Ledipasvir/sofosbuvir regimens for chronic hepatitis C infection: Insights from a work productivity economic model from the United States.

PubMed

Younossi, Zobair M; Jiang, Yushan; Smith, Nathaniel J; Stepanova, Maria; Beckerman, Rachel

2015-05-01

Patients with chronic hepatitis C (CHC) exhibit reduced work productivity owing to their disease. Historically, most regimens indicated for CHC genotype 1 (GT1) patients were administered with pegylated interferon (Peg-IFN) and/or ribavirin (RBV), which further compromised work productivity during treatment. The aim of this study was to model the impact of LDV/SOF (ledipasvir/sofosbuvir), the first Peg-IFN- and RBV-free regimen for CHC GT1 patients, on work productivity from an economic perspective, compared to receiving no treatment. The WPAI-SHP (Work Productivity and Activity Index-Specific Health Problem) questionnaire was administered to patients across the ION clinical trials (N = 1,923 U.S. patients). Before initiation of treatment, patients with CHC GT1 in the ION trials exhibited absenteeism and presenteeism impairments of 2.57% and 7.58%, respectively. Patients with cirrhosis exhibited greater work productivity impairment than patients without cirrhosis. In total, 93.21% of U.S. patients in the ION trials achieved SVR; these patients exhibited absenteeism and presenteeism impairments of 2.62% (P = 0.76, when compared to baseline) and 3.53% (P < 0.0001), respectively. Monetizing these data to the entire U.S. population, our model projects an annual societal cost of $7.1 billion owing to productivity loss in untreated GT1 CHC patients. Our model projects that, when compared to no treatment, treating all CHC GT1 patients with a regimen with very high viral eradication rates (LDV/SOF) would translate to annual productivity loss savings of $2.7 billion over a 1-year time horizon. Patients with untreated HCV impose a substantial societal burden owing to reduced work productivity. As a result of improvements in work productivity, treatment of CHC GT1 patients with LDV/SOF-based regimens is likely to result in significant cost savings from a societal perspective, relative to no treatment. © 2015 by the American Association for the Study of Liver Diseases.

Recovery of lipid metabolic alterations in hepatitis C patients after viral clearance: Incomplete restoration with accelerated ω-oxidation.

PubMed

Chang, Su-Wei; Cheng, Mei-Ling; Shiao, Ming-Shi; Yeh, Chau-Ting; Wang, Chao-Hung; Fan, Chun-Ming; Chiu, Cheng-Tang; Chang, Ming-Ling

2018-03-02

How hepatitis C virus (HCV)-associated lipid metabolic alterations recover after sustained virological response (SVR) remains elusive. The aforementioned recovery pattern was investigated. In a prospective cohort study of 438 chronic hepatitis C (CHC) patients with SVR after anti-HCV therapy, 164 sex- and age-matched genotype I (G1) and G2 patients underwent paired-serum liquid chromatography-tandem mass spectrometry analyses before and 24 weeks after therapy. Subjects without CHC served as controls (n = 100). CHC patients had lower baseline lipid levels than controls. Among CHC patients, pre-therapy total cholesterol levels were positively associated with HCV RNA levels; G1 patients had higher pre-therapy HCV RNA levels than G2 patients. Repeated measures analysis of variance of CHC patients showed that lathosterol, lanosterol, total hydroxysphingomyelin, and total phosphatidylcholines levels, and total dicarboxyacylcarnitine/total acylcarnitine (indicators of ω-oxidation) and pre-β-lipoprotein ratios elevated 24 weeks after therapy compared with the levels before therapy. Levels of total lysophosphatidylcholines and α- and β-lipoprotein ratios decreased. Subgroup analyses showed elevated 7-dehydrocholesterol and lanosterol levels, particularly in G2 and male patients, who had broader spectra of altered phosphatidylcholines and acylcarnitines than G1 and female patients, respectively. Compared with controls, CHC patients had higher post-therapy levels of total lysophosphatidylcholines and hydroxysphingomyelins and ratios of total dicarboxyacylcarnitines/total acylcarnitines but lower cholesterol levels. At 24 weeks after therapy, accelerated cholesterol biosynthesis, hepatic lipid export, ω-oxidation, and decreased systemic inflammation were noted in CHC patients with SVR, with greater efficiency in G2 and male patients. Regardless, HCV-associated lipid metabolic alterations required >24 weeks for restoration or were incompletely reversible after SVR. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Potential diagnostic performance of contrast-enhanced ultrasound and tumor markers in differentiating combined hepatocellular-cholangiocarcinoma from hepatocellular carcinoma and cholangiocarcinoma.

PubMed

Huang, Xiao-Wen; Huang, Yang; Chen, Li-da; Wang, Zhu; Yang, Zheng; Liu, Jin-Ya; Xie, Xiao-Yan; Lu, Ming-De; Shen, Shun-Li; Wang, Wei

2018-04-01

To evaluate the diagnostic performance of the combination of tumor markers [alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9)] and imaging features in differentiating combined hepatocellular-cholangiocarcinoma (CHC) from hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Forty consecutive patients with pathologically proven CHC were retrospectively evaluated with contrast-enhanced ultrasound (CEUS). Additionally, 40 HCC and 40 CC patients who were randomly selected from the same period served as a control group. Images were classified as HCC-like or CC-like pattern according to CEUS guidelines recommended by World and European Federation for Ultrasound in Medicine and Biology (WFUMB-EFSUMB). The diagnostic criteria of CHC were defined as follows: (1) both AFP and CA19-9 are simultaneously elevated (AFP > 20 ng/ml and CA19-9 > 100 units/ml); or (2) elevated AFP with a CC-like pattern on CEUS and without elevated CA19-9 level; or (3) elevated CA19-9 with an HCC-like pattern on CEUS and without elevated AFP level. The diagnostic tests were performed with calculation of the sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). For the 40 CHC patients, the rates of elevated AFP and CA19-9 serology were 55.0 and 30.0%, respectively. Twenty-three (57.5%) patients exhibited an HCC-like pattern, and 15 (37.5%) showed a CC-like pattern. After applying the above diagnostic criteria of CHC in the 120 patients, the sensitivity, specificity, PPV, NPV, accuracy, and AUC were 32.5, 93.8, 72.2, 73.5, 73.3, and 0.631%, respectively. When the actual prevalence rate (0.4-14.3%) was taken into account, the PPV and NPV were modified from 2.1 to 46.7% and 89.3 to 99.7%, respectively. The combination of enhancement patterns on CEUS and serum tumor markers (AFP and CA19-9) may be a potentially specific diagnostic method to differentiate CHC from HCC and CC.

Patient reports of the quality of care in community health centers: the importance of having a regular provider.

PubMed

Beal, Anne; Hernandez, Susan

2010-05-01

To examine the importance of having a regular provider in community health centers (CHCs) for high quality care. Analyses of a national survey-the Commonwealth Fund 2006 Health care Quality Survey-among patients with a private doctor's (PMD) office (n=1,743) or CHC (n=275) as their regular source of care. Outcomes include prevention measures, and measures of patient experience. Patients at CHCs are less likely than patients who use a PMD to report having a regular doctor (53% vs. 95%, p

Treatment Response and Long-Term Outcome of Peginterferon α and Ribavirin Therapy in Korean Patients with Chronic Hepatitis C.

PubMed

Jung, Chang Ho; Um, Soon Ho; Kim, Tae Hyung; Yim, Sun Young; Suh, Sang Jun; Yim, Hyung Joon; Seo, Yeon Seok; Choi, Hyuk Soon; Chun, Hoon Jai

2016-09-15

Peginterferon plus ribavirin remains a standard therapy for patients with chronic hepatitis C (CHC) in Korea. We investigated the efficacy and long-term outcome of peginterferon and ribavirin therapy in Korean patients with CHC, particularly in relation to the stage of liver fibrosis. The incidence of sustained virological response (SVR), hepatic decompensation, hepatocellular carcinoma, and liver-related death was analyzed in 304 patients with CHC; the patients were followed up for a median of 54 months. Among patients with HCV genotype 1, the SVR rate was 36.7% (18/49) and 67% (69/103) for patients with and without cirrhosis, respectively (p<0.001). For patients with non-1 HCV genotypes, the SVR rates were 86.0% (37/43) in cirrhotic patients and 86.2% (94/109) in noncirrhotic patients. SVR significantly reduced the risk of liverrelated death, hepatic decompensation, and hepatocellular carcinoma, which had hazard ratios of 0.27, 0.16, and 0.22, respectively (all p<0.05). However, despite the SVR rate, patients with advanced fibrosis were still at risk of developing liver-related complications. A relatively high SVR rate was achieved by peginterferon plus ribavirin therapy in Korean patients with CHC, which improved their long-term outcomes. However, all CHC patients with advanced hepatic fibrosis should receive close follow-up observations, even after successful antiviral treatment.

Coadministration of ezetimibe with pegylated interferon plus ribavirin could improve early virological response in chronic hepatitis C obese Egyptian patients.

