effective biomarkers for selecting suitable patients for treatment. Because endogenous HGF overexpression often causes autocrine MET activation, and also indicates sensitivity to MET inhibitors, we investigated whether it drives the expression of distinct genes which could serve as a signature indicating vulnerability to MET-targeted therapy in GBM. Interrogation of genomic data from TCGA GBM (Student's t test, GBM patients with high and low HGF expression, p ≤ 0.00001) referenced against patient-derived xenograft (PDX) models (Student's t test, sensitive vs. insensitive models, p ≤ 0.005) was used to identify the HGF-dependent signature. Genomic analysis of GBM xenograft models using both human and mouse gene expression microarrays (Student's t test, treated vs. vehicle tumors, p ≤ 0.01) were performed to elucidate the tumor and microenvironment cross talk. A PDX model with EGFR(amp) was tested for MET activation as a mechanism of erlotinib resistance. We identified a group of 20 genes highly associated with HGF overexpression in GBM and were up- or down-regulated only in tumors sensitive to MET inhibitor. The MET inhibitors regulate tumor (human) and host (mouse) cells within the tumor via distinct molecular processes, but overall impede tumor growth by inhibiting cell cycle progression. EGFR (amp) tumors undergo erlotinib resistance responded to a combination of MET and EGFR inhibitors. Combining TCGA primary tumor datasets (human) and xenograft tumor model datasets (human tumor grown in mice) using therapeutic efficacy as an endpoint may serve as a useful approach to discover and develop molecular signatures as therapeutic biomarkers for targeted therapy. The HGF dependent signature may serve as a candidate predictive signature for patient enrollment in clinical trials using MET inhibitors

Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis.

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Lee, Young Ho; Kim, Jae-Hoon; Song, Gwan Gyu

2015-01-01

The aim of this study was to explore whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism is associated with susceptibility to fibromyalgia and fibromyalgia impact questionnaire (FIQ) score in fibromyalgia patients. We conducted a meta-analysis of the associations of the COMT Val158Met polymorphism with fibromyalgia risk as well as FIQ score in fibromyalgia patients. A total of 993 fibromyalgia patients and 778 controls from 10 studies on the COMT Val158Met polymorphism and 538 fibromyalgia patients from 5 studies on the COMT Val158Met polymorphism and FIQ score were included in this meta-analysis. The meta-analysis revealed an association between fibromyalgia and the COMT Met/Met + Val/Met genotype in all study subjects (odds ratio (OR) 1.635, 95 % confidence interval (CI) 1.029-2.597, p = 0.037). However, stratification by ethnicity indicated no association between the Met/Met + Val/Met genotype and fibromyalgia in the European and Turkish populations (OR 1.202, 95 % CI 0.876-1.649, p = 0.255; OR 2.132, 95 % CI 0.764-5.949, p = 0.148, respectively). Analysis using other genetic models showed no association between the COMT Val158Met polymorphism and fibromyalgia. The meta-analysis also revealed that the FIQ score was significantly higher in individuals with the COMT Met/Met genotype than in those with the Val/Val genotype [weighted mean difference (WMD) = 14.39, 95 % CI 3.316-25.48, p = 0.011] and the Val/Met genotype (WMD = 5.108, 95 % CI 2.212-4.891, p = 0.021). This meta-analysis identified an association between fibromyalgia risk and the COMT Val158Met polymorphism as well as the FIQ score in fibromyalgia patients.

c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma

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Granito A

2015-04-01

Full Text Available Alessandro Granito,1 Elena Guidetti,1 Laura Gramantieri2,3 1Dipartimento di Scienze Mediche e Chirurgiche Università di Bologna, Bologna, Italy; 2Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3Centro di Ricerca Biomedica Applicata (CRBA, Azienda Ospedaliero-Universitaria Policlinico S Orsola-Malpighi e Università di Bologna, Bologna, Italy Abstract: c-MET is the membrane receptor for hepatocyte growth factor (HGF, also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC. In particular, c-MET amplification is a rare event, accounting for 4%–5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC. Keywords: hepatocellular carcinoma, c-MET, clinical trials

The Effects of Comorbidity and Age on RTOG Study Enrollment in Stage III Non-Small Cell Lung Cancer Patients Who Are Eligible for RTOG Studies

International Nuclear Information System (INIS)

Firat, Selim; Byhardt, Roger W.; Gore, Elizabeth

2010-01-01

Purpose: To determine the influence of measured comorbidity in Radiation Therapy Oncology Group (RTOG) combined modality therapy (CMT) study enrollment in Stage III non-small cell lung cancer (NSCLC). Methods and Materials: One hundred and seventy-one patients with a Karnofsky Performance Score ≥70 and clinical Stage III NSCLC were analyzed retrospectively for comorbidity, RTOG study eligibility, and enrollment at initial consultation. Effect of comorbidity scores (Cumulative Illness Rating Scale) were tested on patient selection for CMT, RTOG enrollment, and overall survival. Results: Comorbidity (Grade 4; p 2, p = 0.001), and weight loss (>5%, p = 0.001). Thirty-three patients (19%) were enrolled in a CMT RTOG study (Group 1). Forty-nine patients (29%) were eligible but not enrolled (Group 2), and 57 (33%) were ineligible (Group 3). The most common ineligibility reasons were weight loss (67%) and comorbidity in the exclusion criteria of the RTOG studies (63%). Group 1 patients were the youngest (p = 0.02), with the lowest comorbidity scores (p 2; p = 0.006) and age (≥70; p = 0.05) were independent factors influencing RTOG study enrollment in patients meeting study eligibility requirements (Groups 1 and 2). Conclusions: Comorbidity scales could be useful in stratification of patients in advanced lung cancer trials and interpretation of results particularly regarding the elderly population.

5 CFR 330.1203 - Eligibility.

Science.gov (United States)

2010-01-01

... Employees § 330.1203 Eligibility. (a) In order to be eligible for special selection priority, an eligible...) Eligibility for special selection priority as an eligible displaced employee of the former Panama Canal Zone...) Eligibility for special selection priority as an eligible displaced employee of the former Panama Canal Zone...

Eligibility Requirements

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... explore a list of eligibility information, Search by Keyword or Browse All . Whole Blood Donation Donation frequency: ... Travel Deferrals Still have eligibility questions? Search by Keyword Other Ways to Help Even if you aren' ...

The c-Met Inhibitor MSC2156119J Effectively Inhibits Tumor Growth in Liver Cancer Models

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Bladt, Friedhelm, E-mail: Friedhelm.Bladt@merckgroup.com; Friese-Hamim, Manja; Ihling, Christian; Wilm, Claudia; Blaukat, Andree [EMD Serono, and Merck Serono Research and Development, Merck KGaA, Darmstadt 64293 (Germany)

2014-08-19

The mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase with hepatocyte growth factor (HGF) as its only high-affinity ligand. Aberrant activation of c-Met is associated with many human malignancies, including hepatocellular carcinoma (HCC). We investigated the in vivo antitumor and antimetastatic efficacy of the c-Met inhibitor MSC2156119J (EMD 1214063) in patient-derived tumor explants. BALB/c nude mice were inoculated with MHCC97H cells or with tumor fragments of 10 patient-derived primary liver cancer explants selected according to c-Met/HGF expression levels. MSC2156119J (10, 30, and 100 mg/kg) and sorafenib (50 mg/kg) were administered orally as single-agent treatment or in combination, with vehicle as control. Tumor response, metastases formation, and alpha fetoprotein (AFP) levels were measured. MSC2156119J inhibited tumor growth and induced complete regression in mice bearing subcutaneous and orthotopic MHCC97H tumors. AFP levels were undetectable after 5 weeks of MSC2156119J treatment, and the number of metastatic lung foci was reduced. Primary liver explant models with strong c-Met/HGF activation showed increased responsiveness to MSC2156119J, with MSC2156119J showing similar or superior activity to sorafenib. Tumors characterized by low c-Met expression were less sensitive to MSC2156119J. MSC2156119J was better tolerated than sorafenib, and combination therapy did not improve efficacy. These findings indicate that selective c-Met/HGF inhibition with MSC2156119J is associated with marked regression of c-Met high-expressing tumors, supporting its clinical development as an antitumor treatment for HCC patients with active c-Met signaling.

The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.

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İşcan, Evin; Güneş, Aysim; Korhan, Peyda; Yılmaz, Yeliz; Erdal, Esra; Atabey, Neşe

2017-06-01

The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)-induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c-Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c-Met receptor dimerization and activated c-Met signaling in an HGF independent manner. Heparin-induced c-Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c-Met signaling reversed heparin-induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c-Met signaling in HCC.

Association between the catechol-o-methyltransferase val158met polymorphism with susceptibility and severity of carpal tunnel syndrome

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Erkol İnal E

2015-12-01

Full Text Available Carpal tunnel syndrome (CTS is the most common entrapment neuropathy of the upper extremity. In this study, we aimed to clarify the relationships between the catechol-O-methyltransferase (COMT gene Val158Met (rs4680 polymorphism and development, functional and clinical status of CTS. Ninety-five women with electro diagnostically confirmed CTS and 95 healthy controls were enrolled in the study. The functional and clinical status of the patients was measured by the Turkish version of the Boston Questionnaire and intensity of pain related to the past 2 weeks was evaluated on a visual analog scale (VAS. The Val158Met polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP, method. We divided patients according to the genotypes of the Val158Met polymorphism as Val/Val, Val/Met and Met/Met. There were not any significant differences in terms of Val158Met polymorphisms between patients and healthy controls (p >0.05. We also did not find any relationships between the Val158Met polymorphism and CTS (p >0.05. In conclusion, although we did not find any relationships between CTS and the Val158Met polymorphism, we could not generalize this result to the general population. Future studies are warranted to conclude precise associations.

Samen in Zee met Zelfregulatie: Een Design-Based Aanpak met Vmbo Leraren

NARCIS (Netherlands)

Jossberger, Helen; Brand-Gruwel, Saskia; Boshuizen, Els; Van de Wiel, Margje

2010-01-01

Jossberger, H., Brand-Gruwel, S., Boshuizen, H. P. A., & Van der Wiel, M. (2010, June). Samen in Zee met Zelfregulatie: Een Design-Based Aanpak met Vmbo Leraren. Poster presented at the 37th Onderwijs Research Dagen (ORD), Enschede, Nederland.

Prevalence of Eligibility Criteria for the Systolic Blood Pressure Intervention Trial in US Adults Among Excluded Groups: Age Diabetes Mellitus, or a History of Stroke.

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Bress, Adam P; Tanner, Rikki M; Hess, Rachel; Gidding, Samuel S; Colantonio, Lisandro D; Shimbo, Daichi; Muntner, Paul

2016-07-12

Adults diabetes mellitus, or a history of stroke were not enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). Estimating the size and characteristics of these excluded groups who meet the other SPRINT eligibility criteria may provide information on the potential impact of providers extending the SPRINT findings to these populations. We analyzed the National Health and Nutrition Examination Survey 2003-2012 (n=25 076) to estimate the percentage and characteristics of US adults ≥20 years in 3 populations (age diabetes mellitus, or history of stroke) excluded from SPRINT who otherwise meet the trial eligibility criteria: age ≥50 years, systolic blood pressure (SBP) 130-180 mm Hg, high cardiovascular disease risk, and not having trial exclusion criteria. Overall, 1.0% (95% CI 0.8-1.3) of US adults age diabetes mellitus, and 19.0% (95% CI 16.0-22.4) with history of stroke met the other SPRINT eligibility criteria. Among US adults with SBP ≥130 mm Hg, other SPRINT eligibility criteria were met by 7.5% (95% CI 6.1-9.2) of those age diabetes mellitus, and 23.0% (95% CI 19.4-27.0) with history of stroke. Among US adults meeting the other SPRINT eligibility criteria, antihypertensive medication was being taken by 31.0% (95% CI 23.9-41.3) of those diabetes mellitus, and 68.9% (95% CI 59.4-77.1) with a history of stroke. A substantial percentage of US adults with diabetes mellitus or history of stroke and a small percentage <50 years old meet the other SPRINT eligibility criteria. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Drug resistance mutations in HIV type 1 isolates from naive patients eligible for first line antiretroviral therapy in JJ Hospital, Mumbai, India.

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Deshpande, Alake; Karki, Surendra; Recordon-Pinson, Patricia; Fleury, Herve J

2011-12-01

More than 50 HIV-1-infected patients, naive of antiretroviral therapy (ART) but eligible for first line ART in JJ Hospital, Mumbai, India were investigated for surveillance drug resistance mutations (SDRMs); all but one virus belonged to subtype C; we could observe SDRMs to nonnucleoside reverse transcriptase inhibitors and protease inhibitors in 9.6% of the patients.

Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan.

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Yamawaki, Hiroshi; Futagami, Seiji; Shimpuku, Mayumi; Shindo, Tomotaka; Maruki, Yuuta; Nagoya, Hiroyuki; Kodaka, Yasuhiro; Sato, Hitomi; Gudis, Katya; Kawagoe, Tetsuro; Sakamoto, Choitsu

2015-01-01

There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification. We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) scores to determine status of depression. The Arg51Gln (346G->A), preproghrelin (3056T->C), Leu72Met (408C->A), Gln90Leu (3412T->A) and G-protein 3 (825C->T) polymorphisms were analyzed in the DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. There was a significant relationship between the Gln90Leu3412 genotype and SRQ-D score in FD patients (P = 0.009). Area under the curve at 15 minutes (AUC15) value was significantly associated with the Leu72Met408 genotype (P = 0.015) but not with entire gastric emptying. The Leu72Met (408C->A) single nucleotide polymorphism was significantly associated with early phase of gastric emptying in FD patients. Further studies will be necessary to clarify the association between ghrelin gene single nucleotide polymorphisms and early phase of gastric emptying in FD patients.

Treatment eligibility and retention in clinical HIV care: A regression discontinuity study in South Africa.

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Bor, Jacob; Fox, Matthew P; Rosen, Sydney; Venkataramani, Atheendar; Tanser, Frank; Pillay, Deenan; Bärnighausen, Till

2017-11-01

Loss to follow-up is high among HIV patients not yet receiving antiretroviral therapy (ART). Clinical trials have demonstrated the clinical efficacy of early ART; however, these trials may miss an important real-world consequence of providing ART at diagnosis: its impact on retention in care. We examined the effect of immediate (versus deferred) ART on retention in care using a regression discontinuity design. The analysis included all patients (N = 11,306) entering clinical HIV care with a first CD4 count between 12 August 2011 and 31 December 2012 in a public-sector HIV care and treatment program in rural South Africa. Patients were assigned to immediate versus deferred ART eligibility, as determined by a CD4 count linear regression models with a data-driven bandwidth and with the algorithm for selecting the bandwidth chosen ex ante. Among patients with CD4 counts close to the 350-cells/μl threshold, having an ART-eligible CD4 count (<350 cells/μl) was associated with higher 12-month retention than not having an ART-eligible CD4 count (50% versus 32%), an intention-to-treat risk difference of 18 percentage points (95% CI 11 to 23; p < 0.001). The decision to start ART was determined by CD4 count for one in four patients (25%) presenting close to the eligibility threshold (95% CI 20% to 31%; p < 0.001). In this subpopulation, having an ART-eligible CD4 count was associated with higher 12-month retention than not having an ART-eligible CD4 count (91% versus 21%), a complier causal risk difference of 70 percentage points (95% CI 42 to 98; p < 0.001). The major limitations of the study are the potential for limited generalizability, the potential for outcome misclassification, and the absence of data on longer-term health outcomes. Patients who were eligible for immediate ART had dramatically higher retention in HIV care than patients who just missed the CD4-count eligibility cutoff. The clinical and population health benefits of offering immediate ART regardless

Screening for depression in cancer patients receiving radiotherapy: Feasibility and identification of effective tools in the NRG Oncology RTOG 0841 trial.

Science.gov (United States)

Wagner, Lynne I; Pugh, Stephanie L; Small, William; Kirshner, Jeffrey; Sidhu, Kulbir; Bury, Martin J; DeNittis, Albert S; Alpert, Tracy E; Tran, Binh; Bloom, Beatrice F; Mai, Julie; Yeh, Alexander; Sarma, Kalika; Becker, Mark; James, Jennifer; Bruner, Deborah Watkins

2017-02-01

Brief tools are needed to screen oncology outpatients for depressive symptoms. Patients starting radiotherapy for the first diagnosis of any tumor completed distress screening tools, including the 9-item Patient Health Questionnaire (PHQ-9), the 2-item Patient Health Questionnaire (PHQ-2), the National Comprehensive Cancer Network Distress Thermometer (NCCN-DT), and the Hopkins Symptom Checklist (HSCL) (25-item version). Patients exceeding validated cutoff scores and a systematic sample of patients whose screening was negative completed the Structured Clinical Interview for DSM-IV (SCID) mood disorder modules via telephone. Four hundred sixty-three patients from 35 community-based radiation oncology sites and 2 academic radiation oncology sites were recruited. Sixty-six percent of the 455 eligible patients (n = 299) were women, and the eligible patients had breast (45%), gastrointestinal (11%), lung (10%), gynecologic (6%), or other cancers (27%). Seventy-five (16.5%) exceeded screening cutoffs for depressive symptoms. Forty-two of these patients completed the SCID. Another 37 patients whose screening was negative completed the SCID. Among the 79 patients completing the SCID, 8 (10.1%) met the criteria for major depression, 2 (2.5%) met the criteria for dysthymia, and 6 (7.6%) met the criteria for an adjustment disorder. The PHQ-2 demonstrated good psychometric properties for screening for mood disorders with a cutoff score of ≥3 (receiver operating characteristic area under the curve [AUC], 0.83) and was comparable to the PHQ-9 ( > 9; AUC = 0.85). The NCCN-DT did not detect depression (AUC = 0.59). The PHQ-2 demonstrated good psychometric properties for screening for mood disorders, which were equivalent to the PHQ-9 and superior to the NCCN-DT. These findings support using the PHQ-2 to identify patients in need of further assessment for depression, which has a low prevalence but is a clinically significant comorbidity. These findings could

Simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE): protocol for a randomised evaluation.

Science.gov (United States)

Rosen, Sydney; Fox, Matthew P; Larson, Bruce A; Brennan, Alana T; Maskew, Mhairi; Tsikhutsu, Isaac; Bii, Margaret; Ehrenkranz, Peter D; Venter, Wd Francois

2017-05-28

African countries are rapidly adopting guidelines to offer antiretroviral therapy (ART) to all HIV-infected individuals, regardless of CD4 count. For this policy of 'treat all' to succeed, millions of new patients must be initiated on ART as efficiently as possible. Studies have documented high losses of treatment-eligible patients from care before they receive their first dose of antiretrovirals (ARVs), due in part to a cumbersome, resource-intensive process for treatment initiation, requiring multiple clinic visits over a several-week period. The Simplified Algorithm for Treatment Eligibility (SLATE) study is an individually randomised evaluation of a simplified clinical algorithm for clinicians to reliably determine a patient's eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. SLATE will enrol and randomise (1:1) 960 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa and Kenya. Patients randomised to the standard arm will receive routine, standard of care ART initiation from clinic staff. Patients randomised to the intervention arm will be administered a symptom report, medical history, brief physical exam and readiness assessment. Patients who have positive (satisfactory) results for all four components of SLATE will be dispensed ARVs immediately, at the same clinic visit. Patients who have any negative results will be referred for further clinical investigation, counselling, tests or other services prior to being dispensed ARVs. After the initial visit, follow-up will be by passive medical record review. The primary outcomes will be ART initiation ≤28 days and retention in care 8 months after study enrolment. Ethics approval has been provided by the Boston University Institutional Review Board, the University of the Witwatersrand Human Research Ethics Committee (Medical) and the KEMRI Scientific and Ethics Review Unit. Results will be published in

Predictors of Delayed Antiretroviral Therapy Initiation, Mortality, and Loss to Followup in HIV Infected Patients Eligible for HIV Treatment: Data from an HIV Cohort Study in India

Directory of Open Access Journals (Sweden)

Gerardo Alvarez-Uria

2013-01-01

Full Text Available Studies from Sub-Saharan Africa have shown that a substantial number of HIV patients eligible for antiretroviral therapy (ART do not start treatment. However, data from other low- or middle-income countries are scarce. In this study, we describe the outcomes of 4105 HIV patients who became ART eligible from January 2007 to November 2011 in an HIV cohort study in India. After three years of ART eligibility, 78.4% started ART, 9.3% died before ART initiation, and 10.3% were lost to followup. Diagnosis of tuberculosis, being homeless, lower CD4 count, longer duration of pre-ART care, belonging to a disadvantaged community, being widowed, and not living near a town were associated with delayed ART initiation. Diagnosis of tuberculosis, being homeless, lower CD4 count, shorter duration of pre-ART care, belonging to a disadvantaged community, illiteracy, and age >45 years were associated with mortality. Being homeless, being single, not living near a town, having a CD4 count <150 cells/μL, and shorter duration of pre-ART care were associated with loss to followup. These results highlight the need to improve the timely initiation of ART in HIV programmes in India, especially in ART eligible patients with tuberculosis, low CD4 counts, living in rural areas, or having a low socioeconomic status.

Medicare home health care patient case-mix before and after the Balanced Budget Act of 1997: effect on dual eligible beneficiaries.

Science.gov (United States)

Shih, Huai-Che; Temkin-Greener, Helena; Votava, Kathryn; Friedman, Bruce

2014-01-01

The Balanced Budget Act (BBA) of 1997 changed the payment system for Medicare home health care (HHC) from cost-based to prospective reimbursement. We used Medical Expenditure Panel Survey data to assess the impact of the BBA on Medicare HHC patient case-mix measured by the Centers for Medicare and Medicaid Services Hierarchical Condition Categories (CMS-HCC) model. There was a significant increase in Medicare HHC patient case-mix between the pre-BBA and Prospective Payment System (PPS) periods. The increase in the standardized-predicted risk score from the Interim Payment System period to PPS was nearly 4 times greater for the dual eligibles (Medicare-Medicaid) than for the Medicare-only population. This significantly greater rise in the HHC resources required by dual eligibles as compared to nonduals could be due to a shift in HHC payers from Medicare only to Medicaid rather than be an actual increase in case-mix per se.

Exploring the interest in and the usage of the internet among patients eligible for osteoporosis screening.

Science.gov (United States)

Slomian, J; Reginster, J Y; Gaspard, U; Streel, S; Beaudart, C; Appelboom, G; Buckinx, F; Bruyère, O

2015-06-01

The aim of this study was to evaluate the interest in the Internet and its usage for health-related issues among people eligible for osteoporosis screening. Self-administered questionnaires have been distributed to subjects who were screened for osteoporosis and to menopausal women. 177 patients have responded to the survey (64.5 ± 10.1 years, 88.1% of women). There are 78.5% of Internet users. Among them, 67.2% said searching information about their health and 74.5% said using the Internet for this purpose. All respondents attributed an average score, out of 10, of 5.7 ± 2.3 regarding the reliability of information that they could find on the Internet. The use of the Internet differs significantly depending on age: those who use the Internet are younger (62.1 ± 8.91 years) than those who do not use it (73.3 ± 9.42 years). The socioeconomic status also has an impact on the Internet use: Internet users have a higher education, are more professionally active and have a higher net monthly household income compared to the group of non-users. Even if age and socioeconomic status appear to be determining factors in the use of the Internet for the search of health information in patients eligible for osteoporosis screening, almost 75% of the study population use the Internet for this purpose. Action to promote health through an Internet platform must therefore take these parameters into account.

Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus.

Science.gov (United States)

Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Park, Ji Hyun; Park, Sung Kwang; Yi, Ho Keun; Lee, Dae-Yeol

2006-03-01

Ghrelin is a novel gut-brain peptide, which exerts somatotropic, orexigenic, and adipogenic effects. Genetic variants of ghrelin have been associated with both obesity and insulin metabolism. In this study, we determined a role of preproghrelin Leu72Met polymorphism on type 2 diabetes mellitus and its relationship to variables studied. Genotypes were assessed by polymerase chain reaction. Frequencies of the Leu72Met polymorphism were found to be 35.4% in the type 2 diabetic patients and 32.5% in the normal controls. The Leu72Met polymorphism was not associated with hypertension, macroangiopathy, retinopathy, serum cholesterol, triglyceride, blood urea nitrogen, HbA(1c), lipoprotein (a), fasting insulin, or 24-hour urinary protein levels in the type 2 diabetic group. However, the Leu72Met polymorphism was clearly associated with serum creatinine levels in the diabetic group, as the Met72 carriers exhibited lower serum creatinine levels than the Met72 noncarriers. Our data indicate that the preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. However, the Leu72Met polymorphism is associated with serum creatinine levels. These data suggest that Met72 carrier status may be a predictable marker for diabetic nephropathy or renal impairment in type 2 diabetes mellitus.

Sereniteit met een dip

NARCIS (Netherlands)

dr Ed de Jonge

2015-01-01

Boekbespreking van Serendipiteit. De ongezochte vondst. Het boek opent met een verzameling van citaten die direct of indirect met het onderwerp samenhangen. Daarna volgt een kort voorwoord van Hans Clevers, de toenmalige president van de KNAW, die een lans breekt voor serendipiteit in de biologie.

5 CFR 330.605 - Eligibility.

Science.gov (United States)

2010-01-01

... Employees § 330.605 Eligibility. (a) To be eligible for the special selection priority, an individual must... selection priority when there are no eligible surplus and displaced agency employees within the local...) Eligibility for special selection priority begins on the date the agency issues the employee a reduction in...

DBCG trial 89B comparing adjuvant CMF and ovarian ablation: similar outcome for eligible but non-enrolled and randomized breast cancer patients

DEFF Research Database (Denmark)

Ejlertsen, B.; Jensen, M.B.; Mouridsen, H.T.

2008-01-01

INTRODUCTION: A cohort of premenopausal patients with primary hormone receptor positive breast cancer was prospectively identified to be eligible for the DBCG 89B trial. We perform a long-term follow-up and evaluate the external validity of the trial. MATERIAL AND METHODS: Following registration...

Catechol-O-methyltransferase Val(158)Met association with parahippocampal physiology during memory encoding in schizophrenia.

Science.gov (United States)

Di Giorgio, A; Caforio, G; Blasi, G; Taurisano, P; Fazio, L; Romano, R; Ursini, G; Gelao, B; Bianco, L Lo; Papazacharias, A; Sinibaldi, L; Popolizio, T; Bellomo, A; Bertolino, A

2011-08-01

Catechol-O-methyltransferase (COMT) Val158Met has been associated with activity of the mesial temporal lobe during episodic memory and it may weakly increase risk for schizophrenia. However, how this variant affects parahippocampal and hippocampal physiology when dopamine transmission is perturbed is unclear. The aim of the present study was to compare the effects of the COMT Val158Met genotype on parahippocampal and hippocampal physiology during encoding of recognition memory in patients with schizophrenia and in healthy subjects. Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we studied 28 patients with schizophrenia and 33 healthy subjects matched for a series of sociodemographic and genetic variables while they performed a recognition memory task. We found that healthy subjects had greater parahippocampal and hippocampal activity during memory encoding compared to patients with schizophrenia. We also found different activity of the parahippocampal region between healthy subjects and patients with schizophrenia as a function of the COMT genotype, in that the predicted COMT Met allele dose effect had an opposite direction in controls and patients. Our results demonstrate a COMT Val158Met genotype by diagnosis interaction in parahippocampal activity during memory encoding and may suggest that modulation of dopamine signaling interacts with other disease-related processes in determining the phenotype of parahippocampal physiology in schizophrenia. © Cambridge University Press 2010

Benefits of applying a proxy eligibility period when using electronic health records for outcomes research: a simulation study.

Science.gov (United States)

Yu, Tzy-Chyi; Zhou, Huanxue

2015-06-09

Electronic health records (EHRs) can provide valuable data for outcomes research. However, unlike administrative claims databases, EHRs lack eligibility tables or a standard way to define the benefit coverage period, which could lead to underreporting of healthcare utilization or outcomes, and could result in surveillance bias. We tested the effect of using a proxy eligibility period (eligibility proxy) when estimating a range of health resource utilization and outcomes parameters under varying degrees of missing encounter data. We applied an eligibility proxy to create a benchmark cohort of chronic obstructive pulmonary disease (COPD) patients with 12 months of follow-up, with the assumption of no missing encounter data. The benchmark cohort provided parameter estimates for comparison with 9,000 simulated datasets representing 10-90% of COPD patients (by 10th percentiles) with between 1 and 11 months of continuous missing data. Two analyses, one for datasets using an eligibility proxy and one for those without an eligibility proxy, were performed on the 9,000 datasets to assess estimator performance under increasing levels of missing data. Estimates for each study variable were compared with those from the benchmark dataset, and performance was evaluated using bias, percentage change, and root-mean-square error. The benchmark dataset contained 6,717 COPD patients, whereas the simulated datasets where the eligibility proxy was applied had between 671 and 6,045 patients depending on the percentage of missing data. Parameter estimates had better performance when an eligibility proxy based on the first and last month of observed activity was applied. This finding was consistent across a range of variables representing patient comorbidities, symptoms, outcomes, health resource utilization, and medications, regardless of the measures of performance used. Without the eligibility proxy, all evaluated parameters were consistently underestimated. In a large COPD patient

Treatment eligibility and retention in clinical HIV care: A regression discontinuity study in South Africa.

Directory of Open Access Journals (Sweden)

Jacob Bor

2017-11-01

Full Text Available Loss to follow-up is high among HIV patients not yet receiving antiretroviral therapy (ART. Clinical trials have demonstrated the clinical efficacy of early ART; however, these trials may miss an important real-world consequence of providing ART at diagnosis: its impact on retention in care.We examined the effect of immediate (versus deferred ART on retention in care using a regression discontinuity design. The analysis included all patients (N = 11,306 entering clinical HIV care with a first CD4 count between 12 August 2011 and 31 December 2012 in a public-sector HIV care and treatment program in rural South Africa. Patients were assigned to immediate versus deferred ART eligibility, as determined by a CD4 count < 350 cells/μl, per South African national guidelines. Patients referred to pre-ART care were instructed to return every 6 months for CD4 monitoring. Patients initiated on ART were instructed to return at 6 and 12 months post-initiation and annually thereafter for CD4 and viral load monitoring. We assessed retention in HIV care at 12 months, as measured by the presence of a clinic visit, lab test, or ART initiation 6 to 18 months after initial CD4 test. Differences in retention between patients presenting with CD4 counts just above versus just below the 350-cells/μl threshold were estimated using local linear regression models with a data-driven bandwidth and with the algorithm for selecting the bandwidth chosen ex ante. Among patients with CD4 counts close to the 350-cells/μl threshold, having an ART-eligible CD4 count (<350 cells/μl was associated with higher 12-month retention than not having an ART-eligible CD4 count (50% versus 32%, an intention-to-treat risk difference of 18 percentage points (95% CI 11 to 23; p < 0.001. The decision to start ART was determined by CD4 count for one in four patients (25% presenting close to the eligibility threshold (95% CI 20% to 31%; p < 0.001. In this subpopulation, having an ART-eligible CD

20 CFR 638.300 - Eligibility for funds and eligible deliverers.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Eligibility for funds and eligible deliverers. 638.300 Section 638.300 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Funding, Site Selection...

Metsämaisema ulkoilijoiden kokemana

OpenAIRE

Vuohijoki, Jaana

2010-01-01

Työn aiheena oli tutkia, miten ulkoilijat kokevat metsämaiseman Tampereella. Tavoitteena oli selvittää ulkoilijoiden maisema-arvostuksia sekä suhtautumista metsänhoidon toimenpiteisiin. Tutkimus toteutettiin maastohaastatteluina Tampereella kolmella eri asuinalueella: Hallilassa, Leinolassa ja Tesomajärvellä. Otoskooksi muodostui kymmenen haastattelua aluetta kohti, mutta yhdeltä vastaajalta ei ehditty kysyä kaikkia kysymyksiä. Vastaajat olivat yleisesti ottaen tyytyväisiä alueiden metsän...

The COMTval158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder

Directory of Open Access Journals (Sweden)

Bergström Jan

2010-11-01

Full Text Available Abstract Background Cognitive behavioral therapy (CBT represents a learning process leading to symptom relief and resulting in long-term changes in behavior. CBT for panic disorder is based on exposure and exposure-based processes can be studied in the laboratory as extinction of experimentally acquired fear responses. We have recently demonstrated that the ability to extinguish learned fear responses is associated with a functional genetic polymorphism (COMTval158met in the COMT gene and this study was aimed at transferring the experimental results on the COMTval158met polymorphism on extinction into a clinical setting. Methods We tested a possible effect of the COMTval158met polymorphism on the efficacy of CBT, in particular exposure-based treatment modules, in a sample of 69 panic disorder patients. Results We present evidence that panic patients with the COMTval158met met/met genotype may profit less from (exposure-based CBT treatment methods as compared to patients carrying at least one val-allele. No association was found with the 5-HTTLPR/rs25531 genotypes which is presented as additional material. Conclusions We were thus able to transfer findings on the effect of the COMTval158met polymorphism from an experimental extinction study obtained using healthy subjects to a clinical setting. Furthermore patients carrying a COMT val-allele tend to report more anxiety and more depression symptoms as compared to those with the met/met genotype. Limitations of the study as well as possible clinical implications are discussed. Trial registration Clinical Trial Registry name: Internet-Versus Group-Administered Cognitive Behavior Therapy for Panic Disorder (IP2. Registration Identification number: NCT00845260, http://www.clinicaltrials.gov/ct2/show/NCT00845260

Mars MetNet Mission Status

Science.gov (United States)

Harri, A.-M.; Aleksashkin, S.; Arruego, I.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.; Palin, M.; Nikkanen, T.

2015-10-01

New kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semihard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

Simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE): protocol for a randomised evaluation

OpenAIRE

Rosen, Sydney; Fox, Matthew P; Larson, Bruce A; Brennan, Alana T; Maskew, Mhairi; Tsikhutsu, Isaac; Bii, Margaret; Ehrenkranz, Peter D; Venter, WD Francois

2017-01-01

Introduction African countries are rapidly adopting guidelines to offer antiretroviral therapy (ART) to all HIV-infected individuals, regardless of CD4 count. For this policy of ‘treat all’ to succeed, millions of new patients must be initiated on ART as efficiently as possible. Studies have documented high losses of treatment-eligible patients from care before they receive their first dose of antiretrovirals (ARVs), due in part to a cumbersome, resource-intensive process for treatment initia...

Word je met Donkey Konga een betere muzikant? : Muziek leren spelen met de spelcomputer

NARCIS (Netherlands)

Tom Langhorst

2010-01-01

Kan de spelcomputer behulpzaam zijn bij de ontwikkeling van het muzikale gevoel? Met die vraag in het achterhoofd bekijkt Tom Langhorst hier kritisch het Nintendo-spel Donkey Konga, waarin de speler mee kan drummen met bekende popsongs.

The MET/AXL/FGFR Inhibitor S49076 Impairs Aurora B Activity and Improves the Antitumor Efficacy of Radiotherapy.

Science.gov (United States)

Clémenson, Céline; Chargari, Cyrus; Liu, Winchygn; Mondini, Michele; Ferté, Charles; Burbridge, Mike F; Cattan, Valérie; Jacquet-Bescond, Anne; Deutsch, Eric

2017-10-01

Several therapeutic agents targeting HGF/MET signaling are under clinical development as single agents or in combination, notably with anti-EGFR therapies in non-small cell lung cancer (NSCLC). However, despite increasing data supporting a link between MET, irradiation, and cancer progression, no data regarding the combination of MET-targeting agents and radiotherapy are available from the clinic. S49076 is an oral ATP-competitive inhibitor of MET, AXL, and FGFR1-3 receptors that is currently in phase I/II clinical trials in combination with gefitinib in NSCLC patients whose tumors show resistance to EGFR inhibitors. Here, we studied the impact of S49076 on MET signaling, cell proliferation, and clonogenic survival in MET-dependent (GTL16 and U87-MG) and MET-independent (H441, H460, and A549) cells. Our data show that S49076 exerts its cytotoxic activity at low doses on MET-dependent cells through MET inhibition, whereas it inhibits growth of MET-independent cells at higher but clinically relevant doses by targeting Aurora B. Furthermore, we found that S49076 improves the antitumor efficacy of radiotherapy in both MET-dependent and MET-independent cell lines in vitro and in subcutaneous and orthotopic tumor models in vivo In conclusion, our study demonstrates that S49076 has dual antitumor activity and can be used in combination with radiotherapy for the treatment of both MET-dependent and MET-independent tumors. These results support the evaluation of combined treatment of S49076 with radiation in clinical trials without patient selection based on the tumor MET dependency status. Mol Cancer Ther; 16(10); 2107-19. ©2017 AACR . ©2017 American Association for Cancer Research.

Mars MetNet Mission Status

Science.gov (United States)

Harri, Ari-Matti; Aleksashkin, Sergei; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Haukka, Harri

2015-04-01

New kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. 1. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. 2. Scientific Payload The payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: 1. MetBaro Pressure device 2. MetHumi Humidity device 3. MetTemp Temperature sensors Optical devices: 1. PanCam Panoramic 2. MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer 3. DS Dust sensor The descent processes dynamic properties are monitored by a special 3-axis accelerometer combined with a 3-axis gyrometer. The data will be sent via auxiliary beacon antenna throughout the

Predicting Pathological Features at Radical Prostatectomy in Patients with Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic Resonance Imaging.

Directory of Open Access Journals (Sweden)

Ottavio de Cobelli

Full Text Available The aim of this study was to investigate the prognostic performance of multiparametric magnetic resonance imaging (mpMRI and Prostate Imaging Reporting and Data System (PIRADS score in predicting pathologic features in a cohort of patients eligible for active surveillance who underwent radical prostatectomy.A total of 223 patients who fulfilled the criteria for "Prostate Cancer Research International: Active Surveillance", were included. Mp-1.5 Tesla MRI examination staging with endorectal coil was performed at least 6-8 weeks after TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason score upgrading, extra capsular extension (ECE, unfavorable prognosis (occurrence of both upgrading and ECE, large tumor volume (≥ 0.5 ml, and seminal vesicle invasion (SVI. Receiver Operating Characteristic (ROC curves and Decision Curve Analyses (DCA were performed for models with and without inclusion of PIRADS score.Multivariate analysis demonstrated the association of PIRADS score with upgrading (P < 0.0001, ECE (P < 0.0001, unfavorable prognosis (P < 0.0001, and large tumor volume (P = 0.002. ROC curves and DCA showed that models including PIRADS score resulted in greater net benefit for almost all the outcomes of interest, with the only exception of SVI.mpMRI and PIRADS scoring are feasible tools in clinical setting and could be used as decision-support systems for a more accurate selection of patients eligible for AS.

77 FR 12522 - Tentative Eligibility Determinations; Presumptive Eligibility for Psychosis and Other Mental Illness

Science.gov (United States)

2012-03-01

...; Presumptive Eligibility for Psychosis and Other Mental Illness AGENCY: Department of Veterans Affairs. ACTION... psychosis within specified time periods and for Persian Gulf War veterans who developed a mental illness... eligibility determinations; Presumptive eligibility for psychosis and other mental illness.'' Copies of...

Association of Catechol-O-methyltransferase polymorphism Val158Met and mammographic density: A meta-analysis.

Science.gov (United States)

Kallionpää, Roope A; Uusitalo, Elina; Peltonen, Juha

2017-08-15

The Val158Met polymorphism in catechol-O-methyltransferase (COMT) enzyme reduces the methylation of catechol estrogens, which may affect mammographic density. High mammographic density is a known risk factor of breast cancer. Our aim was to perform meta-analysis of the effect of COMT Val158Met polymorphism on mammographic density. Original studies reporting data on mammographic density, stratified by the presence of COMT Val158Met polymorphism, were identified and combined using genetic models Met/Val vs. Val/Val, Met/Met vs. Val/Val, Val/Met+Met/Met vs. Val/Val (dominant model) and Met/Met vs. Val/Met+Val/Val (recessive model). Subgroup analyses by breast cancer status, menopausal status and use of hormone replacement therapy (HRT) were also performed. Eight studies were included in the meta-analysis. The overall effect in percent mammographic density was -1.41 (CI -2.86 to 0.05; P=0.06) in the recessive model. Exclusion of breast cancer patients increased the effect size to -1.93 (CI -3.49 to -0.37; P=0.02). The results suggested opposite effect of COMT Val158Met for postmenopausal users of HRT versus premenopausal women or postmenopausal non-users of HRT. COMT Val158Met polymorphism may be associated with mammographic density at least in healthy women. Menopausal status and HRT should be taken into account in future studies to avoid masking of the underlying effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of ghrelin Leu72Met polymorphism with type 2 diabetes mellitus in Chinese population.

Science.gov (United States)

Liu, Jing; Liu, Jia; Tian, Li-min; Liu, Ju-xiang; Bing, Ya-jun; Zhang, Ji-ping; Wang, Yun-Fang; Zhang, Lu-yan

2012-08-10

Ghrelin, a novel endogenous ligand for the growth hormone secretagogue receptor, is considered to implicate the development of the type 2 diabetes mellitus (T2DM). The Leu72Met (+408C>A) polymorphism of the preproghrelin, has been linked to obesity, insulin resistance and diabetes. To investigate the distribution of ghrelin gene Leu72Met polymorphism and its association with the type 2 diabetes mellitus in Chinese population. We conducted a case-control study on 877 patients with T2DM and 864 controls, which were genotyped by the polymerase chain reaction (PCR) technique, denaturing high performance liquid chromatography (DHPLC) and DNA sequence analysis. Laboratory analyses were carried out in the hospital laboratory. No significant difference in the Leu72Met genotype distributions and allele frequency was observed between type 2 diabetes mellitus and controls (both P>0.05). The polymorphism was not associated with T2DM. However, among the T2DM group, the patients carrying Leu72Leu genotype had significantly increased levels of FPG and serum creatinine compared with variant genotypes (Leu72Met and Met72Met) (Ppolymorphism of the preproghrelin gene was not associated with T2DM in Chinese population. However, it may have some roles in the etiology of insulin resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma

Directory of Open Access Journals (Sweden)

Zhao Y

2015-08-01

Full Text Available Yuanyuan Zhao,1,* Jing Zhang,2,* Ying Tian,1,* Cong Xue,1 Zhihuang Hu,1 Li Zhang1,3 1Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, the First Affiliated Hospital of Guang Zhou Traditional Chinese Medicine University, 3National Anti-Cancer Drug Research Centre, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this work Purpose: We explored the effect of hepatocyte growth factor (HGF/Met signaling pathway on nasopharyngeal carcinoma (NPC cells in vitro and in vivo, and investigated the ability of Met tyrosine kinase inhibitor (TKI to block HGF-induced biological signaling.Experimental design: Met TKI inhibitor PF-2341066 alone, or in combination with cisplatin, was investigated for its ability to block HGF-induced signaling and biological effects in vitro and in vivo. HGF/Met expression and activation of signaling in NPC cells were detected by using Western blot and immunohistochemistry. Biological evaluation, including wound healing, cell proliferation, and invasion of NPC cells, was also examined, and the correlation between HGF/Met expression of primary and metastatic tumor in NPC patients and clinical prognosis were also analyzed.Results: Met TKI inhibitor, PF-2341066, inhibited growth of NPC cells in vivo with half maximal inhibitory concentration of 0.79±0.21 µmol/L, and suppressed invasion and migration of NPC cells; also, the inhibition of PF-2341066 was synergized with cisplatin treatment. Compared with the control group, Met TKI inhibited metastasis of transplanted NPC in nude mice (the number of live metastases [mean ± SD]: 5.8±2.2 versus 11.8±2.2, P=0.03; the number of lung metastases: 2.3±1.5 versus

Criteria used when deciding on eligibility for total knee arthroplasty

DEFF Research Database (Denmark)

Skou, Søren Thorgaard; Ross, Ewa M.; Laursen, Mogens Berg

2016-01-01

BACKGROUND: Clinical decision-making in total knee arthroplasty (TKA) is a complex process needing further clarification. The aim of this study was to compare TKA eligibility criteria considered most important by orthopedic surgeons (OSs) to characteristics of patients with knee osteoarthritis (OA....... CONCLUSION: Radiographic severity and functional limitations were confirmed as drivers for TKA eligibility, while pain was not. Not responding to non-surgical treatment was not included in the decision-making, suggesting low uptake of clinical guidelines in clinical practice. This study highlights...

Five-year outcome after implantation of zotarolimus- and everolimus-eluting stents in randomized trial participants and nonenrolled eligible patients : A secondary analysis of a randomized clinical trial

NARCIS (Netherlands)

Von Birgelen, Clemens; Van Der Heijden, Liefke C.; Basalus, Mounir Welson Zakhary; Kok, Marlies M.; Sen, Hanim; Louwerenburg, Hans W.; van Houwelingen, Gert K.; Stoel, Martin G.; de Man, Frits H.A.F.; Linssen, Gerard C.M.; Tandjung, Kenneth; Doggen, Carine J.M.; Van Der Palen, Job; Löwik, Marije M.

2017-01-01

IMPORTANCE: Long-term follow-up after a clinical trial of 2 often-used, newer-generation drug-eluting stents (DESs) in a broad patient population is of interest. Comprehensive long-term outcome of eligible nonenrolled patients has never been reported. OBJECTIVE: To assess 5-year safety and efficacy

Selection of high risk groups among prognostically favorable patients with breast cancer.

Science.gov (United States)

Andersen, J A; Fischermann, K; Hou-Jensen, K; Henriksen, E; Andersen, K W; Johansen, H; Brincker, H; Mouridsen, H T; Castberg, T; Rossing, N; Rørth, M

1981-01-01

In a prospective, nationwide, decentralized breast cancer project conducted by The Danish Breast Cancer Cooperative Group (DBCG) the recurrence rate within the first year after surgery was analysed in relation to tumor anaplasia. One thousand forty-eight patients met the requirements of eligibility, i.e. tumor size less than or equal to 5 cm with negative axillary nodes, and no skin or deep invasion. The recurrence rates in tumors with anaplasia Grades I, II, and III were 4, 9, and 14%, respectively (p = 0.001). Therefore, it seems possible, prospectively, among otherwise prognostically favorable patients, to select a group with high risk of recurrence which might benefit from adjuvant systemic therapy. PMID:7247527

24 CFR 330.10 - Eligible collateral.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Eligible collateral. 330.10 Section... SECURITIES § 330.10 Eligible collateral. The Association, in its discretion, shall determine what collateral is eligible for inclusion in the Multiclass Securities program. Eligible collateral may include GNMA...

Microbewerking met behulp van lasers

NARCIS (Netherlands)

Ezendam, M.M.M.

1994-01-01

Het bewerken van materialen met behulp van lasers staat momenteel enorm in de belangstelling, en terecht. De ontwikkeling van bestaande en nieuwe typen lasers staat alles behalve stil. Ontwikkelingen bevinden zich met name in het gebied van hogere vermogens, betere bundelkwaliteit en hogere

MMPM - Mars MetNet Precursor Mission

Science.gov (United States)

Harri, A.-M.; Schmidt, W.; Pichkhadze, K.; Linkin, V.; Vazquez, L.; Uspensky, M.; Polkko, J.; Genzer, M.; Lipatov, A.; Guerrero, H.; Alexashkin, S.; Haukka, H.; Savijarvi, H.; Kauhanen, J.

2008-09-01

We are developing a new kind of planetary exploration mission for Mars - MetNet in situ observation network based on a new semi-hard landing vehicle called the Met-Net Lander (MNL). The eventual scope of the MetNet Mission is to deploy some 20 MNLs on the Martian surface using inflatable descent system structures, which will be supported by observations from the orbit around Mars. Currently we are working on the MetNet Mars Precursor Mission (MMPM) to deploy one MetNet Lander to Mars in the 2009/2011 launch window as a technology and science demonstration mission. The MNL will have a versatile science payload focused on the atmospheric science of Mars. Detailed characterization of the Martian atmospheric circulation patterns, boundary layer phenomena, and climatology cycles, require simultaneous in-situ measurements by a network of observation posts on the Martian surface. The scientific payload of the MetNet Mission encompasses separate instrument packages for the atmospheric entry and descent phase and for the surface operation phase. The MetNet mission concept and key probe technologies have been developed and the critical subsystems have been qualified to meet the Martian environmental and functional conditions. Prototyping of the payload instrumentation with final dimensions was carried out in 2003-2006.This huge development effort has been fulfilled in collaboration between the Finnish Meteorological Institute (FMI), the Russian Lavoschkin Association (LA) and the Russian Space Research Institute (IKI) since August 2001. Currently the INTA (Instituto Nacional de Técnica Aeroespacial) from Spain is also participating in the MetNet payload development. To understand the behavior and dynamics of the Martian atmosphere, a wealth of simultaneous in situ observations are needed on varying types of Martian orography, terrain and altitude spanning all latitudes and longitudes. This will be performed by the Mars MetNet Mission. In addition to the science aspects the

Number of Patients Eligible for PCSK9 Inhibitors Based on Real-world Data From 2.5 Million Patients.

Science.gov (United States)

Zamora, Alberto; Masana, Luís; Comas-Cufi, Marc; Plana, Núria; Vila, Àlex; García-Gil, Maria; Alves-Cabratosa, Lia; Elosua, Roberto; Marrugat, Jaume; Ramos, Rafel

2018-03-29

PCSK9 inhibitors (PCSK9i) are safe and effective lipid-lowering drugs. Their main limitation is their high cost. The aim of this study was to estimate the number of patients eligible for treatment with PCSK9i according to distinct published criteria. Data were obtained from the Information System for the Development of Research in Primary Care. Included patients were equal to or older than 18 years and had at least 1 low-density lipoprotein cholesterol measurement recorded between 2006 and 2014 (n = 2 500 907). An indication for treatment with PCSK9i was assigned according to the following guidelines: National Health System, Spanish Society of Arteriosclerosis, Spanish Society of Cardiology, National Institute for Health and Care Excellence, and the European Society of Cardiology/European Atherosclerosis Society Task Force. Lipid-lowering treatment was defined as optimized if it reduced low-density lipoprotein levels by ≥ 50% and adherence was > 80%. Among the Spanish population aged 18 years or older, the number of possible candidates to receive PCSK9i in an optimal lipid-lowering treatment scenario ranged from 0.1% to 1.7%, depending on the guideline considered. The subgroup of patients with the highest proportion of potential candidates consisted of patients with familial hypercholesterolemia, and the subgroup with the highest absolute number consisted of patients in secondary cardiovascular prevention. The number of candidates to receive PCSK9i in conditions of real-world clinical practice is high and varies widely depending on the recommendations of distinct scientific societies. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Statin Eligibility and Outpatient Care Prior to ST-Segment Elevation Myocardial Infarction.

Science.gov (United States)

Miedema, Michael D; Garberich, Ross F; Schnaidt, Lucas J; Peterson, Erin; Strauss, Craig; Sharkey, Scott; Knickelbine, Thomas; Newell, Marc C; Henry, Timothy D

2017-04-12

The impact of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines on statin eligibility in individuals otherwise destined to experience cardiovascular disease (CVD) events is unclear. We analyzed a prospective cohort of consecutive ST-segment elevation myocardial infarction (STEMI) patients from a regional STEMI system with data on patient demographics, low-density lipoprotein cholesterol levels, CVD risk factors, medication use, and outpatient visits over the 2 years prior to STEMI. We determined pre-STEMI eligibility according to American College of Cardiology/American Heart Association guidelines and the prior Third Report of the Adult Treatment Panel guidelines. Our sample included 1062 patients with a mean age of 63.7 (13.0) years (72.5% male), and 761 (71.7%) did not have known CVD prior to STEMI. Only 62.5% and 19.3% of individuals with and without prior CVD were taking a statin before STEMI, respectively. In individuals not taking a statin, median (interquartile range) low-density lipoprotein cholesterol levels in those with and without known CVD were low (108 [83, 138]  mg/dL and 110 [87, 133] mg/dL). For individuals not taking a statin, only 38.7% were statin eligible by ATP III guidelines. Conversely, 79.0% would have been statin eligible according to American College of Cardiology/American Heart Association guidelines. Less than half of individuals with (49.2%) and without (41.1%) prior CVD had seen a primary care provider during the 2 years prior to STEMI. In a large cohort of STEMI patients, application of American College of Cardiology/American Heart Association guidelines more than doubled pre-STEMI statin eligibility compared with Third Report of the Adult Treatment Panel guidelines. However, access to and utilization of health care, a necessity for guideline implementation, was suboptimal prior to STEMI. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

7 CFR 1260.114 - Eligible organization.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Eligible organization. 1260.114 Section 1260.114... Promotion and Research Order Definitions § 1260.114 Eligible organization. Eligible organization means any organization which has been certified by the Secretary pursuant to the Act and this part as being eligible to...

Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study.

Science.gov (United States)

Deuschl, Cornelius; Moenninghoff, Christoph; Goericke, Sophia; Kirchner, Julian; Köppen, Susanne; Binse, Ina; Poeppel, Thorsten D; Quick, Harald H; Forsting, Michael; Umutlu, Lale; Herrmann, Ken; Hense, Joerg; Schlamann, Marc

2017-08-01

The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM.

Response assessment of bevacizumab therapy in GBM with integrated 11C-MET-PET/MRI: a feasibility study

Energy Technology Data Exchange (ETDEWEB)

Deuschl, Cornelius [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Duisburg (Germany); Moenninghoff, Christoph; Goericke, Sophia; Forsting, Michael; Umutlu, Lale [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Kirchner, Julian [University Hospital Duesseldorf, Institute of Diagnostic and Interventional Radiology, Duesseldorf (Germany); Koeppen, Susanne [University Hospital Essen, Department of Neurology, Essen (Germany); Binse, Ina; Poeppel, Thorsten D.; Herrmann, Ken [University Hospital Essen, Department of Nuclear Medicine, Essen (Germany); Quick, Harald H. [University of Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Duisburg (Germany); University Hospital Essen, High Field and Hybrid MR Imaging, Essen (Germany); Hense, Joerg [University Hospital Essen, Department of Medical Oncology, West German Cancer Center, Essen (Germany); Schlamann, Marc [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); University Hospital Giessen, Department of Neuroradiology, Essen (Germany)

2017-08-15

The objective of this study was to evaluate the potential of integrated 11C-MET PET/MR for response assessment of relapsed glioblastoma (GBM) receiving bevacizumab treatment. Eleven consecutive patients with relapsed GBM were enrolled for an integrated 11C-MET PET/MRI at baseline and at follow-up. Treatment response for MRI was evaluated according to Response Assessment in Neuro-oncology (RANO) criteria and integrated 11C-MET PET was assessed by the T/N ratio. MRI showed no patient with complete response (CR), six of 11 patients with PR, four of 11 patients with SD, and one of 11 patients with progressive disease (PD). PET revealed metabolic response in five of the six patients with partial response (PR) and in two of the four patients with stable disease (SD), whereas metabolic non-response was detected in one of the six patients with PR, in two of the four patients with SD, and in the one patient with PD. Morphological imaging was predictive for PFS and OS when response was defined as CR, PR, SD, and non-response as PD. Metabolic imaging was predictive when using T/N ratio reduction of >25 as discriminator. Based on the morphologic and metabolic findings of this study a proposal for applying integrated PET/MRI for treatment response in relapsed GBM was developed, which was significantly predictive for PFS and OS (P = 0.010 respectively 0,029, log). This study demonstrates the potential of integrated 11C-MET-PET/MRI for response assessment of GBM and the utility of combined assessment of morphologic and metabolic information with the proposal for assessing relapsed GBM. (orig.)

20 CFR 628.505 - Eligibility.

Science.gov (United States)

2010-04-01

... THE JOB TRAINING PARTNERSHIP ACT Program Design Requirements for Programs Under Title II of the Job Training Partnership Act § 628.505 Eligibility. (a) Eligibility criteria. (1) Individuals who apply to... disadvantage. Specific eligibility criteria for programs under title II, parts A, B, and C are described in...

Metástasis hipofisaria Hypophyseal metastasis

Directory of Open Access Journals (Sweden)

Miguel Ángel Yanes Quesada

2009-04-01

Full Text Available mayoría son lesiones silentes descubiertas accidentalmente en las autopsia. La aparición de metástasis sintomáticas es, en cambio, excepcional. DESARROLLO: se describen aquí los hallazgos clínicos y radiológicos de una paciente femenina de 69 años, con un carcinoma indiferenciado del pulmón, diagnosticado hace 2 años y medio, que comenzó con cefalea y trastornos visuales sin hipopituitarismo ni diabetes insípida. Se le realizó resonancia magnética nuclear y se le diagnosticó una lesión hipofisaria, que fue operada por vía tranesfenoidal, y se informó por anatomía patológica una metástasis del carcinoma del pulmón. CONCLUSIONES: la paciente se encuentra en estos momentos recibiendo quimioterapia, radioterapia y anticuerpo monoclonal con evolución favorable.INTRODUCTION: metastatic tumors of hypophyseal gland are infrequent. Most are silent lesions discovered accidentally in necropsy. Appearance of symptomatic metastasis is however, exceptional. DEVELOPMENT: we describe here clinical and radiological findings in a female patient aged 69, presenting with a non-differential carcinoma of lung, diagnosed two years a half ago, starting with headache and visual disorders without hypopituitarism and insipidus diabetes. We made a nuclear magnetic resonance and diagnosis was a hypophyseal lesion operated on by trans-esphenoidal route, and Pathological Anatomy Service reports a metastasis of lung carcinoma. CONCLUSIONS: patient receives chemotherapy, radiotherapy, and monoclonal antibody with a favorable evolution.

Performance Evaluation of the MyT4 Technology for Determining ART Eligibility.

Science.gov (United States)

Sitoe, Nádia; Macamo, Rosa; Meggi, Bindiya; Tobaiwa, Ocean; Loquiha, Osvaldo; Bollinger, Timothy; Vojnov, Lara; Jani, Ilesh

2016-01-01

In resource-limited countries, CD4 T-cell (CD4) testing continues to be used for determining antiretroviral therapy (ART) initiation eligibility and opportunistic infection monitoring. To support expanded access to CD4 testing, simple and robust technologies are necessary. We conducted this study to evaluate the performance of a new Point-of-Care (POC) CD4 technology, the MyT4, compared to conventional laboratory CD4 testing. EDTA venous blood from 200 HIV-positive patients was tested in the laboratory using the MyT4 and BD FACSCalibur™. The MyT4 had an r2 of 0.82 and a mean bias of 12.3 cells/μl. The MyT4 had total misclassifications of 14.7% and 8.8% when analyzed using ART eligibility thresholds of 350 and 500 cells/μl, respectively. We conclude that the MyT4 performed well in classifying patients using the current ART initiation eligibility thresholds in Mozambique when compared to the conventional CD4 technology.

7 CFR 1160.114 - Eligible organization.

Science.gov (United States)

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Eligible organization. 1160.114 Section 1160.114... Order Definitions § 1160.114 Eligible organization. Eligible organization means an organization eligible... organization pursuant to section 501(c) (3), (5), or (6) of the Internal Revenue Code (26 U.S.C. 501(c) (3), (5...

COMT Val158Met polymorphism, cognitive stability and cognitive flexibility: an experimental examination

Directory of Open Access Journals (Sweden)

Rosa Elise C

2010-09-01

Full Text Available Abstract Background Dopamine in prefrontal cortex (PFC modulates core cognitive processes, notably working memory and executive control. Dopamine regulating genes and polymorphisms affecting PFC - including Catechol-O-Methyltransferase (COMT Val158Met - are crucial to understanding the molecular genetics of cognitive function and dysfunction. A mechanistic account of the COMT Val158Met effect associates the Met allele with increased tonic dopamine transmission underlying maintenance of relevant information, and the Val allele with increased phasic dopamine transmission underlying the flexibility of updating new information. Thus, consistent with some earlier work, we predicted that Val carriers would display poorer performance when the maintenance component was taxed, while Met carriers would be less efficient when rapid updating was required. Methods Using a Stroop task that manipulated level of required cognitive stability and flexibility, we examined reaction time performance of patients with schizophrenia (n = 67 and healthy controls (n = 186 genotyped for the Val/Met variation. Results In both groups we found a Met advantage for tasks requiring cognitive stability, but no COMT effect when a moderate level of cognitive flexibility was required, or when a conflict cost measure was calculated. Conclusions Our results do not support a simple stability/flexibility model of dopamine COMT Val/Met effects and suggest a somewhat different conceptualization and experimental operationalization of these cognitive components.

Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks.

Science.gov (United States)

Dodds, Chris M; Henson, Richard N; Suckling, John; Miskowiak, Kamilla W; Ooi, Cinly; Tait, Roger; Soltesz, Fruzsina; Lawrence, Phil; Bentley, Graham; Maltby, Kay; Skeggs, Andrew; Miller, Sam R; McHugh, Simon; Bullmore, Edward T; Nathan, Pradeep J

2013-01-01

It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks.

Directory of Open Access Journals (Sweden)

Chris M Dodds

Full Text Available It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review.

Science.gov (United States)

Gaudry, Stéphane; Messika, Jonathan; Ricard, Jean-Damien; Guillo, Sylvie; Pasquet, Blandine; Dubief, Emeline; Boukertouta, Tanissia; Dreyfuss, Didier; Tubach, Florence

2017-12-01

Intensivists' clinical decision making pursues two main goals for patients: to decrease mortality and to improve quality of life and functional status in survivors. Patient-important outcomes are gaining wide acceptance in most fields of clinical research. We sought to systematically review how well patient-important outcomes are reported in published randomized controlled trials (RCTs) in critically ill patients. Literature search was conducted to identify eligible trials indexed from January to December 2013. Articles were eligible if they reported an RCT involving critically ill adult patients. We excluded phase II, pilot and physiological crossover studies. We assessed study characteristics. All primary and secondary outcomes were collected, described and classified using six categories of outcomes including patient-important outcomes (involving mortality at any time on the one hand and quality of life, functional/cognitive/neurological outcomes assessed after ICU discharge on the other). Of the 716 articles retrieved in 2013, 112 RCTs met the inclusion criteria. Most common topics were mechanical ventilation (27%), sepsis (19%) and nutrition (17%). Among the 112 primary outcomes, 27 (24%) were patient-important outcomes (mainly mortality, 21/27) but only six (5%) were patient-important outcomes besides mortality assessed after ICU discharge (functional disability = 4; quality of life = 2). Among the 598 secondary outcomes, 133 (22%) were patient-important outcomes (mainly mortality, 92/133) but only 41 (7%) were patient-important outcomes besides mortality assessed after ICU discharge (quality of life = 20, functional disability = 14; neurological/cognitive performance = 5; handicap = 1; post-traumatic stress = 1). Seventy-three RCTs (65%) reported at least one patient-important outcome but only 11 (10%) reported at least one patient-important outcome besides mortality assessed after ICU discharge. Patient-important outcomes are rarely primary

The Eligibility of Surface Electromyography in the Assessment of Paraspinal Muscles Fatigue Following Interventions in Patients with Chronic Low Back Pain: A Systematic Review

OpenAIRE

Nahid Rahmani; Mohammad Ali Mohseni-Bandpei; Iraj Abdollahi

2013-01-01

Objective: Evaluation of paraspinal muscles endurance in patients with chronic low back pain (LBP) seems to be of great importance. Many studies demonstrated that surface electromyography has merit to assess muscle fatigue using frequency spectrum. The purpose of this study was to systematically review the eligibility of the surface electromyography in the assessment of paraspinal muscles fatigue changes following different interventions in patients with chronic LBP. Materials & Methods: ...

YKL-40/c-Met expression in rectal cancer biopsies predicts tumor regression following neoadjuvant chemoradiotherapy: a multi-institutional study.

Science.gov (United States)

Senetta, Rebecca; Duregon, Eleonora; Sonetto, Cristina; Spadi, Rossella; Mistrangelo, Massimiliano; Racca, Patrizia; Chiusa, Luigi; Munoz, Fernando H; Ricardi, Umberto; Arezzo, Alberto; Cassenti, Adele; Castellano, Isabella; Papotti, Mauro; Morino, Mario; Risio, Mauro; Cassoni, Paola

2015-01-01

Neoadjuvant chemo-radiotherapy (CRT) followed by surgical resection is the standard treatment for locally advanced rectal cancer, although complete tumor pathological regression is achieved in only up to 30% of cases. A clinicopathological and molecular predictive stratification of patients with advanced rectal cancer is still lacking. Here, c-Met and YKL-40 have been studied as putative predictors of CRT response in rectal cancer, due to their reported involvement in chemoradioresistance in various solid tumors. A multicentric study was designed to assess the role of c-Met and YKL-40 expression in predicting chemoradioresistance and to correlate clinical and pathological features with CRT response. Immunohistochemistry and fluorescent in situ hybridization for c-Met were performed on 81 rectal cancer biopsies from patients with locally advanced rectal adenocarcinoma. All patients underwent standard (50.4 gy in 28 fractions + concurrent capecitabine 825 mg/m2) neoadjuvant CRT or the XELOXART protocol. CRT response was documented on surgical resection specimens and recorded as tumor regression grade (TRG) according to the Mandard criteria. A significant correlation between c-Met and YKL-40 expression was observed (R = 0.43). The expressions of c-Met and YKL-40 were both significantly associated with a lack of complete response (86% and 87% of c-Met and YKL-40 positive cases, prectal cancer. Targeted therapy protocols could take advantage of prior evaluations of c-MET and YKL-40 expression levels to increase therapeutic efficacy.

Catechol-O-Methyltransferase (COMT) Gene (Val158Met) and Brain-Derived Neurotropic Factor (BDNF) (Val66Met) Genes Polymorphism in Schizophrenia: A Case-Control Study.

Science.gov (United States)

Saravani, Ramin; Galavi, Hamid Reza; Lotfian Sargazi, Marzieh

2017-10-01

Objective: Several studies have shown that some polymorphisms of genes encoding catechol-O-methyltransferase (COMT), the key enzyme in degrading dopamine, and norepinephrine and the human brain-derived neurotropic factor (BDNF), a nerve growth factor, are strong candidates for risk of schizophrenia (SCZ). In the present study, we aimed at examining the effects of COMT Val158Met (G>A) and BDNF Val66Met (G>A) polymorphisms on SCZ risk in a sample of Iranian population. Method: This case- control study included 92 SCZ patients and 92 healthy controls (HCs). Genotyping of both variants (COMT Val158Met (G>A) and BDNF Val66Met (G>A)) were conducted using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). Results: The findings revealed that the COMT Val158Met (G>A) polymorphism was not associated with the risk/protective of SCZ in all models (OR=0.630, 95%CI=0.299-1.326, P=0.224, GA vs. GG, OR=1.416, 95%CI=0.719-2.793, P=0.314, AA vs. GG, OR=1.00, 95%CI=0.56-1.79, P=1.00 GA+AA vs. GG, OR=1.667, 95%CI=0.885-3.125, P=0.11, AA vs. GG+GA, OR=1.247, 95%CI=0.825-1.885, P=0.343, A vs. G,). However, BDNF Val66Met (G>A) variant increased the risk of SCZ (OR = 2.008 95%CI = 1.008-4.00, P = 0.047, GA vs. GG, OR = 3.876 95%CI = 1.001-14.925, P = 0.049. AA vs. GG, OR = 2.272. 95%CI = 1.204-4.347, P = 0.011, GA+AA vs. GG, OR = 2.22 95%CI = 1.29-3.82. P = 0.005, A vs. G). Conclusion: The results did not support an association between COMT Val158Met (G>A) variant and risk/protective of SCZ. Moreover, it was found that BDNF Val66Met (G>A) polymorphism may increase the risk of SCZ development. Further studies and different ethnicities are recommended to confirm the findings.

Gezondheidsrisico's in verband met het werken met Polychloorbifenylen : een onderzoek

NARCIS (Netherlands)

Geuskens, R.B.M.; Nossent, S.M.; Koëter, H.B.W.M.; Dreef-van der Meulen, H.C.; Stijkel, A.; Zielhuis, R.L.

1989-01-01

Met behulp van gegevens verkregen uit een werkplekinventarisatie naar gegevens over produktie/gebruik, risicopopulatie en (mogelijke) blootstelling aan polychloorbifenylen (PCB's), en een literatuurstudie naar mogelijke schadelijke eigenschappen van PCB's op het reproductiesysteem en/of nageslacht

Phosphorylated hepatocyte growth factor receptor/c-Met is associated with tumor growth and prognosis in patients with bladder cancer: correlation with matrix metalloproteinase-2 and -7 and E-cadherin.

Science.gov (United States)

Miyata, Yasuyoshi; Sagara, Yuji; Kanda, Shigeru; Hayashi, Tomayoshi; Kanetake, Hiroshi

2009-04-01

Hepatocyte growth factor receptor/c-Met is associated with malignant aggressiveness and survival in various cancers including bladder cancer. Although phosphorylation of hepatocyte growth factor receptor/c-Met is essential for its function, the pathologic significance of phosphorylated hepatocyte growth factor receptor/c-Met in bladder cancer remains elusive. We investigated the clinical significance of its expression, and its correlation with cancer cell progression-related molecules. The expression levels of 2 tyrosine residues of hepatocyte growth factor receptor/c-Met (pY1234/1235 and pY1349) were examined immunohistochemically in 133 specimens with nonmetastatic bladder cancer. We also investigated their correlation with matrix metalloproteinase-1, -2, -7, and -14; urokinase-type plasminogen activator; E-cadherin; CD44 standard, variant 3, and variant 6; and vascular endothelial growth factor. Expression of phosphorylated hepatocyte growth factor receptor/c-Met was detected in cancer cells, but was rare in normal urothelial cells. Although hepatocyte growth factor receptor/c-Met, pY1234/1235 hepatocyte growth factor receptor/c-Met, and pY1349 hepatocyte growth factor receptor/c-Met were associated with pT stage, multivariate analysis identified pY1349 hepatocyte growth factor receptor/c-met expression only as a significant factor for high pT stage. Expression of pY1349 hepatocyte growth factor receptor/c-Met was a marker of metastasis and (P = .001) and cause-specific survival (P = .003). Expressions of matrix metalloproteinase-2, matrix metalloproteinase-7, and E-cadherin correlated with pY1349 hepatocyte growth factor receptor/c-Met expression. Our results demonstrated that pY1349 hepatocyte growth factor receptor/c-Met plays an important role in tumor development, and its expression is a significant predictor of metastasis and survival of patients with bladder cancer. The results suggest that these activities are mediated, at least in part, by matrix

Knee function and knee muscle strength in middle-aged patients with degenerative meniscal tears eligible for arthroscopic partial meniscectomy

DEFF Research Database (Denmark)

Stensrud, Silje; Risberg, May Arna; Roos, Ewa M.