PubMed

Helal, Gouda K; Gad, Magdy A; Abd-Ellah, Mohamed F; Mahgoup, Elsayed M

2016-05-01

Ezetimibe has been reported to inhibit viral entry and to reduce BMI and has been proposed as a novel therapeutic agent for chronic hepatitis C (CHC), potentiating the effects of pegylated interferon and ribavirin (peg-IFN/RBV). The aim of the study was to assess the effects of ezetimibe coadministration with peg-IFN/RBV combination on the early virological response (EVR) rates in nonobese and obese patients with CHC genotype 4 (CHC-4). A total of 144 CHC-4 patients were divided into two groups; group 1 included nonobese patients (n=76) and group 2 included obese patients (n=68). Each group was further subclassified into equal control and treated groups. The control groups received peg-IFN/RBV combination for 24 weeks, and the treated groups received peg-IFN/RBV plus ezetimibe for 12 weeks and then only peg-IFN/RBV for the remaining 12 weeks. The study revealed that EVR significantly improved in the obese patients (85.3 vs. 64.7% in the treated and control groups, respectively, at P<0.05) without any significant improvement in the nonobese patients. Biochemical responses (defined as normalization of alanine aminotransferase at week 12) were markedly improved in the treated groups in both the nonobese and obese groups compared with their respective controls. The addition of ezetimibe to peg-IFN/RBV combination significantly improves EVR rates in obese patients compared with nonobese patients, and remarkably improves the biochemical responses in both obese and nonobese patients with CHC-4. This may shed light on a new strategy for the treatment of CHC, particularly in obese Egyptian patients.

Systematic review: patient-reported outcomes in chronic hepatitis C--the impact of liver disease and new treatment regimens.

PubMed

Younossi, Z; Henry, L

2015-03-01

Treatment for chronic hepatitis C (CH-C) is rapidly changing and moving away from an interferon and ribavirin-based therapy to interferon-free ribavirin-free all oral regimens. These regimens are simpler and shorter to administer with very high efficacy rates and better side effect profiles. As advances in the treatment of CH-C occur, it is imperative to capture both clinical outcomes (efficacy and safety) as well as patient-reported outcomes (PROs). In fact, PROs assesses and quantifies the impact of these regimens on patient experience. PROs assess patients' health-related quality of life (HRQOL) especially in the realms of fatigue and neuropsychiatric issues such as depression which can affect treatment adherence and work productivity. To review the literature related to PRO's in HCV patients and summarise the impact of CH-C and its treatment on PROs. Databases Ovid MEDLINE and PubMed were searched from 1990 to October 2014 using a combination of MEsh, thesaurus terms and relevant text words: hepatitis C, CH-C, treatment, quality of life, health-related quality of life, fatigue, work productivity, adherence, patient-reported outcomes, direct acting anti-viral agents and second generation direct acting anti-viral agents. Each manuscript was assessed for pertinence to the issue of PROs in CH-C as well as the quality of study design and publications. From the literature, it is evident that CH-C patients have baseline PRO impairment. Furthermore, treatment with interferon with or without ribavirin and first generation DAAs causes additional PRO burden which can negatively impact treatment adherence and indirectly, treatment efficacy and work productivity. The new treatment regimens with interferon- and ribavirin-free regimens not only have very high efficacy, but also result in the improvement of PRO scores as early as 2 weeks into treatment as well as possibly better adherence to treatment regimens. CH-C and its treatment have been associated with patient-reported outcome impairment. The new IF-free and RBV-free regimens are associated with high efficacy and substantial improvement of patient-reported outcomes in clinical trial setting. Although very encouraging, more data are needed to assess patient-reported outcomes, adherence and work productivity of CH-C patients in the real world setting of clinical practice. © 2015 John Wiley & Sons Ltd.

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus.

PubMed

Antonelli, Alessandro; Ferrari, Silvia Martina; Giuggioli, Dilia; Di Domenicantonio, Andrea; Ruffilli, Ilaria; Corrado, Alda; Fabiani, Silvia; Marchi, Santino; Ferri, Clodoveo; Ferrannini, Ele; Fallahi, Poupak

2014-10-15

Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients.

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus

PubMed Central

Antonelli, Alessandro; Ferrari, Silvia Martina; Giuggioli, Dilia; Di Domenicantonio, Andrea; Ruffilli, Ilaria; Corrado, Alda; Fabiani, Silvia; Marchi, Santino; Ferri, Clodoveo; Ferrannini, Ele; Fallahi, Poupak

2014-01-01

Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients. PMID:25317237

Serum DHCR24 Auto-antibody as a new Biomarker for Progression of Hepatitis C

PubMed Central

Ezzikouri, Sayeh; Kimura, Kiminori; Sunagozaka, Hajime; Kaneko, Shuichi; Inoue, Kazuaki; Nishimura, Tomohiro; Hishima, Tsunekazu; Kohara, Michinori; Tsukiyama-Kohara, Kyoko

2015-01-01

Background New biomarkers are needed to identify the stage of hepatitis C virus (HCV)-infected diseases in order to reduce the mortality rates. Herein, we investigated whether serum 3β-hydroxysterol Δ24-reductase antibody (DHCR24 Ab) may serve as a prognostic marker for hepatitis C infection progression to hepatocellular carcinoma (HCC). Methods Serum DHCR24 Abs from 395 HCV-positive patients, including 133 chronic hepatitis (CHC), 85 liver cirrhosis (LCC), and 177 HCC (HCC-C) patients; 232 hepatitis B virus (HBV)-positive patients, including 103 chronic hepatitis (CHB), 56 liver cirrhosis (LCB), and 73 HCC (HCC-B) patients; and 24 healthy controls, were measured using enzyme-linked immunosorbent assay. Results The serum DHCR24 Ab levels were significantly higher in patients with CHC than in healthy controls, in LCC than in CHC, and in LCC than in HCC-C (P < 0.0001 for all). The concentration of serum DHCR24 Ab in HCC-B patients showed no significant difference compared to CHB and LCB patients (P = 0.1247). The DHCR24 Ab levels were significantly higher in early HCC-C than CHC or LCC patients and in late HCC-C compared to early HCC-C patients. The sensitivity of the DHCR24 Ab for HCC-C detection (70.6%) was higher than that of alpha-fetoprotein (AFP; 54.8%) and protein induced by vitamin K absence or antagonist-II (PIVKA-II; 42 · 5%). Moreover, DHCR24 was up-regulated in HCV-positive, but not HBV-positive tissues or HBV-negative, HCV-negative HCC specimens. Conclusions DHCR24 auto-antibody represents a potential noninvasive biomarker for HCV-related liver disease and may facilitate the diagnosis of PIVKA-II and AFP-negative HCC. PMID:26288822

Open source electronic health records and chronic disease management

PubMed Central

Goldwater, Jason C; Kwon, Nancy J; Nathanson, Ashley; Muckle, Alison E; Brown, Alexa; Cornejo, Kerri

2014-01-01

Objective To study and report on the use of open source electronic health records (EHR) to assist with chronic care management within safety net medical settings, such as community health centers (CHC). Methods and Materials The study was conducted by NORC at the University of Chicago from April to September 2010. The NORC team undertook a comprehensive environmental scan, including a literature review, a dozen key informant interviews using a semistructured protocol, and a series of site visits to CHC that currently use an open source EHR. Results Two of the sites chosen by NORC were actively using an open source EHR to assist in the redesign of their care delivery system to support more effective chronic disease management. This included incorporating the chronic care model into an CHC and using the EHR to help facilitate its elements, such as care teams for patients, in addition to maintaining health records on indigent populations, such as tuberculosis status on homeless patients. Discussion The ability to modify the open-source EHR to adapt to the CHC environment and leverage the ecosystem of providers and users to assist in this process provided significant advantages in chronic care management. Improvements in diabetes management, controlled hypertension and increases in tuberculosis vaccinations were assisted through the use of these open source systems. Conclusions The flexibility and adaptability of open source EHR demonstrated its utility and viability in the provision of necessary and needed chronic disease care among populations served by CHC. PMID:23813566

Gene expression profile associated with superimposed non-alcoholic fatty liver disease and hepatic fibrosis in patients with chronic hepatitis C.

PubMed

Younossi, Zobair M; Afendy, Arian; Stepanova, Maria; Hossain, Noreen; Younossi, Issah; Ankrah, Kathy; Gramlich, Terry; Baranova, Ancha

2009-10-01

Hepatic steatosis occurs in 40-70% of patients chronically infected with hepatitis C virus [chronic hepatitis C (CH-C)]. Hepatic steatosis in CH-C is associated with progressive liver disease and a low response rate to antiviral therapy. Gene expression profiles were examined in CH-C patients with and without hepatic steatosis, non-alcoholic steatohepatitis (NASH) and fibrosis. This study included 65 CH-C patients who were not receiving antiviral treatment. Total RNA was extracted from peripheral blood mononuclear cells, quantified and used for one-step reverse transcriptase-polymerase chain reaction to profile 153 mRNAs that were normalized with six 'housekeeping' genes and a reference RNA. Multiple regression and stepwise selection assessed differences in gene expression and the models' performances were evaluated. Models predicting the grade of hepatic steatosis in patients with CH-C genotype 3 involved two genes: SOCS1 and IFITM1, which progressively changed their expression level with the increasing grade of steatosis. On the other hand, models predicting hepatic steatosis in non-genotype 3 patients highlighted MIP-1 cytokine encoding genes: CCL3 and CCL4 as well as IFNAR and PRKRIR. Expression levels of PRKRIR and SMAD3 differentiated patients with and without superimposed NASH only in the non-genotype 3 cohort (area under the receiver operating characteristic curve=0.822, P-value 0.006]. Gene expression signatures related to hepatic fibrosis were not genotype specific. Gene expression might predict moderate to severe hepatic steatosis, NASH and fibrosis in patients with CH-C, providing potential insights into the pathogenesis of hepatic steatosis and fibrosis in these patients.

PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease

PubMed Central

Salameh, Habeeb; Masadeh, Maen; Al Hanayneh, Muhannad; Petros, Vincent; Maslonka, Matthew; Nanda, Arjun; Singal, Ashwani K

2016-01-01

AIM To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. METHODS Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms. RESULTS Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. CONCLUSION PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients. PMID:28050240

Estimation of direct medical cost related to the management of chronic hepatitis C and its complications in South Korea

PubMed Central

Kim, Do Young; Yoon, Ki Tae; Kim, Won; Lee, Jung Il; Hong, Sung Hwi; Lee, Danbi; Jang, Jeong Won; Choi, Jong Won; Kim, Ilsu; Paik, Yong Han

2016-01-01

Abstract Background: This study aimed to estimate the direct medical costs of managing chronic hepatitis C (CHC) and its complications based on health-care resources in South Korea. Methods: The study design was multicenter, retrospective, non-interventional, and observational. Between September 2013 and April 2014, health-care resource data from patients chronically infected with hepatitis C virus, regardless of genotype, were collected from 8 institutions, including data related to outpatient management, emergency care, and hospitalization. The observation period was between January 2011 and December 2012. The disease state was classified as CHC, compensated cirrhosis (CC), decompensated cirrhosis (DC), or hepatocellular carcinoma (HCC). Results: A total of 445 patients were recruited and mean age was 60.1 ± 12.3 years. Among 155 patients with reported outcomes of antiviral therapy, 107 (69%) had sustained virologic response (SVR). The rate of patients who did not receive antiviral therapy was 52.8% (n = 235). The distribution of disease state was CHC in 307 patients (69.0%), CC in 75 (16.9%), HCC in 45 (10.1%), and DC in 18 (4.0%). All direct medical costs, whether reimbursed or nonreimbursed by the National Health Insurance System, were included. After excluding patients whose observational period was <1 month for each disease status, the mean costs per month increased as disease state progressed (CHC: 77 ± 80 USD; CC: 98 ± 94 USD; DC: 512 ± 1115 USD; HCC: 504 ± 717 USD). The mean total costs per person were 3590 ± 8783 USD, and approximately 72% of patients were reimbursed. When 44 patients with an observation period <1 month were excluded, the mean medical costs per month for patients with CHC who achieved SVR (n = 69) were significantly lower than for those (n = 215) who did not (42 ± 16 vs 79 ± 83 USD, P < 0.001). The cost also tended to be lower for patients with CC with SVR (n = 8) than for those without SVR (n = 70; 48 ± 20 vs 95 ± 96 USD, P = 0.177). The cost of antiviral therapy (pegylated interferon and ribavirin) corresponded to 19.0% of total medical costs and 53.7% of prescription/pharmacy. Conclusion: The direct medical costs increased as disease state progressed from CHC to cirrhosis or HCC. The achievement of SVR by antiviral therapy would decrease the costs. PMID:27472670

The CHC22 Clathrin-GLUT4 Transport Pathway Contributes to Skeletal Muscle Regeneration

PubMed Central

Griffin, Christine A.; Esk, Christopher; Torres, Jorge A.; Ohkoshi, Norio; Ishii, Akiko; Tamaoka, Akira; Funke, Birgit H.; Kucherlapati, Raju; Margeta, Marta; Rando, Thomas A.; Brodsky, Frances M.

2013-01-01

Mobilization of the GLUT4 glucose transporter from intracellular storage vesicles provides a mechanism for insulin-responsive glucose import into skeletal muscle. In humans, clathrin isoform CHC22 participates in formation of the GLUT4 storage compartment in skeletal muscle and fat. CHC22 function is limited to retrograde endosomal sorting and is restricted in its tissue expression and species distribution compared to the conserved CHC17 isoform that mediates endocytosis and several other membrane traffic pathways. Previously, we noted that CHC22 was expressed at elevated levels in regenerating rat muscle. Here we investigate whether the GLUT4 pathway in which CHC22 participates could play a role in muscle regeneration in humans and we test this possibility using CHC22-transgenic mice, which do not normally express CHC22. We observed that GLUT4 expression is elevated in parallel with that of CHC22 in regenerating skeletal muscle fibers from patients with inflammatory and other myopathies. Regenerating human myofibers displayed concurrent increases in expression of VAMP2, another regulator of GLUT4 transport. Regenerating fibers from wild-type mouse skeletal muscle injected with cardiotoxin also showed increased levels of GLUT4 and VAMP2. We previously demonstrated that transgenic mice expressing CHC22 in their muscle over-sequester GLUT4 and VAMP2 and have defective GLUT4 trafficking leading to diabetic symptoms. In this study, we find that muscle regeneration rates in CHC22 mice were delayed compared to wild-type mice, and myoblasts isolated from these mice did not proliferate in response to glucose. Additionally, CHC22-expressing mouse muscle displayed a fiber type switch from oxidative to glycolytic, similar to that observed in type 2 diabetic patients. These observations implicate the pathway for GLUT4 transport in regeneration of both human and mouse skeletal muscle, and demonstrate a role for this pathway in maintenance of muscle fiber type. Extrapolating these findings, CHC22 and GLUT4 can be considered markers of muscle regeneration in humans. PMID:24204966

Glucose abnormalities in Asian patients with chronic hepatitis C.

PubMed

Bo, Qingyan; Orsenigo, Roberto; Wang, Junyi; Griffel, Louis; Brass, Clifford

2015-01-01

Many studies have demonstrated a potential association between type 2 diabetes (T2D) and hepatitis C virus infection in Western countries, while similar evidence is limited in Asia. We compared the prevalence of glucose abnormalities (impaired fasting glucose [IFG] and T2D) and their risk factors between Asian and non-Asian chronic hepatitis C (CHC) patients, and evaluated whether glucose abnormalities impacted the viral responses to peginterferon plus ribavirin treatment (current standard of care in most Asian countries). This study retrospectively analyzed data of 1,887 CHC patients from three Phase II/III studies with alisporivir (DEB025) as treatment for CHC. The chi-square test was used to compare the prevalence of IFG/T2D between Asian and non-Asian CHC patients, and logistic regression was used to adjust for sex, age, and cirrhosis status. Risk factors for IFG/T2D were evaluated using univariate and multivariate analysis. Our results indicated that the prevalence of IFG/T2D was high in both Asian and non-Asian CHC patients (23.0% vs 20.9%), and no significant difference was found between these two populations (adjusted odds ratio: 1.3, 95% confidence interval: 0.97, 1.7; P=0.08). Age, sex, and cirrhosis status were risk factors for IFG/T2D in both populations, while body mass index was positively associated with IFG/T2D in non-Asian but not in Asian participants. No significant differences in sustained virological response rates were seen between patients with normal fasting glucose and patients with IFG/T2D for both populations. These results demonstrate that the prevalence of glucose abnormalities in Asian CHC patients was similar to that in non-Asians, and glucose abnormalities had no impact on viral response to peginterferon plus ribavirin.

Glucose abnormalities in Asian patients with chronic hepatitis C

PubMed Central

Bo, Qingyan; Orsenigo, Roberto; Wang, Junyi; Griffel, Louis; Brass, Clifford

2015-01-01

Many studies have demonstrated a potential association between type 2 diabetes (T2D) and hepatitis C virus infection in Western countries, while similar evidence is limited in Asia. We compared the prevalence of glucose abnormalities (impaired fasting glucose [IFG] and T2D) and their risk factors between Asian and non-Asian chronic hepatitis C (CHC) patients, and evaluated whether glucose abnormalities impacted the viral responses to peginterferon plus ribavirin treatment (current standard of care in most Asian countries). This study retrospectively analyzed data of 1,887 CHC patients from three Phase II/III studies with alisporivir (DEB025) as treatment for CHC. The chi-square test was used to compare the prevalence of IFG/T2D between Asian and non-Asian CHC patients, and logistic regression was used to adjust for sex, age, and cirrhosis status. Risk factors for IFG/T2D were evaluated using univariate and multivariate analysis. Our results indicated that the prevalence of IFG/T2D was high in both Asian and non-Asian CHC patients (23.0% vs 20.9%), and no significant difference was found between these two populations (adjusted odds ratio: 1.3, 95% confidence interval: 0.97, 1.7; P=0.08). Age, sex, and cirrhosis status were risk factors for IFG/T2D in both populations, while body mass index was positively associated with IFG/T2D in non-Asian but not in Asian participants. No significant differences in sustained virological response rates were seen between patients with normal fasting glucose and patients with IFG/T2D for both populations. These results demonstrate that the prevalence of glucose abnormalities in Asian CHC patients was similar to that in non-Asians, and glucose abnormalities had no impact on viral response to peginterferon plus ribavirin. PMID:26609222

Neutrophil to lymphocyte ratio as a reliable marker to predict insulin resistance and fibrosis stage in chronic hepatitis C virus infection.