2014-01-01

BACKGROUND: Functional limitations exist postmeniscectomy, but preoperative data are scarce. PURPOSE: To examine knee function, knee muscle strength and performance in middle-aged patients with degenerative meniscal tears, eligible for arthroscopic partial meniscectomy. STUDY DESIGN: Cross......-sectional study. METHODS: Eighty-two participants with MRI verified degenerative meniscal tear (35% women, mean age 49 years) answered the Knee injury and Osteoarthritis Outcome Score (KOOS) and were tested for isokinetic knee muscle strength and lower extremity performance (one-leg hop for distance, 6 m timed...

Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice

OpenAIRE

Martinić, Roko; Šošić, Hrvoje; Turčić, Petra; Konjevoda, Paško; Fučić, Aleksandra; Stojković, Ranko; Aralica, Gorana; Gabričević, Mario; Weitner, Tin; Štambuk, Nikola

2014-01-01

Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.5 mg/kg, which corresponds to the protective dose reported for se...

Comparison of MET-PET and FDG-PET for differentiation between benign lesions and lung cancer in pneumoconiosis

International Nuclear Information System (INIS)

Kanegae, Kakuko; Kuge, Yuji; Shiga, Tohru; Zhao, Songji; Okamoto, Shouzo; Tamaki, Nagara; Nakano, Ikuo; Kimura, Kiyonobu; Kaji, Hiroshi

2007-01-01

The aim of this study was to evaluate and compare the ability of C-11-methionine (MET) and F-18 fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) to diagnose lung cancer in patients with pneumoconiosis. Twenty-six subjects underwent both wholebody MET-PET and FDG-PET on the same day. The first group was a lung cancer group, which consisted of 15 patients, and included those with pneumoconiosis with increased nodules (13 cases), hemoptysis (1 case), and positive sputum cytology (1 case). The second group was a no-malignancy control group, consisting of 11 patients with pneumoconiosis. Significant correlations between nodule size and the maximum standardized uptake value (SUV max ) of the two PET tracers were observed in the control group. The larger the nodule size, the greater were the amounts of these tracers accumulated (MET: r=0.771, P max of MET was significantly lower than that of FDG in the pneumoconiotic nodules (P max of MET was significantly higher in the lung cancer than in the pneumoconiotic nodules, with 3.48±1.18 (mean ± SE) for the lung cancer and 1.48±0.08 for the pneumoconiotic nodules (P max of FDG, with 7.12±2.36 and 2.85±0.24 (P<0.05), respectively. On the basis of the criteria for the control group, FDG and MET identified lung cancer with sensitivities of 60% and 80%, specificities of 100% and 93%, accuracies of 90% and 90%, positive predictive values of 100% and 80%, and negative predictive values of 88% and 93%, respectively. Our results indicate that nodules with an intense uptake of MET and FDG relative to their size should be carefully observed because of a high risk for lung cancer. (author)

Statin eligibility and cardiovascular risk burden assessed by coronary artery calcium score: comparing the two guidelines in a large Korean cohort.

Science.gov (United States)

Rhee, Eun-Jung; Park, Se Eun; Oh, Hyung Geun; Park, Cheol-Young; Oh, Ki-Won; Park, Sung-Woo; Blankstein, Ron; Plutzky, Jorge; Lee, Won-Young

2015-05-01

To investigate the statin eligibility and the predictabilities for cardiovascular disease between AHA/ACC and ATPIII guidelines, comparing those results to concomitant coronary artery calcium scores (CACS) in a large cohort of Korean individuals who met statin-eligibility criteria. Among 19,920 participants in a health screening program, eligibility for statin treatment was assessed by the two guidelines. The presence and extent of coronary artery calcification (CAC) was measured by multi-detector computed tomography and compared among the various groups defined by the two guidelines. Applying the new ACC/AHA guideline to the health screening cohort increased the statin-eligible population from 18.7% (as defined by ATP III) to 21.7%. Statin-eligible subjects as defined only by ACC/AHA guideline manifested a higher proportion of subjects with CAC compared with those meeting only ATP-III criteria even after adjustment for age and sex (47.1 vs. 33.8%, pguideline showed higher odds ratio for the presence of CACS>0 compared with those meeting ATP-III criteria {3.493 (3.245∼3.759) vs. 2.865 (2.653∼3.094)}, which was attenuated after adjusted for age and sex. In this large Korean cohort, more subjects would have qualified for statin initiation under the new ACC/AHA guideline as compared with the proportion recommended for statin treatment by ATP III guideline. Among statin-eligible Korean health screening subjects, the new ACC/AHA guideline identified a greater extent of atherosclerosis as assessed by CACS as compared to ATP III guideline assessment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

No association of the BDNF val66met polymorphism with implicit associative vocabulary and motor learning.

Directory of Open Access Journals (Sweden)

Nils Freundlieb

Full Text Available Brain-derived neurotrophic factor (BDNF has been suggested to play a major role in plasticity, neurogenesis and learning in the adult brain. The BDNF gene contains a common val66met polymorphism associated with decreased activity-dependent excretion of BDNF and a potential influence on behaviour, more specifically, on motor learning. The objective of this study was to determine the influence of the BDNF val66met polymorphism on short-term implicit associative learning and whether its influence is cognitive domain-specific (motor vs. language. A sample of 38 young healthy participants was genotyped, screened for background and neuropsychological differences, and tested with two associative implicit learning paradigms in two different cognitive domains, i.e., motor and vocabulary learning. Subjects performed the serial reaction time task (SRTT to determine implicit motor learning and a recently established associative vocabulary learning task (AVL for implicit learning of action and object words. To determine the influence of the BDNF polymorphism on domain-specific implicit learning, behavioural improvements in the two tasks were compared between val/val (n = 22 and met carriers (val/met: n = 15 and met/met: n = 1. There was no evidence for an impact of the BDNF val66met polymorphism on the behavioural outcome in implicit short-term learning paradigms in young healthy subjects. Whether this polymorphism plays a relevant role in long-term training paradigms or in subjects with impaired neuronal plasticity or reduced learning capacity, such as aged individuals, demented patients or patients with brain lesions, has to be determined in future studies.

Mars MetNet Precursor Mission Status

Science.gov (United States)

Harri, A.-M.; Aleksashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.; Haukka, H.

2013-09-01

We are developing a new kind of planetary exploration mission for Mars in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology–Friends of Cancer Research HIV Working Group

Science.gov (United States)

Uldrick, Thomas S.; Ison, Gwynn; Rudek, Michelle A.; Noy, Ariela; Schwartz, Karl; Bruinooge, Suanna; Schenkel, Caroline; Miller, Barry; Dunleavy, Kieron; Wang, Judy; Zeldis, Jerome; Little, Richard F.

2018-01-01

Purpose People with HIV are living longer as a result of effective antiretroviral therapy. Cancer has become a leading cause of morbidity and mortality in this patient population. However, studies of novel cancer therapeutics have historically excluded patients with HIV. Critical review of eligibility criteria related to HIV is required to accelerate development of and access to effective therapeutics for HIV-infected patients with cancer and make studies more generalizable to this patient population. Methods From January through April 2016, the HIV Working Group conducted a series of teleconferences; a review of 46 New Drug Applications from registration studies of unique agents studied in adults with cancer that led to the initial US Food and Drug Administration approval of that agent from 2011 to 2015; and a review of HIV-related eligibility criteria from National Cancer Institute–sponsored studies. Results were discussed and refined at a multistakeholder workshop held May 12, 2016. The HIV Working Group developed recommendations for eligibility criteria that focus on pharmacologic and immunologic considerations in this patient population and that balance patient safety, access to appropriate investigational agents, and study integrity. Results Exclusion of patients with HIV remains common in most studies of novel cancer agents. Models for HIV-related eligibility criteria in National Cancer Institute–sponsored studies are instructive. HIV infection itself should no longer be an exclusion criterion for most studies. Eligibility criteria related to HIV infection that address concurrent antiretroviral therapy and immune status should be designed in a manner that is appropriate for a given cancer. Conclusion Expanding clinical trial eligibility to be more inclusive of patients with HIV is justified in most cases and may accelerate the development of effective therapies in this area of unmet clinical need. PMID:28968173

Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology-Friends of Cancer Research HIV Working Group.

Science.gov (United States)

Uldrick, Thomas S; Ison, Gwynn; Rudek, Michelle A; Noy, Ariela; Schwartz, Karl; Bruinooge, Suanna; Schenkel, Caroline; Miller, Barry; Dunleavy, Kieron; Wang, Judy; Zeldis, Jerome; Little, Richard F

2017-11-20

Purpose People with HIV are living longer as a result of effective antiretroviral therapy. Cancer has become a leading cause of morbidity and mortality in this patient population. However, studies of novel cancer therapeutics have historically excluded patients with HIV. Critical review of eligibility criteria related to HIV is required to accelerate development of and access to effective therapeutics for HIV-infected patients with cancer and make studies more generalizable to this patient population. Methods From January through April 2016, the HIV Working Group conducted a series of teleconferences; a review of 46 New Drug Applications from registration studies of unique agents studied in adults with cancer that led to the initial US Food and Drug Administration approval of that agent from 2011 to 2015; and a review of HIV-related eligibility criteria from National Cancer Institute-sponsored studies. Results were discussed and refined at a multistakeholder workshop held May 12, 2016. The HIV Working Group developed recommendations for eligibility criteria that focus on pharmacologic and immunologic considerations in this patient population and that balance patient safety, access to appropriate investigational agents, and study integrity. Results Exclusion of patients with HIV remains common in most studies of novel cancer agents. Models for HIV-related eligibility criteria in National Cancer Institute-sponsored studies are instructive. HIV infection itself should no longer be an exclusion criterion for most studies. Eligibility criteria related to HIV infection that address concurrent antiretroviral therapy and immune status should be designed in a manner that is appropriate for a given cancer. Conclusion Expanding clinical trial eligibility to be more inclusive of patients with HIV is justified in most cases and may accelerate the development of effective therapies in this area of unmet clinical need.

Patient and primary care provider attitudes and adherence towards lung cancer screening at an academic medical center

Directory of Open Access Journals (Sweden)

Duy K. Duong

2017-06-01

Full Text Available Low dose CT (LDCT for lung cancer screening is an evidence-based, guideline recommended, and Medicare approved test but uptake requires further study. We therefore conducted patient and provider surveys to elucidate factors associated with utilization. Patients referred for LDCT at an academic medical center were questioned about their attitudes, knowledge, and beliefs on lung cancer screening. Adherent patients were defined as those who met screening eligibility criteria and completed a LDCT. Referring primary care providers within this same medical system were surveyed in parallel about their practice patterns, attitudes, knowledge and beliefs about screening. Eighty patients responded (36%, 48 of whom were adherent. Among responders, non-Hispanic patients (p = 0.04 were more adherent. Adherent respondents believed that CT technology is accurate and early detection is useful, and they trusted their providers. A majority of non-adherent patients (79% self-reported an intention to obtain a LDCT in the future. Of 36 of 87 (41% responding providers, only 31% knew the correct lung cancer screening eligibility criteria, which led to a 37% inappropriate referral rate from 2013 to 2015. Yet, 75% had initiated lung cancer screening discussions, 64% thought screening was at least moderately effective, and 82% were interested in learning more of the 33 providers responding to these questions. Overall, patients were motivated and providers engaged to screen for lung cancer by LDCT. Non-adherent patient “procrastinators” were motivated to undergo screening in the future. Additional follow through on non-adherence may enhance screening uptake, and raising awareness for screening eligibility through provider education may reduce inappropriate referrals.

23 CFR 650.405 - Eligible projects.

Science.gov (United States)

2010-04-01

... FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS BRIDGES, STRUCTURES, AND HYDRAULICS Highway Bridge Replacement and Rehabilitation Program § 650.405 Eligible projects... rehabilitation. (b) Types of projects which are eligible. The following types of work are eligible for...

Pilot study of a point-of-use decision support tool for cancer clinical trials eligibility.

Science.gov (United States)

Breitfeld, P P; Weisburd, M; Overhage, J M; Sledge, G; Tierney, W M

1999-01-01

Many adults with cancer are not enrolled in clinical trials because caregivers do not have the time to match the patient's clinical findings with varying eligibility criteria associated with multiple trials for which the patient might be eligible. The authors developed a point-of-use portable decision support tool (DS-TRIEL) to automate this matching process. The support tool consists of a hand-held computer with a programmable relational database. A two-level hierarchic decision framework was used for the identification of eligible subjects for two open breast cancer clinical trials. The hand-held computer also provides protocol consent forms and schemas to further help the busy oncologist. This decision support tool and the decision framework on which it is based could be used for multiple trials and different cancer sites.

7 CFR 1150.108 - Eligible organization.

Science.gov (United States)

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Eligible organization. 1150.108 Section 1150.108 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Order Definitions § 1150.108 Eligible organization. Eligible organization means any organization which...

Motivational counselling and SMS-reminders for reduction of daily sitting time in patients with rheumatoid arthritis

DEFF Research Database (Denmark)

Thomsen, T; Aadahl, Mette; Beyer, Nina Ann-Marie

2016-01-01

for daily leisure time sitting > 4 h. The 16-week intervention included 1) three individual motivational counselling sessions and 2) individual text message reminders aimed at reducing daily sitting time. The control group was encouraged to maintain their usual lifestyles. Outcomes were assessed at baseline...... and screened before 20 met eligibility criteria and consented; reasons for declining study participation were mostly flares, lack of time and co-morbidities. One patient from the control group dropped out before end of intervention (due to a RA flare). Intervention participants completed all counselling...... tailored, theory-based behavioural intervention targeting reduction in daily sitting time in patients with RA. METHODS: A randomised, controlled trial with two parallel groups. RA patients >18 years of age and Health Assessment Questionnaire (HAQ) score 

7 CFR 1709.109 - Eligible projects.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Eligible projects. 1709.109 Section 1709.109... projects. Eligible projects are those that acquire, construct, extend, repair, upgrade or otherwise improve... are eligible. Projects providing or improving service to communities with extremely high energy costs...

7 CFR 760.303 - Eligible livestock producer.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Eligible livestock producer. 760.303 Section 760.303... AGRICULTURE SPECIAL PROGRAMS INDEMNITY PAYMENT PROGRAMS Livestock Forage Disaster Program § 760.303 Eligible livestock producer. (a) To be considered an eligible livestock producer, the eligible producer on a farm...

Mars MetNet Mission Payload Overview

Science.gov (United States)

Harri, A.-M.; Haukka, H.; Alexashkin, S.; Guerrero, H.; Schmidt, W.; Genzer, M.; Vazquez, L.

2012-09-01

A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide crucial scientific data about the Martian atmospheric phenomena.

Mice with GFAP-targeted loss of neurofibromin demonstrate increased axonal MET expression with aging.

Science.gov (United States)

Su, Weiping; Xing, Rubing; Guha, Abhijit; Gutmann, David H; Sherman, Larry S

2007-05-01

Neurofibromatosis 1 (NF1) is a common genetic disease that predisposes patients to peripheral nerve tumors and central nervous system (CNS) abnormalities including low-grade astrocytomas and cognitive disabilities. Using mice with glial fibrillary acidic protein (GFAP)-targeted Nf1 loss (Nf1(GFAP)CKO mice), we found that Nf1(-/-) astrocytes proliferate faster and are more invasive than wild-type astrocytes. In light of our previous finding that aberrant expression of the MET receptor tyrosine kinase contributes to the invasiveness of human NF1-associated malignant peripheral nerve sheath tumors, we sought to determine whether MET expression is aberrant in the brains of Nf1 mutant mice. We found that Nf1(-/-) astrocytes express slightly more MET than wild-type cells in vitro, but do not express elevated MET in situ. However, fiber tracts containing myelinated axons in the hippocampus, midbrain, cerebral cortex, and cerebellum express higher than normal levels of MET in older (> or =6 months) Nf1(GFAP)CKO mice. Both Nf1(GFAP)CKO and wild-type astrocytes induced MET expression in neurites of wild-type hippocampal neurons in vitro, suggesting that astrocyte-derived signals may induce MET in Nf1 mutant mice. Because the Nf1 gene product functions as a RAS GTPase, we examined MET expression in the brains of mice with GFAP-targeted constitutively active forms of RAS. MET was elevated in axonal fiber tracts in mice with active K-RAS but not H-RAS. Collectively, these data suggest that loss of Nf1 in either astrocytes or GFAP(+) neural progenitor cells results in increased axonal MET expression, which may contribute to the CNS abnormalities in children and adults with NF1. (c) 2007 Wiley-Liss, Inc.

7 CFR 1220.109 - Eligible organization.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Eligible organization. 1220.109 Section 1220.109... CONSUMER INFORMATION Soybean Promotion and Research Order Definitions § 1220.109 Eligible organization. The term eligible organization means any organization which has been certified by the Secretary pursuant to...

7 CFR 1250.313 - Eligible organization.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Eligible organization. 1250.313 Section 1250.313... Research and Promotion Order Definitions § 1250.313 Eligible organization. Eligible organization means any organization, association, or cooperative which represents egg producers of any egg producing area of the...

38 CFR 21.3040 - Eligibility; child.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Eligibility; child. 21.3040 Section 21.3040 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED.... Chapter 35 Eligibility and Entitlement § 21.3040 Eligibility; child. (a) Commencement. A program of...

The COMT Val158Met Polymorphism Is Associated With Response to Add-on Dextromethorphan Treatment in Bipolar Disorder.

Science.gov (United States)

Lee, Sheng-Yu; Chen, Shiou-Lan; Wang, Tzu-Yun; Chang, Yun-Hsuan; Chen, Po See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Chen, Kao Ching; Yang, Yen Kuang; Lu, Ru-Band

2017-02-01

We previously conducted a randomized, double-blind, controlled, 12-week study evaluating the effect of add-on dextromethorphan (DM), a noncompetitive N-methyl-D-aspartate receptor antagonist, on patients with bipolar disorder (BD) treated using valproate (VPA), which showed negative clinical differences. The genetic variation between each individual may be responsible for interindividual differences. The catechol-O-methyltransferase (COMT) gene has been a candidate gene for BD. In the current study, we investigated whether the COMT Val158Met polymorphism predicts treatment response to VPA + add-on DM and to VPA + placebo. Patients with BD (n = 309) undergoing regular VPA treatments were randomly assigned to groups given either add-on DM (30 mg/d) (n = 102), DM (60 mg/d) (n = 101), or placebo (n = 106) for 12 weeks. The Hamilton Depression Rating Scale and Young Mania Rating Scale were used to evaluate clinical response during weeks 0, 1, 2, 4, 8, and 12. The genotypes of the COMT Val158Met polymorphism were determined using polymerase chain reaction plus restriction fragment length polymorphism analysis. To adjust for within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used. When stratified by the COMT Val158Met genotypes, significantly greater decreases in Hamilton Depression Rating Scale scores were found in the VPA + DM (30 mg/d) group in patients with the Val/Met genotype (P = 0.008). We conclude that the COMT Val158Met polymorphism may influence responses to DM (30 mg/d) by decreasing depressive symptoms in BD patients.

Ervaringen met beeldverwerking.

NARCIS (Netherlands)

Meuleman, J.

1989-01-01

Verslag van een werkbezoek aan het Franse instituut Cemagref, met nadruk op beeldverwerking. Toepassingen van beeldverwerking zijn onder andere: een plukrobot voor appels; het detecteren van oppervlaktebeschadigingen bij appels; het detecteren van breuk in eieren; remote sensing

20 CFR 628.702 - Eligibility.

Science.gov (United States)

2010-04-01

... THE JOB TRAINING PARTNERSHIP ACT The Summer Youth Employment and Training Program § 628.702 Eligibility. (a) Age and economic disadvantage. An individual is eligible to participate in programs funded...

Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer

International Nuclear Information System (INIS)

Yeh, Chen-Yun; Tseng, Vincent S; Lee, Yuan-Chii G; Shen, Cheng-Huang; Chow, Nan-Haw; Liu, Hsiao-Sheng; Shin, Shin-Mei; Yeh, Hsuan-Heng; Wu, Tsung-Jung; Shin, Jyh-Wei; Chang, Tsuey-Yu; Raghavaraju, Giri; Lee, Chung-Ta; Chiang, Jung-Hsien

2011-01-01

A cross-talk between different receptor tyrosine kinases (RTKs) plays an important role in the pathogenesis of human cancers. Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA) silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients. A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α) with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p < 0.05), and overexpression of c-Met/Axl/PDGFR-α or c-Met alone showed the most significant correlation with poor survival (p < 0.01). In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy

24 CFR 35.1135 - Eligible costs.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Eligible costs. 35.1135 Section 35....1135 Eligible costs. A PHA may use financial assistance received under the modernization program (CIAP....112 of this title. Eligible costs include: (a) Evaluation and insurance costs. Evaluation and hazard...

23 CFR 810.302 - Eligible projects.

Science.gov (United States)

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Eligible projects. 810.302 Section 810.302 Highways... SPECIAL USE HIGHWAY PROJECTS Federal-Aid Urban System Nonhighway Public Mass Transit Projects § 810.302 Eligible projects. (a) Eligible projects are those defined as nonhighway public mass transit projects in...

12 CFR 615.5140 - Eligible investments.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Eligible investments. 615.5140 Section 615.5140... POLICIES AND OPERATIONS, AND FUNDING OPERATIONS Investment Management § 615.5140 Eligible investments. (a) You may hold only the following types of investments listed in the Investment Eligibility Criteria...

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and post-stroke dementia: a hospital-based study from northern Iran.

Science.gov (United States)

Rezaei, Sajjad; Asgari Mobarake, Karim; Saberi, Alia; Keshavarz, Parvaneh; Leili, Ehsan Kazemnejad

2016-06-01

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with functional and cognitive outcomes of stroke and plays a key role in preventing neuronal death. This study aimed to answer the following question: does BDNF Val66Met polymorphism prognosticate survival status and risk of post-stroke dementia (PSD)? In a retrospective cohort study, 206 patients with ischemic stroke (IS) entered the study. They were consecutively being admitted to the neurology clinic in Poursina Hospital (northern Iran) from 2012 to 2014. The diagnosis of PSD was based on DSM-5 criteria. The current and the premorbid cognitive statuses of the patients were respectively assessed through the third edition of Addenbrooke's Cognitive Examination and the Informant Questionnaire on Cognitive Decline in the Elderly. BDNF Val66Met gene polymorphism was determined by PCR-RFLP. On average, 48 patients (23.3 %) developed PSD 6 months after IS. Log-rank test showed that the survival rate of at least one Val-allele carriers was significantly lower than that of Met/Met homozygotes (P = 0.0005), and the former developed PSD sooner than the latter (375, 492 days, respectively). Cox model showed that heterozygous carriers of Val/Met were at greater risk of PSD over time (HR 2.280, 95 % CI 1.566-4.106, P = 0.006). However, the risk ratio of patients with PSD among different BDNF genotypes decreased after adjusting demographic, clinical, and vascular risk factors, and was no longer statistically significant (AHR 2.434, 95 % CI 0.597-9.926, P = 0.215). Val-allele carriers or Val/Met genotypes were more quickly diagnosed as having dementia after IS. However, this genetic vulnerability became more destructive when it was added to demographic, clinical, and vascular risk factors.

Alkaline transition of pseudoazurin Met16X mutant proteins: protein stability influenced by the substitution of Met16 in the second sphere coordination.

Science.gov (United States)

Abdelhamid, Rehab F; Obara, Yuji; Kohzuma, Takamitsu

2008-01-01

Several blue copper proteins are known to change the active site structure at alkaline pH (alkaline transition). Spectroscopic studies of Met16Phe, Met16Tyr, Met16Trp, and Met16Val pseudoazurin variants were performed to investigate the second sphere role through alkaline transition. The visible electronic absorption and resonance Raman spectra of Met16Phe, Met16Tyr, and Met16Trp variants showed the increasing of axial component at pH approximately 11 like wild-type PAz. The visible electronic absorption and far-UV CD spectra of Met16Val demonstrated that the destabilization of the protein structure was triggered at pH>11. Resonance Raman (RR) spectra of PAz showed that the intensity-weighted averaged Cu-S(Cys) stretching frequency was shifted to higher frequency region at pH approximately 11. The higher frequency shift of Cu-S(Cys) bond is implied the stronger Cu-S(Cys) bond at alkaline transition pH approximately 11. The visible electronic absorption and far-UV CD spectra of Met16X PAz revealed that the Met16Val variant is denatured at pH>11, but Met16Phe, Met16Tyr, and Met16Trp mutant proteins are not denatured even at pH>11. These observations suggest that Met16 is important to maintain the protein structure through the possible weak interaction between methionine -SCH3 part and coordinated histidine imidazole moiety. The introduction of pi-pi interaction in the second coordination sphere may be contributed to the enhancement of protein structure stability.

38 CFR 21.3041 - Periods of eligibility; child.

Science.gov (United States)

2010-07-01

...; child. 21.3041 Section 21.3041 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... 38 U.S.C. Chapter 35 Eligibility and Entitlement § 21.3041 Periods of eligibility; child. (a) Eligibility derived from a veteran with a P&T disability. An eligible child's period of eligibility generally...

Intracardiale chirurgie met behulp van een cirrestor : een experimentele en klinische studie

NARCIS (Netherlands)

Homan van der Heide, Jan Nico

1960-01-01

SAMENVATTING De intracardiale chirurgie is op grote schaal mogelijk geworden dank zij het feit, dat afwijkingen in bloedvrije hartholten met direct zicht hersteld kunnen worden. Voordat de operatieve correctie plaats vindt, moet de patient in een bepaalde, voor de operatie geschikte conditie

31 CFR 321.2 - Eligible organizations.

Science.gov (United States)

2010-07-01

... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false Eligible organizations. 321.2 Section... § 321.2 Eligible organizations. (a) Organizations eligible to apply for qualification and to serve as.... (b)(1) An organization that desires to redeem securities must first qualify as a paying agent. An...

7 CFR 1739.11 - Eligible project.

Science.gov (United States)

2010-01-01

... 7 Agriculture 11 2010-01-01 2010-01-01 false Eligible project. 1739.11 Section 1739.11 Agriculture... BROADBAND GRANT PROGRAM Community Connect Grant Program § 1739.11 Eligible project. To be eligible for a grant, the Project must: (a) Serve a Rural Area where Broadband Transmission Service does not currently...

20 CFR 628.605 - Eligibility.

Science.gov (United States)

2010-04-01

... THE JOB TRAINING PARTNERSHIP ACT The Adult Program § 628.605 Eligibility. (a) Age and economic disadvantage. Except as provided in paragraph (b) of this section, an individual shall be eligible to...

The Hepatocyte Growth Factor (HGF/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

Directory of Open Access Journals (Sweden)

Marjorie Boissinot

2014-08-01

Full Text Available Met is the receptor of hepatocyte growth factor (HGF, a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML, and myeloproliferative neoplasms (MPNs. The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs.

The Hepatocyte Growth Factor (HGF)/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

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Boissinot, Marjorie [Translational Neuro-Oncology Group, Leeds Institute of Cancer and Pathology, University of Leeds, Level 5 Wellcome Trust Brenner Building, St James’s Hospital, Leeds LS9 7TF (United Kingdom); Vilaine, Mathias [Institute of Research on Cancer and Aging (IRCAN), CNRS-Inserm-UNS UMR 7284, U 1081, Centre A. Lacassagne, 33 Avenue Valombrose, Nice 06189 (France); Hermouet, Sylvie, E-mail: sylvie.hermouet@univ-nantes.fr [Centre Hospitalier Universitaire (CHU), Place Alexis Ricordeau, Nantes 44093 (France); Inserm UMR892, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 8 quai Moncousu, Nantes cedex 44007 (France)

2014-08-12

Met is the receptor of hepatocyte growth factor (HGF), a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML), and myeloproliferative neoplasms (MPNs). The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs)

Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice

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Roko Martinić

2014-08-01

Full Text Available Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.5 mg/kg, which corresponds to the protective dose reported for several different animal disease models. In this group plasma alanine aminotransferase and aspartate aminotransferase enzyme activities, as well as liver necrosis score were significantly reduced in comparison to control animals treated with physiological saline (p > 0.01. The specificity of the peptide hepatoprotection was investigated from the standpoint of the receptor and peptide blockade. It was concluded that Met-enkephalin effects on the liver were mediated via δ and ζ opioid receptors. Genotoxic testing of Met-enkephalin confirmed the safety of the peptide.

Autorijden met ADHD

NARCIS (Netherlands)

Fuermaier, Anselm B.M.; Tucha, Lara; de Vries, Stefanie M.; Koerts, Janneke; de Waard, Dick; Brookhuis, Karel; Tucha, Oliver

Volwassenen met attention deficit hyperactivity disorder (ADHD) hebben uiteenlopende cognitieve beperkingen, die een aanzienlijke invloed kunnen hebben op verschillende aspecten van het dagelijks leven. Een van deze aspecten is het besturen van een auto. Autorijden is een belangrijke activiteit in

32 CFR 147.30 - Temporary eligibility for access at the confidential and secret levels and temporary eligibility...

Science.gov (United States)

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Temporary eligibility for access at the confidential and secret levels and temporary eligibility for âLâ access authorization. 147.30 Section 147.30... Temporary Access § 147.30 Temporary eligibility for access at the confidential and secret levels and...

Research progress in c-Met and hepatocellular carcinoma

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WANG Changqing

2015-06-01

Full Text Available c-Met plays a pivotal role in the development and progression of hepatocellular carcinoma (HCC, which can lead to proliferation, survival, cytoskeleton reorganization, separation and diffusion, and angiogenesis of tumor cells. Moreover, c-Met is an important prognostic factor for HCC. In HCC, c-Met acts as an activator of a series of signaling pathways, including PI3K/AKT/mTOR, ERK/MAPK, and Rac-Pak. In recent years, it has been reported that small-molecule kinase inhibitors can abolish phosphorylation at the intracellular carboxyl terminal of c-Met, and then inhibit the recruitment of signal convertors and downstream signaling pathways, which finally achieve anti-tumor activities. Based on the carcinogenic activity of c-Met in HCC, this paper points out that selective inhibitors of c-Met hold promise for targeted therapies for HCC.

Phenotypic similarities and differences in patients with a p.Met112Ile mutation in SOX10.

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Pingault, Veronique; Pierre-Louis, Laurence; Chaoui, Asma; Verloes, Alain; Sarrazin, Elisabeth; Brandberg, Goran; Bondurand, Nadege; Uldall, Peter; Manouvrier-Hanu, Sylvie

2014-09-01

Waardenburg syndrome (WS) is characterized by an association of pigmentation abnormalities and sensorineural hearing loss. Four types, defined on clinical grounds, have been delineated, but this phenotypic classification correlates imperfectly with known molecular anomalies. SOX10 mutations have been found in patients with type II and type IV WS (i.e., with Hirschsprung disease), more complex syndromes, and partial forms of the disease. The phenotype induced by SOX10 mutations is highly variable and, except for the neurological forms of the disease, no genotype-phenotype correlation has been characterized to date. There is no mutation hotspot in SOX10 and most cases are sporadic, making it particularly difficult to correlate the phenotypic and genetic variability. This study reports on three independent families with SOX10 mutations predicted to result in the same missense mutation at the protein level (p.Met112Ile), offering a rare opportunity to improve our understanding of the mechanisms underlying phenotypic variability. The pigmentation defects of these patients are very similar, and the neurological symptoms showed a somewhat similar evolution over time, indicating a potential partial genotype-phenotype correlation. However, variability in gastrointestinal symptoms suggests that other genetic factors contribute to the expression of these phenotypes. No correlation between the rs2435357 polymorphism of RET and the expression of Hirschsprung disease was found. In addition, one of the patients has esophageal achalasia, which has rarely been described in WS. © 2014 Wiley Periodicals, Inc.

An assessment of Prostate Cancer Research International: Active Surveillance (PRIAS) criteria for active surveillance of clinically low-risk prostate cancer patients

Science.gov (United States)

da Silva, Vitor; Cagiannos, Ilias; Lavallée, Luke T.; Mallick, Ranjeeta; Witiuk, Kelsey; Cnossen, Sonya; Eastham, James A.; Fergusson, Dean A.; Morash, Chris; Breau, Rodney H.

2017-01-01

Introduction Active surveillance is a strategy to delay or prevent treatment of indolent prostate cancer. The Prostate Cancer Research International: Active Surveillance (PRIAS) criteria were developed to select patients for prostate cancer active surveillance. The objective of this study was to compare pathological findings from PRIAS-eligible and PRIAS-ineligible clinically low-risk prostate cancer patients. Methods A D’Amico low-risk cohort of 1512 radical prostatectomy patients treated at The Ottawa Hospital or Memorial Sloan Kettering Cancer Centre between January 1995 and December 2007 was reviewed. Pathological outcomes (pT3 tumours, Gleason sum ≥7, lymph node metastases, or a composite) and clinical outcomes (prostate-specific antigen [PSA] recurrence, secondary cancer treatments, and death) were compared between PRIAS-eligible and PRIAS-ineligible cohorts. Results The PRIAS-eligible cohort (n=945) was less likely to have Gleason score ≥7 (odds ratio [OR] 0.61; 95% confidence interval [CI] 0.49–0.75), pT3 (OR 0.41; 95% CI 0.31–0.55), nodal metastases (OR 0.37; 95% CI 0.10–1.31), or any adverse feature (OR 0.56; 95% CI 0.45–0.69) compared to the PRIAS-ineligible cohort. The probability of any adverse pathology in the PRIAS-eligible cohort was 41% vs. 56% in the PRIAS-ineligible cohort. At median follow-up of 3.7 years, 72 (4.8%) patients had a PSA recurrence, 24 (1.6%) received pelvic radiation, and 13 (0.9%) received androgen deprivation. No difference was detected for recurrence-free and overall survival between groups (recurrence hazard ratio [HR] 0.71; 95% CI 0.46–1.09 and survival HR 0.72; 95% CI 0.36–1.47). Conclusions Low-risk prostate cancer patients who met PRIAS eligibility criteria are less likely to have higher-risk cancer compared to those who did not meet at least one of these criteria. PMID:28798822

Jeugd met beperkingen

NARCIS (Netherlands)

Sjoerd Kooiker

2006-01-01

Voor kinderen en jongeren met een lichamelijke of verstandelijke beperking is 'gewoon meedoen' in de samenleving geen vanzelfsprekendheid.  Zij ervaren vaak meer obstakels bij het naar school gaan, het vinden van een baan en in hun vrijetijdsbesteding dan andere kinderen en jongeren. Ook

SPSS met syntax

NARCIS (Netherlands)

Grotenhuis, H.F. te; Visscher, C.A.M.

2007-01-01

Dit boekje wijkt af van de gebruikelijke statistiekboeken omdat het sec gaat over het bekende statistische computerprogramma SPSS, en dan alleen nog de oorspronkelijke variant waarin wordt gewerkt met syntax (intypen commando's -zoals bij DOS) i.p.v. de later ontwikkelde 'Windows-schil' (aanklikken

Transcriptional activation of the Axl and PDGFR-α by c-Met through a ras- and Src-independent mechanism in human bladder cancer

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Tseng Vincent S

2011-04-01

Full Text Available Abstract Background A cross-talk between different receptor tyrosine kinases (RTKs plays an important role in the pathogenesis of human cancers. Methods Both NIH-Met5 and T24-Met3 cell lines harboring an inducible human c-Met gene were established. C-Met-related RTKs were screened by RTK microarray analysis. The cross-talk of RTKs was demonstrated by Western blotting and confirmed by small interfering RNA (siRNA silencing, followed by elucidation of the underlying mechanism. The impact of this cross-talk on biological function was demonstrated by Trans-well migration assay. Finally, the potential clinical importance was examined in a cohort of 65 cases of locally advanced and metastatic bladder cancer patients. Results A positive association of Axl or platelet-derived growth factor receptor-alpha (PDGFR-α with c-Met expression was demonstrated at translational level, and confirmed by specific siRNA knock-down. The transactivation of c-Met on Axl or PDGFR-α in vitro was through a ras- and Src-independent activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK pathway. In human bladder cancer, co-expression of these RTKs was associated with poor patient survival (p p Conclusions In addition to c-Met, the cross-talk with Axl and/or PDGFR-α also contributes to the progression of human bladder cancer. Evaluation of Axl and PDGFR-α expression status may identify a subset of c-Met-positive bladder cancer patients who may require co-targeting therapy.

Dissection of combinatorial control by the Met4 transcriptional complex.

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Lee, Traci A; Jorgensen, Paul; Bognar, Andrew L; Peyraud, Caroline; Thomas, Dominique; Tyers, Mike

2010-02-01

Met4 is the transcriptional activator of the sulfur metabolic network in Saccharomyces cerevisiae. Lacking DNA-binding ability, Met4 must interact with proteins called Met4 cofactors to target promoters for transcription. Two types of DNA-binding cofactors (Cbf1 and Met31/Met32) recruit Met4 to promoters and one cofactor (Met28) stabilizes the DNA-bound Met4 complexes. To dissect this combinatorial system, we systematically deleted each category of cofactor(s) and analyzed Met4-activated transcription on a genome-wide scale. We defined a core regulon for Met4, consisting of 45 target genes. Deletion of both Met31 and Met32 eliminated activation of the core regulon, whereas loss of Met28 or Cbf1 interfered with only a subset of targets that map to distinct sectors of the sulfur metabolic network. These transcriptional dependencies roughly correlated with the presence of Cbf1 promoter motifs. Quantitative analysis of in vivo promoter binding properties indicated varying levels of cooperativity and interdependency exists between members of this combinatorial system. Cbf1 was the only cofactor to remain fully bound to target promoters under all conditions, whereas other factors exhibited different degrees of regulated binding in a promoter-specific fashion. Taken together, Met4 cofactors use a variety of mechanisms to allow differential transcription of target genes in response to various cues.

Innoveren met serious games : Wat is serious gaming?

NARCIS (Netherlands)

Werkhoven, P.J.

2008-01-01

Het begrip serious gaming is inmiddels gekaapt door vele aanbieders van wat vroeger simulatie en virtual reality technologie genoemd werd. Met die technologie kunnen we mensen laten rondlopen in virtuele gebouwen en landschappen, al dan niet met grote projectieschermen of met brillen op. Maar dat is

Medicaid and Children's Health Insurance Programs: essential health benefits in alternative benefit plans, eligibility notices, fair hearing and appeal processes, and premiums and cost sharing; exchanges: eligibility and enrollment. Final rule.

Science.gov (United States)

2013-07-15

This final rule implements provisions of the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010 (collectively referred to as the Affordable Care Act. This final rule finalizes new Medicaid eligibility provisions; finalizes changes related to electronic Medicaid and the Children's Health Insurance Program (CHIP) eligibility notices and delegation of appeals; modernizes and streamlines existing Medicaid eligibility rules; revises CHIP rules relating to the substitution of coverage to improve the coordination of CHIP coverage with other coverage; and amends requirements for benchmark and benchmark-equivalent benefit packages consistent with sections 1937 of the Social Security Act (which we refer to as ``alternative benefit plans'') to ensure that these benefit packages include essential health benefits and meet certain other minimum standards. This rule also implements specific provisions including those related to authorized representatives, notices, and verification of eligibility for qualifying coverage in an eligible employer-sponsored plan for Affordable Insurance Exchanges. This rule also updates and simplifies the complex Medicaid premium and cost sharing requirements, to promote the most effective use of services, and to assist states in identifying cost sharing flexibilities. It includes transition policies for 2014 as applicable.

5 CFR 330.704 - Eligibility.

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2010-01-01

... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS RECRUITMENT, SELECTION, AND PLACEMENT (GENERAL) Interagency Career Transition Assistance Plan for Displaced Employees § 330.704 Eligibility. (a) To be eligible for the special selection priority, an individual must meet all of the...

Influence of COMT val158met genotype on the depressed brain during emotional processing and working memory.

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Esther M Opmeer

Full Text Available Major depressive disorder (MDD has been associated with abnormal prefrontal-limbic interactions and altered catecholaminergic neurotransmission. The val158met polymorphism on the catechol-O-methyltransferase (COMT gene has been shown to influence prefrontal cortex (PFC activation during both emotional processing and working memory (WM. Although COMT-genotype is not directly associated with MDD, it may affect MDD pathology by altering PFC activation, an endophenotype associated with both COMT and MDD. 125 participants, including healthy controls (HC, n=28 and MDD patients were genotyped for the COMT val158met polymorphism and underwent functional magnetic resonance imaging (fMRI-neuroimaging during emotion processing (viewing of emotional facial expressions and a WM task (visuospatial planning. Within HC, we observed a positive correlation between the number of met-alleles and right inferior frontal gyrus activation during emotional processing, whereas within patients the number of met-alleles was not correlated with PFC activation. During WM a negative correlation between the number of met-alleles and middle frontal gyrus activation was present in the total sample. In addition, during emotional processing there was an effect of genotype in a cluster including the amygdala and hippocampus. These results demonstrate that COMT genotype is associated with relevant endophenotypes for MDD. In addition, presence of MDD only interacts with genotype during emotional processing and not working memory.

40 CFR 35.133 - Programs eligible for inclusion.

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2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Programs eligible for inclusion. 35.133... Programs eligible for inclusion. (a) Eligible programs. Except as provided in paragraph (b) of this section, the environmental programs eligible, in accordance with appropriation acts, for inclusion in a...

Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.

Science.gov (United States)

Robinson, Bruce G; Paz-Ares, Luis; Krebs, Annetta; Vasselli, James; Haddad, Robert

2010-06-01

Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.

The HGF Receptor c-Met Is Overexpressed in Esophageal Adenocarcinoma

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Luis J. Herrera

2005-01-01

Full Text Available The hepatocyte growth factor (HGF receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE, and normal esophagus (NE using immunohistochemistry (IHC and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100% EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2-overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted.

40 CFR 35.533 - Programs eligible for inclusion.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Programs eligible for inclusion. 35.533... § 35.533 Programs eligible for inclusion. (a) Eligible programs. Except as provided in paragraph (b) of this section, the environmental programs eligible for inclusion in a Performance Partnership Grant are...

Lack of association between urotensin-II (UTS2 gene polymorphisms (Thr21Met and Ser89Asn and migraine

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Betül Ozan

2017-08-01

Full Text Available Migraine is a common neurovascular brain disorder with heterogeneous clinical presentation, including recurrent headache attacks. The pathophysiology of migraine is complex, and a number of genomic regions have been associated with the development of migraine. In this study, we analyzed the allele and genotype frequencies of the urotensin-II gene (UTS2 polymorphisms, Thr21Met and Ser89Asn, among Turkish patients with migraine. A total of 146 patients with migraine (14 with aura [MA group] and 132 without aura [MO group] were genotyped for Thr21Met and Ser89Asn polymorphisms and compared with 154 age- and sex-matched healthy controls. The UTS2 gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. No significant differences were observed in allele and genotype frequencies for Thr21Met and Ser89Asn polymorphisms between the patients with migraine and control group. Similarly, we did not observe significant differences in allele and genotype frequencies between MA and MO and control group. Moreover, the haplotype analysis showed no association between UTS2 gene haplotypes (MN, MS, TN, and TS and migraine. In summary, Thr21Met and Ser89Asn polymorphisms of the UTS2 gene are not risk factors for migraine in our sample of Turkish migraine patients.

Nisine geholpen met hordentechnologie

NARCIS (Netherlands)

Jong, de L.S.

2001-01-01

Een combinatie van nisine met carvacrol, thymol of carvon leidde tot een synergistische reductie van het aantal levensvatbare cellen van Listeria monocytogenes en Bacillus cereus. Verslag van een promotieonderzoek

Prevalência de metástases oculares em pacientes com doença metastática reconhecida: resultados preliminares Prevalence of ocular metastasis in patients with known metastatic disease: preliminary results

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Zélia Maria da Silva Corrêa

2005-04-01

Full Text Available OBJETIVO: Avaliar de forma prospectiva a prevalência de metástases oculares, tumor primário mais freqüente e tecido ocular comprometido com mais freqüência pela metástase. MÉTODOS: Foram avaliados consecutivamente pacientes internados em Hospital de referência em Oncologia (HSR durante o período de janeiro 2001 a julho de 2002, portadores de neoplasia maligna e metástases sistêmicas. Todos os pacientes foram submetidos a exame oftalmológico completo incluindo oftalmoscopia binocular indireta sob midríase farmacológica usando lente de 28 dioptrias e, em casos suspeitos de neoplasia, realizados ultra-som e angiografia fluorescente. Nos casos de dúvida diagnóstica, os pacientes foram submetidos à biópsia aspirativa com agulha fina. O diagnóstico de tumor ocular metastático foi estabelecido com base nas características clínicas e no resultado dos exames complementares citados. RESULTADOS: Os 100 pacientes estudados apresentaram idades entre 17 a 87 anos, sendo 71 do sexo feminino e 29 do masculino. Houve predomínio de indivíduos brancos (n=88 nesse grupo. Vinte e um pacientes apresentaram lesões oculares sugestivas de metástase. O tumor primário que originou metástase ocular mais freqüentemente foi o câncer de mama (28,6%. Avaliando o tipo tumoral separadamente, o carcinoma de pulmão apresentou maior prevalência de metástase para o olho nesta amostra (71,5%. A coróide foi comprometida em 57% dos casos e a queixa ocular principal desses pacientes foi embaçamento ou diminuição da visão. Não houve diferença na freqüência de acometimento entre olho direito e esquerdo. CONCLUSÃO: A prevalência de metástases oculares em pacientes com neoplasia maligna e doença metastática na amostra estudada pareceu significativa. As neoplasias que provocaram metástase ocular com maior freqüência foram: carcinoma de mama e pulmão, sendo que a coróide foi comprometida com maior freqüência.PURPOSE: To evaluate, in a

A comparison of metabolic syndrome (MetS) risk factors in Filipino women and Filipino American women: a pilot study.

Science.gov (United States)

Ancheta, Irma B; Battie, Cynthia A; Tuason, Teresa; Ancheta, Christine V

2012-01-01

Cardiovascular disease (CVD) is a significant cause of morbidity and mortality in women of Filipino ethnicity. The objective of our work was to determine if metabolic syndrome (MetS), a modifiable CVD risk factor, differs in women as a function of country of residency and to determine if, CVD prevention strategies need to differ for these groups of Filipino women. Data were collected in community-based health screenings for this cross-sectional study. PARTICIPANTS were recruited at places of worship in southeast United States (n=60) and Central Visayas, Philippines (n=56). Prevalence of MetS and its component factors as defined by the International Diabetes Federation criteria. The prevalence of MetS in Filipino women (FW) and Filipino American women (FAW) groups was similar (52% vs 55%, P=.08) although the prevalence of elevated waist circumference was greater for FAW (78% vs 59%, P=.03). Conversely, the percentage of FW women with risk-associated high-density lipoprotein (HDL) levels was higher than the FAW group (84% vs 42%, PFilipino women regardless of the country of residency although the FAW tended to have higher rates of central obesity while the FW tended to have higher rates of risk-associated HDL levels. Further research should examine the cause of these differences in order to develop better cardiovascular screening and intervention strategies.

Met1-linked Ubiquitination in Immune Signalling

DEFF Research Database (Denmark)

Fiil, Berthe Katrine; Gyrd-Hansen, Mads

2014-01-01

Methionine 1-linked ubiquitin chains (Met1-Ub), or linear ubiquitin, has emerged as a central post-translational modification in innate immune signalling. Molecular machinery that assembles, senses and, more recently, disassembles Met1-Ub has been identified, and technical advances have enabled...... identification of physiological substrates for Met1-Ub in response to activation of innate immune receptors. These discoveries have significantly advanced our understanding of how non-degradative ubiquitin modifications control pro-inflammatory responses mediated by nuclear factor κB and mitogen...

47 CFR 54.601 - Eligibility.

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2010-10-01

... teaching hospital or medical school; (ii) Community health center or health center providing health care to migrants; (iii) Local health department or agency; (iv) Community mental health center; (v) Not-for-profit... eligible health care providers; with schools, libraries, and library consortia eligible under Subpart F...

10 CFR 455.71 - Eligibility.

Science.gov (United States)

2010-01-01

... ENERGY ENERGY CONSERVATION GRANT PROGRAMS FOR SCHOOLS AND HOSPITALS AND BUILDINGS OWNED BY UNITS OF LOCAL GOVERNMENT AND PUBLIC CARE INSTITUTIONS Energy Conservation Measures for Schools and Hospitals § 455.71 Eligibility. (a) To be eligible to receive financial assistance for an energy conservation measure, including...

Athletic Eligibility: Right or Privilege?

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Reeves, Kimberly

1998-01-01

Berkeley High School, with the nation's largest sports program, had numerous student eligibility violations in 1997. Many districts are defending the validity of their eligibility practices, as parents push harder for their children's right to compete on school teams. This article covers legal battles, competitive environments, legislative…

7 CFR 1738.16 - Eligible entities.

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2010-01-01

... cooperative, nonprofit, limited dividend or mutual associations, limited liability companies, commercial... or partnerships of individuals are not eligible entities. (2) An entity is not eligible if it serves...

Effects of the BDNF Val66Met polymorphism and met allele load on declarative memory related neural networks

DEFF Research Database (Denmark)

Dodds, Chris M; Henson, Richard N; Suckling, John

2013-01-01

It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activatio...

Hydrogen storage capacity of titanium met-cars

International Nuclear Information System (INIS)

Akman, N; Durgun, E; Yildirim, T; Ciraci, S

2006-01-01

The adsorption of hydrogen molecules on the titanium metallocarbohedryne (met-car) cluster has been investigated by using the first-principles plane wave method. We have found that, while a single Ti atom at the corner can bind up to three hydrogen molecules, a single Ti atom on the surface of the cluster can bind only one hydrogen molecule. Accordingly, a Ti 8 C 12 met-car can bind up to 16 H 2 molecules and hence can be considered as a high-capacity hydrogen storage medium. Strong interaction between two met-car clusters leading to the dimer formation can affect H 2 storage capacity slightly. Increasing the storage capacity by directly inserting H 2 into the met-car or by functionalizing it with an Na atom have been explored. It is found that the insertion of neither an H 2 molecule nor an Na atom could further promote the H 2 storage capacity of a Ti 8 C 12 cluster. We have also tested the stability of the H 2 -adsorbed Ti 8 C 12 met-car with ab initio molecular dynamics calculations which have been carried out at room temperature

10 CFR 455.81 - Eligibility.

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2010-01-01

... ENERGY ENERGY CONSERVATION GRANT PROGRAMS FOR SCHOOLS AND HOSPITALS AND BUILDINGS OWNED BY UNITS OF LOCAL GOVERNMENT AND PUBLIC CARE INSTITUTIONS State Administrative Expenses § 455.81 Eligibility. To be eligible to receive financial assistance for administrative expenses, a State must: (a) Have in place a State Plan...

12 CFR 618.8005 - Eligibility.

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2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Eligibility. 618.8005 Section 618.8005 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM GENERAL PROVISIONS Related Services § 618.8005 Eligibility. (a) Farm Credit Banks and associations may offer related services appropriate to on...

BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses.

Science.gov (United States)

Aas, Monica; Haukvik, Unn K; Djurovic, Srdjan; Bergmann, Ørjan; Athanasiu, Lavinia; Tesli, Martin S; Hellvin, Tone; Steen, Nils Eiel; Agartz, Ingrid; Lorentzen, Steinar; Sundet, Kjetil; Andreassen, Ole A; Melle, Ingrid

2013-10-01

Brain derived neurotrophic factor (BDNF) is important for brain development and plasticity, and here we tested if the functional BDNF val66met variant modulates the association between high levels of childhood abuse, cognitive function, and brain abnormalities in psychoses. 249 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited to the TOP research study (mean±age: 30.7±10.9; gender: 49% males). History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Cognitive function was assessed through a standardized neuropsychological test battery. BDNF val66met was genotyped using standardized procedures. A sub-sample of n=106 Caucasians with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder (mean±age: 32.67±10.85; 49% males) had data on sMRI. Carriers of the Methionine (met) allele exposed to high level of childhood abuse demonstrated significantly poorer cognitive functioning compared to homozygotic Valine (val/val) carriers. Taking in consideration multiple testing, using a more conservative p value, this was still shown for physical abuse and emotional abuse, as well as a trend level for sexual abuse. Further, met carriers exposed to high level of childhood sexual abuse showed reduced right hippocampal volume (r(2)=0.43; p=0.008), and larger right and left lateral ventricles (r(2)=0.37; p=0.002, and r(2)=0.27; p=0.009, respectively). Our findings were independent of age, gender, diagnosis and intracranial volume. Our data demonstrate that in patients with psychoses, met carriers of the BDNF val66met with high level of childhood abuse have more cognitive and brain abnormalities than all other groups. © 2013.

Is neurofeedback effectief bij kinderen met ADHD?

NARCIS (Netherlands)

de Hen, M.H.; Geurts, H.M.

2008-01-01

Kan neurofeedback verantwoord ingezet worden bij de behandeling van kinderen met ADHD? Omdeze vraag te beantwoorden worden zeven recente onderzoeken naar de effectiviteit van neurofeedback bij kinderen met ADHD geanalyseerd. Ondanks dat de resultaten in eerste instantie lijken te suggereren dat

Proef met duurzaam watergebruik in de bollenstreek

NARCIS (Netherlands)

Fliegenthart, F.; Dik, P.E.; Groenendijk, P.

2009-01-01

In 2007 begon in de Wieringermeer een praktijkproef met alternatieve waterbeheersystemen voor de bollenteelt. Met drie verschillende teeltsystemen wordt onderzoek verricht naar zo optimaal mogelijk gebruik van zoet water door recirculatie en hergebruik. Ook loopt onderzoek naar de emissie van

10 CFR 455.91 - Eligibility.

Science.gov (United States)

2010-01-01

... Marketing § 455.91 Eligibility. To be eligible to receive financial assistance for technical assistance, program assistance, and marketing, a State must: (a) Have in place a State Plan approved by DOE which... assistance, and marketing, pursuant to § 455.20(j)(1); (b) Have established a program consistent with this...

Comparative evaluation of 11C-MET PET-CT and MRI for GTV delineation in precision radiotherapy for gliomas

International Nuclear Information System (INIS)

Wang Ru; Qian Liting; Wang Shicun; Liu Wei; Luo Wenguang; Zhang Hongbo; Li Guanghu; Hu Zhigang; Liu Lei

2014-01-01

Objective: To evaluate the difference between MRI and 11 C-MET PET-CT for gross tumor volume (GTV) delineation in the precision radiotherapy for gliomas. Methods: Six patients with a pathologically confirmed diagnosis of gliomas were selected for target delineation. Five physicians in our department were called to delineate the GTV based on the preoperative MRI and 11 C-MET PET-CT images of these patients. The GTVs based on the two methods were compared. Results: There was no significant difference between the GTVs based on MRI and 11 C-MET PET-CT (P=0.917), and their coefficients of variation were also similar (P=0.600). The coincidences of GTVs were different among the patients, with a maximum value of 73.0% and a minimum value of 51.8%. GTV showed no significant difference when defined by different physicians on MRI and PET-CT (P=0.709); the biggest difference was 27.66 cm 3 on PET-CT and 40.37 cm 3 on MRI. Conclusions: The boundaries of gliomas defined on MRI and PET-CT are different. The GTVs delineated by different physicians on MRI and PET-CT are similar, and the biggest difference on PET-CT is smaller than that on MRI, which suggests that 11 C-MET PET-CT is a more direct way for displaying GTV. (authors)

10 CFR 611.102 - Eligible project costs.

Science.gov (United States)

2010-01-01

... Accounting Principles and these costs may be considered by DOE in determining the Borrower's contribution to... 10 Energy 4 2010-01-01 2010-01-01 false Eligible project costs. 611.102 Section 611.102 Energy... PROGRAM Direct Loan Program § 611.102 Eligible project costs. (a) Eligible costs are: (1) Those costs that...

Mars MetNet Mission Pressure and Humidity Devices

Science.gov (United States)

Haukka, H.; Harri, A.-M.; Schmidt, W.; Genzer, M.; Polkko, J.; Kemppinen, O.; Leinonen, J.

2012-09-01

A new kind of planetary exploration mission for Mars is being developed in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission [1] is based on a new semi-hard landing vehicle called MetNet Lander (MNL). MetBaro and MetHumi are part of the scientific payload of the MNL. Main scientific goal of both devices is to measure the meteorological phenomena (pressure and humidity) of the Martian atmosphere and complement the previous Mars mission atmospheric measurements (Viking and Phoenix) for better understanding of the Martian atmospheric conditions.

Aptamers Binding to c-Met Inhibiting Tumor Cell Migration.

Directory of Open Access Journals (Sweden)

Birgit Piater

Full Text Available The human receptor tyrosine kinase c-Met plays an important role in the control of critical cellular processes. Since c-Met is frequently over expressed or deregulated in human malignancies, blocking its activation is of special interest for therapy. In normal conditions, the c-Met receptor is activated by its bivalent ligand hepatocyte growth factor (HGF. Also bivalent antibodies can activate the receptor by cross linking, limiting therapeutic applications. We report the generation of the RNA aptamer CLN64 containing 2'-fluoro pyrimidine modifications by systematic evolution of ligands by exponential enrichment (SELEX. CLN64 and a previously described single-stranded DNA (ssDNA aptamer CLN3 exhibited high specificities and affinities to recombinant and cellular expressed c-Met. Both aptamers effectively inhibited HGF-dependent c-Met activation, signaling and cell migration. We showed that these aptamers did not induce c-Met activation, revealing an advantage over bivalent therapeutic molecules. Both aptamers were shown to bind overlapping epitopes but only CLN3 competed with HGF binding to cMet. In addition to their therapeutic and diagnostic potential, CLN3 and CLN64 aptamers exhibit valuable tools to further understand the structural and functional basis for c-Met activation or inhibition by synthetic ligands and their interplay with HGF binding.

32 CFR 147.31 - Temporary eligibility for access at the top secret levels and temporary eligibility for “Q...

Science.gov (United States)

2010-07-01

... Guidelines for Temporary Access § 147.31 Temporary eligibility for access at the top secret levels and... 32 National Defense 1 2010-07-01 2010-07-01 false Temporary eligibility for access at the top secret levels and temporary eligibility for âQâ access authorization: For someone who is the subject of a...

When Historiography Met Epistemology

Directory of Open Access Journals (Sweden)

Jean-François Stoffel

2017-06-01

Full Text Available Review of Bordoni, Stefano. When historiography met epistemology: Sophisticated histories and philosophies of science in French-speaking countries in the second half of the nineteenth century. Reviewed by Jean-François Stoffel.

32 CFR 147.32 - Temporary eligibility for access at the top secret and SCI levels and temporary eligibility for...

Science.gov (United States)

2010-07-01

... Guidelines for Temporary Access § 147.32 Temporary eligibility for access at the top secret and SCI levels... 32 National Defense 1 2010-07-01 2010-07-01 false Temporary eligibility for access at the top secret and SCI levels and temporary eligibility for âQâ access authorization: For someone who is not the...

Diagnostic accuracy of the WHO clinical staging system for defining eligibility for ART in sub-Saharan Africa: a systematic review and meta-analysis.

Science.gov (United States)

Munthali, Chigomezgo; Taegtmeyer, Miriam; Garner, Paul G; Lalloo, David G; Squire, S Bertel; Corbett, Elizabeth L; Ford, Nathan; MacPherson, Peter

2014-01-01

The World Health Organization (WHO) recommends that HIV-positive adults with CD4 count ≤500 cells/mm(3) initiate antiretroviral therapy (ART). In many countries of sub-Saharan Africa, CD4 count is not widely available or consistently used and instead the WHO clinical staging system is used to determine ART eligibility. However, concerns have been raised regarding its discriminatory ability to identify patients eligible to start ART. We therefore reviewed the accuracy of WHO stage 3 or 4 assessment in identifying ART eligibility according to CD4 count thresholds for ART initiation. We systematically searched PubMed and Global Health databases and conference abstracts using a comprehensive strategy for studies that compared the results of WHO clinical staging with CD4 count thresholds. Studies performed in sub-Saharan Africa and published in English between 1998 and 2013 were eligible for inclusion according to our predefined study protocol. Two authors independently extracted data and assessed methodological quality and risk of bias using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) tool. Summary estimates of sensitivity and specificity were derived for each CD4 count threshold and hierarchical summary receiver operator characteristic curves were plotted. Fifteen studies met the inclusion criteria, including 25,032 participants from 14 countries. Most studies assessed individuals attending ART clinics prior to treatment initiation. WHO clinical stage 3 or 4 disease had a sensitivity of 60% (95% CI: 45-73%, Q=914.26, p<0.001) and specificity of 73% (95% CI: 60-83%, Q=1439.43, p<0.001) for a CD4 threshold of ≤200 cells/mm(3) (11 studies); sensitivity and specificity for a threshold of CD4 count ≤350 cells/mm(3) were 45% (95% CI: 26-66%, Q=1607.31, p<0.001) and 85% (95% CI: 69-93%, Q=896.70, p<0.001), respectively (six studies). For the threshold of CD4 count ≤500 cells/mm(3) sensitivity was 14% (95% CI: 13-15%) and specificity was 95

Classical Hodgkin's lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant.

Science.gov (United States)

Van Den Neste, Eric; Casasnovas, Olivier; André, Marc; Touati, Mohamed; Senecal, Delphine; Edeline, Véronique; Stamatoullas, Aspasia; Fornecker, Luc; Deau, Bénédicte; Gastinne, Thomas; Reman, Oumédaly; Gaillard, Isabelle; Borel, Cécile; Brice, Pauline; Fermé, Christophe

2013-08-01

The Hodgkin's Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin's lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin's lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including (18)fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin's lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

Clinical usefulness of PET in the management of oral cancer. Comparison between FDG-PET and MET-PET

International Nuclear Information System (INIS)

Kitagawa, Yoshimasa; Saitoh, Masaaki; Nakamura, Mikiko

2007-01-01

Inductive chemoradiotherapy has played an important role in preserving organs and functions in patients with oral squamous cell carcinoma (SCC). To determine whether a reduced form of surgery should be performed after chemoradiotherapy, accurate evaluation of residual tumor cells is essential. We investigated the clinical value of positron emission tomography with 18 F labeled fluorodeoxyglucose (FDG-PET) in the management of oral SCCs. Forty-five patients underwent two FDG-PET studies, one prior to and one at 6 weeks after the chemoradiotherapy. Pretreatment FDG-PET was useful in predicting the response to treatment. Posttreatment FDG-PET could evaluate residual viable cells and prognosis. Organ preservation may be feasible based on PET evaluation. Hence FDG-PET is a valuable tool in the treatment of oral cancer. 11 C-Methionine (MET) is another promising tracer for PET that can be used to assess metabolic demand for amino acids in cancer cells. A MET-PET and FDG-PET study was performed during the same period to investigate diagnostic accuracy in 40 oral malignancies. Sensitivity and positive predictive value of MET-PET were 95% and 100%, respectively, and were comparable with those of FDG-PET. Further study is required to determine the diagnostic significance of MET-PET in evaluating response to chemoradiotherapy. (author)

Local hemostatic measures in anticoagulated patients undergoing oral surgery: a systematized literature review

Directory of Open Access Journals (Sweden)

Fábio Wildson Gurgel Costa

2013-01-01

Full Text Available PURPOSE: To conduct a systematized review of the literature about the main local hemostatic measures to control postoperative bleeding in anticoagulated patients. METHODS: A systematized review of literature was performed in the electronic database Medline (PubMed without restriction of the publication date. The eligibility criteria were studies involving maintenance of the anticoagulant therapy, prospective studies, retrospective studies, randomized clinical trials, controlled clinical studies, comparative studies, multicentric studies or case-control studies. Studies discontinuing anticoagulant therapy, case reports, literature reviews, in vitro studies, animal experiments and articles written in language not compatible with the search strategy adopted in this work were excluded. RESULTS: Twenty-four articles that met the adopted eligibility criteria were selected, enrolling 3891 subjects under anticoagulant therapy. A total of 171 cases of hemorrhage was observed. Tranexamic acid was the main local hemostatic measure used to controlling of postoperative bleeding. CONCLUSION: The local hemostatic measures proved to be effective according to previously published studies. Nevertheless, further clinical studies should be conducted to confirm this effectiveness.

Saving energy with paint. Coating with ceramic globules; Energie besparen met verf. Coating met keramische bolletjes

Energy Technology Data Exchange (ETDEWEB)

Willemse, R. [Coateq Coatings, Haarlem (Netherlands)

2011-07-01

The special paint coating of ThermoShield saves energy. The coating consists for 50% of hollow, vacuum ceramic globules. The waterborne damp-open coating with capillary function resists rain water and removes redundant water in case of draught and it reflects sunlight. [Dutch] Met de speciale verfcoating ThermoShield kan energie worden bespaard. De coating bestaat voor 50% uit holle, vacuum getrokken keramische bolletjes. De watergedragen damp-open coating met capillaire werking stoot bij regen water af en voert bij droogte overtollig vocht af en reflecteert zonlicht.

12 CFR 1805.301 - Eligible activities.

Science.gov (United States)

2010-01-01

... Banks and Banking COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS FUND, DEPARTMENT OF THE TREASURY COMMUNITY DEVELOPMENT FINANCIAL INSTITUTIONS PROGRAM Use of Funds/Eligible Activities § 1805.301 Eligible... liquidity, or other means of finance: (a) Commercial facilities that promote revitalization, community...

Groen proceswater: zuivering brouwerijprocesafvalwater met microalgen : Resultaten onderzoek 2013

NARCIS (Netherlands)

Dijk, van W.; Diem, van A.; Doornbusch, P.; Grobben-Gaastra, S.A.; Kleinhout, G.; Kroon, A.; Weide, van der R.Y.

2014-01-01

Afgelopen jaar is de pilot met het kweken van algen met afvalwater van de brouwerijlocatie Zoeterwoude geslaagd. Dit is gedaan in een samenwerkingsverband van Heineken Nederland BV, Algae Food & Fuel en WUR-Acrres. Dit is de eerste inline pilot in de wereld waarbij met LED verlichting op 1000 L

Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity.

Science.gov (United States)

Miraglia del Giudice, E; Santoro, N; Cirillo, G; Raimondo, P; Grandone, A; D'Aniello, A; Di Nardo, M; Perrone, L

2004-03-01

To test whether ghrelin variants could play a role in modulating some aspects of the obese phenotype during childhood. We screened the ghrelin gene in 300 Italian obese children and adolescents (mean age 10.5+/-3.2 y; range 4-19 y) and 200 controls by using the single-strand conformation polymorphism and the restriction fragment length polymoprhism analysis. No mutations were detected with the exception of two previously described polymorphisms, Arg51Gln and Leu72Met. For both variations, allelic frequencies were similar between patients and controls. Interestingly, we showed that the Leu72Met polymorphism was associated with differences in the age at obesity onset. Patients with the Met72 allele became obese earlier than homozygous patients for the wild Leu72 allele. The logrank test comparing the plots of the complement of Kaplan-Meier estimates between the two groups of patients was statistically significant (Pghrelin variations cause the obesity due to single-gene mutations. The Leu72Met polymorphism of the ghrelin gene seems to play a role in anticipating the onset of obesity among children suggesting, therefore, that ghrelin may be involved in the pathophysiology of human adiposity.

Efficacy of c-Met inhibitor for advanced prostate cancer

International Nuclear Information System (INIS)

Tu, William H; Zhu, Chunfang; Clark, Curtis; Christensen, James G; Sun, Zijie

2010-01-01

Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer

Development and validation of a multilateral index to determine economic status in developing countries: the Patient Financial Eligibility Tool (PFET).

Science.gov (United States)

Saba, Joseph; Audureau, Etienne; Bizé, Marion; Koloshuk, Barbara; Ladner, Joël

2013-04-01

The objective was to develop and validate a multilateral index to determine patient ability to pay for medication in low- and middle-income countries. Primary data were collected in 2009 from 117 cancer patients in China, India, Thailand, and Malaysia. The initial tool included income, expenditures, and assets-based items using ad hoc determined brackets. Principal components analysis was performed to determine final weights. Agreement (Kappa) was measured between results from the final tool and from an Impact Survey (IS) conducted after beginning drug therapy to quantify a patient's actual ability to pay in terms of number of drug cycles per year. The authors present the step-by-step methodology employed to develop the tool on a country-by-country basis. Overall Cronbach value was 0.84. Agreement between the Patient Financial Eligibility Tool (PFET) and IS was perfect (equal number of drug cycles) for 58.1% of patients, fair (1 cycle difference) for 29.1%, and poor (>1 cycle) for 12.8%. Overall Kappa was 0.76 (Ptool for determining an individual's ability to pay for medication. Combined with tiered models for patient participation in the cost of medication, it could help to increase access to high-priced products in developing countries.

MET Signaling Mediates Intestinal Crypt-Villus Development, Regeneration, and Adenoma Formation and Is Promoted by Stem Cell CD44 Isoforms.

Science.gov (United States)

Joosten, Sander P J; Zeilstra, Jurrit; van Andel, Harmen; Mijnals, R Clinton; Zaunbrecher, Joost; Duivenvoorden, Annet A M; van de Wetering, Marc; Clevers, Hans; Spaargaren, Marcel; Pals, Steven T

2017-10-01

/Met fl/fl /LacZ mice. Lgr5 Creert2 /Met fl/fl /LacZ mice had impaired regeneration of MET-deficient ISCs. Adenoma organoids stimulated with EGF or HGF expanded to almost twice the size of nonstimulated organoids. MET-deficient adenoma organoids did not respond to HGF stimulation, but did respond to EGF. ISC-specific disruption of Met (Lgr5 Creert2 /Met fl/fl /Apc fl/fl mice) caused a twofold increase in apoptosis in microadenomas, resulting in an approximately 50% reduction of microadenoma numbers and significantly reduced average adenoma size. Total epithelial disruption of Met (Ah Cre /Met fl/fl /Apc fl/+ mice) resulted in an approximate 50% reduction in (micro)adenoma numbers. Intestinal crypts from Cd44 -/- mice did not expand to the same extent as crypts from Cd44 +/+ mice on stimulation with HGF, but had the same response to EGF. The negative effect on HGF-mediated growth was overcome by expression of CD44v4-10, but not by CD44s. Similarly, HGF-mediated expansion of adenoma organoids required CD44v4-10. In studies of intestinal organoid cultures and mice with inducible deletion of MET, we found HGF receptor signaling to regulate intestinal homeostasis and regeneration, as well as adenoma formation. These activities of MET are promoted by the stem cell CD44 isoform CD44v4-10. Our findings provide rationale for targeting signaling via MET and CD44 during anti-EGF receptor therapy of patients with colorectal cancer or in patients resistant to EGF receptor inhibitors. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

28 CFR 92.13 - Program eligibility.

Science.gov (United States)

2010-07-01

... (COPS) Police Recruitment Program Guidelines § 92.13 Program eligibility. (a) Eligible organizations for the Police Recruitment program grant are certified nonprofit organizations that have training and/or... encounter problems throughout the application process; and (4) The program provides retention services to...