PubMed

Abdel-Razik, Ahmed; Mousa, Nasser; Besheer, Tarek A; Eissa, Mohamed; Elhelaly, Rania; Arafa, Mohammad; El-Wakeel, Niveen; Eldars, Waleed

2015-12-01

Hepatitis C virus (HCV) is one of the most noxious infectious diseases. Chronic hepatitis C (CHC) had biochemical evidence of insulin resistance (IR). The neutrophil/lymphocyte ratio (NLR) integrates information on the inflammatory milieu and physiological stress. We aimed to investigate the clinical utility of NLR to predict the presence of IR and fibrosis in CHCvirus infection. The study included 234 CHC patients and 50 healthy controls. The CHC group was divided into two subgroups ; CHC with HOMA-IR>3 and CHC with HOMA-IR≤3. Liver biopsy, homeostasis model assessment-IR (HOMA-IR), neutrophil and lymphocyte counts were recorded ; and NLR was calculated. Proinflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)] were measured by an enzyme-linked immunosorbent assay. Patients with HOMA-IR>3 had a higher NLR compared with patients with HOMA-IR≤3 [2.61±0.95 and 1.92±0.86, respectively, P<0.001]. The NLR ratio was positively correlated with HOMA-IR, C-reactive protein, TNF-α and IL-6 cytokines ; P<0.001). Patients with advanced fibrosis (F3-4) had an elevated N/L ratio [2.4±0.99] compared with patients with fibrosis stage 1-2 [1.86±0.66], P<0.001. The N/L ratio is higher in patients with CHC with HOMA-IR>3 and advanced fibrosis. This ratio can be used as a novel noninvasive marker to predict IR and advanced disease. © Acta Gastro-Enterologica Belgica.

Real-time elastography as a noninvasive assessment of liver fibrosis in chronic hepatitis C Egyptian patients: a prospective study

PubMed Central

Mobarak, Lamiaa; Nabeel, Mohammed M.; Hassan, Ehsan; Omran, Dalia; Zakaria, Zeinab

2016-01-01

Background Hepatitis C virus is a worldwide problem. Noninvasive methods for liver fibrosis assessment as ultrasound-based approaches have emerged to replace liver biopsy. The aim of this study was to evaluate the diagnostic accuracy of real-time elastography (RTE) in the assessment of liver fibrosis in patients with chronic hepatitis C (CHC), compared with transient elastography and liver biopsy. Methods RTE, FibroScan and liver biopsy were performed in 50 CHC patients. In addition, aspartate aminotransferase to platelet ratio index (APRI) and routine laboratory values were included in the analysis. Results RTE was able to diagnose significant hepatic fibrosis (F ≥2) according to METAVIR scoring system at cut-off value of 2.49 with sensitivity 100%, specificity 66%, and area under the receiver-operating characteristics (AUROC) 0.8. FibroScan was able to predict significant fibrosis at cut-off value 7.5 KPa with sensitivity 88%, specificity 100%, and AUROC 0.94.APRI was able to predict significant hepatic fibrosis (F ≥2) with sensitivity 54%, specificity 80%, and AUROC 0.69. There was a significant positive correlation between the FibroScan score and RTE score (r=0.6, P=0.001). Conclusions Although FibroScan is superior in determining significant hepatic fibrosis, our data suggest that RTE may be a useful and promising noninvasive method for liver fibrosis assessment in CHC patients especially in cases with technical limitations for FibroScan. PMID:27366038

Prevalence of steatosis and insulin resistance in patients with chronic hepatitis B compared with chronic hepatitis C and non-alcoholic fatty liver disease.

PubMed

Pais, Raluca; Rusu, Elena; Zilisteanu, Diana; Circiumaru, Alexandra; Micu, Laurentiu; Voiculescu, Mihai; Poynard, Thierry; Ratziu, Vlad

2015-01-01

The association of NAFLD with chronic hepatitis C (CHC) has been extensively studied but little is known about its coexistence with chronic hepatitis B (CHB). To investigate the prevalence and determinants of steatosis and insulin resistance (IR) in CHB and its consequences on liver injury compared with CHC and NAFLD. Patients with CHB (N=110), CHC (N=111) and NAFLD (N=136) were evaluated by biomarkers of steatosis (SteatoTest>0.38 as a surrogate for steatosis >5%), IR (HOMA-IR>2.7 as a surrogate for IR) and fibrosis (FibroTest>0.48 as a surrogate for significant fibrosis, ≥F2). HOMA-IR gradually increased in CHB, CHC and NAFLD: 2.3±1.8; 3±2.6 and 3.8±2.7 (p<0.001). The prevalence of steatosis >5% was 21% (CHB), 43% (CHC) and 82% (NAFLD), (p<0.001). The prevalence of fibrosis≥F2 was 10% (CHB), 42% (CHC) and 21% (NAFLD), p<0.001. In CHB, IR was related to host and not viral factors. CHB patients with steatosis had higher BMI (29±5.7kg/m(2) vs. 24±4kg/m(2), p<0.001), waist circumference (96±14cm vs. 84±11cm, p=0.001) and HOMA-IR (3.9±2.6 vs. 1.8±1.2, p<0.001) than those without steatosis. HOMA-IR independently predicted steatosis in CHB (OR=1.9, 95% CI, 1.09-3.27, p<0.05) and CHC (OR=1.38; 95% CI, 1.07-1.78, p<0.02). In CHB, metabolic risk factors and HOMA-IR were not associated with significant fibrosis. HOMA-IR was an independent predictor of fibrosis in CHC. Steatosis may co-exist in CHB patients but with a lower prevalence than in CHC and NAFLD. In CHB steatosis is related to host and not viral factors, and is not associated with the severity of fibrosis. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

HCV genotype 3 and squamous cell carcinoma antigen (SCCA)-IgM are independently associated with histological features of NASH in HCV-infected patients.

PubMed

Martini, A; Fattovich, G; Guido, M; Bugianesi, E; Biasiolo, A; Ieluzzi, D; Gallotta, A; Fassina, G; Merkel, C; Gatta, A; Negro, F; Pontisso, P

2015-10-01

Nonalcoholic steatohepatitis (NASH) enhances the risk of progressive liver disease. In chronic hepatitis C (CHC), liver steatosis is frequent, especially in genotype 3, but its clinical significance is debated. As squamous cell carcinoma antigen (SCCA)-IgM has been associated with advanced liver disease and risk of tumour development, we evaluated its occurrence in CHC and the possible relation with NASH at liver biopsy. Using a validated ELISA, serum SCCA-IgM was measured in 91 patients with CHC at the time of liver biopsy performed before antiviral treatment, at the end of treatment and 6 months thereafter, and in 93 HCV-negative patients with histological diagnosis of nonalcoholic fatty liver disease, as controls. SCCA-IgM was detected in 33% of CHC patients and in 4% of controls. This biomarker was found more elevated in CHC patients with histological NASH, and at multivariate analysis, SCCA-IgM and HCV genotype 3 were independently associated with NASH [OR (95% CI): 6.94 (1.21-40) and 27.02 (4.44-166.6)]. As predictors of NASH, HCV genotype 3 and SCCA-IgM had a specificity and a sensitivity of 97% and 44%, and of 95% and 27%, respectively. PPV and NPV were 80% and 86% for HCV genotype 3 vs 73% and 72% for SCCA-IgM. In patients with sustained virologic response to therapy, SCCA-IgM levels decreased significantly, while these remained unchanged in nonresponders. In conclusion, SCCA-IgM is detectable in one-third of patients with CHC and significantly correlates with histological NASH. © 2015 John Wiley & Sons Ltd.

Gene expression profiles associated with depression in patients with chronic hepatitis C (CH-C)

PubMed Central

Birerdinc, Aybike; Afendy, Arian; Stepanova, Maria; Younossi, Issah; Baranova, Ancha; Younossi, Zobair M

2012-01-01

The standard treatment for CH-C, pegylated interferon-α and ribavirin (PEG-IFN + RBV), is associated with depression. Recent studies have proposed a new role for cytokines in the pathogenesis of depression. We aimed to assess differential gene expression related to depression in CH-C patients treated with PEG-IFN + RBV. We included 67 CH-C patients being treated with PEG-IFN+RBV. Of the entire study cohort, 22% had pre-existing depression, while another 37% developed new depression in course of the treatment. Pretreatment blood samples were collected into PAXgene™ RNA tubes, the RNAs extracted from peripheral blood mononuclear cells (PBMCs) were used for one step RT-PCR to profile 160 mRNAs. Differentially expressed genes were separated into up- and down-regulated genes according to presence or absence of depression at baseline (pre-existing depression) or following the initiation of treatment (treatment-related depression). The mRNA expression profile associated with any depression and with treatment-related depression included four and six genes, respectively. Our data demonstrate a significant down-regulation of TGF-β1 and the shift of Th1-Th2 cytokine balance in the depression associated with IFN-based treatment of HCV infection. We propose that TGF-β1 plays an important role in the imbalance of Th1/Th2 in patients with CH-C and depression. With further validation, TGF-β1 and other components of Th1/Th2 regulation pathway may provide a future marker for CH-C patients predisposed to depression. PMID:23139898

Gene expression profiles associated with depression in patients with chronic hepatitis C (CH-C).

PubMed

Birerdinc, Aybike; Afendy, Arian; Stepanova, Maria; Younossi, Issah; Baranova, Ancha; Younossi, Zobair M

2012-09-01

The standard treatment for CH-C, pegylated interferon-α and ribavirin (PEG-IFN + RBV), is associated with depression. Recent studies have proposed a new role for cytokines in the pathogenesis of depression. We aimed to assess differential gene expression related to depression in CH-C patients treated with PEG-IFN + RBV. We included 67 CH-C patients being treated with PEG-IFN+RBV. Of the entire study cohort, 22% had pre-existing depression, while another 37% developed new depression in course of the treatment. Pretreatment blood samples were collected into PAXgene™ RNA tubes, the RNAs extracted from peripheral blood mononuclear cells (PBMCs) were used for one step RT-PCR to profile 160 mRNAs. Differentially expressed genes were separated into up- and down-regulated genes according to presence or absence of depression at baseline (pre-existing depression) or following the initiation of treatment (treatment-related depression). The mRNA expression profile associated with any depression and with treatment-related depression included four and six genes, respectively. Our data demonstrate a significant down-regulation of TGF-β1 and the shift of Th1-Th2 cytokine balance in the depression associated with IFN-based treatment of HCV infection. We propose that TGF-β1 plays an important role in the imbalance of Th1/Th2 in patients with CH-C and depression. With further validation, TGF-β1 and other components of Th1/Th2 regulation pathway may provide a future marker for CH-C patients predisposed to depression.

Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

PubMed Central

Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

2012-01-01

Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

PubMed

Shigefuku, Ryuta; Takahashi, Hideaki; Nakano, Hiroyasu; Watanabe, Tsunamasa; Matsunaga, Kotaro; Matsumoto, Nobuyuki; Kato, Masaki; Morita, Ryo; Michikawa, Yousuke; Tamura, Tomohiro; Hiraishi, Tetsuya; Hattori, Nobuhiro; Noguchi, Yohei; Nakahara, Kazunari; Ikeda, Hiroki; Ishii, Toshiya; Okuse, Chiaki; Sase, Shigeru; Itoh, Fumio; Suzuki, Michihiro

2016-09-14

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

Studies on collagen-tannic acid-collagenase ternary system: Inhibition of collagenase against collagenolytic degradation of extracellular matrix component of collagen.

PubMed

Krishnamoorthy, Ganesan; Sehgal, Praveen Kumar; Mandal, Asit Baran; Sadulla, Sayeed

2012-06-01

We report the detailed studies on the inhibitory effect of tannic acid (TA) on Clostridium histolyticum collagenase (ChC) activity against degradation of extracellular matrix component of collagen. The TA treated collagen exhibited 64% resistance against collagenolytic hydrolysis by ChC, whereas direct interaction of TA with ChC exhibited 99% inhibition against degradation of collagen and the inhibition was found to be concentration dependant. The kinetic inhibition of ChC has been deduced from the extent of hydrolysis of N-[3-(2-furyl) acryloyl]-Leu-Gly-Pro-Ala (FALGPA). This data provides a selective competitive mode of inhibition on ChC activity seems to be influenced strongly by the nature and structure of TA. TA showed inhibitor activity against the ChC by molecular docking method. This result demonstrated that TA containing digalloyl radical possess the ability to inhibit the ChC. The inhibition of ChC in gaining new insight into the mechanism of stabilization of collagen by TA is discussed.

Disease burden of chronic hepatitis C among immigrants in Canada.

PubMed

Chen, W; Krahn, M

2015-12-01

Immigrants with chronic hepatitis C (CHC) in Canada have doubled risk of hepatocellular carcinoma. To measure the burden of CHC among immigrants in Canada. A decision analytic model was developed to compare immigrants with CHC and age-matched immigrants without CHC for survival years, quality-adjusted life-years (QALYs) and medical costs per life year. Hepatitis C epidemiology among immigrants was based on hepatitis C prevalence in their home countries. A cohort of immigrant patients was retrospectively followed up to estimate fibrosis stage distribution, treatment patterns and prognosis of compensated cirrhosis. Other model variables were based on published sources. Base case analysis, one-way sensitivity analysis and probabilistic sensitivity analysis were performed to measure the burden of CHC and assess the impact of uncertainty associated with model variables on the burden of CHC. CHC could reduce survival by 9.6 years [95% credible interval (CI): 8.0-10.9 years], reduce QALYs by 9.5 years (95% CI: 6.0-13.8 years) and increase medical costs per life year by $1950 (95% CI: $1518 to $2486, 2006 Canadian dollars). Because nearly half of immigrants with CHC were not diagnosed until the development of cirrhosis, the burden of CHC was highly sensitive to the risks of liver-related complications and mortality but insensitive to pegylated interferon plus ribavirin. The burden of CHC among immigrants in Canada is substantial mainly due to liver-related complications and mortality. The delay in diagnosis was another important contributor to the burden of CHC among immigrants. © 2015 John Wiley & Sons Ltd.

Real-time elastography as a noninvasive assessment of liver fibrosis in chronic hepatitis C Egyptian patients: a prospective study.

PubMed

Mobarak, Lamiaa; Nabeel, Mohammed M; Hassan, Ehsan; Omran, Dalia; Zakaria, Zeinab

2016-01-01

Hepatitis C virus is a worldwide problem. Noninvasive methods for liver fibrosis assessment as ultrasound-based approaches have emerged to replace liver biopsy. The aim of this study was to evaluate the diagnostic accuracy of real-time elastography (RTE) in the assessment of liver fibrosis in patients with chronic hepatitis C (CHC), compared with transient elastography and liver biopsy. RTE, FibroScan and liver biopsy were performed in 50 CHC patients. In addition, aspartate aminotransferase to platelet ratio index (APRI) and routine laboratory values were included in the analysis. RTE was able to diagnose significant hepatic fibrosis (F ≥2) according to METAVIR scoring system at cut-off value of 2.49 with sensitivity 100%, specificity 66%, and area under the receiver-operating characteristics (AUROC) 0.8. FibroScan was able to predict significant fibrosis at cut-off value 7.5 KPa with sensitivity 88%, specificity 100%, and AUROC 0.94.APRI was able to predict significant hepatic fibrosis (F ≥2) with sensitivity 54%, specificity 80%, and AUROC 0.69. There was a significant positive correlation between the FibroScan score and RTE score (r=0.6, P=0.001). Although FibroScan is superior in determining significant hepatic fibrosis, our data suggest that RTE may be a useful and promising noninvasive method for liver fibrosis assessment in CHC patients especially in cases with technical limitations for FibroScan.

Combining semiquantitative measures of fibrosis and qualitative features of parenchymal remodelling to identify fibrosis regression in hepatitis C: a multiple biopsy study.

PubMed

Pattullo, Venessa; Thein, Hla-Hla; Heathcote, Elizabeth Jenny; Guindi, Maha

2012-09-01

A fall in hepatic fibrosis stage may be observed in patients with chronic hepatitis C (CHC); however, parenchymal architectural changes may also signify hepatic remodelling associated with fibrosis regression. The aim of this study was to utilize semiquantitative and qualitative methods to report the prevalence and factors associated with fibrosis regression in CHC. Paired liver biopsies were scored for fibrosis (Ishak), and for the presence of eight qualitative features of parenchymal remodelling, to derive a qualitative regression score (QR score). Combined fibrosis regression was defined as ≥2-stage fall in Ishak stage (Reg-I) or <2-stage fall in Ishak stage with a rise in QR score (Reg-Qual). Among 159 patients (biopsy interval 5.4 ± 3.1 years), Reg-I was observed in 12 (7.5%) and Reg-Qual in 26 (16.4%) patients. The combined diagnostic criteria increased the diagnosis rate for fibrosis regression (38 patients, 23.9%) compared with use of Reg-I alone (P < 0.001). Combined fibrosis regression was observed in nine patients (50%) who achieved sustained virological response (SVR), and in 29 of 141 (21%) patients despite persistent viraemia. SVR was the only clinical factor associated independently with combined fibrosis regression (odds ratio 3.05). The combination of semiquantitative measures and qualitative features aids the identification of fibrosis regression in CHC. © 2012 Blackwell Publishing Ltd.

Angiopoietin-2/angiopoietin-1 as non-invasive biomarker of cirrhosis in chronic hepatitis C

PubMed Central

Hernández-Bartolomé, Ángel; López-Rodríguez, Rosario; Borque, María Jesús; González-Moreno, Leticia; Real-Martínez, Yolanda; García-Buey, Luisa; Moreno-Otero, Ricardo; Sanz-Cameno, Paloma

2016-01-01

AIM To evaluate the efficacy of peripheral blood concentrations of angiopoietins (Ang) as cirrhosis biomarkers of chronic hepatitis C (CHC). METHODS Ang1 and Ang2 serum levels were measured by enzyme-linked immunosorbent assays (ELISA) in samples from 179 cirrhotic and non-cirrhotic CHC patients, classified according to the METAVIR system. Groups were compared by non-parametric Mann-Whitney U test. Subsequently, the association of peripheral concentrations of angiopoietins with the stage of fibrosis was analyzed using Spearman correlation test. Finally, the accuracy, sensitivity and specificity of circulating angiopoietins for cirrhosis diagnosis were determined by the study of the respective area under the curve of receiver operator characteristics (AUC-ROC). RESULTS Peripheral blood concentrations of Ang1 and Ang2 in CHC patients were significantly related to fibrosis. While Ang1 was decreased in cirrhotic subjects compared to non-cirrhotic (P < 0.0001), Ang2 was significantly increased as CHC progressed to the end stage of liver disease (P < 0.0001). Consequently, Ang2/Ang1 ratio was notably amplified and significantly correlated with fibrosis (P < 0.0001). Interestingly, the individual performance of each angiopoietin for the diagnosis of cirrhosis reached notable AUC-ROC values (above 0.7, both), but the Ang2/Ang1 ratio was much better (AUC-ROC = 0.810) and displayed outstanding values of sensitivity (71%), specificity (84%) and accuracy (82.1%) at the optimal cut-off (10.33). Furthermore, Ang2/Ang1 ratio improved the performance of many other previously described biomarkers or scores of liver cirrhosis in CHC. CONCLUSION Ang2/Ang1 ratio might constitute a useful tool for monitoring the progression of chronic liver disease towards cirrhosis and play an important role as therapeutic target. PMID:27956798

Liver cirrhosis: a risk factor for gallstone disease in chronic hepatitis C patients in China.