Mars MetNet Mission - Martian Atmospheric Observational Post Network

Science.gov (United States)

Hari, Ari-Matti; Haukka, Harri; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Siikonen, Timo; Palin, Matti

2017-04-01

A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested. 1. MetNet Lander The MetNet landing vehicles are using an inflatable entry and descent system instead of rigid heat shields and parachutes as earlier semi-hard landing devices have used. This way the ratio of the payload mass to the overall mass is optimized. The landing impact will burrow the payload container into the Martian soil providing a more favorable thermal environment for the electronics and a suitable orientation of the telescopic boom with external sensors and the radio link antenna. It is planned to deploy several tens of MNLs on the Martian surface operating at least partly at the same time to allow meteorological network science. 2. Strawman Scientific Payload The strawman payload of the two MNL precursor models includes the following instruments: Atmospheric instruments: - MetBaro Pressure device - MetHumi Humidity device - MetTemp Temperature sensors Optical devices: - PanCam Panoramic - MetSIS Solar irradiance sensor with OWLS optical wireless system for data transfer - DS Dust sensor Composition and Structure Devices: Tri-axial magnetometer MOURA Tri-axial System Accelerometer The descent processes dynamic properties are monitored by a special 3-axis

45 CFR 1356.71 - Federal review of the eligibility of children in foster care and the eligibility of foster care...

Science.gov (United States)

2010-10-01

..., DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION ON CHILDREN, YOUTH AND FAMILIES, FOSTER CARE... foster care and the eligibility of foster care providers in title IV-E programs. 1356.71 Section 1356.71... § 1356.71 Federal review of the eligibility of children in foster care and the eligibility of foster care...

76 FR 16354 - Per Diem Payments for the Care Provided to Eligible Veterans Evacuated From a State Home as a...

Science.gov (United States)

2011-03-23

... Payments for the Care Provided to Eligible Veterans Evacuated from a State Home as a Result of an Emergency..., Office of Patient Care Services (114), Veterans Health Administration, Department of Veterans Affairs... for each eligible veteran receiving nursing home care, domiciliary care, and adult day health care in...

HIV treatment eligibility expansion and timely antiretroviral treatment initiation following enrollment in HIV care: A metaregression analysis of programmatic data from 22 countries

Science.gov (United States)

Brazier, Ellen; Yiannoutsos, Constantin; Wools-Kaloustian, Kara; Althoff, Keri; Van Nguyen, Kinh; Sinayobye, Jean d'Amour; Anderegg, Nanina; Ford, Nathan; Wikramanayake, Radhika; Nash, Denis

2018-01-01

Background The effect of antiretroviral treatment (ART) eligibility expansions on patient outcomes, including rates of timely ART initiation among those enrolling in care, has not been assessed on a large scale. In addition, it is not known whether ART eligibility expansions may lead to “crowding out” of sicker patients. Methods and findings We examined changes in timely ART initiation (within 6 months) at the original site of HIV care enrollment after ART eligibility expansions among 284,740 adult ART-naïve patients at 171 International Epidemiology Databases to Evaluate AIDS (IeDEA) network sites in 22 countries where national policies expanding ART eligibility were introduced between 2007 and 2015. Half of the sites included in this analysis were from Southern Africa, one-third were from East Africa, and the remainder were from the Asia-Pacific, Central Africa, North America, and South and Central America regions. The median age of patients enrolling in care at contributing sites was 33.5 years, and the median percentage of female patients at these clinics was 62.5%. We assessed the 6-month cumulative incidence of timely ART initiation (CI-ART) before and after major expansions of ART eligibility (i.e., expansion to treat persons with CD4 ≤ 350 cells/μL [145 sites in 22 countries] and CD4 ≤ 500 cells/μL [152 sites in 15 countries]). Random effects metaregression models were used to estimate absolute changes in CI-ART at each site before and after guideline expansion. The crude pooled estimate of change in CI-ART was 4.3 percentage points (95% confidence interval [CI] 2.6 to 6.1) after ART eligibility expansion to CD4 ≤ 350, from a baseline median CI-ART of 53%; and 15.9 percentage points (pp) (95% CI 14.3 to 17.4) after ART eligibility expansion to CD4 ≤ 500, from a baseline median CI-ART of 57%. The largest increases in CI-ART were observed among those newly eligible for treatment (18.2 pp after expansion to CD4 ≤ 350 and 47.4 pp after

HIV treatment eligibility expansion and timely antiretroviral treatment initiation following enrollment in HIV care: A metaregression analysis of programmatic data from 22 countries.

Directory of Open Access Journals (Sweden)

Olga Tymejczyk

2018-03-01

Full Text Available The effect of antiretroviral treatment (ART eligibility expansions on patient outcomes, including rates of timely ART initiation among those enrolling in care, has not been assessed on a large scale. In addition, it is not known whether ART eligibility expansions may lead to "crowding out" of sicker patients.We examined changes in timely ART initiation (within 6 months at the original site of HIV care enrollment after ART eligibility expansions among 284,740 adult ART-naïve patients at 171 International Epidemiology Databases to Evaluate AIDS (IeDEA network sites in 22 countries where national policies expanding ART eligibility were introduced between 2007 and 2015. Half of the sites included in this analysis were from Southern Africa, one-third were from East Africa, and the remainder were from the Asia-Pacific, Central Africa, North America, and South and Central America regions. The median age of patients enrolling in care at contributing sites was 33.5 years, and the median percentage of female patients at these clinics was 62.5%. We assessed the 6-month cumulative incidence of timely ART initiation (CI-ART before and after major expansions of ART eligibility (i.e., expansion to treat persons with CD4 ≤ 350 cells/μL [145 sites in 22 countries] and CD4 ≤ 500 cells/μL [152 sites in 15 countries]. Random effects metaregression models were used to estimate absolute changes in CI-ART at each site before and after guideline expansion. The crude pooled estimate of change in CI-ART was 4.3 percentage points (95% confidence interval [CI] 2.6 to 6.1 after ART eligibility expansion to CD4 ≤ 350, from a baseline median CI-ART of 53%; and 15.9 percentage points (pp (95% CI 14.3 to 17.4 after ART eligibility expansion to CD4 ≤ 500, from a baseline median CI-ART of 57%. The largest increases in CI-ART were observed among those newly eligible for treatment (18.2 pp after expansion to CD4 ≤ 350 and 47.4 pp after expansion to CD4 ≤ 500, with no

Eligibility of sacubitril-valsartan in a real-world heart failure population: a community-based single-centre study.

Science.gov (United States)

Norberg, Helena; Bergdahl, Ellinor; Lindmark, Krister

2018-04-01

This study aims to investigate the eligibility of the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor (ARNI) with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) study to a real-world heart failure population. Medical records of all heart failure patients living within the catchment area of Umeå University Hospital were reviewed. This district consists of around 150 000 people. Out of 2029 patients with a diagnosis of heart failure, 1924 (95%) had at least one echocardiography performed, and 401 patients had an ejection fraction of ≤35% at their latest examination. The major PARADIGM-HF criteria were applied, and 95 patients fulfilled all enrolment criteria and thus were eligible for sacubitril-valsartan. This corresponds to 5% of the overall heart failure population and 24% of the population with ejection fraction ≤ 35%. The eligible patients were significantly older (73.2 ± 10.3 vs. 63.8 ± 11.5 years), had higher blood pressure (128 ± 17 vs. 122 ± 15 mmHg), had higher heart rate (77 ± 17 vs. 72 ± 12 b.p.m.), and had more atrial fibrillation (51.6% vs. 36.2%) than did the PARADIGM-HF population. Only 24% of our real-world heart failure and reduced ejection fraction population was eligible for sacubitril-valsartan, and the real-world heart failure and reduced ejection fraction patients were significantly older than the PARADIGM-HF population. The lack of data on a majority of the patients that we see in clinical practice is a real problem, and we are limited to extrapolation of results on a slightly different population. This is difficult to address, but perhaps registry-based randomized clinical trials will help to solve this issue. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

30 CFR 875.20 - Contractor eligibility.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Contractor eligibility. 875.20 Section 875.20 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR ABANDONED MINE LAND RECLAMATION CERTIFICATION AND NONCOAL RECLAMATION § 875.20 Contractor eligibility. Every...

30 CFR 874.16 - Contractor eligibility.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Contractor eligibility. 874.16 Section 874.16 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR ABANDONED MINE LAND RECLAMATION GENERAL RECLAMATION REQUIREMENTS § 874.16 Contractor eligibility. To receive...

The Prevalence of Japanese Outpatients with Hypertension Who Meet the Definition of Treatment Resistant Hypertension and Are Eligible for Enrolment in Clinical Trials of Endovascular Ultrasound Renal Denervation.

Science.gov (United States)

Okamura, Keisuke; Shirai, Kazuyuki; Okuda, Tetsu; Urata, Hidenori

2018-01-01

Objective A clinical trial (REQUIRE) was started to investigate the use of an ultrasound renal denervation system in the treatment of resistant hypertension (RHT). We analyzed the prevalence of patients who were eligible for inclusion in this cross-sectional study at the time of screening. Methods Nine-hundred ninety-nine consecutive hypertension (HT) patients who were treated in our hospital as outpatients were classified into the following categories: patients treated with at least 3 types of antihypertensive drugs including diuretic agents who were eligible for enrolment in SYMPLICITY HTN-Japan (SH-J) with an office systolic blood pressure (SBP) of ≥160 mmHg, who were ≤80 years of age, and an estimated glomerular filtration rate (eGFR) of ≥45 mL/min/1.73 m 2 (RHT-S); and patients who were treated similar medications and who were eligible for enrolment in REQUIRE, with an SBP of ≥150 mmHg, ≤75 years of age, and an eGFR of ≥40 mL/min/1.73 m 2 (RHT-R). We investigated the proportion of patients in each category. We also investigated HT patients (1,423 cases) who were enrolled in the Chikushi Anti-Hypertension Trial (CHAT), a research network that includes general practitioners. Results Eleven patients (1.1%) with RHT-S and 18 patients (1.8%) with RHT-R were identified. After the exclusion of patients with secondary HT and a diastolic blood pressure (DBP) of <90 mmHg (applied in REQUIRE), 5 patients (0.5%) with RHT-S and 4 patients (0.4%) with RHT-R remained. In the analysis of the CHAT study, only 2 (0.1%) patients with RHT-R remained. Conclusion The number of eligible patients in the REQUIRE trial was decreased, largely due to the strict age restriction and the new DBP limitation. The prevalence of eligible patients in REQUIRE was estimated to be approximately 0.5 to 0.8 times that in SH-J. Since patient enrollment will be difficult, drastic measures may be required to recruit eligible patients.

Studeren met Hans Rosenberg

NARCIS (Netherlands)

Rutten, R.J.

2001-01-01

Hoe was het om in de jaren zestig te studeren? Laat ik een terugblik ophangen aan een studiemakker, Hans Rosenberg. We vormden samen de sterrekundejaar- gang 1961. Hans studeerde af in 1966 met hoofdvak wiskunde, promoveerde op radiostralingsprocessen in de zonnecorona in 1973, verliet de

Higher Levels of c-Met Expression and Phosphorylation Identify Cell Lines With Increased Sensitivity to AMG-458, a Novel Selective c-Met Inhibitor With Radiosensitizing Effects

International Nuclear Information System (INIS)

Li Bo; Torossian, Artour; Sun, Yunguang; Du, Ruihong; Dicker, Adam P.; Lu Bo

2012-01-01

Purpose: c-Met is overexpressed in some non-small cell lung cancer (NSCLC) cell lines and tissues. Cell lines with higher levels of c-Met expression and phosphorylation depend on this receptor for survival. We studied the effects of AMG-458 on 2 NSCLC cell lines. Methods and Materials: 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium assays assessed the sensitivities of the cells to AMG-458. Clonogenic survival assays illustrated the radiosensitizing effects of AMG-458. Western blot for cleaved caspase 3 measured apoptosis. Immunoblotting for c-Met, phospho-Met (p-Met), Akt/p-Akt, and Erk/p-Erk was performed to observe downstream signaling. Results: AMG-458 enhanced radiosensitivity in H441 but not in A549. H441 showed constitutive phosphorylation of c-Met. A549 expressed low levels of c-Met, which were phosphorylated only in the presence of exogenous hepatocyte growth factor. The combination of radiation therapy and AMG-458 treatment was found to synergistically increase apoptosis in the H441 cell line but not in A549. Radiation therapy, AMG-458, and combination treatment were found to reduce p-Akt and p-Erk levels in H441 but not in A549. H441 became less sensitive to AMG-458 after small interfering RNA knockdown of c-Met; there was no change in A549. After overexpression of c-Met, A549 became more sensitive, while H441 became less sensitive to AMG-458. Conclusions: AMG-458 was more effective in cells that expressed higher levels of c-Met/p-Met, suggesting that higher levels of c-Met and p-Met in NSCLC tissue may classify a subset of tumors that are more sensitive to molecular therapies against this receptor.

Klimaatverandering en de stadsboom (interview met Jitze Kopinga)

NARCIS (Netherlands)

Bennink, P.; Kopinga, J.

2010-01-01

Bomen in de stad staan vaak op warme plaatsen met een gebrekkige waterhuishouding. Volgens het KNMI zal Nederland in de toekomst steeds vaker met hitte en droogte te maken hebben. Wat betekent dat voor onze stadsbomen?

The prevalence and characteristics of metabolic syndrome in patients with vertigo.

Science.gov (United States)

Yamanaka, Toshiaki; Fukuda, Takehiko; Shirota, Shiho; Sawai, Yachiyo; Murai, Takayuki; Fujita, Nobuya; Hosoi, Hiroshi

2013-01-01

Metabolic syndrome (MetS) is a condition that increases the risk of coronary artery disease and cerebral infarction. We determined the prevalence of MetS in vertigo patients and clinically investigated the association between MetS and vertigo. Case-control study. The subjects were 333 patients, including 107 males and 226 females, who presented with vertigo as a primary symptom. MetS was diagnosed according to the International Diabetes Federation definition, which is based on waist circumference, blood serum levels, and blood pressure. MetS was detected in 53 (15.9%) of 333 vertigo patients, including 24 males (22.4%) and 29 females (12.8%); i.e., the frequency of MetS was significantly higher among the male patients than the female patients. The overall prevalence of MetS (15.9%) among vertigo patients did not differ from that observed among general adults in previous Japanese surveillance studies; however, MetS was significantly more common among the vertigo patients in males than general adult males. The prevalence of MetS was also examined in five types of vertigo, Concomitant MetS was noted in many males with vertebrobasilar insufficiency (VBI) and isolated vertigo of unknown etiology. It was suggested that MetS is involved in the development of vertigo in males. MetS might be a risk factor for vascular vertigo such as VBI in males. The high frequency of MetS among males with vertigo of unknown etiology suggested that the pathogenesis of metabolic syndrome is involved in this type of isolated vertigo.

The Prevalence and Characteristics of Metabolic Syndrome in Patients with Vertigo

Science.gov (United States)

Yamanaka, Toshiaki; Fukuda, Takehiko; Shirota, Shiho; Sawai, Yachiyo; Murai, Takayuki; Fujita, Nobuya; Hosoi, Hiroshi

2013-01-01

Objectives/Hypothesis Metabolic syndrome (MetS) is a condition that increases the risk of coronary artery disease and cerebral infarction. We determined the prevalence of MetS in vertigo patients and clinically investigated the association between MetS and vertigo. Study Design Case-control study Methods The subjects were 333 patients, including 107 males and 226 females, who presented with vertigo as a primary symptom. MetS was diagnosed according to the International Diabetes Federation definition, which is based on waist circumference, blood serum levels, and blood pressure. Results MetS was detected in 53 (15.9%) of 333 vertigo patients, including 24 males (22.4%) and 29 females (12.8%); i.e., the frequency of MetS was significantly higher among the male patients than the female patients. The overall prevalence of MetS (15.9%) among vertigo patients did not differ from that observed among general adults in previous Japanese surveillance studies; however, MetS was significantly more common among the vertigo patients in males than general adult males. The prevalence of MetS was also examined in five types of vertigo, Concomitant MetS was noted in many males with vertebrobasilar insufficiency (VBI) and isolated vertigo of unknown etiology. Conclusion It was suggested that MetS is involved in the development of vertigo in males. MetS might be a risk factor for vascular vertigo such as VBI in males. The high frequency of MetS among males with vertigo of unknown etiology suggested that the pathogenesis of metabolic syndrome is involved in this type of isolated vertigo. PMID:24312461

7 CFR 1499.3 - Eligibility determination.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Eligibility determination. 1499.3 Section 1499.3 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT... determination. (a) An entity will be eligible to become a participant only after FAS determines that the entity...

7 CFR 4280.122 - Project eligibility.

Science.gov (United States)

2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Project eligibility. 4280.122 Section 4280.122 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND... Efficiency Improvements Program Section B. Guaranteed Loans § 4280.122 Project eligibility. For a project to...

23 CFR 810.102 - Eligible projects.

Science.gov (United States)

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Eligible projects. 810.102 Section 810.102 Highways... SPECIAL USE HIGHWAY PROJECTS Highway Public Transportation Projects and Special Use Highway Facilities § 810.102 Eligible projects. Under this subpart the Federal Highway Administrator may approve on any...

28 CFR 104.32 - Eligibility review.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Eligibility review. 104.32 Section 104.32 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) SEPTEMBER 11TH VICTIM COMPENSATION FUND OF 2001 Claim Intake, Assistance, and Review Procedures § 104.32 Eligibility review. Any claimant deemed...

The eligibility of the natural gas consumers

International Nuclear Information System (INIS)

2004-07-01

The eligible consumers are allowed to chose freely their natural gas producers and negotiate the prices and the supply modalities. In this context this information paper presents the legislative and regulation framework of the natural gas consumers eligibility, a definition of the possible eligible consumers and a list at the 30 january 2004. It provides also recommendations and answers to the more often asked questions on the administrative procedures and the contracts. (A.L.B.)

Evaluating depressive symptoms in mania: a naturalistic study of patients with bipolar disorder

Science.gov (United States)

Young, Allan H; Eberhard, Jonas

2015-01-01

Objective This study aimed to evaluate patients with bipolar I disorder (BD-I) who have mania with depressive symptoms and who meet the new “with mixed features” specifier of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). Method This prospective, multinational, naturalistic study surveyed psychiatrists and their patients with BD-I from October 2013 to March 2014. Eligible patients had BD-I, had a (current) manic episode, and had experienced onset of a manic episode within the previous 3 months. Psychiatrists provided patient information on depressive symptoms (DSM-5 criteria); symptoms of anxiety, irritability, and agitation; suicide attempts; and physician satisfaction with treatment response. Data were stratified according to whether patients met the criteria for the BD-I “with mixed features” specifier of DSM-5 (≥3 depressive symptoms) or not, and characteristics were compared between the two subgroups. Patients also self-reported on depressive symptoms using the Mini-International Neuropsychiatric Interview module questionnaire. Results Overall, 34% of 1,035 patients met the criteria for BD-I “with mixed features,” exhibiting ≥3 depressive symptoms during their current manic episode. This correlated with the matched patient self-reports of depressive symptoms. During their current manic episode, BD-I patients “with mixed features” had more severe symptoms of anxiety, irritability, and agitation (average composite severity score of 4.1 vs 3.4), a higher incidence of suicide attempts (38% vs 9%), and more physician dissatisfaction with treatment response (22% vs 14%), compared to patients with 0–2 depressive symptoms (all P<0.05). Conclusion This study found that patients with BD-I “with mixed features” (ie, ≥3 depressive symptoms during a manic episode), suffered, on average, from a greater burden of disease than patients with pure mania. Improved identification of these patients may help to optimize

MetNet Network Mission for Martian Atmospheric Investigations

Science.gov (United States)

Harri, A.-M.; Alexashkin, S.; Arrugeo, I.; Schmidt, W.; Vazquez, L.; Genzer, M.; Haukka, H.

2014-07-01

A new kind of planetary exploration mission for Mars called MetNet is being developed for martian atmospheric investigations. The eventual scope of the MetNet Mission is to deploy tens of small landers on the martian surface.

Requirements to be met by the operation manual

International Nuclear Information System (INIS)

1981-03-01

The rule applies to the contents and the lay-out of the operating manual for stationary nuclear power plants. The draft contains: 1. General requirement to be met by the contents of the operating manual. The operating manual to be arranged in 4 parts (part 1: internal rules and regulations; part 2: operation overall plant; part 3: incidents; part 4: operation systems). Safety specifications to be included in the manual, the exemption being the system of technical documentation. 2. General requirements to be met by the lay-out of the operating manual. Comprehensibility; legibility; structure and subdivisions; arrangement of the instructions and design of the manuals cover. 3. Requirements to be met by part 1. Defining the various internal rules and regulations (personnel management); rules and regulations concerning inspections and shift work; maintenance and repair; radiation protection; guard duty and admission; alarm; fire protection; first aid. 4. Requirements to be met by part 2. Provisions and operational limitations; limit values important from the point of view of safety; normal operation; anomalous operation; in-service inspections. 6. Requirements to be met by part 3. 7. Annex: Rules, regulations and stipulations mentioned in the rule draft. (orig.)

7 CFR 249.6 - Participant eligibility.

Science.gov (United States)

2010-01-01

... participation in the SFMNP in a language other than English, reasonable steps must be taken to provide this... have provided for my eligibility determination is correct, to the best of my knowledge. This... solely because of lack of sufficient funding to provide SFMNP benefits to all eligible applicants. (5...

7 CFR 1786.99 - Eligibility criteria.

Science.gov (United States)

2010-01-01

... Eligibility criteria. To be eligible to prepay RUS Notes at the Discounted Present Value, a borrower must... the RUS Notes between the amount outstanding on the RUS Note and the Discounted Present Value of the... a substantial portion of its assets, whether now owned or hereafter acquired. Notwithstanding the...

24 CFR 954.102 - Eligible applicants.

Science.gov (United States)

2010-04-01

... eligible recipient under Title I of the Indian Self-Determination and Education Assistance Act (25 U.S.C. 450). Eligible recipients under the Indian Self-Determination and Education Assistance Act are... Indian Self-Determination and Education Assistance Act may apply for funds on behalf of any Indian Tribe...

Dimensionering van de Uniqfill chemischer wasser met lamellen

NARCIS (Netherlands)

Starmans, D.A.J.

2006-01-01

In dit rapport wordt een eerste aanzet gegeven tot de modellering van een kruisstroom chemische wasser met lamellen. Met behulp van bestaande metingen is de stofoverdrachtscoëfficiënt afgeschat, waarna scenario's voor nieuwe wassers doorgerekend konden worden.

45 CFR 233.51 - Eligibility of sponsored aliens.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false Eligibility of sponsored aliens. 233.51 Section... CONDITIONS OF ELIGIBILITY IN FINANCIAL ASSISTANCE PROGRAMS § 233.51 Eligibility of sponsored aliens... affidavit(s) of support or similar agreement on behalf of an alien (who is not the child of the sponsor or...

50 CFR 296.4 - Claims eligible for compensation.

Science.gov (United States)

2010-10-01

... compensation. (a) Claimants. Damage or loss eligible for Fund compensation must be suffered by a commercial fisherman. (b) Damage or loss of fishing gear. Damage or loss is eligible for Fund compensation if it was... is not eligible for Fund compensation: (1) If the damage or loss was caused by the negligence or...

Evaluating depressive symptoms in mania: a naturalistic study of patients with bipolar disorder.

Science.gov (United States)

Young, Allan H; Eberhard, Jonas

2015-01-01

This study aimed to evaluate patients with bipolar I disorder (BD-I) who have mania with depressive symptoms and who meet the new "with mixed features" specifier of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). This prospective, multinational, naturalistic study surveyed psychiatrists and their patients with BD-I from October 2013 to March 2014. Eligible patients had BD-I, had a (current) manic episode, and had experienced onset of a manic episode within the previous 3 months. Psychiatrists provided patient information on depressive symptoms (DSM-5 criteria); symptoms of anxiety, irritability, and agitation; suicide attempts; and physician satisfaction with treatment response. Data were stratified according to whether patients met the criteria for the BD-I "with mixed features" specifier of DSM-5 (≥3 depressive symptoms) or not, and characteristics were compared between the two subgroups. Patients also self-reported on depressive symptoms using the Mini-International Neuropsychiatric Interview module questionnaire. Overall, 34% of 1,035 patients met the criteria for BD-I "with mixed features," exhibiting ≥3 depressive symptoms during their current manic episode. This correlated with the matched patient self-reports of depressive symptoms. During their current manic episode, BD-I patients "with mixed features" had more severe symptoms of anxiety, irritability, and agitation (average composite severity score of 4.1 vs 3.4), a higher incidence of suicide attempts (38% vs 9%), and more physician dissatisfaction with treatment response (22% vs 14%), compared to patients with 0-2 depressive symptoms (all Pmixed features" (ie, ≥3 depressive symptoms during a manic episode), suffered, on average, from a greater burden of disease than patients with pure mania. Improved identification of these patients may help to optimize treatment outcomes.

Peripheral blood progenitor cell transplantation mobilised by r-metHuG-CSF (filgrastim); a less costly alternative to autologous bone marrow transplantation

NARCIS (Netherlands)

C.A. Uyl-de Groot (Carin); D.J. Richel (Dirk); F.F.H. Rutten (Frans)

1994-01-01

textabstractIn a retrospective study, we calculated the treatment costs of 63 patients who received either autologous bone marrow transplantation (ABMT) with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) (filgrastim) (n=13) or without r-metHuG-CSF (n=22) or altenatively,

Eligibility for interventions, co-occurrence and risk factors for unhealthy behaviours in patients consulting for routine primary care: results from the Pre-Empt study

OpenAIRE

Randell, Elizabeth; Pickles, Timothy; Simpson, Sharon A.; Spanou, Clio; McCambridge, Jim; Hood, Kerenza; Butler, Christopher C.

2015-01-01

Background:\\ud Smoking, excessive drinking, lack of exercise and a poor diet remain key causes of premature morbidity and mortality globally, yet it is not clear what proportion of patients attending for routine primary care are eligible for interventions about these behaviours, the extent to which they co-occur within individuals, and which individuals are at greatest risk for multiple unhealthy behaviours. The aim of the trial was to examine ‘intervention eligibility’ and co-occurrence of t...

Mindfulness voor volwassenen met een licht verstandelijke beperking

NARCIS (Netherlands)

Punt, M.; Helmond, P.E.; Meirmans, M.; Otten, R.; Speckens, A.E.M.

2016-01-01

Mensen met een licht verstandelijke beperking (LVB) hebben veelal te maken met een opeenstapeling van verschillende biologische, psychologische en sociale factoren, waardoor zij vijf tot zes keer meer kans hebben op het ontwikkelen van psychopathologie dan normaal begaafden (Allen, 2008; Buckles,

Anxiolytic effect of music exposure on BDNFMet/Met transgenic mice.

Science.gov (United States)

Li, Wen-Jing; Yu, Hui; Yang, Jian-Min; Gao, Jing; Jiang, Hong; Feng, Min; Zhao, Yu-Xia; Chen, Zhe-Yu

2010-08-06

Brain-derived neurotrophic factor (BDNF) has been reported to play important roles in the modulation of anxiety, mood stabilizers, and pathophysiology of affective disorders. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (Val66Met) has been found to be associated with depression and anxiety disorders. The humanized BDNF(Met/Met) knock-in transgenic mice exhibited increased anxiety-related behaviors that were unresponsive to serotonin reuptake inhibitors, fluoxetine. Music is known to be able to elicit emotional changes, including anxiolytic effects. In this study, we found that music treatment could significantly decrease anxiety state in BDNF(Met/Met) mice, but not in BDNF(+/)(-), mice compared with white noise exposure in open field and elevated plus maze test. Moreover, in contrast to white noise exposure, BDNF expression levels in the prefrontal cortex (PFC), amygdala and hippocampus were significantly increased in music-exposed adult BDNF(Met/Met) mice. However, music treatment could not upregulate BDNF levels in the PFC, amygdala, and hippocampus in BDNF(+/)(-) mice, which suggests the essential role of BDNF in the anxiolytic effect of music. Together, our results imply that music may provide an effective therapeutic intervention for anxiety disorders in humans with this genetic BDNF(Met) variant. Copyright 2010 Elsevier B.V. All rights reserved.

The prevalence and characteristics of metabolic syndrome in patients with vertigo.

Directory of Open Access Journals (Sweden)

Toshiaki Yamanaka

Full Text Available OBJECTIVES/HYPOTHESIS: Metabolic syndrome (MetS is a condition that increases the risk of coronary artery disease and cerebral infarction. We determined the prevalence of MetS in vertigo patients and clinically investigated the association between MetS and vertigo. STUDY DESIGN: Case-control study. METHODS: The subjects were 333 patients, including 107 males and 226 females, who presented with vertigo as a primary symptom. MetS was diagnosed according to the International Diabetes Federation definition, which is based on waist circumference, blood serum levels, and blood pressure. RESULTS: MetS was detected in 53 (15.9% of 333 vertigo patients, including 24 males (22.4% and 29 females (12.8%; i.e., the frequency of MetS was significantly higher among the male patients than the female patients. The overall prevalence of MetS (15.9% among vertigo patients did not differ from that observed among general adults in previous Japanese surveillance studies; however, MetS was significantly more common among the vertigo patients in males than general adult males. The prevalence of MetS was also examined in five types of vertigo, Concomitant MetS was noted in many males with vertebrobasilar insufficiency (VBI and isolated vertigo of unknown etiology. CONCLUSION: It was suggested that MetS is involved in the development of vertigo in males. MetS might be a risk factor for vascular vertigo such as VBI in males. The high frequency of MetS among males with vertigo of unknown etiology suggested that the pathogenesis of metabolic syndrome is involved in this type of isolated vertigo.

Strengths, Limitations, and Geographical Discrepancies in the Eligibility Criteria for Sport Participation in Young Patients With Congenital Heart Disease.

Science.gov (United States)

Cantinotti, Massimiliano; Giordano, Raffaele; Assanta, Nadia; Murzi, Bruno; Melo, Manuel; Franchi, Eliana; Crocetti, Maura; Iervasi, Giorgio; Kutty, Shelby

2017-07-21

Benefits of physical activity has been shown in children with congenital heart disease (CHD). In several forms of CHD, the risk of sudden death remains a major concern both for parents and clinicians, who in turn will have to consider the risk-benefit ratio of sport participation versus restriction. A literature search was performed within the National Library of Medicine using the keywords: Sport, CHD, and Eligibility. The search was further refined by adding the keywords: Children, Adult, and Criteria. Fifteen published studies evaluating sport eligibility criteria in CHD were included. Seven documents from various scientific societies have been published in the past decade but which of them should be adopted remains unclear. Our research highlighted accuracy and consistency of the latest documents; however, differences have emerged between the US and European recommendations. Eligibility criteria were consistent between countries for simple congenital heart defects, whereas there are discrepancies for borderline conditions including moderate valvular lesions and mild or moderate residual defects after CHD repair. Furthermore, some of the more severe defects were not evaluated. Multiple recommendations have been made for the same CHD, and cut-off values used to define disease severity have varied. Published eligibility criteria have mainly focused on competitive sports. Little attention was paid to recreational activities, and the psychosocial consequences of activity restriction were seldom evaluated. Comprehensive consensus recommendations for sport eligibility evaluating all CHD types and stages of repair are needed. These should include competitive and recreational activities, use standardized classifications to grade disease severity, and address the consequences of restriction.

Preproghrelin Leu72Met polymorphism in obese Korean children.

Science.gov (United States)

Jo, Dae-Sun; Kim, Se-Lim; Kim, Sun-Young; Hwang, Pyoung Han; Lee, Kee-Hyoung; Lee, Dae-Yeol

2005-11-01

Ghrelin is a novel gut-brain peptide that has somatotropic, orexigenic, and adipogenic effects. We examined the preproghrelin Leu72Met polymorphism in 222 obese Korean children to determine whether it is associated with obesity. The frequencies of the Leu72Met polymorphism were 29.3% in obese, 32.3% in overweight, and 32.5% in lean Korean children. No significant difference was found between Met72 carrier and non-carrier obese children with respect to BMI, total body fat, serum triglycerides, total cholesterol, or LDL-cholesterol levels. Our data suggest that the preproghrelin Leu72Met polymorphism is not associated with obesity in children.

36 CFR 64.5 - Eligible projects.

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Eligible projects. 64.5... Eligible projects. (a) Abandoned railroad projects will be for recreation and/or conservation purposes including the acquisition of the rights-of-way involved and will be sponsored by a project applicant who has...

23 CFR 650.703 - Eligible projects.

Science.gov (United States)

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Eligible projects. 650.703 Section 650.703 Highways..., STRUCTURES, AND HYDRAULICS Discretionary Bridge Candidate Rating Factor § 650.703 Eligible projects. (a..., provided that the total project cost for a discretionary bridge candidate is at least $10 million or twice...

Effect of MET on formation and vigor of wheat roots

International Nuclear Information System (INIS)

Wang Bingkui; Jin Ziyu; Zhao Miaozhen; Zhao Yanshen

1993-01-01

Effect of MET on the formation and vigor of roots of wheat seedlings were studied. The results showed that 50 ∼ 200 ppm MET inhibited vertical elongation of roots, increased root, shoot ratio and enhanced the formation and vigor of roots. But MET had no effect on the dry weight of roots. The activity of peroxidase was decreased and the proportion of assimilates in roots was increased by MET treatment compared with the control

The elderly patient with spinal injury: treat or transfer?

Science.gov (United States)

Barmparas, Galinos; Cooper, Zara; Haider, Adil H; Havens, Joaquim M; Askari, Reza; Salim, Ali

2016-05-01

The purpose of this investigation was to delineate whether elderly patients with spinal injuries benefit from transfers to higher level trauma centers. Retrospective review of the National Trauma Data Bank 2007 to 2011, including patients > 65 (y) with any spinal fracture and/or spinal cord injury from a blunt mechanism. Patients who were transferred to level I and II centers from other facilities were compared to those admitted and received their definitive treatment at level III or other centers. Of 3,313,117 eligible patients, 43,637 (1.3%) met inclusion criteria: 19,588 (44.9%) were transferred to level I-II centers, and 24,049 (55.1%) received definitive treatment at level III or other centers. Most of the patients (95.8%) had a spinal fracture without a spinal cord injury. Transferred patients were more likely to require an intensive care unit admission (48.5% versus 36.0%, P spinal cord injury (22.3% versus 21.0%, P elderly patients with spinal injuries to higher level trauma centers is not associated with improved survival. Future studies should explore the justifications used for these transfers and focus on other outcome measures such as functional status to determine the potential benefit from such practices. Copyright © 2016 Elsevier Inc. All rights reserved.

7 CFR 632.13 - Eligible lands and water.

Science.gov (United States)

2010-01-01

... 7 Agriculture 6 2010-01-01 2010-01-01 false Eligible lands and water. 632.13 Section 632.13... lands and water. Lands and water eligible for reclamation are those that were mined for coal or were... lands and water are not eligible if: (a) There is continuing reclamation responsibility on the part of a...

The 20S proteasome splicing activity discovered by SpliceMet.

Directory of Open Access Journals (Sweden)

Juliane Liepe

2010-06-01

Full Text Available The identification of proteasome-generated spliced peptides (PSP revealed a new unpredicted activity of the major cellular protease. However, so far characterization of PSP was entirely dependent on the availability of patient-derived cytotoxic CD8+ T lymphocytes (CTL thus preventing a systematic investigation of proteasome-catalyzed peptide splicing (PCPS. For an unrestricted PSP identification we here developed SpliceMet, combining the computer-based algorithm ProteaJ with in vitro proteasomal degradation assays and mass spectrometry. By applying SpliceMet for the analysis of proteasomal processing products of four different substrate polypeptides, derived from human tumor as well as viral antigens, we identified fifteen new spliced peptides generated by PCPS either by cis or from two separate substrate molecules, i.e., by trans splicing. Our data suggest that 20S proteasomes represent a molecular machine that, due to its catalytic and structural properties, facilitates the generation of spliced peptides, thereby providing a pool of qualitatively new peptides from which functionally relevant products may be selected.

Psychological morbidities in adolescent and young adult blood cancer patients during curative-intent therapy and early survivorship.

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Muffly, Lori S; Hlubocky, Fay J; Khan, Niloufer; Wroblewski, Kristen; Breitenbach, Katherine; Gomez, Joseline; McNeer, Jennifer L; Stock, Wendy; Daugherty, Christopher K

2016-03-15

Adolescents and young adults (AYAs) with cancer face unique psychosocial challenges. This pilot study was aimed at describing the prevalence of psychological morbidities among AYAs with hematologic malignancies during curative-intent therapy and early survivorship and at examining provider perceptions of psychological morbidities in their AYA patients. Patients aged 15 to 39 years with acute leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma who were undergoing curative-intent therapy (on-treatment group) or were in remission within 2 years of therapy completion (early survivors) underwent a semistructured interview that incorporated measures of anxiety, depression, and posttraumatic stress (PTS). A subset of providers (n = 15) concomitantly completed a survey for each of the first 30 patients enrolled that evaluated their perception of each subject's anxiety, depression, and PTS. Sixty-one of 77 eligible AYAs participated. The median age at diagnosis was 26 years (range, 15-39 years), 64% were male, and 59% were non-Hispanic white. On-treatment demographics differed significantly from early-survivor demographics only in the median time from diagnosis to interview. Among the 61 evaluable AYAs, 23% met the criteria for anxiety, 28% met the criteria for depression, and 13% met the criteria for PTS; 46% demonstrated PTS symptomatology. Thirty-nine percent were impaired in 1 or more psychological domains. Psychological impairments were as frequent among early survivors as AYAs on treatment. Provider perceptions did not significantly correlate with patient survey results. AYAs with hematologic malignancies experience substantial psychological morbidities while they are undergoing therapy and during early survivorship, with more than one-third of the patients included in this study meeting the criteria for anxiety, depression, or traumatic stress. This psychological burden may not be accurately identified by their oncology providers. © 2016 American Cancer Society.

Partial spleen embolization reduces the risk of portal hypertension-induced upper gastrointestinal bleeding in patients not eligible for TIPS implantation.

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Buechter, Matthias; Kahraman, Alisan; Manka, Paul; Gerken, Guido; Dechêne, Alexander; Canbay, Ali; Wetter, Axel; Umutlu, Lale; Theysohn, Jens M

2017-01-01

Upper gastrointestinal bleeding (UGIB) is a severe and life-threatening complication among patients with portal hypertension (PH). Covered transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for patients with refractory or recurrent UGIB despite pharmacological and endoscopic therapy. In some patients, TIPS implantation is not possible due to co-morbidity or vascular disorders. Spleen embolization (SE) may be a promising alternative in this setting. We retrospectively analyzed 9 patients with PH-induced UGIB who underwent partial SE between 2012 and 2016. All patients met the following criteria: (i) upper gastrointestinal hemorrhage with primary or secondary failure of endoscopic interventions and (ii) TIPS implantation not possible. Each patient was followed for at least 6 months after embolization. Five patients (56%) suffered from cirrhotic PH, 4 patients (44%) from non-cirrhotic PH. UGIB occured in terms of refractory hemorrhage from gastric varices (3/9; 33%), hemorrhage from esophageal varices (3/9; 33%), and finally, hemorrhage from portal-hypertensive gastropathy (3/9; 33%). None of the patients treated with partial SE experienced re-bleeding episodes or required blood transfusions during a total follow-up time of 159 months, including both patients with cirrhotic- and non-cirrhotic PH. Partial SE, as a minimally invasive intervention with low procedure-associated complications, may be a valuable alternative for patients with recurrent PH-induced UGIB refractory to standard therapy.

Krüppel-like factor 4 promotes c-Met amplification-mediated gefitinib resistance in non-small-cell lung cancer.

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Feng, Wei; Xie, Qianyi; Liu, Suo; Ji, Ying; Li, Chunyun; Wang, Chunle; Jin, Longyu

2018-06-01

Gefitinib has been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met-overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells by inhibiting the expression of apoptosis-related proteins under gefitinib treatment and activating the c-Met/Akt signaling pathway by decreasing the inhibition of β-catenin on phosphorylation of c-Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c-Met overexpression. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Patient factors associated with lung transplant referral and waitlist for patients with cystic fibrosis and pulmonary fibrosis.

Science.gov (United States)

Liu, Yuan; Vela, Monica; Rudakevych, Tanya; Wigfield, Christopher; Garrity, Edward; Saunders, Milda R

2017-03-01

Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to fibrosis (CF) and pulmonary fibrosis (PF). We analyzed the times from transplant eligibility to referral, work-up and waitlisting using Kaplan-Meier curves and log-rank tests. Overall, the referral rate for transplant-eligible patients was 64%. Of those referred, approximately 36% reach the lung transplant waitlist. Referred CF patients were significantly more likely to reach the transplant waitlist than PF patients (CF 60% vs PF 22%, p < 0.05). In addition, CF patients had a shorter wait from transplant eligibility to waitlist than PF patients (329 vs 2,369 days, respectively [25th percentile], p < 0.05). Patients with PF and CF both faced delays from eligibility to referral and waitlist. Quality improvement efforts are needed to better identify and refer appropriate patients for lung transplant evaluation. Targeted interventions may facilitate more efficient evaluation completion and waitlist appearance. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Deelname aan de samenleving van mensen met een beperking: participatiemonitor 2007.

NARCIS (Netherlands)

Hoogen, P. van den; Cardol, M.; Speet, M.; Spreeuwenberg, P.; Rijken, M.

2008-01-01

Hoe doen mensen met een beperking mee in de maatschappij? Mensen met een lichamelijke beperking wonen en werken meestal net als iedereen, en ook zij zijn niet altijd tevreden met hun werk. Mensen met een verstandelijke beperking wonen en werken vaak in een speciale omgeving. Het overheidsbeleid

{sup 89}Zr-Onartuzumab PET imaging of c-MET receptor dynamics

Energy Technology Data Exchange (ETDEWEB)

Pool, Martin; Kol, Arjan; Giesen, Danique; Vries, Elisabeth G.E. de [University of Groningen, Department of Medical Oncology, University Medical Center Groningen, Groningen (Netherlands); Terwisscha van Scheltinga, Anton G.T. [University of Groningen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen (Netherlands); Lub-de Hooge, Marjolijn N. [University of Groningen, Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen (Netherlands); University of Groningen, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen (Netherlands)

2017-08-15

c-MET and its ligand hepatocyte growth factor are often dysregulated in human cancers. Dynamic changes in c-MET expression occur and might predict drug efficacy or emergence of resistance. Noninvasive visualization of c-MET dynamics could therefore potentially guide c-MET-directed therapies. We investigated the feasibility of {sup 89}Zr-labelled one-armed c-MET antibody onartuzumab PET for detecting relevant changes in c-MET levels induced by c-MET-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib resistance or heat shock protein-90 (HSP90) inhibitor NVP-AUY-922 treatment in human non-small-cell lung cancer (NSCLC) xenografts. In vitro membrane c-MET levels were determined by flow cytometry. HCC827ErlRes, an erlotinib-resistant clone with c-MET upregulation, was generated from the exon-19 EGFR-mutant human NSCLC cell line HCC827. Mice bearing HCC827 and HCC827ErlRes tumours in opposite flanks underwent {sup 89}Zr-onartuzumab PET scans. The HCC827-xenografted mice underwent {sup 89}Zr-onartuzumab PET scans before treatment and while receiving biweekly intraperitoneal injections of 100 mg/kg NVP-AUY-922 or vehicle. Ex vivo, tumour c-MET immunohistochemistry was correlated with the imaging results. In vitro, membrane c-MET was upregulated in HCC827ErlRes tumours by 213 ± 44% in relation to the level in HCC827 tumours, while c-MET was downregulated by 69 ± 9% in HCC827 tumours following treatment with NVP-AUY-922. In vivo, {sup 89}Zr-onartuzumab uptake was 26% higher (P < 0.05) in erlotinib-resistant HCC827ErlRes than in HCC827 xenografts, while HCC827 tumour uptake was 33% lower (P < 0.001) following NVP-AUY-922 treatment. The results show that {sup 89}Zr-onartuzumab PET effectively discriminates relevant changes in c-MET levels and could potentially be used clinically to monitor c-MET status. (orig.)

BDNF VAL66MET Polymorphism Elevates the Risk of Bladder Cancer via MiRNA-146b in Micro-Vehicles

Directory of Open Access Journals (Sweden)

Cong Li

2018-01-01

Full Text Available Background/Aims: Emerging studies on brain-derived neurotrophic factor (BDNF have shown that might be novel biomarkers and therapeutic targets for cancer. We explore the role of BDNF in the tumorigenesis of bladder cancer and the underlying molecular mechanism. Methods: 368 patients with diagnosed bladder cancer and 352 healthy controls were enrolled to evaluate the association of BDNF and the miR-146b. Bioinformatics algorithm analysis and luciferase assay were performed to identify the target genes of miR-146b. Real-time PCR and western-blot were carried out to validate the relationship between miR-146b and CRK. MTT assay and FACS were used to evaluated the proliferation and apoptosis of cancer cells. MVs were isolated and transfect into the culture cells to confirm the above observation. Results: The clinical study shows that BDNF Met/Met was significantly associated with the risk of bladder cancer. In addition, comparing with Val/Val and Val/Met, Met/Met has lower miR-146b level. Luciferase assay shows that BDNF Val/Val is apparently enhanced miR-146b promoter-luciferase, but not BDNF Met/Met. Based on luciferase assay, CRK is a direct target gene of miR-146b. MiR-146b mimics significantly inhibited the expression of CRK and activation of AKT level. The expression of CRK and the activation of AKT (p-AKT were significantly inhibited by MV-BDNF Val/Val-miR-146b or MV-BDNF Val/Met-miR-146b, but not MV-BDNF Met/Met-miR-146b. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b obviously inhibited cell proliferation, which eliminated by CRK. Meanwhile, with MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not affect the proliferation. MV-BDNF Val/Val-miR-146b or Val/Met-miR-146b enhanced cell apoptosis, which could be eliminated by CRK. Meanwhile, MV-BDNF Met/Met-miR-146b or Met/Met-miR-146b+CRK did not promote apoptosis. Conclusion: BDNF VAL66MET polymorphism is associated with miR-146b and its target gene CRK. MiR-146b and CRK mediated BDNF VAL66

Ran GTPase promotes cancer progression via Met receptor-mediated downstream signaling

Science.gov (United States)

Yuen, Hiu-Fung; Chan, Ka-Kui; Platt-Higgins, Angela; Dakir, El-Habib; Matchett, Kyle B.; Haggag, Yusuf Ahmed; Jithesh, Puthen V.; Habib, Tanwir; Faheem, Ahmed; Dean, Fennell A.; Morgan, Richard; Rudland, Philip S.; El-Tanani, Mohamed

2016-01-01

It has been shown previously that cancer cells with an activated oncogenic pathway, including Met activation, require Ran for growth and survival. Here, we show that knockdown of Ran leads to a reduction of Met receptor expression in several breast and lung cancer cell lines. This, in turn suppressed HGF expression and the Met-mediated activation of the Akt pathway, as well as cell adhesion, migration, and invasion. In a cell line model where Met amplification has previously been shown to contribute to gefitinib resistance, Ran knockdown sensitized cells to gefitinib-mediated inhibition of Akt and ERK1/2 phosphorylation and consequently reduced cell proliferation. We further demonstrate that Met reduction-mediated by knockdown of Ran, occurs at the post-transcriptional level, probably via a matrix metalloproteinase. Moreover, the level of immunoreactive Ran and Met are positively associated in human breast cancer specimens, suggesting that a high level of Ran may be a pre-requisite for Met overexpression. Interestingly, a high level of immunoreactive Ran dictates the prognostic significance of Met, indicating that the co-overexpression of Met and Ran may be associated with cancer progression and could be used in combination as a prognostic indicator. PMID:27716616

Systematic literature review: xerostomia in advanced cancer patients.

Science.gov (United States)

Hanchanale, Sarika; Adkinson, Lucy; Daniel, Sunitha; Fleming, Michelle; Oxberry, Stephen G

2015-03-01

Dry mouth (xerostomia) is one of the commonest symptoms in cancer patients and can adversely affect quality of life. The aim of this review was to determine the effectiveness of pharmacological and non-pharmacological interventions in treating xerostomia in adult advanced cancer patients. The literature search was performed in February 2014 using databases including EMBASE, MEDLINE, CINAHL, BNI and Cochrane library. The search was carried out using standard MeSH terms and was limited to adult population and English language. Studies investigating xerostomia secondary to head and neck cancer treatment and autoimmune disease were excluded. Titles and abstracts were screened and reviewed for eligibility. Only studies involving primary research were included in the analysis. Six studies met the eligibility criteria for review: three randomized controlled trials and three prospective studies. The quality assessment and reporting was performed using PRISMA, Jadad and STROBE. These studies compared acupuncture, pilocarpine, Saliva Orthana and chewing gum with each other or with placebo. All interventions were considered effective in treating xerostomia. However, effectiveness versus placebo could not be demonstrated for Saliva Orthana. Meta-analysis could not be performed due to heterogeneity of the study type and intervention. Limited published data exists reporting the effectiveness of measures in the treatment of xerostomia in cancer patients. Based on primary research of low quality, firm conclusions cannot be drawn. However, pilocarpine, artificial saliva, chewing gum and acupuncture can be tried based on the available data. This highlights the explicit need to improve our evidence base. Properly constructed randomized controlled trials demonstrating effectiveness of pharmacological and non-pharmacological interventions for dry mouth are required.

Effectiveness of emergency nurses' use of the Ottawa Ankle Rules to initiate radiographic tests on improving healthcare outcomes for patients with ankle injuries: A systematic review.

Science.gov (United States)

Ho, Jonathan Ka-Ming; Chau, Janita Pak-Chun; Cheung, Nancy Man-Ching

2016-11-01

The Ottawa Ankle Rules provide guidelines for clinicians on the recommendation of radiographic tests to verify fractures in patients with ankle injuries. The use of the Ottawa Ankle Rules by emergency nurses has been suggested to minimise unnecessary radiographic-test requests and reduce patients' length of stay in emergency departments. However, the findings of studies in this area are inconsistent. A systematic review was conducted to synthesise the most accurate evidence available on the extent to which emergency nurses' use of the Ottawa Ankle Rules to initiate radiographic tests improves healthcare outcomes for patients with ankle injuries. The systematic review attempted to identify all relevant published and unpublished studies in English and Chinese from databases such as Ovid MEDLINE, EMBASE, ProQuest Health and Medical Complete, EBM Reviews, SPORTDiscus, CINAHL Plus, the British Nursing Index, Scopus, the Chinese Biomedical Literature Database, China Journal Net, WanFang Data, the National Central Library Periodical Literature System, HyRead, the Digital Dissertation Consortium, MedNar and Google Scholar. Two reviewers independently assessed the eligibility of all of the studies identified during the search, based on their titles and abstracts. If a study met the criteria for inclusion, or inconclusive information was available in its title and abstract, the full text was retrieved for further analysis. The methodological quality of all of the eligible studies was assessed independently by the two reviewers. The search of databases and other sources yielded 1603 records. The eligibility of 17 full-text articles was assessed, and nine studies met the inclusion criteria. All nine studies were subjected to narrative analysis, and five were meta-analysed. All of the studies investigated the use of the refined Ottawa Ankle Rules. The results indicated that emergency nurses' use of the refined Ottawa Ankle Rules minimised unnecessary radiographic-test requests

Met .naturalis in zee: Nederlands koraalrifonderzoek in de Indo-Pacific

NARCIS (Netherlands)

Hoeksema, B.W.

2003-01-01

In een serie arikelen onder de naam 'Met Naturalis in zee', zal Onderwatersport in samenwerking met het Leidse museum Naturalis met enige regelmaat aandacht besteden aan Nederlands biologisch koraalrifonderzoek in de Indische en de Stille Oceaan. Bert Hoeksema schreef de introductie van de serie.

The BDNF Val66Met polymorphism moderates the relationship between Posttraumatic Stress Disorder and fear extinction learning.

Science.gov (United States)

Felmingham, Kim L; Zuj, Daniel V; Hsu, Ken Chia Ming; Nicholson, Emma; Palmer, Matthew A; Stuart, Kimberley; Vickers, James C; Malhi, Gin S; Bryant, Richard A

2018-05-01

The low expression Met allele of the BDNF Val66Met polymorphism is associated with impaired fear extinction in healthy controls, and poorer response to exposure therapy in patients with Posttraumatic Stress Disorder (PTSD). Given that fear extinction underlies exposure therapy, this raises the question of the impact of BDNFVal66Met polymorphism on fear extinction in PTSD, yet this question has not yet been examined. One hundred and six participants (22 PTSD, 46 trauma-exposed controls (TC) and 38 non-trauma exposed controls (NTC)) completed a fear conditioning and extinction task and saliva samples were taken for DNA extraction and genotyped for the BDNF Val66Met polymorphism. Moderation analyses using PROCESS examined whether BDNF genotype (Val-Val vs Met carriers) moderated the relationship between PTSD symptom severity (and diagnostic status) and skin conductance response (SCR) amplitude during fear extinction. The PTSD group displayed significantly slower fear extinction learning compared to TC and NTC in the early extinction phase. The BDNF Val66Met polymorphism moderated the relationship between PTSD and fear extinction learning, such that poorer fear extinction learning was associated with greater PTSD symptom severity (and PTSD diagnostic status) in individuals with the low-expression Met allele, but no relationship was demonstrated in individuals with the Val-Val allele. This study reveals that impaired fear extinction learning is particularly evident in individuals with PTSD who carry the low-expression BDNF Met allele and importantly not in those with the Val-Val allele. This provides novel evidence of a link between BDNF and impaired fear extinction learning in PTSD, which may contribute to poorer response to exposure therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of the BDNF Val66Met Polymorphism and Met Allele Load on Declarative Memory Related Neural Networks

OpenAIRE

Dodds, Chris M.; Henson, Richard N.; Suckling, John; Miskowiak, Kamilla W.; Ooi, Cinly; Tait, Roger; Soltesz, Fruzsina; Lawrence, Phil; Bentley, Graham; Maltby, Kay; Skeggs, Andrew; Miller, Sam R.; McHugh, Simon; Bullmore, Edward T.; Nathan, Pradeep J.

2013-01-01

It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including...

7 CFR 1434.4 - Eligible producer.

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2010-01-01

... of the loan; (4) Store the honey pledged as loan collateral in eligible storage and in eligible... paragraph (a) of this section, who enters into a contract to sell the honey used as collateral for a loan... are tendering for a loan; and (2) The commingled honey is not used as collateral for an individual...

44 CFR 361.7 - General eligible expenditures.

Science.gov (United States)

2010-10-01

... consistent with the definition of eligible activities in § 361.2. (b) The following is a list of eligible... full-time earthquake staff person must be employed and the equipment must be dedicated entirely to the...

Deelname aan de samenleving van mensen met een beperking: participatiemonitor 2007.

OpenAIRE

Hoogen, P. van den; Cardol, M.; Speet, M.; Spreeuwenberg, P.; Rijken, M.

2008-01-01

Hoe doen mensen met een beperking mee in de maatschappij? Mensen met een lichamelijke beperking wonen en werken meestal net als iedereen, en ook zij zijn niet altijd tevreden met hun werk. Mensen met een verstandelijke beperking wonen en werken vaak in een speciale omgeving. Het overheidsbeleid is erop gericht dat iedereen – dus ook mensen met een beperking – zoveel mogelijk ‘gewoon mee kan doen’ in de maatschappij. Bijvoorbeeld werken bij een gewone werkgever, schoolgaan op een gewone school...

Radiation Chemical Studies of Gly-Met-Gly in Aqueous Solution

NARCIS (Netherlands)

Barata-Vallejo, Sebastian; Ferreri, Carla; Zhang, Tao; Permentier, Hjalmar; Bischoff, Rainer; Bobrowski, Krzysztof; Chatgilialoglu, Chryssostomos

2016-01-01

Important biological consequences are related to the reaction of HO(•) radicals with methionine (Met). Several fundamental aspects remain to be defined when Met is an amino acid residue incorporated in the interior of peptides and proteins. The present study focuses on Gly-Met-Gly, the simplest

Lack of neural compensatory mechanisms of BDNF val66met met carriers and APOE E4 carriers in healthy aging, mild cognitive impairment, and Alzheimer's disease.

Science.gov (United States)

Gomar, Jesus J; Conejero-Goldberg, Concepcion; Huey, Edward D; Davies, Peter; Goldberg, Terry E

2016-03-01

Compromises in compensatory neurobiologic mechanisms due to aging and/or genetic factors (i.e., APOE gene) may influence brain-derived neurotrophic factor (BDNF) val66met polymorphism effects on temporal lobe morphometry and memory performance. We studied 2 cohorts from Alzheimer's Disease Neuroimaging Initiative: 175 healthy subjects and 222 with prodromal and established Alzheimer's disease. Yearly structural magnetic resonance imaging and cognitive performance assessments were carried out over 3 years of follow-up. Both cohorts had similar BDNF Val/Val and Met allele carriers' (including both Val/Met and Met/Met individuals) distribution. In healthy subjects, a significant trend for thinner posterior cingulate and precuneus cortices was detected in Met carriers compared to Val homozygotes in APOE E4 carriers, with large and medium effect sizes, respectively. The mild cognitive impairment/Alzheimer's disease cohort showed a longitudinal decline in entorhinal thickness in BDNF Met carriers compared to Val/Val in APOE E4 carriers, with effect sizes ranging from medium to large. In addition, an effect of BDNF genotype was found in APOE E4 carriers for episodic memory (logical memory and ADAS-Cog) and semantic fluency measures, with Met carriers performing worse in all cases. These findings suggest a lack of compensatory mechanisms in BDNF Met carriers and APOE E4 carriers in healthy and pathological aging. Copyright © 2016 Elsevier Inc. All rights reserved.

29 CFR 825.110 - Eligible employee.

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2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Eligible employee. 825.110 Section 825.110 Labor... employee. (a) An “eligible employee” is an employee of a covered employer who: (1) Has been employed by the... worksite where 50 or more employees are employed by the employer within 75 miles of that worksite. (See...

Comparative evaluation of 11C-MET PET-CT and MRI for GTV delineation in precision radiotherapy for gliomas%基于11C-MET PET-CT与MRI对脑胶质瘤精确放疗GTV勾画的比较研究

Institute of Scientific and Technical Information of China (English)

王如; 钱立庭; 汪世存; 刘伟; 罗文广; 张洪波; 李广虎; 胡智刚; 刘磊

2014-01-01

目的 探讨11C-MET PET-CT和MRI图像对脑胶质瘤GTV确定的差异.方法 选取6例经病理证实为胶质瘤患者的术前MRI及11C-MET PET-CT图像,分别由我科5位医师在两种图像资料上勾画GTV,比较两者差异.结果 在MRI11C-MET PET-CT上勾画的GTV体积相似(P=0.917),GTV变异系数也相似(P =0.600).勾画的GTV重合度最大为73.0％、最小为51.8％.方差分析显示不同勾画者之间在两种图像资料上勾画的GTV相似(P =0.709),但PET-CT组GTV最大差值为27.66 cm3,而MRI组的为40.37 cm3.结论 MRI与PET-CT显示的肿瘤边界存在差异,不同勾画者勾画的GTV相似,PET-CT组的GTV最大差值较MRI组的小,11C-MET PET-CT显示GTV较为直观.%Objective To evaluate the difference between MRI and 11C-MET PET-CT for gross tumor volume (GTV) delineation in the precision radiotherapy for gliomas.Methods Six patients with a pathologically confirmed diagnosis of gliomas were selected for target delineation.Five physicians in our department were called to delineate the GTV based on the preoperative MRI and 11C-MET PET-CT images of these patients.The GTVs based on the two methods were compared.Results There was no significant difference between the GTVs based on MRI and 11C-MET PET-CT (P =0.917),and their coefficients of variation were also similar (P =0.600).The coincidences of GTVs were different among the patients,with a maximum value of 73.0％ and a minimum value of 51.8％.GTV showed no significant difference when defined by different physicians on MRI and PET-CT (P =0.709) ; the biggest difference was 27.66 cm3 on PET-CT and 40.37 cm3 on MRI.Conclusions The boundaries of gliomas defined on MRI and PET-CT are different.The GTVs delineated by different physicians on MRI and PET-CT are similar,and the biggest difference on PET-CT is smaller than that on MRI,which suggests that 11C-MET PET-CT is a more direct way for displaying GTV.

Association study between COMT 158Met and creativity scores in bipolar disorder and healthy controls

Directory of Open Access Journals (Sweden)

Márcio Gerhardt Soeiro-de-Souza

2014-03-01

Full Text Available Background Bipolar disorder (BD patients have been reported to be associated higher creativity abilities, and recent data tend to support the hypothesis that dopaminergic system that could be associated with creativity. Catechol-O-methyltransferase (COMT is one of the major enzymes involved in the metabolic degradation of dopamine. The COMT gene polymorphism (rs4680 or Val158Met Met allele is reported to cause decreased activity of this enzyme in prefrontal cortex and improve performance in several cognitive domains. Objective The objective of this study was to evaluate the influence of Val158Met on creativity in BD type I and healthy controls. Methods Ninety-seven healthy volunteers and 120 BD type I were genotyped for COMT rs4680 and tested for creativity (Barrow Welsh Art Scale – BWAS and intelligence Wechsler Abbreviated Scale of Intelligence (WASI. Results COMT Met allele positively influenced creativity scores in healthy controls but not in BD subjects during mood episodes and euthymia. The presence of allele Met did not influence IQ scores. No influence of IQ total score on creativity was observed. Limitations control group presented higher IQ scores and euthymic group was under medication use. Discussion Our research suggests positive effect of COMT rs4680 (allele Met on creativity scores in healthy controls. One possible interpretation is that creativity is more likely to be associated with lesser degrees of bipolarity. The fact that the same results were not observed in BD may be associated to dysfunctions in the dopaminergic system that characterizes this disorder. Further studies with larger samples and other types of BD should explore the role of the dopaminergic system in creativity.

Metabolic syndrome in Iranian patients with systemic lupus erythematosus and its determinants.

Science.gov (United States)

Fatemi, Alimohammad; Ghanbarian, Azadeh; Sayedbonakdar, Zahra; Kazemi, Mehdi; Smiley, Abbas

2018-01-05

The aim of this study was to determine the prevalence of metabolic syndrome (MetS) in Iranian patients with systemic lupus erythematosus (SLE) and its determinants. In a cross-sectional study, 98 patients with SLE and 95 controls were enrolled. Prevalence of MetS was determined based on American Heart Association and National Heart, Lung, and Blood Institute (AHA/NHLBI) and 2009 harmonizing criteria. In addition, demographic features and lupus characteristics such as disease duration, pharmacological treatment, laboratory data, SLE disease activity index (SLEDAI), and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage index (SDI) were recorded. The predictors of MetS were obtained by backward stepwise regression analysis. Using AHA/NHLBI, MetS was observed in 35 (35.7%) patients and 28 (29.8%) controls (P = 0.4). Using harmonizing criteria, MetS was observed in 37 (37.7%) patients and 33 (35.1%) controls (P = 0.7). There was no difference in frequency distribution of MetS components between the patients and the controls. In multivariate regression analysis, low C3, blood urea nitrogen (BUN), and body mass index were independent determinants of MetS in lupus patients. BUN, low C3, and body mass index were the major determinants of MetS in lupus patients.

The HGF/c-MET Axis as a Critical Driver of Resistance to Androgen Suppression in Metastatic Castrate-Resistant Prostate Cancer

Science.gov (United States)

2016-10-01

signaling inhibition in AR-positive CRPC models increased MET expression and resulted in susceptibility to ligand (HGF) activation. Likewise, our work...positive CRPC models , as detailed in the initial proposal, we found that combined MET inhibition and enzalutamide (AR antagonist) treatment was more...wide analyses, we will be able to better test the study hypothesis with increased patient accrual. Figure: Waterfall plots showing association

The Effects of Expressive Writing Interventions for Patients With Cancer: A Meta-Analysis.

Science.gov (United States)

Oh, Pok-Ja; Kim, Soo Hyun

2016-07-01

To evaluate the effects of expressive writing (EW) interventions in patients with cancer.
. Electronic databases searched included both international and Korean databases through January 2015.
. Of the 20 trials that met the eligibility criteria of this review, a meta-analysis was conducted of 14 articles involving 13 randomized and 1 nonrandomized trials with 1,718 patients with cancer. EW interventions were compared with a neutral writing intervention or usual care (no writing). A significant small effect was noted on relieving cancer symptoms; however, the effects on psychological and cognitive outcomes were not significant. When subgroup analysis by control condition was performed, a significant effect on health-related quality of life was found between the EW intervention group and the usual care group. 
. EW had significant small effects only on cancer symptoms. The findings suggest that the traditional EW intervention protocol may need to be intensified to confirm its effect on patients with cancer.
. Current evidence for EW as a nursing intervention for improving physical, psychological, and cognitive outcomes among patients with cancer is promising, but not conclusive.

Mars MetNet Mission - Martian Atmospheric Observational Post Network

Science.gov (United States)

Harri, A.-M.; Haukka, H.; Aleksashkin, S.; Arruego, I.; Schmidt, W.; Genzer, M.; Vazquez, L.; Siikonen, T.; Palin, M.

2017-09-01

A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL). The scientific payload of the Mars MetNet Precursor [1] mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior. The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.

El acertijo de la metáfora visual

OpenAIRE

De la Rosa Alzate, Adriana; Universidad Autónoma de Occidente

2016-01-01

En este artículo se presentan los resultados de la investigación sobre el proceso de interpretación de la metáfora visual, en niños entre tres y cuatro años de edad. El propósito de la investigación fue dar cuenta del proceso de interpretación de la metáfora visual y del razonamiento involucrado. La metáfora visual se entiende como un fenómeno en el que los objetos representados presentan transformaciones que traen como consecuencia la emergencia de nuevas categorías e incluso la ambigüedad, ...

Resultaten boomkorsurvey 2013: BTS met onderzoeksvaartuigen Isis en Tridens (interview met Ingeborg de Boois)

NARCIS (Netherlands)

Boois, de I.J.

2013-01-01

Van begin augustus tot half september heeft IMARES de boomkorsurvey (BTS) uitgevoerd met de onderzoeksschepen Isis en Tridens. Op 29 maart 2014 wordt een bijeenkomst georganiseerd voor geinteresseerden, waar de resultaten van zowel de BTS als de bedrijfssurvey gepresenteerd worden. De BTS wordt

Examination of Chronic Smoking Behavior and Eligibility for Low-Dose Computed Tomography for Lung Cancer Screening Among Older Chinese Male Smokers.

Science.gov (United States)

Li, Chien-Ching; Matthews, Alicia K; Dong, XinQi

2017-07-01

Low-dose computed tomography lung cancer (LDCT) screening is an effective way to decrease lung cancer mortality. Both Medicare and private insurers offer coverage of LDCT screening to beneficiaries who are at high risk of developing lung cancer. In this study, we examined rates and predictors of chronic smoking behavior and eligibility for coverage of LDCT screening among older Chinese men living in the greater Chicago area. Data were obtained from the Population Study of Chinese Elderly in Chicago, a population-based survey of community-dwelling, older Chinese adults in the Chicago metropolitan area. Eligibility criteria according to Centers of Medicare and Medicaid Services (CMS) and U.S. Preventive Services Task Force (USPSTF) for LDCT screening were used. Multivariate logistic regression was conducted to determine predictors of chronic smoking behavior which was operationalized as meeting criteria for LDCT screening. A quarter of the sample were current smokers and 42.5% reported a prior history of smoking. Eighteen percent and 22% of older Chinese men met the eligibility criteria for appropriateness for CMS and USPSTF LDCT screening, respectively. Furthermore, education, marital status, and number of children were significantly associated with chronic smoking behavior. Older Chinese men with chronic smoking behavior are at high risk of developing lung cancer and nearly one in five meet eligibility for LDCT screening. Increased outreach and education regarding early detection of lung cancer and smoking cessation are needed for this vulnerable and high-risk population. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

14 CFR 61.83 - Eligibility requirements for student pilots.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Eligibility requirements for student pilots... TRANSPORTATION (CONTINUED) AIRMEN CERTIFICATION: PILOTS, FLIGHT INSTRUCTORS, AND GROUND INSTRUCTORS Student Pilots § 61.83 Eligibility requirements for student pilots. To be eligible for a student pilot...

Unrecognized hypoxia and respiratory depression in emergency department patients sedated for psychomotor agitation: pilot study.