PubMed

Li, Xu; Wang, Zhongfeng; Wang, Le; Pan, Meng; Gao, Pujun

2017-06-01

We investigated the possible link between liver cirrhosis and gallstone risk in chronic hepatitis C (CHC) patients in China.To analyze the association between liver cirrhosis and gallstone development, we compared outcomes of 133 Chinese CHC patients with gallstones and an age-, sex-, and hepatitis C virus RNA level-matched control group of 431 CHC patients without gallstones.We found that liver cirrhosis was more prevalent in gallstone patients (40.6%) than in the control group (24.4%). Logistic regression analyses adjusting for demographic features and other gallstone risk factors revealed that liver cirrhosis increased the risk of gallstone development 2-fold (adjusted odds ratio [AOR]: 2.122; 95% confidence interval [CI]: 1.408-3.198). Moreover, multivariate analyses comparing the risk of gallstone development in liver cirrhosis patients with decompensated or compensated liver cirrhosis yielded an estimated AOR (95% CI) of 2.869 (1.277-6.450) in patients with decompensated liver cirrhosis. Gallstone risk also increased significantly with older age (>60 years) (AOR: 2.019; 95% CI: 1.017-4.009).Liver cirrhosis significantly correlates with increased risk of gallstone development in CHC patients in China. Decompensated liver cirrhosis and older age further heighten this risk in patients diagnosed with hepatitis C-related cirrhosis.

Holistic Health Care for the Medically Uninsured: The Church Health Center of Memphis.

PubMed

Morris, G Scott

2015-11-05

The Church Health Center (CHC) in Memphis was founded in 1987 to provide quality, affordable health care for working, uninsured people and their families. With numerous, dedicated financial supporters and health care volunteers, CHC has become the largest faith-based health care organization of its type nationally, serving >61,000 patients. CHC embraces a holistic approach to health by promoting wellness in every dimension of life. It offers on-site services including medical care, dentistry, optometry, counseling, social work, and nutrition and fitness education, to promote wellness in every dimension of life. A 2012 economic analysis estimated that a $1 contribution to the CHC provided roughly $8 in health services. The CHC has trained >1200 Congregational Health Promoters to be health leaders and is conducting research on the effectiveness of faith community nurses partnering with congregations to assist in home care for patients recently discharged from Memphis hospitals. The MEMPHIS Plan, CHC's employer-sponsored health care plan for small business and the self-employed, offers uninsured people in lower-wage jobs access to quality, affordable health care. The CHC also conducts replications workshops several times a year to share their model with leaders in other communities. The Institute for Healthcare Improvement (IHI) recently completed a case study that concluded: "The CHC is one of a very few organizations successfully embodying all three components of the IHI Triple Aim by improving population health outcomes, enhancing the individual's health care experience, and controlling costs. All three have been part of the Center's DNA since its inception, and as a transforming force in the community, the model is well worth national attention."

Low Prevalence of Insulin Resistance among Iranian Patients with Chronic Hepatitis C Virus Infection: A Case-Control Study.

PubMed

Eshraghian, Kavous; Lankarani, Kamran B; Fattahi, Mohammad Reza; Esmailnejad, Atefeh; Peymani, Payam

2017-07-14

Association between chronic hepatitis C virus (CHC) infection and type 2 diabetes mellitus has been challenging in recent decades. Despite of extensive research in this area, there is no general agreement on the direct effect of HCV infection on insulin resistance. The study was performed in 52 CHC patients (mean age = 39.48) and 52 and sex‑matched healthy Iranian controls, referred to the Hepatitis Clinic, Department of Gastroenterohepatology, Shiraz University of medical sciences, Shiraz, Iran, from 2012 to 2015. Fasting blood glucose level, fasting insulin level and insulin resistance defined as a homeostasis model assessment of insulin resistance (HOMA-IR) index were determined and compared between two groups. Insulin resistance was present in 26.9% of CHC patients and 34.62% of healthy controls. Mean HOMA index was 1.93 in patients and 2.18 in controls. There were no statistically significant differences between patient and control groups with regard to fasting insulin level, fasting blood glucose, HOMA index and insulin resistance. HOMA index and fasting insulin level were significantly higher in IR CHC patients relative to IR controls. Fasting blood glucose was also significantly higher in controls younger than 40 years. Results obtained in this study showed that chronic hepatitis C cannot be considered as a risk factor for insulin resistance and diabetes in Iranian population. However, regular screening for insulin resistance is recommended in CHC patients with age ≥ 40 years and fasting blood glucose ≥ 100 mg/dl. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Direct-acting antivirals combination for elderly patients with chronic hepatitis C: A cost-effectiveness analysis.

PubMed

Ciaccio, Antonio; Cortesi, Paolo A; Bellelli, Giuseppe; Rota, Matteo; Conti, Sara; Okolicsanyi, Stefano; Rota, Monica; Cesana, Giancarlo; Mantovani, Lorenzo G; Annoni, Giorgio; Strazzabosco, Mario

2017-07-01

Chronic hepatitis C (CHC) has been undertreated among elderly patients. Interferon-free treatment represents an opportunity for these patients. The aim of this study was to assess the cost-effectiveness of directly acting antivirals (DAAs) in CHC elderly patients. A Markov model of CHC natural history was built. This study focuses on CHC patients older than 65 years, stratified according to genotype (1/4, 2 and 3), liver fibrosis (METAVIR F1 to F4), age and frailty phenotype (robust, pre-frail and frail). DAAs combination vs no treatment was simulated for each theoretical population, assessing life years, quality-adjusted life years (QALYs), costs, incremental cost-effectiveness ratios (ICERs) in a lifetime time horizon and by the Healthcare System perspective. Incremental cost-effectiveness ratio increased with age and frailty status in all fibrosis stages. For robust F3 and F4 patients ICERs remained below the willingness-to-pay threshold (WTP) of 40 000€/QALY up to age 75 and 86 years, respectively, depending on drug price and sustained virological response probability (sensitivity analysis). Notably, in F4 and frail subjects older than 75 years, ICER was more sensitive to non-liver-related mortality rate. In elderly F1 and F2 patients, ICERs were below WTP only up to 77 years old, with wide variability among frailty phenotypes. Cost-effectiveness of DAAs treatment of elderly CHC patients is solid in those with advanced fibrosis, but it depends strongly on frailty status and age, particularly in patients with milder fibrosis stages. Accurate assessment of clinical variables, including frailty, is necessary to allocate limited resources to this special population. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Primary care quality: community health center and health maintenance organization.

PubMed

Shi, Leiyu; Starfield, Barbara; Xu, Jiahong; Politzer, Robert; Regan, Jerrilyn

2003-08-01

This study compares the primary health care quality of community health centers (CHCs) and health maintenance organizations (HMOs) in South Carolina to elucidate the quality of CHC performance relative to mainstream settings such as the HMO. Mail surveys were used to obtain data from 350 randomly selected HMO users. Surveys with follow-up interviews were conducted to obtain data from 540 randomly selected CHC users. A validated adult primary care assessment tool was used in both surveys. Multivariate analyses were performed to assess the association of health care setting (HMO versus CHC) with primary care quality while controlling for sociodemographic and health care characteristics. After controlling for sociodemographic and health care use measures, CHC patients demonstrated higher scores in several primary care domains (ongoing care, coordination of service, comprehensiveness, and community orientation) as well as total primary care performance. Users of CHC are more likely than HMO users to rate their primary health care provider as good, except in the area of ease of first contact. The positive rating of the CHC is particularly impressive after taking into account that many CHC users have characteristics associated with poorer ratings of care.

Predictive value of the fibrosis scores in patients with chronic hepatitis C associated with liver fibrosis and metabolic syndrome.

PubMed

Miyaaki, Hisamitsu; Ichikawa, Tatsuki; Taura, Naota; Miuma, Satoshi; Shibata, Hidetaka; Isomoto, Hajime; Takeshima, Fuminao; Nakao, Kazuhiko

2011-01-01

We evaluated patients with chronic hepatitis C (CHC) and compared the clinical and pathological features of steatosis and metabolic syndrome to identify the risk factors for CHC with severe fibrosis. One hundred seventy-one patients with biopsy-confirmed CHC were included in the study: 90 males and 81 females, age 56.2 ± 12.8 years; 46 with obesity (BMI≥25 kg/m(2)); 51 with hypertension; 36 with type 2 diabetes mellitus; and 20 with hypertriglyceridemia. Steatosis was detected in 79 patients (46%); 92 patients (54%) showed no steatosis. Seventy-four patients (43%) showed mild fibrosis and 97 patients (56%) showed severe fibrosis. The variables that were significantly associated with steatosis were obesity [odds ratio 2.160 (1.010-4.727), p=0.046] and type 2 diabetes [odds ratio 3.667 (1.559-8.430), p=0.027]. The variables that were significantly associated with severe fibrosis were older age [odds ratio 2.675 (1.309-5.464), p=0.007], obesity [odds ratio 2.156 (1.006-4.619), p=0.048] and type 2 diabetes [odds ratio 8.739 (2.845-26.846), p=0.0002]. Nagasaki (N) score (the total number of specific risk factors, namely an older age, obesity, and type 2 diabetes) was higher in the severe fibrosis group than in the mild fibrosis group (mild fibrosis: severe fibrosis=1.48 ± 1.14 vs.2.66 ± 94, p<0.001). Metabolic syndrome factors, including obesity and diabetes, play a critical role in the pathogenesis of fibrosis in CHC. The N score was therefore found to be a significant predictor of severe fibrosis in CHC.

Response to hepatitis A and B vaccination in patients with chronic hepatitis C: 8-year follow-up.

PubMed

Kalyoncu, Derya; Urganci, Nafiye

2012-08-01

In patients with chronic hepatitis C (CHC), superinfection with hepatitis A (HAV) or B (HAB) viruses is associated with increased morbidity and mortality. The seroconversion rate of these patients following vaccination is considered to be lower than in healthy subjects. To evaluate the response to HAV and HBV vaccination in children with CHC. Thirty patients with CHC aged from 7.3 to 18 years were compared with 50 healthy age-, gender- and body-mass-index-matched controls. Post-vaccination serological evaluation was performed 1 month after the last dose of primary vaccination, 1 month after the booster dose and once a year during follow-up. Twenty-two patients received hepatitis A vaccine and response rate was 95.4%. Thirty patients received hepatitis B vaccine and 80% responded (hepatitis Bs titres ≥10 mIU/ml). Thirty-five controls received hepatitis A vaccine and protective anti-HAV antibodies developed in all. All of the controls were vaccinated against hepatitis B virus and 90% responded. After the whole vaccination series, overall seroprotection rates were 86% in patients and 96% in controls. No significant reduction in antibody response was observed in patients or controls during 8-years follow-up. The rate of seroconversion to the HBV vaccine is lower in patients with CHC than in healthy controls but response to HAV is adequate.

Rural-Urban Differences in Consumer Governance at Community Health Centers

PubMed Central

Wright, David Bradley

2017-01-01

Context Community health centers (CHCs) are primary care clinics that serve mostly low-income patients in rural and urban areas. They are required to be governed by a consumer majority. What little is known about the structure and function of these boards in practice, suggests that CHC boards in rural areas may look and act differently than CHC boards in urban areas. Purpose To identify differences in the structure and function of consumer governance at CHCs in rural and urban areas. Methods Semi-structured telephone interviews were conducted with 30 CHC board members from 14 different states. Questions focused on board members’ perceptions of board composition and the role of consumers on the board. Findings CHCs in rural areas are more likely to have representative boards, are better able to convey confidence in the organization, and are better able to assess community needs than CHCs in urban areas. However, CHCs in rural areas often have problems achieving objective decision-making, and may have fewer means for objectively evaluating quality of care due to the lack of patient board member anonymity. Conclusions Consumer governance is implemented differently in rural and urban communities, and the advantages and disadvantages in each setting are unique. PMID:23551642

Clinical features of hepatitis B and C virus infections, with high α-fetoprotein levels but not hepatocellular carcinoma

PubMed Central

Kim, Cha Young; Kim, Bo Ra; Lee, Sang Soo; Jeon, Dae-Hong; Lee, Chang Min; Kim, Wan Soo; Cho, Hyun Chin; Kim, Jin Joo; Lee, Jae Min; Kim, Hong Jun; Ha, Chang Yoon; Kim, Hyun Jin; Kim, Tae Hyo; Jung, Woon Tae; Lee, Ok-Jae

2017-01-01

Abstract The appropriate α-fetoprotein (AFP) level to confirm hepatocellular carcinoma (HCC) could be 100 ng/mL; however, the clinical significance of falsely elevated AFP in patients without HCC has not been fully studied. We investigated the clinical features and outcome of patients without HCC but with high AFP levels (100 ng/mL), especially with chronic hepatitis B (CHB) or C (CHC). The sample included 124 consecutive patients with CHB (n = 97) or CHC (n = 27), with AFP levels >100 ng/mL and without HCC at baseline. Multivariate Cox proportional regression analysis was performed to determine the factors associated with AFP normalization and HCC development. During the mean 52-month follow-up, the proportion of patients with CHB with AFP normalization (90.7%) was significantly higher than the proportion of patients with CHC (59.3%, P < 0.001). Initial aspartate aminotransferase levels (hazard ratio [HR] = 1.02 per 10 U/L increase, P = 0.021) and antiviral therapy (HR = 2.89, P < 0.001) were significantly associated with AFP normalization. Of the 16 (12.9%) patients who developed HCC, hepatitis B virus infection (HR = 10.82, P = 0.001), initiation of antiviral treatment postenrollment (HR = 0.23, P = 0.030), and AFP normalization within 12 months (HR = 0.13, P = 0.011) were associated with HCC development. CHB and CHC were the most common causes of falsely elevated AFP (>100 ng/mL). With either CHB or CHC, persistent AFP elevation (>12 months), regardless of antiviral treatment, might be an important marker of HCC development. PMID:28079817

Chronic hepatitis C infection is associated with insulin resistance and lipid profiles.

PubMed

Dai, Chia-Yen; Yeh, Ming-Lun; Huang, Chung-Feng; Hou, Chen-Hsiu; Hsieh, Ming-Yen; Huang, Jee-Fu; Lin, I-Ling; Lin, Zu-Yau; Chen, Shinn-Chern; Wang, Liang-Yen; Chuang, Wan-Long; Yu, Ming-Lung; Tung, Hung-Da

2015-05-01

Chronic hepatitis C virus (HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance (IR) and lipid profiles with chronic hepatitis C (CHC) patients in Taiwan. We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment (HOMA-IR) were tested. When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR (P < 0.001, P = 0.023, P = 0.017, and P = 0.011, respectively), and significantly lower TG level (P = 0.023), total cholesterol, and HDL-C and LDL-C levels (all P < 0.001) than 480 controls. In multivariate logistic regression analyses, a low total cholesterol, a low TGs, and a high HOMA-IR are independent factors significantly associated with chronic HCV infection. In the 160 CHC patients (41 patients with high HOMA-IR [> 2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses. Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

[Improving the continuous care process in primary care during weekends and holidays: redesigning and FMEA].

PubMed

Cañada Dorado, A; Cárdenas Valladolid, J; Espejo Matorrales, F; García Ferradal, I; Sastre Páez, S; Vicente Martín, I

2010-01-01

To describe a project carried out in order to improve the process of Continuous Health Care (CHC) on Saturdays and bank holidays in Primary Care, area number 4, Madrid. The aim of this project was to guarantee a safe and error-free service to patients receiving home health care on weekends. The urgent need for improving CHC process was identified by the Risk Management Functional Unit (RMFU) of the area. In addition, some complaints had been received from the nurses involved in the process as well as from their patients. A SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis performed in 2009 highlighted a number of problems with the process. As a result, a project for improvement was drawn up, to be implemented in the following stages: 1. Redesigning and improving the existing process. 2. Application of failure mode and effect analysis (FMEA) to the new process. 3. Follow up, managing and leading the project. 4. Nurse training. 5. Implementing the process in the whole area. 6. CHC nurse satisfaction surveys. After carrying out this project, the efficiency and level of automation improved considerably. Since implementation of the process enhancement measures, no complaints have been received from patients and surveys show that CHC nurse satisfaction has improved. By using FMEA, errors were given priority and enhancement steps were taken in order to: Inform professionals, back-up personnel and patients about the process. Improve the specialist follow-up report. Provide training in ulcer patient care. The process enhancement, and especially its automation, has resulted in a significant step forward toward achieving greater patient safety. FMEA was a useful tool, which helped in taking some important actions. Finally, CHC nurse satisfaction has clearly improved. Copyright © 2009 SECA. Published by Elsevier Espana. All rights reserved.

Assessing Integration of Clinical and Public Health Skills in Preventive Medicine Residencies: Using Competency Mapping

PubMed Central

Sarigiannis, Amy N.; Boulton, Matthew L.

2012-01-01

Objectives. We evaluated the utility of a competency mapping process for assessing the integration of clinical and public health skills in a newly developed Community Health Center (CHC) rotation at the University of Michigan School of Public Health Preventive Medicine residency. Methods. Learning objectives for the CHC rotation were derived from the Accreditation Council for Graduate Medical Education core clinical preventive medicine competencies. CHC learning objectives were mapped to clinical preventive medicine competencies specific to the specialty of public health and general preventive medicine. Objectives were also mapped to The Council on Linkages Between Academia and Public Health Practice’s tier 2 Core Competencies for Public Health Professionals. Results. CHC learning objectives mapped to all 4 (100%) of the public health and general preventive medicine clinical preventive medicine competencies. CHC population-level learning objectives mapped to 32 (94%) of 34 competencies for public health professionals. Conclusions. Utilizing competency mapping to assess clinical–public health integration in a new CHC rotation proved to be feasible and useful. Clinical preventive medicine learning objectives for a CHC rotation can also address public health competencies. PMID:22690972

Patient-reported Outcomes in Asian Patients With Chronic Hepatitis C Treated With Ledipasvir and Sofosbuvir

PubMed Central

Younossi, Zobair M.; Stepanova, Maria; Chan, Henry L.Y.; Lee, Mei H.; Yu, Ming-Lung; Dan, Yock Y.; Choi, Moon S.; Henry, Linda