Science.gov (United States)

Deitch, Kenneth; Rowden, Adam; Damiron, Kathia; Lares, Claudia; Oqroshidze, Nino; Aguilera, Elizabeth

2014-07-01

The incidence of respiratory depression in patients who are chemically sedated in the emergency department (ED) is not well understood. As the drugs used for chemical restraint are respiratory depressants, improving respiratory monitoring practice in the ED may be warranted. The objective of this study is to describe the incidence of respiratory depression in patients chemically sedated for violent behavior and psychomotor agitation in the ED. Adult patients who met eligibility criteria with psychomotor agitation and violent behavior who were chemically sedated were eligible. SpO2 and ETCO2 (end-tidal CO2) was recorded and saved every 5 seconds. Demographic data, history of drug or alcohol abuse, medical and psychiatric history, HR and BP every 5 minutes, any physician intervention for hypoxia or respiratory depression, or adverse events were also recorded. We defined respiratory depression as an ETCO2 of ≥50 mmHg, a change of 10% above or below baseline, or a loss of waveform for ≥15 seconds. Hypoxia was defined as a SpO2 of ≤93% for ≥15 seconds. We enrolled 59 patients, and excluded 9 because of ≥35% data loss. Twenty-eight (28/50) patients developed respiratory depression at least once during their chemical restraint (56%, 95% CI 42-69%); the median number of events was 2 (range 1-6). Twenty-one (21/50) patients had at least one hypoxic event during their chemical restraint (42%, 95% CI 29-55%); the median number of events was 2 (range 1-5). Nineteen (19/21) (90%, 95% CI 71-97%) of the patients that developed hypoxia had a corresponding ETCO2 change. Fifteen (15/19) (79%, 95% CI 56-91%) patients who became hypoxic met criteria for respiratory depression before the onset of hypoxia. The sensitivity of ETCO2 to predict the onset of a hypoxic event was 90.48% (95% CI: 68-98%) and specificity 69% (95% CI: 49-84%). Five patients received respiratory interventions from the healthcare team to improve respiration [Airway repositioning: (2), Verbal stimulation

Computational challenges and human factors influencing the design and use of clinical research participant eligibility pre-screening tools

Directory of Open Access Journals (Sweden)

Pressler Taylor R

2012-05-01

Full Text Available Abstract Background Clinical trials are the primary mechanism for advancing clinical care and evidenced-based practice, yet challenges with the recruitment of participants for such trials are widely recognized as a major barrier to these types of studies. Data warehouses (DW store large amounts of heterogenous clinical data that can be used to enhance recruitment practices, but multiple challenges exist when using a data warehouse for such activities, due to the manner of collection, management, integration, analysis, and dissemination of the data. A critical step in leveraging the DW for recruitment purposes is being able to match trial eligibility criteria to discrete and semi-structured data types in the data warehouse, though trial eligibility criteria tend to be written without concern for their computability. We present the multi-modal evaluation of a web-based tool that can be used for pre-screening patients for clinical trial eligibility and assess the ability of this tool to be practically used for clinical research pre-screening and recruitment. Methods The study used a validation study, usability testing, and a heuristic evaluation to evaluate and characterize the operational characteristics of the software as well as human factors affecting its use. Results Clinical trials from the Division of Cardiology and the Department of Family Medicine were used for this multi-modal evaluation, which included a validation study, usability study, and a heuristic evaluation. From the results of the validation study, the software demonstrated a positive predictive value (PPV of 54.12% and 0.7%, respectively, and a negative predictive value (NPV of 73.3% and 87.5%, respectively, for two types of clinical trials. Heuristic principles concerning error prevention and documentation were characterized as the major usability issues during the heuristic evaluation. Conclusions This software is intended to provide an initial list of eligible patients to a

La metáfora

DEFF Research Database (Denmark)

Agustin, Oscar Garcia

2007-01-01

2002 y principios de 2003, anteriores a la proclamación de las Juntas de Buen Gobierno. Nuestro objetivo es comprobar cómo las metáforas crean nuevas significaciones, que intentan deshacer una lógica comúnmente asumida, y promover otros modos de comprender la acción y la realidad político-social. Este...

24 CFR 5.510 - Documents of eligible immigration status.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Documents of eligible immigration... Noncitizens § 5.510 Documents of eligible immigration status. (a) General. A responsible entity shall request and review original documents of eligible immigration status. The responsible entity shall retain...

45 CFR 1639.4 - Permissible representation of eligible clients.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Permissible representation of eligible clients... CORPORATION WELFARE REFORM § 1639.4 Permissible representation of eligible clients. Recipients may represent an individual eligible client who is seeking specific relief from a welfare agency. [62 FR 30766...

13 CFR 127.400 - What is an eligibility examination?

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What is an eligibility examination? 127.400 Section 127.400 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION WOMEN-OWNED SMALL BUSINESS FEDERAL CONTRACT ASSISTANCE PROCEDURES Eligibility Examinations § 127.400 What is an eligibility...

Anthropometric Indicators Predict Metabolic Syndrome Diagnosis in Maintenance Hemodialysis Patients.

Science.gov (United States)

Vogt, Barbara Perez; Ponce, Daniela; Caramori, Jacqueline Costa Teixeira

2016-06-01

Obesity has been considered the key in metabolic syndrome (MetS) development, and fat accumulation may be responsible for the occurrence of metabolic abnormalities in hemodialysis patients. The use of gold-standard methods to evaluate obesity is limited, and anthropometric measures may be the simplest methods. However, no study has investigated the association between anthropometric indexes and MetS in these patients. Therefore, the aim was to determine which anthropometric indexes had the best association and prediction for MetS in patients undergoing hemodialysis. Cross-sectional study that included patients older than 18 years, undergoing hemodialysis for at least 3 months. Patients with liver disease and cancer or those receiving corticosteroids or antiretroviral therapy were excluded. Diagnostic criteria from Harmonizing Metabolic Syndrome were used for the diagnosis of MetS. Anthropometric indexes evaluated were body mass index (BMI); percent standard of triceps skinfold thickness and of middle arm muscle circumference; waist circumference (WC); sagittal abdominal diameter; neck circumference; waist-to-hip, waist-to-thigh, and waist-to-height ratios; sagittal index; conicity index; and body fat percentage. Ninety-eight patients were included, 54.1% male, and mean age was 57.8 ± 12.9 years. The prevalence of MetS was 74.5%. Individuals with MetS had increased accumulation of abdominal fat and general obesity. Waist-to-height ratio was the variable independently associated with MetS diagnosis (odds ratio, 1.21; 95% confidence interval, 1.09-1.34; P < .01) and that better predicts MetS, followed by WC and BMI (area under the curve of 0.840, 0.836, and 0.798, respectively, P < .01). Waist-to-height ratio was the best anthropometric predictor of MetS in maintenance hemodialysis patients. © 2015 American Society for Parenteral and Enteral Nutrition.

Effectiveness of omega-3 fatty acid supplementation in patients with Alzheimer disease: A systematic review and meta-analysis.

Science.gov (United States)

Araya-Quintanilla, F; Gutiérrez-Espinoza, H; Sánchez-Montoya, U; Muñoz-Yañez, M J; Baeza-Vergara, A; Petersen-Yanjarí, M; Fernández-Lecaros, L

2017-10-03

Alzheimer disease (AD) is a neurodegenerative disease characterised by progressive dementia associated with global cognitive dysfunction. We conducted a systematic review and meta-analysis of clinical trials evaluating omega-3 supplementation in patients with AD. To determine if there is scientific evidence of the effectiveness of omega-3 supplementation in improving cognitive function in patients with AD. We included only randomised controlled trials (RCTs) from the following databases: Medline, Cochrane Central, Cinahl, and LILACS. An electronic search was also conducted using Google Scholar. Six articles met the eligibility criteria. The risk of bias was assessed following the Cochrane method. There is no consistent evidence to support the effectiveness of omega-3 supplementation in improving cognitive function in AD patients in the short and medium term. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays.

Science.gov (United States)

Sotoudeh, Kambiz; Hashemi, Forough; Madjd, Zahra; Sadeghipour, Alireza; Molanaei, Saadat; Kalantary, Elham

2012-05-28

c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008-2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044). The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were observed. c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429.

Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells

Energy Technology Data Exchange (ETDEWEB)

Husmann, Knut, E-mail: khusmann@research.balgrist.ch [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland); Ducommun, Pascal [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland); Division of Plastic Surgery and Hand Surgery, Department of Surgery, University Hospital Zurich, Zurich (Switzerland); Sabile, Adam A.; Pedersen, Else-Marie; Born, Walter; Fuchs, Bruno [Laboratory for Orthopedic Research, Department of Orthopedics, Balgrist University Hospital, University of Zurich, Zurich (Switzerland)

2015-09-04

The poor outcome of osteosarcoma (OS), particularly in patients with metastatic disease and a five-year survival rate of only 20%, asks for more effective therapeutic strategies targeting malignancy-promoting mechanisms. Dysregulation of C-MET, its ligand hepatocyte growth factor (HGF) and the fusion oncogene product TPR-MET, first identified in human MNNG-HOS OS cells, have been described as cancer-causing factors in human cancers. Here, the expression of these molecules at the mRNA and the protein level and of HGF-stimulated signaling and downregulation of C-MET was compared in the parental low metastatic HOS and MG63 cell lines and the respective highly metastatic MNNG-HOS and 143B and the MG63-M6 and MG63-M8 sublines. Interestingly, expression of TPR-MET was only observed in MNNG-HOS cells. HGF stimulated the phosphorylation of Akt and Erk1/2 in all cell lines investigated, but phospho-Stat3 remained at basal levels. Downregulation of HGF-stimulated Akt and Erk1/2 phosphorylation was much faster in the HGF expressing MG63-M8 cells than in HOS cells. Degradation of HGF-activated C-MET occurred predominantly through the proteasomal and to a lesser extent the lysosomal pathway in the cell lines investigated. Thus, HGF-stimulated Akt and Erk1/2 signaling as well as proteasomal degradation of HGF activated C-MET are potential therapeutic targets in OS. - Highlights: • Expression of TPR-MET was only observed in MNNG-HOS cells. • HGF stimulated the phosphorylation of Akt and Erk1/2 but not of Stat3 in osteosarcoma cell lines. • Degradation of HGF-activated C-MET occurred predominantly through the proteasomal pathway.

Metáforas metalinguísticas de Euclides da Cunha

Directory of Open Access Journals (Sweden)

Carlos Antônio Magalhães Guedelha

2016-03-01

Full Text Available Este artigo apresenta uma leitura das metáforas metalinguísticas do escritor Euclides da Cunha, ou seja, as metáforas que ele utilizou para se referir aos seus dois principais livros, Os Sertões (sobre a guerra de Canudos e Um paraíso perdido (sobre a Amazônia. O conceito de metalinguagem estabelecido por Jakobson foi fundamental para a pesquisa, que teve como suporte teórico básico o postulado da metáfora conceptual, proposta por Lakoff e Johnson. As metáforas analisados neste artigo (VINGAR-SE É ESCREVER e UM LIVRO É UM FILHO foram colhidas de ensaios do escritor e de cartas que ele escreveu a amigos e familiares, “escriturando” a sua escrita por meio da metalinguagem. A análise das metáforas assume, com base em Lakoff e Johnson, que a metáfora não é uma questão apenas de linguagem. Ela é também – e fundamentalmente – uma questão de pensamento e ação.

Feasibility of pre-operative autologous blood donation in Indian patients with elective orthopaedic surgery.

Science.gov (United States)

Saluja, Karan; Marwaha, Neelam; Thakral, Beenu; Goni, Vijay; Sharma, R R; Puri, G D

2006-11-01

Pre-operative autologous blood donation (PABD) in elective orthopaedic surgeries is a well known procedure in the West. We initiated this programme at a tertiary care hospital in north India to study its feasibility in Indian patients. In a prospective case-control study, 144 patients undergoing primary total hip or knee replacement, inter-vertebral discectomy, mal-union and non-union reconstruction were educated and motivated to pre-donate. Patients fulfilling the inclusion criteria and making autologous donation formed the PABD group (n=22). Patients eligible for PABD, but unwilling to participate; age, sex, pre-operative haemoglobin and operative procedure matched acted as controls (n=27). Unit(s) collected was processed like an allogeneic unit. Unit(s) found reactive for infectious markers or not utilized was discarded. Mean blood losses, transfusion trigger, allogeneic exposure and wastage between the two groups were compared. Of the 144 patients motivated, 40 per cent of the eligible subjects pre-deposited. The main motivational factor was fear of getting infection from someone's blood. Cardiac events and anaemia prevented 61.8 per cent patients to participate. Of the 50 units ordered, autologous units with a mean of 1.4 units/patient contributed 62 per cent. For total hip and total knee replacement (THR and TKR), autologous units met 76.2 and 80 per cent respectively of the total blood requirement. A significant decrease in the allogeneic exposure was observed between PABD and control group (18.2 vs 66.7%); 32.3 per cent of the autologous units were discarded. Comprehensive PABD programme may be an effective method for reducing the need for allogeneic transfusion in patients undergoing joint replacement surgeries in our country, where transfusion transmitted infections due to high percentage of replacement donations and lack of sensitive assays for testing are still a cause for concern.

Reporting the methodology of height and weight acquisition in studies of body mass index-based prognosis in critically ill patients.

Science.gov (United States)

Oud, Lavi

2013-10-01

Conflicting findings were reported on the body mass index (BMI)-based prognosis of critically patients. Errors in source weight and height data can confound BMI group allocation. The aim of the present work was to examine investigators' reporting on the methods of height and weight acquisition (HWA). PubMed and Embase databases were searched for studies describing BMI group-based risk of death in critically ill patients. Eligible studies were examined for reporting on (1) the use of measured and/or estimated HWA, (2) details of measuring devices, (3) device accuracy, and (4) methods of adjustment for acute and chronic fluid-related weight changes. Thirty studies met the eligibility criteria, including 159,565 patients. No data were provided in 13 studies (52% of reported patients) on whether estimates or measurements were used for HWA. Measured HWA was used exclusively in 6 studies (3% of patients), and an unspecified combination of estimated and/or measured HWA was reported for the remainder. Only 1 study reported the specific devices used. None of the studies provided data on the bias and precision of measuring devices. Adjustment for chronic and/or acute fluid-related weight changes was addressed in 2 studies for each. These findings demonstrate the prevalent risk for BMI group misallocation in the reviewed studies, which may confound BMI-based prognosis, raising concerns about the validity of reported BMI-related prognostic impact. Copyright © 2013 Elsevier Inc. All rights reserved.

45 CFR 1626.7 - Verification of eligible alien status.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Verification of eligible alien status. 1626.7... CORPORATION RESTRICTIONS ON LEGAL ASSISTANCE TO ALIENS § 1626.7 Verification of eligible alien status. (a) An alien seeking representation shall submit appropriate documents to verify eligibility, unless the only...

7 CFR 1424.4 - General eligibility rules.

Science.gov (United States)

2010-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS BIOENERGY PROGRAM § 1424.4 General eligibility... be eligible for program payments, a producer must maintain records indicating for all relevant FY's.... (d) For producers not purchasing raw commodity inputs, the production must equal or exceed that...

XRCC3 Thr241Met Polymorphism is not Associated with Lung Cancer Risk in a Romanian Population.

Science.gov (United States)

Catana, Andreea; Pop, Monica; Marginean, Dragos Horea; Blaga, Ioana Cristina; Porojan, Mihai Dumitru; Popp, Radu Anghel; Pop, Ioan Victor

2016-01-01

Deoxyribonucleic Acid (DNA) repair mechanisms play a critical role in protecting the cellular genome against carcinogens. X-ray cross-complementing gene 3 (XRCC3) is involved in DNA repair and therefore certain genetic polymorphisms that occur in DNA repair genes may affect the ability to repair DNA defects and may represent a risk factor in carcinogenesis. The purpose of our study was to investigate the association between XRCC3 gene substitution of Threonine with Methionine in codon 241 of XRCC3 gene (Thr241Met) polymorphism and the risk of lung cancer, in a Romanian population. We recruited 93 healthy controls and 85 patients with lung cancer, all smokers. Thr241Met, XRCC3 gene genotyping was determined by multiplex Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Statistical analysis (OR, recessive model), did not revealed an increased risk for lung cancer, for the variant 241Met allele and Thr241Met genotypes (p=0.138, OR=0.634, CI=0.348-1.157; p=0.023, OR=0.257, CI=0.085-6.824). Also, there were no positive statistical associations between Thr241Met polymorphism of XRCC3 gene, gender, tobacco and various histopathological tumor type of lung cancer. In conclusion, the results of the study suggest that the XRCC3 gene Thr241Met polymorphism is not associated with an increased risk for the development of lung cancer in this Romanian group.

45 CFR 400.94 - Determination of eligibility for Medicaid.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false Determination of eligibility for Medicaid. 400.94... Determination of eligibility for Medicaid. (a) The State must determine Medicaid and SCHIP eligibility under its Medicaid and SCHIP State plans for each individual member of a family unit that applies for medical...

48 CFR 922.608-3 - Protests against eligibility.

Science.gov (United States)

2010-10-01

... SOCIOECONOMIC PROGRAMS APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITION Walsh-Healey Public Contracts Act 922.608-3 Protests against eligibility. When an eligibility determination made by the contracting officer...

Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody.

Science.gov (United States)

Cignetto, Simona; Modica, Chiara; Chiriaco, Cristina; Fontani, Lara; Milla, Paola; Michieli, Paolo; Comoglio, Paolo M; Vigna, Elisa

2016-06-01

The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable to the original MvDN30 in vitro, acting as full Met antagonists, impairing Met phosphorylation and activation of downstream signaling pathways. As a consequence, Met-mediated biological responses were inhibited, including anchorage-dependent and -independent cell growth. In vivo DCD-1 and DCD-2 showed a pharmacokinetic profile significantly improved over the original MvDN30, doubling the circulating half-life and reducing the clearance. In pre-clinical models of cancer, generated by injection of tumor cells or implant of patient-derived samples, systemic administration of the engineered molecules inhibited the growth of Met-addicted tumors. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

32 CFR 99.5 - Eligibility for indemnification.

Science.gov (United States)

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Eligibility for indemnification. 99.5 Section 99.5 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE PERSONNEL, MILITARY AND CIVILIAN PROCEDURES FOR STATES AND LOCALITIES TO REQUEST INDEMNIFICATION § 99.5 Eligibility for...

15 CFR 923.93 - Eligible implementation costs.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Eligible implementation costs. 923.93... MANAGEMENT COASTAL ZONE MANAGEMENT PROGRAM REGULATIONS Applications for Program Development or Implementation Grants § 923.93 Eligible implementation costs. (a) Costs claimed must be beneficial and necessary to the...

48 CFR 919.7005 - Eligibility to be a Mentor.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Eligibility to be a Mentor... PROGRAMS SMALL BUSINESS PROGRAMS The Department of Energy Mentor-Protege Program 919.7005 Eligibility to be a Mentor. To be eligible for recognition by DOE as a Mentor, an entity must be performing at least...

MetReS, an Efficient Database for Genomic Applications.

Science.gov (United States)

Vilaplana, Jordi; Alves, Rui; Solsona, Francesc; Mateo, Jordi; Teixidó, Ivan; Pifarré, Marc

2018-02-01

MetReS (Metabolic Reconstruction Server) is a genomic database that is shared between two software applications that address important biological problems. Biblio-MetReS is a data-mining tool that enables the reconstruction of molecular networks based on automated text-mining analysis of published scientific literature. Homol-MetReS allows functional (re)annotation of proteomes, to properly identify both the individual proteins involved in the processes of interest and their function. The main goal of this work was to identify the areas where the performance of the MetReS database performance could be improved and to test whether this improvement would scale to larger datasets and more complex types of analysis. The study was started with a relational database, MySQL, which is the current database server used by the applications. We also tested the performance of an alternative data-handling framework, Apache Hadoop. Hadoop is currently used for large-scale data processing. We found that this data handling framework is likely to greatly improve the efficiency of the MetReS applications as the dataset and the processing needs increase by several orders of magnitude, as expected to happen in the near future.

Role of Met Axis in Head and Neck Cancer

Energy Technology Data Exchange (ETDEWEB)

Xu, Yiru, E-mail: xuyiru@umich.edu; Fisher, Gary J., E-mail: xuyiru@umich.edu [Department of Dermatology, University of Michigan, Ann Arbor, MI 48109 (United States)

2013-11-26

Head and neck cancer is the sixth most common type of cancer worldwide. Despite advances in aggressive multidisciplinary treatments, the 5-year survival rate for this dreadful disease is only 50%, mostly due to high rate of recurrence and early involvement of regional lymph nodes and subsequent metastasis. Understanding the molecular mechanisms responsible for invasion and metastasis is one of the most pressing goals in the field of head and neck cancer. Met, also known as hepatocyte growth factor receptor (HGFR), is a member of the receptor protein tyrosine kinase (RPTK) family. There is compelling evidence that Met axis is dysregulated and plays important roles in tumorigenesis, progression, metastasis, angiogenesis, and drug resistance in head and neck cancer. We describe in this review current understanding of Met axis in head and neck cancer biology and development of therapeutic inhibitors targeting Met axis.

Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes.

Science.gov (United States)

Chua, Benjamin; Min, Myo; Wood, Maree; Edwards, Sarah; Hoffmann, Matthew; Greenham, Stuart; Kovendy, Andrew; McKay, Michael J; Shakespeare, Thomas P

2013-08-01

There is substantial interest in implementation of image-guided intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We describe our implementation of IG-IMRT, and examine how often published organ-at-risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol. Patients were eligible if they received post-prostatectomy radiotherapy (PPRT). Planning data were collected prospectively, and toxicity assessments were collected before, during and after treatment. Seventy-five eligible patients received either 64 Gy (19%) or 66 Gy (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of V40Gy < 60% and V60Gy < 40% were met in 64 (85%) and 75 (100%) patients, respectively. IMRT-specific rectal dose-constraints of V40Gy < 35% and V65Gy < 17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint (V50Gy < 50%) was met in 58 (77%) patients. Two patients (3%) experienced new grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3 gastroinestinal toxicity. All grade 3 toxicities had improved by 3-month review. Overall deterioration in urinary and gastrointestinal symptoms occurred in 33 (44%) and 35 (47%) of patients respectively. We report on our implementation of PPRT which takes into account nationally adopted guidelines, with a margin reduction supported by use of daily image guidance. Non-IMRT OAR constraints were met in most cases. IMRT-specific constraints were less often achieved despite margin reductions, suggesting the need for review of guidelines. Severe toxicity was rare, and most patients did not experience deterioration in urinary or bowel function attributable to radiotherapy. © 2013 The Authors. Journal of Medical Imaging and Radiation Oncology © 2013 The Royal Australian and New Zealand College of Radiologists.

Implementation of an image guided intensity-modulated protocol for post-prostatectomy radiotherapy: planning data and acute toxicity outcomes

International Nuclear Information System (INIS)

Chua, Benjamin; Min, Myo; Wood, Maree; Edwards, Sarah; Hoffmann, Matthew; Greenham, Stuart; Kovendy, Andrew; McKay, Michael J.; Shakespeare, Thomas P.

2013-01-01

There is substantial interest in implementation of image-guided intensity-modulated radiotherapy (IG-IMRT) in the post-prostatectomy setting. We describe our implementation of IG-IMRT, and examine how often published organ-at-risk (OAR) constraints were met. Furthermore, we evaluate the incidence of acute genitourinary and gastrointestinal toxicities when patients were treated according to our protocol. Patients were eligible if they received post-prostatectomy radiotherapy (PPRT). Planning data were collected prospectively, and toxicity assessments were collected before, during and after treatment. Seventy-five eligible patients received either 64Gy (19%) or 66Gy (81%) in a single phase to the prostate bed. Suggested rectal dose-constraints of V40Gy<60% and V60Gy<40% were met in 64 (85%) and 75 (100%) patients, respectively. IMRT-specific rectal dose-constraints of V40Gy<35% and V65Gy<17% were achieved in 5 (7%) and 57 (76%) of patients. Bladder dose-constraint (V50Gy<50%) was met in 58 (77%) patients. Two patients (3%) experienced new grade 3 genitourinary toxicity and one patient (1%) experienced new grade 3 gastrointestinal toxicity. All grade 3 toxicities had improved by 3-month review. Overall deterioration in urinary and gastrointestinal symptoms occurred in 33 (44%) and 35 (47%) of patients respectively. We report on our implementation of PPRT which takes into account nationally adopted guidelines, with a margin reduction supported by use of daily image guidance. Non-IMRT OAR constraints were met in most cases. IMRT-specific constraints were less often achieved despite margin reductions, suggesting the need for review of guidelines. Severe toxicity was rare, and most patients did not experience deterioration in urinary or bowel function attributable to radiotherapy.

45 CFR 1308.15 - Eligibility criteria: Autism.

Science.gov (United States)

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Eligibility criteria: Autism. 1308.15 Section 1308... Services Performance Standards § 1308.15 Eligibility criteria: Autism. A child is classified as having autism when the child has a developmental disability that significantly affects verbal and non-verbal...

19 CFR 212.04 - Eligibility of applicants.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 3 2010-04-01 2010-04-01 false Eligibility of applicants. 212.04 Section 212.04 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE IMPLEMENTATION OF THE EQUAL ACCESS TO JUSTICE ACT General Provisions § 212.04 Eligibility of...

Invloed krachtvoerniveau op vleesproduktiekenmerken van Piemontese met zwartbont kruislingstieren

NARCIS (Netherlands)

Hanekamp, W.J.A.

1989-01-01

Met 3 ronden van elk 36 Piemontese X zwartbonte kruislingstieren is het effect van extra krachtvoer vergeleken met de normaal gangbare gift naast onbeperkt snijmaoskuil. De stieren waren gehuisvest in een natuurlijk geventileerde stal (space-boarding)en op een volledige roostervloer.

Pastoors naar de PFA: nieuwe impuls voor samenwerking met de wetenschap (interview met Martin Pastoors)

NARCIS (Netherlands)

Pastoors, M.A.

2014-01-01

De Pelagic Freezer-trawler Association (PFA) heeft visserijonderzoeler Martin Pastoors aangenomen als 'Chief Science Officer'. De afgelopen tien jaar is de PFA zich steeds meer bezig gaan houden met wetenschappelijk onderzoek. Bijvoorbeeld door het ontwikkelen van nieuwe manieren om data te

Met Ed gets reprieve: banks lend tax money

International Nuclear Information System (INIS)

Utroska, D.

1981-01-01

A consortium of banks agreed to loan Metropolitan Edison $23 million to pay its April 15 state taxes and temporarily relieve a cash-flow problem that is leading to default after the Pennsylvania Public Utility Commission expedited a rate request. The continued solvency of Met Ed is a matter of speculation because the present credit formula is based on liquid assets which the PUC did not address. While the action taken by the bankers gives Met Ed a reprieve, it does not provide a long-term solution. The Revolving Credit Agreement will expire on October 1. Met Ed is still faced with the problem of relicensing Three Mile Island-1 unit and the cost of underwriting the cleanup of the No. 2 unit

Myocardial hipertrophy in hypertensive patients with and without metabolic syndrome

Directory of Open Access Journals (Sweden)

Ivanović Branislava

2008-01-01

Full Text Available Background/Aim. Beside arterial hypertension as the most important factor of a myocardial hypertension development, very important risk factors are obesity, hypercholesterolemia, insulin resistance, etc. The aim of the study was to examine the influence of metabolic syndrome (MetS on left ventricular hypertrophy in patients with arterial hypertension. Methods. We checked medical records for 138 patients with arterial hypertension, and compared them with the control group of 44 normotensive subjects. The patients with arterial hypertension were divided into two groups considering the presence of MetS: with MetS (59 patients, and without MetS (79 patients. We defined MetS as presence of three (or more within five criteria: central obesity (> 102 cm male, > 88 cm female, raised triglycerides (> 1.7 mmol/L, or drug treatment for elevated triglycerides, reduced high density lipoprotein (HDL cholesterol (< 1.03 mmol/L male, < 1.3 mmol/L female, raised blood pressure (> 130 mmHg systolic, > 90 mmHg diastolic, raised fasting glucose (> 6.11 mmol/L, or drug treatment for elevated glucose level. In each group routine laboratory, echocardiography and 24-hour ambulatory blood pressure monitoring were performed. Results. We found statisticaly significant higher left ventricular mass in both subgroups hypertensive patients in comparison with the control group (p < 0.05. We did not find statistically significant difference (227.31±63.44 vs 219±59.5, p > 0.05 in left ventricular mass between these two groups of patients. In the patients with arterial hypertension and MetS we found hypertrophy more frequently than in the subgroup without MetS (43/57 vs 34/69, p < 0.001. Conclusion. Our results suggest that associated cardiometabolic risks increase the prevalence of myocardial hypertrophy, but do not influence left ventricular mass.

Recent advances in the discovery of small molecule c-Met Kinase inhibitors.

Science.gov (United States)

Parikh, Palak K; Ghate, Manjunath D

2018-01-01

c-Met is a prototype member of a subfamily of heterodimeric receptor tyrosine kinases (RTKs) and is the receptor for hepatocyte growth factor (HGF). Binding of HGF to its receptor c-Met, initiates a wide range of cellular signalling, including those involved in proliferation, motility, migration and invasion. Importantly, dysregulated HGF/c-Met signalling is a driving factor for numerous malignancies and promotes tumour growth, invasion, dissemination and/or angiogenesis. Dysregulated HGF/c-Met signalling has also been associated with poor clinical outcomes and resistance acquisition to some approved targeted therapies. Thus, c-Met kinase has emerged as a promising target for cancer drug development. Different therapeutic approaches targeting the HGF/c-Met signalling pathway are under development for targeted cancer therapy, among which small molecule inhibitors of c-Met kinase constitute the largest effort within the pharmaceutical industry. The review is an effort to summarize recent advancements in medicinal chemistry development of small molecule c-Met kinase inhibitors as potential anti-cancer agents which would certainly help future researchers to bring further developments in the discovery of small molecule c-Met kinase inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Design and synthesis of 3,3'-biscoumarin-based c-Met inhibitors.

Science.gov (United States)

Xu, Jimin; Ai, Jing; Liu, Sheng; Peng, Xia; Yu, Linqian; Geng, Meiyu; Nan, Fajun

2014-06-14

A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3'-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells.

24 CFR 1003.201 - Basic eligible activities.

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2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Basic eligible activities. 1003.201... Activities § 1003.201 Basic eligible activities. ICDBG funds may be used for the following activities: (a... interest rates and mortgage principal amounts for low-and moderate-income homebuyers; (2) Finance the...

12 CFR 263.103 - Eligibility of applicants.

Science.gov (United States)

2010-01-01

... will be presumed to have been made for this purpose. (3) The net worth of a financial institution shall... guidelines on the financial institution's financial report to its supervisory agency for the last reporting....103 Eligibility of applicants. (a) General rule. To be eligible for an award under this subpart, an...

Metáfora y estructura conceptual

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Emilia Castaño

2012-01-01

Full Text Available La lingüística cognitiva siempre ha argumentado que la metáfora no pertenece exclusivamente al lenguaje, sino que es una competencia que se basa en la habilidad humana de concebir un dominio de experiencia en términos de otro. Entendida así, la metáfora no puede ser otra cosa que un fenómeno conceptual. No obstante, pocos adeptos de la lingüística cognitiva han concentrados sus esfuerzos en catalogar manifestaciones metafóricas en ámbitos no lingüísticos. En este trabajo, sugerimos que es factible encontrar pruebas de que la metáfora es un proceso conceptual y, como tal, se manifiesta en esferas que no son estrictamente lingüísticas. Para ello, aportamos un seguido de evidencias muy diversas, como por ejemplo su papel en el razonamiento lógico-matemático de los niños en la fase preoperacional del desarrollo cognitivo, la programación de interfaces para aplicaciones informáticas y los resultados de tres estudios empíricos realizados recientemente en el campo  de la psicología cognitiva que analizan los efectos whorfianos en la conceptualización del tiempo y los efectos del espacio en la memoria emocional.

34 CFR 600.10 - Date, extent, duration, and consequence of eligibility.

Science.gov (United States)

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Date, extent, duration, and consequence of eligibility... EDUCATION ACT OF 1965, AS AMENDED General § 600.10 Date, extent, duration, and consequence of eligibility... statutory and regulatory requirements governing its eligibility. (e) Consequence of eligibility. (1) If, as...

22 CFR 228.23 - Eligibility of marine insurance.

Science.gov (United States)

2010-04-01

...-Related Services for USAID Financing § 228.23 Eligibility of marine insurance. The eligibility of marine... commodities procured with USAID funds be insured in the United States against marine loss. The decision of any...

47 CFR 54.201 - Definition of eligible telecommunications carriers, generally.

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2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Definition of eligible telecommunications carriers, generally. 54.201 Section 54.201 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... § 54.201 Definition of eligible telecommunications carriers, generally. (a) Carriers eligible to...

Activated HGF-c-Met Axis in Head and Neck Cancer

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Levi Arnold

2017-12-01

Full Text Available Head and neck squamous cell carcinoma (HNSCC is a highly morbid disease. Recent developments including Food and Drug Administration (FDA approved molecular targeted agent’s pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal–epithelial transition factor (c-Met and its ligand hepatocyte growth factor (HGF are overexpressed in head and neck squamous cell carcinoma (HNSCC; and regulates tumor progression and response to therapy. The c-Met pathway has been shown to regulate many cellular processes such as cell proliferation, invasion, and angiogenesis. The c-Met pathway is involved in cross-talk, activation, and perpetuation of other signaling pathways, curbing the cogency of a blockade molecule on a single pathway. The receptor and its ligand act on several downstream effectors including phospholipase C gamma (PLCγ, cellular Src kinase (c-Src, phosphotidylinsitol-3-OH kinase (PI3K alpha serine/threonine-protein kinase (Akt, mitogen activate protein kinase (MAPK, and wingless-related integration site (Wnt pathways. They are also known to cross-talk with other receptors; namely epidermal growth factor receptor (EGFR and vascular endothelial growth factor receptor (VEGFR and specifically contribute to treatment resistance. Clinical trials targeting the c-Met axis in HNSCC have been undertaken because of significant preclinical work demonstrating a relationship between HGF/c-Met signaling and cancer cell survival. Here we focus on HGF/c-Met impact on cellular signaling in HNSCC to potentiate tumor growth and disrupt therapeutic efficacy. Herein we summarize the current understanding of HGF/c-Met signaling and its effects on HNSCC. The intertwining of c-Met signaling with other signaling pathways provides opportunities for more robust and specific therapies, leading to better clinical outcomes.

COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of 'switching on' hallucinations in the flow of daily life.

Science.gov (United States)

Henquet, C; Rosa, A; Delespaul, P; Papiol, S; Fananás, L; van Os, J; Myin-Germeys, I

2009-02-01

A functional polymorphism in the catechol-o-methyltransferase gene (COMT Val(158)Met) may moderate the psychosis-inducing effects of cannabis. In order to extend this finding to dynamic effects in the flow of daily life, a momentary assessment study of psychotic symptoms in response to cannabis use was conducted. The experience sampling technique was used to collect data on cannabis use and occurrence of symptoms in daily life in patients with a psychotic disorder (n = 31) and healthy controls (n = 25). Carriers of the COMT Val(158)Met Val allele, but not subjects with the Met/Met genotype, showed an increase in hallucinations after cannabis exposure, conditional on prior evidence of psychometric psychosis liability. The findings confirm that in people with psychometric evidence of psychosis liability, COMT Val(158)Met genotype moderates the association between cannabis and psychotic phenomena in the flow of daily life.

Anti-c-MET Nanobody - a new potential drug in multiple myeloma treatment.

Science.gov (United States)

Slørdahl, Tobias Schmidt; Denayer, Tinneke; Moen, Siv Helen; Standal, Therese; Børset, Magne; Ververken, Cedric; Rø, Torstein Baade

2013-11-01

c-MET is the tyrosine kinase receptor of the hepatocyte growth factor (HGF). HGF-c-MET signaling is involved in many human malignancies, including multiple myeloma (MM). Recently, multiple agents have been developed directed to interfere at different levels in HGF-c-MET signaling pathway. Nanobodies are therapeutic proteins based on the smallest functional fragments of heavy-chain-only antibodies. In this study, we wanted to determine the anticancer effect of a novel anti-c-MET Nanobody in MM. We examined the effects of an anti-c-MET Nanobody on thymidine incorporation, migration, adhesion of MM cells, and osteoblastogenesis in vitro. Furthermore, we investigated the effects of the Nanobody on HGF-dependent c-MET signaling by Western blotting. We show that the anti-c-MET Nanobody effectively inhibited thymidine incorporation of ANBL-6 MM cells via inhibition of an HGF autocrine growth loop and thymidine incorporation in INA-6 MM cells induced by exogenous HGF. HGF-induced migration and adhesion of INA-6 were completely and specifically blocked by the Nanobody. Furthermore, the Nanobody abolished the inhibiting effect of HGF on bone morphogenetic protein-2-induced alkaline phosphatase activity and the mineralization of human mesenchymal stem cells. Finally, we show that the Nanobody reduced phosphorylation of tyrosine residues in c-MET, MAPK, and Akt. We also compared the Nanobody with anti-c-MET monoclonal antibodies and revealed the similar or better effect. The anti-c-MET Nanobody inhibited MM cell migration, thymidine incorporation, and adhesion, and blocked the HGF-mediated inhibition of osteoblastogenesis. The anti-c-MET Nanobody might represent a novel therapeutic agent in the treatment of MM and other cancers driven by HGF-c-MET signaling. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of a framework to improve the process of recruitment to randomised controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised) framework.

Science.gov (United States)

Wilson, Caroline; Rooshenas, Leila; Paramasivan, Sangeetha; Elliott, Daisy; Jepson, Marcus; Strong, Sean; Birtle, Alison; Beard, David J; Halliday, Alison; Hamdy, Freddie C; Lewis, Rebecca; Metcalfe, Chris; Rogers, Chris A; Stein, Robert C; Blazeby, Jane M; Donovan, Jenny L

2018-01-19

Research has shown that recruitment to trials is a process that stretches from identifying potentially eligible patients, through eligibility assessment, to obtaining informed consent. The length and complexity of this pathway means that many patients do not have the opportunity to consider participation. This article presents the development of a simple framework to document, understand and improve the process of trial recruitment. Eight RCTs integrated a QuinteT Recruitment Intervention (QRI) into the main trial, feasibility or pilot study. Part of the QRI required mapping the patient recruitment pathway using trial-specific screening and recruitment logs. A content analysis compared the logs to identify aspects of the recruitment pathway and process that were useful in monitoring and improving recruitment. Findings were synthesised to develop an optimised simple framework that can be used in a wide range of RCTs. The eight trials recorded basic information about patients screened for trial participation and randomisation outcome. Three trials systematically recorded reasons why an individual was not enrolled in the trial, and further details why they were not eligible or approached, or declined randomisation. A framework to facilitate clearer recording of the recruitment process and reasons for non-participation was developed: SEAR - Screening, to identify potentially eligible trial participants; Eligibility, assessed against the trial protocol inclusion/exclusion criteria; Approach, the provision of oral and written information and invitation to participate in the trial, and Randomised or not, with the outcome of randomisation or treatment received. The SEAR framework encourages the collection of information to identify recruitment obstacles and facilitate improvements to the recruitment process. SEAR can be adapted to monitor recruitment to most RCTs, but is likely to add most value in trials where recruitment problems are anticipated or evident. Further work

Mogelijkheden om vroeg tijdig bladrandproblemen te signaleren met MIPS bij Hortensia

NARCIS (Netherlands)

Noort, van F.R.; Jalink, H.

2010-01-01

Met geavanceerde camera technieken zijn beelden vast te leggen van fotosynthese activiteit en het is ook mogelijk gebleken om bladgedeelten met stress vast te leggen, zonder dat deze stress met het blote oog al te zien is. Dit opent perspectieven om monitorringonderzoek te doen naar het ontstaan van

Design and Implementation of Image Research for the Columbia Mets

Science.gov (United States)

1992-01-01

the other hand, developed an unusual camaraderie through identifying with their underdog Mets." (7) Teams are finding good public relations programs do...supports the club. Question 24 was designed to measure brand loyalty by respondents to Mets sponsors versus non-Mets sponsors. Finally, question 27...be done to attract crowds. Especially with a brand new stadium. The Carolinas, in my opinion, are big minor league baseball states. Let’s get people

Alternative Fuels Data Center: Workplace Charging Success: MetLife

Science.gov (United States)

future." Several others noted that their decision to purchase or lease a PEV was based on MetLife's : MetLife " By making PEV charging stations more readily available to employees, we can encourage more promote alternative transportation. By making PEV charging stations more readily available to employees

Development of antibody-based c-Met inhibitors for targeted cancer therapy

Directory of Open Access Journals (Sweden)

Lee D

2015-02-01

Full Text Available Dongheon Lee, Eun-Sil Sung, Jin-Hyung Ahn, Sungwon An, Jiwon Huh, Weon-Kyoo You Hanwha Chemical R&D Center, Biologics Business Unit, Daejeon, Republic of Korea Abstract: Signaling pathways mediated by receptor tyrosine kinases (RTKs and their ligands play important roles in the development and progression of human cancers, which makes RTK-mediated signaling pathways promising therapeutic targets in the treatment of cancer. Compared with small-molecule compounds, antibody-based therapeutics can more specifically recognize and bind to ligands and RTKs. Several antibody inhibitors of RTK-mediated signaling pathways, such as human epidermal growth factor receptor 2, vascular endothelial growth factor, epidermal growth factor receptor or vascular endothelial growth factor receptor 2, have been developed and are widely used to treat cancer patients. However, since the therapeutic options are still limited in terms of therapeutic efficacy and types of cancers that can be treated, efforts are being made to identify and evaluate novel RTK-mediated signaling pathways as targets for more efficacious cancer treatment. The hepatocyte growth factor/c-Met signaling pathway has come into the spotlight as a promising target for development of potent cancer therapeutic agents. Multiple antibody-based therapeutics targeting hepatocyte growth factor or c-Met are currently in preclinical or clinical development. This review focuses on the development of inhibitors of the hepatocyte growth factor/c-Met signaling pathway for cancer treatment, including critical issues in clinical development and future perspectives for antibody-based therapeutics. Keywords: hepatocyte growth factor, ligands, receptor tyrosine kinase, signaling pathway, therapeutic agent

Metabolic syndrome in human immunodeficiency virus positive patients

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Sarita Bajaj

2013-01-01

Full Text Available Aims and Objectives : To assess the prevalence of metabolic syndrome (MetS in human immunodeficiency virus (HIV positive patients. Prevalence of MetS was compared in patients who were not on highly active antiretroviral therapy (HAART to patients who were on HAART. Materials and Methods: Seventy HIV positive cases were studied. Pregnant and lactating women, patients on drugs other than HAART known to cause metabolic abnormalities and those having diabetes or hypertension were excluded. Cases were evaluated for MetS by using National Cholesterol Education Program Adult Treatment Panel-III. Results: 47 cases were on HAART and 23 cases were not on HAART. Fasting Blood Glucose ≥100 mg/dl was present in 28.6% cases, out of whom 27.7% were on HAART and 30.4% were not on HAART (P = 0.8089. 12.9% cases had BP ≥130/≥85 mm Hg, out of whom 14.9% were on HAART and 8.7% were not on HAART (P = 0.4666. 42.9% cases had TG ≥150 mg/dl, out of whom 44.7% were on HAART and 39.1% were not on HAART (P = 0.6894. HDL cholesterol was low (males <40 mg/dl, females <50 mg/dl in 50% cases, out of whom 55.3% were on HAART and 39.1% were not on HAART (P = 0.2035. Conclusions: Prevalence of MetS was 20%. Majority of patients had only one component of MetS (32.9%. Low HDL was present in 50%, followed by raised triglycerides in 42.9%. Waist circumference was not increased in any of the patients. There was no statistically significant difference between those on HAART and those not on HAART in distribution of risk factors and individual components of MetS.

The Clinical Stages of Sporadic Creutzfeldt-Jakob Disease with Met/Met Genotype in Korean Patients.

Science.gov (United States)

Park, So Young; Wang, Min Jeong; Jang, Jae-Won; Park, Young Ho; Lim, Jae-Sung; Youn, Young Chul; Kim, Jungeun; Kim, SangYun

2016-01-01

Clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is currently based on changes occurring in the late disease stages, which limits early-stage detection. Therefore, we investigated the disease course from the vague symptomatic to the terminal phase. We retrospectively reviewed 36 sCJD patient records, classifying the disease progression into 4 stages based on clinical manifestations: vague symptomatic, possible CJD, probable CJD and chronic vegetative state. We analyzed findings from diffusion-weighted imaging (DWI), electroencephalography (EEG) and cerebrospinal fluid (CSF) 14-3-3 protein testing performed at each stage. In stage 1, the most distinctive feature was DWI hyperintensities in the neocortex, even with negative CSF 14-3-3 protein and EEG results. In stage 2, DWI hyperintensities in the limbic cortex were more remarkable. CSF 14-3-3 protein testing yielded positive results in >80% of patients; EEG showed sensitivity in disease stage-dependent differences in clinical symptoms and laboratory test results will facilitate early and accurate diagnosis. © 2016 S. Karger AG, Basel.

24 CFR 1000.102 - What are eligible affordable housing activities?

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false What are eligible affordable housing activities? 1000.102 Section 1000.102 Housing and Urban Development Regulations Relating to... § 1000.102 What are eligible affordable housing activities? Eligible affordable housing activities are...

Development of an ICF-based eligibility procedure for education in Switzerland.

Science.gov (United States)

Hollenweger, Judith

2011-05-31

Starting in January 2011, Switzerland will implement a multidimensional, context-sensitive procedure to establish eligibility in education systems. This paper provides a brief overview of the different eligibility-related practices with a special focus on children with disabilities. The paper then outlines the philosophical and conceptual framework of the eligibility procedure based on the International Classification of Functioning, Disability and Health, and the UN Convention on the Rights of Persons with Disability. The different components and methodology applied to organise information in the process towards establishing eligibility are also presented. Finally, some observations are made regarding transparent and just applications of the eligibility procedure, and the implementation of this new eligibility procedure.

7 CFR 760.305 - Eligible grazing losses.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false Eligible grazing losses. 760.305 Section 760.305... grazing losses. (a) A grazing loss due to drought is eligible for LFP only if the grazing loss for the... period for the specific type of grazing land or pastureland for the county.) (b) A grazing loss is not...

Determining eligibility for antiretroviral therapy in resource-limited settings using total lymphocyte counts, hemoglobin and body mass index

Directory of Open Access Journals (Sweden)

Solberg Peter

2007-01-01

Full Text Available Abstract Background CD4+ T lymphocyte (CD4 cell count testing is the standard method for determining eligibility for antiretroviral therapy (ART, but is not widely available in sub-Saharan Africa. Total lymphocyte counts (TLCs have not proven sufficiently accurate in identifying subjects with low CD4 counts. We developed clinical algorithms using TLCs, hemoglobin (Hb, and body mass index (BMI to identify patients who require ART. Methods We conducted a cross-sectional study of HIV-infected adults in Uganda, who presented for assessment for ART-eligibility with WHO clinical stages I, II or III. Two by two tables were constructed to examine TLC thresholds, which maximized sensitivity for CD4 cell counts ≤ 200 cells μL, while minimizing the number offered ART with counts > 350 cells μL. Hb and BMI values were then examined to try to improve model performance. Results 1787 subjects were available for analysis. Median CD4 cell counts and TLCs, were 239 cells/μL and 1830 cells/μL, respectively. Offering ART to all subjects with a TLCs ≤ 2250 cells/μL produced a sensitivity of 0.88 and a false positive ratio of 0.21. Algorithms that treated all patients with a TLC 3000 cells/μL, and used Hb and/or BMI values to determine eligibility for those with TLC values between 2000 and 3000 cells/μL, marginally improved accuracy. Conclusion TLCs appear useful in predicting who would be eligible for ART based on CD4 cell count criteria. Hb and BMI values may be useful in prioritizing patients for ART, but did not improve model accuracy.

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

Directory of Open Access Journals (Sweden)

Sotoudeh Kambiz

2012-05-01

Full Text Available Abstract Background c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. Methods In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008–2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. Results Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124 of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04, deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014, neural invasion (P = 0.002 and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044. The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065 and vascular invasion (P = 0.078 were observed. Conclusions c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429

Efficacy of A Fluoropyrimidine plus Mitomycin C in Pretreated Patients with Metastatic Colorectal Cancer Eligible for Regorafenib: A Retrospective Study

Directory of Open Access Journals (Sweden)

Federica Martorana

2017-11-01

Full Text Available Objective: In the placebo-controlled CORRECT study, individuals with metastatic colorectal cancer (mCRC receiving Regorafenib (RGR achieved significant benefits in both median overall survival (OS: 6.4 months and progression-free survival (PFS 1.9 months. Patients included in the study had previously failed all standard therapies, which must have included Fluoropyrimidines (FPDs, Oxaliplatin, Irinotecan, Bevacizumab, and Cetuximab or Panitumumab for K-RAS wild-type subjects. FPDs plus Mitomycin C (MMC represent one of the few treatment options for mCRC patients currently eligible for RGR. We wanted to investigate the therapeutic benefit of this pharmacological association in the same clinical setting defined for RGR. Methods: We retrospectively evaluated the records of mCRC patients followed in our Institutions that would have fulfilled inclusion/exclusion criteria for the CORRECT trial and received instead the combination of FPDs and MMC. We therefore collected data from 87 patients: 61 fulfilled the criteria required for this analysis. Results: Median OS was 9.3 months (95% CI 9.0–15.4, with a median PFS of 3.3 months (95% CI 2.9–3.8. One third of the patients (29.5% achieved disease control. No significant differences in OS and PFS were found between K-RAS WT and K-RAS mutant individuals. Likewise, Performance Status (PS and the primary site of disease were not associated with differences in response rates. Conclusions: These results suggest the need for a prospective study assessing RGR cost-effectiveness compared to FPDs plus MMC for mCRC patients that progress after standard treatments.

Cetuximab-Induced MET Activation Acts as a Novel Resistance Mechanism in Colon Cancer Cells

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Na Song

2014-04-01

Full Text Available Aberrant MET expression and hepatocyte growth factor (HGF signaling are implicated in promoting resistance to targeted agents; however, the induced MET activation by epidermal growth factor receptor (EGFR inhibitors mediating resistance to targeted therapy remains elusive. In this study, we identified that cetuximab-induced MET activation contributed to cetuximab resistance in Caco-2 colon cancer cells. MET inhibition or knockdown sensitized Caco-2 cells to cetuximab-mediated growth inhibition. Additionally, SRC activation promoted cetuximab resistance by interacting with MET. Pretreatment with SRC inhibitors abolished cetuximab-mediated MET activation and rendered Caco-2 cells sensitive to cetuximab. Notably, cetuximab induced MET/SRC/EGFR complex formation. MET inhibitor or SRC inhibitor suppressed phosphorylation of MET and SRC in the complex, and MET inhibitor singly led to disruption of complex formation. These results implicate alternative targeting of MET or SRC as rational strategies for reversing cetuximab resistance in colon cancer.

7 CFR 631.7 - Conservation treatment eligible for cost sharing.

Science.gov (United States)

2010-01-01

..., conservation practices, or identifiable units eligible for GPCP cost sharing in the state. (b) The designated... conservation systems, practices, or identifiable units eligible for GPCP cost sharing in the county. ... 7 Agriculture 6 2010-01-01 2010-01-01 false Conservation treatment eligible for cost sharing. 631...

Metabolic Syndrome and Physical Activity in Hemodialysis Patients

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derya atik

2014-06-01

Full Text Available Purpose: This descriptive study was carried out to reveal the level of physical activity in patients who receive hemodialysis due to chronic kidney failure and to identify its relationship with the prevalence of metabolic syndrome (MetS. Material and method: The study was conducted with 55 patients at the hemodialysis units of Alanya State Hospital and Private Alanya Anadolu Hospital between 10 and 30 June 2013. The study data were collected using the National Cholesterol Education Program, the Adult Treatment Panel III (NCEP-ATP III, a data collection form containing Metabolic Syndrome Diagnosis Criteria, and the International Physical Activity Questionnaire (IPAQ. The data were analyzed using arithmetic mean +/- standard deviation (SD, number and percentage distributions, independent sample t test, crosstabs, One Way Anova, and Pearson and #8217;s Correlation Analysis. Conclusion and suggestions: It was found that 41.8% of the patients were between 50 and 65 years of age, the majority of them were male (58.2%, hemodialysis had been administered to 69.1% of them for at least 36 months, and 50.9% of them met three and more of the MetS criteria. There was no statistically significant relationship between MetS and physical activity levels, but the length of physical activity was longer in those who did not meet the MetS diagnosis criteria (p>0.05. An increase in sedentary time raised the MetS criteria (p<0.05. Conclusion: Nearly 1/2 of the patients were at risk of MetS. Physical activity level being statistically ineffective on MetS can be associated with low physical activity level and longer sedentary time. It can be said that being completely sedentary increases BMI and therefore MetS. The study can be repeated on different samples and the results can be compared. [J Contemp Med 2014; 4(2.000: 69-75

Predictors of receiving therapy among very low birth weight 2-year olds eligible for Part C early intervention in Wisconsin.

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McManus, Beth Marie; Robert, Stephanie; Albanese, Aggie; Sadek-Badawi, Mona; Palta, Mari

2013-07-11

The Individuals with Disabilities Education Act (Part C) authorizes states to establish systems to provide early intervention services (e.g., therapy) for children at risk, with the incentive of federal financial support. This study examines family and neighborhood characteristics associated with currently utilizing physical, occupational, or speech therapy among very low birthweight (VLBW) 2-year-old children who meet Wisconsin eligibility requirements for early intervention services (EI) due to developmental delay. This cross-sectional analysis used data from the Newborn Lung Project, a regional cohort study of VLBW infants hospitalized in Wisconsin's newborn intensive care units during 2003-2004. We included the 176 children who were age two at follow-up, and met Wisconsin state eligibility requirements for EI based on developmental delay. Exact logistic regression was used to describe child and neighborhood socio-demographic correlates of parent-reported receipt of therapy. Among VLBW children with developmental delay, currently utilizing therapy was higher among children with Medicaid (aOR = 5.3, 95% CI: 1.3, 28.3) and concomitant developmental disability (aOR = 5.2, 95% CI: 2.1, 13.3) and lower for those living in a socially more disadvantaged neighborhood (aOR=0.48, 95% CI: 0.21, 0.98, per tertile). Among a sample of VLBW 2-year olds with developmental delays who are EI-eligible in WI, 4 out of 5 were currently receiving therapy, per parent report. Participation in Medicaid positively influences therapy utilization. Children with developmental difficulties who live in socially disadvantaged neighborhoods are at highest risk for not receiving therapy.

MetWAMer: eukaryotic translation initiation site prediction

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Brendel Volker

2008-09-01

Full Text Available Abstract Background Translation initiation site (TIS identification is an important aspect of the gene annotation process, requisite for the accurate delineation of protein sequences from transcript data. We have developed the MetWAMer package for TIS prediction in eukaryotic open reading frames of non-viral origin. MetWAMer can be used as a stand-alone, third-party tool for post-processing gene structure annotations generated by external computational programs and/or pipelines, or directly integrated into gene structure prediction software implementations. Results MetWAMer currently implements five distinct methods for TIS prediction, the most accurate of which is a routine that combines weighted, signal-based translation initiation site scores and the contrast in coding potential of sequences flanking TISs using a perceptron. Also, our program implements clustering capabilities through use of the k-medoids algorithm, thereby enabling cluster-specific TIS parameter utilization. In practice, our static weight array matrix-based indexing method for parameter set lookup can be used with good results in data sets exhibiting moderate levels of 5'-complete coverage. Conclusion We demonstrate that improvements in statistically-based models for TIS prediction can be achieved by taking the class of each potential start-methionine into account pending certain testing conditions, and that our perceptron-based model is suitable for the TIS identification task. MetWAMer represents a well-documented, extensible, and freely available software system that can be readily re-trained for differing target applications and/or extended with existing and novel TIS prediction methods, to support further research efforts in this area.

The Prevalence and Characteristics of Metabolic Syndrome in Patients with Vertigo

OpenAIRE

Yamanaka, Toshiaki; Fukuda, Takehiko; Shirota, Shiho; Sawai, Yachiyo; Murai, Takayuki; Fujita, Nobuya; Hosoi, Hiroshi

2013-01-01

OBJECTIVES/HYPOTHESIS: Metabolic syndrome (MetS) is a condition that increases the risk of coronary artery disease and cerebral infarction. We determined the prevalence of MetS in vertigo patients and clinically investigated the association between MetS and vertigo. STUDY DESIGN: Case-control study. METHODS: The subjects were 333 patients, including 107 males and 226 females, who presented with vertigo as a primary symptom. MetS was diagnosed according to the International Diabetes Federation...

BDNF val66met polymorphism is associated with age at onset and intensity of symptoms of paranoid schizophrenia in a Polish population.

Science.gov (United States)

Suchanek, Renata; Owczarek, Aleksander; Paul-Samojedny, Monika; Kowalczyk, Małgorzata; Kucia, Krzysztof; Kowalski, Jan

2013-01-01

The brain-derived neurotrophic factor (BDNF) is one of the candidate genes for schizophrenia. There is evidence that val66met polymorphism may be involved in the pathophysiology of schizophrenia. The authors genotyped val66met (rs6265) polymorphism of the BDNF gene in 208 inpatients with paranoid schizophrenia and 254 control subjects in a Polish population. There was no association between val66met polymorphism and development of paranoid schizophrenia in either men or women. However, an association was found between this polymorphism and age at onset and psychopathology of paranoid schizophrenia. Men with the val/met genotype had an earlier age at onset, and the val/val genotype predisposed to more severe symptoms, particularly on the General Psychopathology Scale of the Positive and Negative Symptoms Scale (PANSS-G). The analysis of PANSS single items has shown that patients with the val/met genotype had higher scores on a hallucinatory behavior item than those with other genotypes.

Prevalence and characteristics of the metabolic syndrome among newly diagnosed hypertensive patients

Science.gov (United States)

Osuji, Charles U.; Omejua, Emeka G.

2012-01-01

Background: Cardiovascular disease risk factors have a tendency to cluster. The presence of such a cluster in an individual has been designated the metabolic syndrome (MetS). There is a paucity of reports of the prevalence of MetS in hypertensive patients in south east Nigeria. This study was undertaken to determine the prevalence of the metabolic syndrome (MetS) among newly diagnosed hypertensive patients using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria in a tertiary healthcare centre in South East Nigeria. Materials and Methods: A population of 250 consecutive newly diagnosed adult hypertensive patients (126 males and 124 females) was evaluated. Blood pressure and anthropometric measurements were done using standardized techniques. After an overnight fast, blood samples were taken for glucose and lipid profile assays. The NCEP ATP III criteria were then applied for the diagnosis of MetS. Results: The prevalence of the MetS among the study population was 31.2%. The sex-specific prevalences were 15.1% and 47.6% among male and female patients respectively. A large number of the patients (40.4%) were at a high potential risk of developing the MetS as they already met 2 of the criteria. The MetS prevalence increased progressively from 14.3% through 23.8%, in the patients aged 24-33years and 34-43 years, respectively to a peak (40.4%) among those aged 44-53 years before declining in those aged 54-63 years (31.8%), 64-73 years (33.3%) and 74 years and above (20.6%). Central obesity was the most common component of the MetS being present in 50.4% of patients (28.6% of males and 72.6% of females). Of the other components, low HDL-C was present in 38.8% (26.2% of males and 51.6% of females), elevated FBS in 12.8% (6.3% of males and 19.4% of females) and elevated triglycerides in 8.8% (11.9% of males and 5.6% of females). Conclusion: The prevalence of the MetS is high among newly diagnosed hypertensive patients in Nnewi

What proportion of prescription items dispensed in community pharmacies are eligible for the New Medicine Service?

Science.gov (United States)

Wells, Katharine M; Boyd, Matthew J; Thornley, Tracey; Boardman, Helen F

2014-03-07

The payment structure for the New Medicine Service (NMS) in England is based on the assumption that 0.5% of prescription items dispensed in community pharmacies are eligible for the service. This assumption is based on a theoretical calculation. This study aimed to find out the actual proportion of prescription items eligible for the NMS dispensed in community pharmacies in order to compare this with the theoretical assumption. The study also aimed to investigate whether the proportion of prescription items eligible for the NMS is affected by pharmacies' proximity to GP practices. The study collected data from eight pharmacies in Nottingham belonging to the same large chain of pharmacies. Pharmacies were grouped by distance from the nearest GP practice and sampled to reflect the distribution by distance of all pharmacies in Nottingham. Data on one thousand consecutive prescription items were collected from each pharmacy and the number of NMS eligible items recorded. All NHS prescriptions were included in the sample. Data were analysed and proportions calculated with 95% confidence intervals used to compare the study results against the theoretical figure of 0.5% of prescription items being eligible for the NMS. A total of 8005 prescription items were collected (a minimum of 1000 items per pharmacy) of which 17 items were eligible to receive the service. The study found that 0.25% (95% confidence intervals: 0.14% to 0.36%) of prescription items were eligible for the NMS which differs significantly from the theoretical assumption of 0.5%. The opportunity rate for the service was lower, 0.21% (95% confidence intervals: 0.10% to 0.32%) of items, as some items eligible for the NMS did not translate into opportunities to offer the service. Of all the prescription items collected in the pharmacies, 28% were collected by patient representatives. The results of this study show that the proportion of items eligible for the NMS dispensed in community pharmacies is lower than

Erlotinib e metástases cerebrais

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Fernando Barata

2008-10-01

Full Text Available Resumo: Relatamos dois casos de carcinoma pulmonar de não pequenas células (CPNPC com metástases cerebrais que após quimioterapia sistémica receberam em segunda e terceira linha erlotinib 150 mg/dia, oral, com resposta completa das lesões secundárias cerebrais e franca resposta parcial das lesões torácicas.A metastização cerebral, bastante prevalente no contexto do CPNPC, está associada a escassas opções terapêuticas eficazes e, consequentemente, a uma sobre-vida mediana de 4 a 6 meses.Estes casos alertam para o erlotinib como uma excelente opção terapêutica para estes doentes. Os autores propõem um ensaio clínico com este fármaco neste grupo de doentes, procurando determinar da resposta objectiva.Rev Port Pneumol 2008; XIV (Supl 3: S35-S42 Abstract: We report two cases of brain metastases in context of non small cell lung cancer (NSCLC. After having progressed to chemotherapy they received erlotinib 150 mg/m2 orally daily, with complete response of brain metastasis and partial response of thoracic lesions.Brain metastases are both prevalent and a major cause of mortality in NSCLC, with few systemic treatment options. Median survival after whole brain radiotherapy is 4-6 months and the role of systemic therapy for brain metastases is limited with the most drugs use to stage IV disease ineffective in this setting.This case demonstrates that brain metastases may be sensitive to erlotinib and give to us growing body of evidence that EGFR-associated tyrosine kinase inhibition is a feasible strategy in the management of NSCLC patients with brain metastasesWe propose further study into the continued use of this drug in the situation where there is a differential response.Rev Port Pneumol 2008; XIV (Supl 3: S35-S42 Palavras-chave: Erlotinib, metástase cerebral, cancro do pulmão, Key-words: Erlotinib, brain metastasis, lung cancer

OTULIN antagonizes LUBAC signaling by specifically hydrolyzing met1-linked polyubiquitin

DEFF Research Database (Denmark)

Keusekotten, K.; Elliott, P.R.; Kulathu, Y.

2013-01-01

The linear ubiquitin (Ub) chain assembly complex (LUBAC) is an E3 ligase that specifically assembles Met1-linked (also known as linear) Ub chains that regulate nuclear factor κB (NF-κB) signaling. Deubiquitinases (DUBs) are key regulators of Ub signaling, but a dedicated DUB for Met1 linkages has...... not been identified. Here, we reveal a previously unannotated human DUB, OTULIN (also known as FAM105B), which is exquisitely specific for Met1 linkages. Crystal structures of the OTULIN catalytic domain in complex with diubiquitin reveal Met1-specific Ub-binding sites and a mechanism of substrate...

Treatment eligibility in Alaska Native and American Indian persons with hepatitis C virus infection

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Stephen E. Livingston

2012-04-01

Full Text Available Objectives. Treatment with pegylated interferon and ribavirin may prevent progression of liver disease among patients with chronic hepatitis C virus infection (HCV. Treatment initiation is based on published clinical eligibility criteria, patients’ willingness to undergo treatment and likelihood of success. We examined treatment eligibility in a cohort of Alaska Native and American Indian persons with chronic HCV infection. Study design. Retrospective cohort study. Methods. Medical records of all treatment naïve HCV RNA positive patients given an appointment by hepatology specialty clinic staff in 2003 and 2007 were evaluated by a hepatology provider to investigate documented reasons for treatment deferral. Results. Treatment was initiated in 4 of 94 patients (4% in 2003 and 14 of 146 patients (10% in 2007. Major reasons for treatment deferral in 2003 versus 2007 included inconsistent appointment attendance (36% of deferrals vs. 18%, active substance abuse (17% vs. 22%, patient decision (17% vs. 27%, liver biopsy without fibrosis or normal ALT (8% vs. 3%, uncontrolled psychiatric condition (7% vs. 7% and concurrent medical condition (6% vs. 9%. There was significant improvement in proportion of appointments attended in 2007 versus 2003 (76% vs. 67%, p = 0.04 and the percentage of patients attending at least 1 appointment (84% vs. 66%, p = 0.002. Conclusions. Multiple reasons for treatment deferral were documented. Despite a significant improvement in hepatology clinic attendance and an increase in the number of patients started on treatment in 2007 compared to 2003, the overall percentage of those treated remained low.

A clinical study on cognitive impairment in post-ischemic stroke patients with metabolic syndrome

Directory of Open Access Journals (Sweden)

LI Chen

2012-02-01

Full Text Available Objective To explore the relation between metabolic syndrome (MetS and cognitive impairment after ischemic stroke. Methods Ninety-four cases of first ischemic stroke patients were divided into stroke without MetS group (n = 54 and stroke with MetS group (n = 40 according to the diagnostic criteria for MetS defined by Metabolic Syndrome Researching Group of Chinese Diabetes Society. All patients underwent Mini-Mental State Examination (MMSE, Clock Drawing Test (CDT, animal Verbal Fluency Test (aVFT, Trial Making Test-A (TMT-A at 2 weeks and 3 months after stroke to evaluate mental state such as verbal learning memory, and executive, attentional and visuospatial abilities. The incidence and development of cognitive impairment were also assessed. Results At 2 weeks and 3 months after stroke, the incidence of cognitive impairment were 24.47% (23/94 and 22.34% (21/94, respectively, and in the cognitive impairment patients the incidence of non-dementia were 21.28% (20/94 and 19.15% (18/94, while the incidence of dementia were 3.19% (3/94 and 3.19% (3/94, respectively. The incidence of cognitive impairment was higher in the stroke patients with MetS than the stroke patients without MetS, 37.50% (15/40 vs 14.81% (8/54 (Z = 2.500, P = 0.012 at 2 weeks after stroke and 35.00% (14/40 vs 12.96% (7/54 (Z = 2.513, P = 0.012 at 3 months after stroke. In the scores of MMSE, delay recall and CDT of the stroke patients with MetS were all lower than those without MetS at 2 weeks after stroke and at 3 months after stroke (P < 0.05, for all. The stroke patients with MetS had more cognition deterioration than the stroke patients without MetS at 3 months after stroke, the difference was significant (Z = 2.134, P = 0.033. Conclusion MetS can increase the incidence of cognitive impairment, especially non-dementia cognitive impairment in post ischemic stroke. Executive dysfunction and hypomnesis are often seen. The development of cognitive impairment in stroke patients

De Doop met de Heilige Geest

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S. C.W. Duvenage.

1965-03-01

Full Text Available Ds. Molenaar begin sy boek, waarvan hy self die publikasienie beleef het nie, deur te wys op 'n groot tekort, ’n manko,nie alleen in die Gereformeerde vroomheid of lewe nie maarook in die Gereformeerde teologie. Hy beskou dit as hoogsmerkwaardig dat die Gereformeerde teologie in die verledeso goed as niks raakgesien het van die groot betekenis vandie sogenaamde doop met die Heilige Gees nie. Daarby meenhy dat die Gereformeerde predikante verleë sit met die Pinkterfees.Talle probleme meen hy vir die Gereformeerde teoloograak te sien, veral ten aansien van die moontlikhede van dieGees teenoor die so tasbare „onmoontIikhede” in ons lewe. Dieprobleme is syns insiens nie onoplosbaar nie, as mens maardie moontlikhede van die Gees nie beperk tot die verlede nie.

Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression.

Science.gov (United States)

Lalani, Aly-Khan A; Gray, Kathryn P; Albiges, Laurence; Callea, Marcella; Pignon, Jean-Christophe; Pal, Soumitro; Gupta, Mamta; Bhatt, Rupal S; McDermott, David F; Atkins, Michael B; Woude, G F Vande; Harshman, Lauren C; Choueiri, Toni K; Signoretti, Sabina

2017-11-28

In preclinical models, c-Met promotes survival of renal cancer cells through the regulation of programmed death-ligand 1 (PD-L1). However, this relationship in human clear cell renal cell carcinoma (ccRCC) is not well characterized. We evaluated c-Met expression in ccRCC patients using paired primary and metastatic samples and assessed the association with PD-L1 expression and other clinical features. Areas with predominant and highest Fuhrman nuclear grade (FNG) were selected. c-Met expression was evaluated by IHC using an anti-Met monoclonal antibody (MET4 Ab) and calculated by a combined score (CS, 0-300): intensity of c-Met staining (0-3) x % of positive cells (0-100). PD-L1 expression in tumor cells was previously assessed by IHC and PD-L1+ was defined as PD-L1 > 0% positive cells. Our cohort consisted of 45 pairs of primary and metastatic ccRCC samples. Overall, c-Met expression was higher in metastatic sites compared to primary sites (average c-Met CS: 55 vs. 28, p = 0.0003). Higher c-Met expression was associated with higher FNG (4 vs. 3) in primary tumors (average c-Met CS: 52 vs. 20, p = 0.04). c-Met expression was numerically greater in PD-L1+ vs. PD-L1- tumors. Higher c-Met expression in metastatic sites compared to primary tumors suggests that testing for biomarkers of response to c-Met inhibitors should be conducted in metastases. While higher c-Met expression in PD-L1+ tumors requires further investigation, it supports exploring these targets in combination clinical trials.

24 CFR 982.628 - Homeownership option: Eligible units.

Science.gov (United States)

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: Eligible units. 982.628 Section 982.628 Housing and Urban Development Regulations Relating to Housing and Urban... Types Homeownership Option § 982.628 Homeownership option: Eligible units. (a) Initial requirements...

44 CFR 78.12 - Eligible types of projects.

Science.gov (United States)

2010-10-01

..., DEPARTMENT OF HOMELAND SECURITY INSURANCE AND HAZARD MITIGATION National Flood Insurance Program FLOOD MITIGATION ASSISTANCE § 78.12 Eligible types of projects. The following types of projects are eligible for.... (g) Minor physical flood mitigation projects that reduce localized flooding problems and do not...

49 CFR 37.123 - ADA paratransit eligibility: Standards.