2016-01-01

Abstract Prevalence of chronic hepatitis C (CH-C) infection in patients of Asian ancestry ranges between 1% and 20%. Interferon (IFN)- and ribavirin (RBV)-containing regimens for CH-C have a negative impact on patient-reported outcomes (PROs) during treatment. The aim of this study was to assess the impact of IFN-free RBV-free sofosbuvir (SOF)-based regimens on PROs in CH-C patients of Asian ancestry. In this observational retrospective study, the PRO data from 12 multicenter multinational phase 3 clinical trials (2012–2015, conducted in Europe, North America, Australia, and New Zealand) of SOF-based regimens with and without IFN, ledipasvir (LDV), and/or RBV were used. At baseline, during treatment, and post-treatment, patients completed 4 validated PRO questionnaires (SF-36, CLDQ-HCV, FACIT-F, and WPAI:SHP). The resulting PROs in Asian patients were compared across the treatment regimens. Of 4485 of the trials’ participants, 106 patients were of Asian ancestry (55.7% male, 69.8% treatment-naïve, 17.0% cirrhotic). In comparison with other patients, the Asian CH-C cohort was younger, had lower BMI, and lower rates of pre-treatment psychiatric comorbidities (anxiety, depression, sleep disorders) (all P < .05). At baseline, Asian patients also had lower SF-36 physical functioning scores (on average, by −5.6% on a normalized 0–100% PRO scale, P = .001). During treatment, Asian CH-C patients experienced a decline in their PRO scores while receiving IFN and/or RBV-containing regimens (up to −19.6%, P < .001). In contrast, patients receiving LDV/SOF experienced no PRO decrement and improvement of some PRO scores during treatment (+9.0% in general health of SF-36, P = .03). After achieving SVR-12, some of the PRO scores in Asian patients improved regardless of the regimen (up to +9.3%, P < .001). In multivariate analysis of Asian patients, the use of LDV/SOF was independently associated with higher PRO scores during and soon after the end of treatment (betas +15.0% to +29.3%, all P < .05). Other predictors of PRO impairment included depression, type 2 diabetes mellitus, and cirrhosis. The use of IFN- and RBV-free LDV/SOF regimens leads to PRO improvement in Asian patients with CH-C during treatment. Achieving SVR-12 results in improvement of PRO scores. PMID:26945356

Type I Interferon Elevates Co-Regulatory Receptor Expression on CMV- and EBV-Specific CD8 T Cells in Chronic Hepatitis C

PubMed Central

Owusu Sekyere, Solomon; Suneetha, Pothakamuri Venkata; Hardtke, Svenja; Falk, Christine Susanne; Hengst, Julia; Manns, Michael Peter; Cornberg, Markus; Wedemeyer, Heiner; Schlaphoff, Verena

2015-01-01

Hepatitis C virus (HCV) readily sets up persistence in a large fraction of infected hosts. Mounting epidemiological and immunological evidence suggest that HCV’s persistence could influence immune responses toward unrelated pathogens and vaccines. Nonetheless, the fundamental contribution of the inflammatory milieu during persistent HCV infection in impacting immune cells specific for common pathogens such as CMV and EBV has not been fully studied. As the co-regulatory receptors PD-1, Tim-3, and 2B4 have all been shown to be vital in regulating CD8+ T cell function, we assessed their expression on CMV/EBV-specific CD8+ T cells from patients with chronic hepatitis C (CHC) and healthy controls ex vivo and upon stimulation with virus-specific peptides in vitro. Total and CMV/EBV-specific CD8+ T cells expressing PD-1, Tim-3, and 2B4 were highly enriched in patients with CHC compared to healthy individuals ex vivo. In vitro peptide stimulation further potentiated the differential co-regulatory receptor expression of PD-1, Tim-3, and 2B4, which then culminated in an enhanced functionality of CMV/EBV-specific CD8+ T cells in CHC patients. Comprehensively analyzing plasma cytokines between the two cohorts, we observed that not only was IFNα-2a dominant among 21 other inflammatory mediators elevated in CHC patients but it also correlated with PD-1 and Tim-3 expressions ex vivo. Importantly, IFNα-2a further caused upregulation of these markers upon in vitro peptide stimulation. Finally, we could prospectively study patients receiving novel IFN-free antiviral therapy. Here, we observed that treatment-induced clearance of HCV resulted in a partial reversion of the phenotype of CMV/EBV-specific CD8+ T cells in patients with CHC. These data reveal an alteration of the plasma concentrations of IFNα-2a together with other inflammatory mediators during CHC, which appeared to pervasively influence co-regulatory receptor expression on CMV/EBV-specific CD8+ T cells. PMID:26113847

Patients with chronic hepatitis type C and interferon-alpha-induced hyperthyroidism in two-years clinical follow-up.

PubMed

Czarnywojtek, Agata; Zgorzalewicz-Stachowiak, Magorzata; Wasko, Ryszard; Czepczynski, Rafal; Szczepanek-Parulska, Ewelina; Waligorska-Stachura, Joanna; Kurdybacha, Peter; Bereszynska, Iwona; Florek, Ewa; Stangierski, Adam; Zdanowska, Joanna; Nikisch, Elżbieta; Sowinski, Jerzy; Ruchala, Marek

2013-01-01

Interferon-α (IFN-α) is a gold standard in the therapy of viral chronic hepatitis type C (CHC). However, such treatment might lead to thyroid dysfunction. Patients usually present hypothyroidism, but rarely also hyperthyroidism may develop. The aim of the study is to present two-year clinical follow-up of patients with CHC and IFN-α-induced hyperthyroidism (IIH), with special regard to the methods and efficacy of the therapy. A group of 106 patients with CHC and IIH were analyzed. Subjects were divided into two groups according to etiology: group 1, with Graves' disease (GD) and group 2, with Hashitoxicosis (HT). The diagnosis of GD and HT was based on: clinical signs of hyperthyroidism, hormonal profile (TSH, fT4, fT3), level of thyroid autoantibodies (Tg-Abs, TPO-Abs, TSHRAbs). Treatment of hyperthyroidism was monitored by repeated clinical assessment and laboratory tests. RESULST: 28 patients (26 with GD of which 5 exhibited mild orbitopathy and 2 with HT) were treated with radioiodine [the average dose of was 17 mCi [668 MBq]. In adition 78 out of 80 patients with HT mostly β-blocker therapy was successful (transient hyperthyroidism). At the end of the observation period, in group 1 remission was achieved in 17 (65.4%) cases, 6 (23.1%) patients showed hypothyroidism and 3 (11.5%) presented recurrence of hyperthyroidism. Most patients with IIH present Hashitoxicosis, while a minority of them develop Graves' disease. In a majority of patients with HT spontaneous remission of disease occurs. In patients with long-term hyperthyroidism, radioiodine therapy is an effective and well-tolerated.

Effect of branched-chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients.

PubMed

Ocaña-Mondragón, Alicia; Mata-Marín, José Antonio; Uriarte-López, Mario; Bekker-Méndez, Carolina; Alcalá-Martínez, Enrique; Ribas-Aparicio, Rosa María; Uribe-Noguéz, Luis Antonio; Rodríguez-Galindo, Dulce María; Martínez-Rodríguez, María de La Luz

2018-01-01

The incidence rate of insulin resistance (IR) in patients with chronic hepatitis C (CHC) is high. Recently, branched-chain amino acids (BCAA) have been shown to attenuate IR in CHC patients; however, their effect on patient quality of life remains unclear. Therefore, the aim of the current prospective study was to determine the effects of BCAA supplement on IR and health-related quality of life (HR-QoL) in patients with CHC. In the study, 20 non-diabetic patients with CHC, who were non-responders to peginterferon-α and ribavirin, were recruited. Patients took a BCAA supplement once a day (30 g, after a minimum 10-h overnight fast) for 3 months. Serum levels of glucose, insulin, albumin, triglycerides and cholesterol were measured at 0 and 3 months. Additionally, IR was measured using the Homeostasis Model Assessment-IR, HR-QoL was assessed using the 36-item Short Form Health Survey and viral load was measured by reverse transcription polymerase chain reaction using Taqman probes. The Wilcoxon signed-rank test was used to determine statistical significance. The results indicated that 70% of the subjects were positive for IR, which decreased to 50% by the end of the study; furthermore, 85% of the subjects demonstrated some level of improvement. Overall, the BCAA treatment significantly decreased IR (P=0.006) and augmented serum albumin concentration (P=0.008) compared with basal values. Additionally, by the end of the treatment, viral load and triglycerides levels had decreased, though these results were not significant (P=0.084 and P=0.080, respectively). BCAA treatment also improved HR-QoL regarding role limitations due to physical health problems (P=0.017), role limitations due to emotional problems (P=0.026) and social function (P=0.008). In conclusion, BCAA supplementation reduced IR and improved HR-QoL in patients with CHC. These findings support the application of IR therapy as a possible therapeutic strategy for hepatitis C infection.

Prevalence and predictive factors of moderate/severe liver steatosis in chronic hepatitis C (CHC) infected patients evaluated with Controlled Attenuation Parameter (CAP).

PubMed

Cardoso, Ana Carolina; Perez, Renata M; de Figueiredo-Mendes, Claudio; Carvalho Leite, Nathalie; Coelho, Henrique Sergio Moraes; Villela-Nogueira, Cristiane A

2018-05-16

A novel controlled attenuation parameter (CAP) using FibroScan ® has been developed for assessment of liver steatosis. The aim was to evaluate the frequency and associated factors for moderate/severe steatosis evaluated by CAP in CHC patients submitted to transient elastography (TE) by FibroScan ® . CHC patients underwent TE with CAP evaluation. The classification of steatosis was defined as: CAP < 222 dB/m = S0; CAP ≥ 222 dB/m and <233dB /m = S1; ≥233 dB/m <290dB/m = S2 and >= 290 dB/m = S3. The prevalence of moderate/severe steatosis (CAP ≥ S2) and the related independent factors were identified by a logistic regression analysis. A significance level of 5% was adopted. 1104 CHC patients, 85% genotype-1 were included (mean age 55 ± 11 yrs; 46% male, mean BMI 25 ± 4 Kg/m 2 ). Systemic arterial hypertension and type 2 diabetes mellitus prevalences were 39% and 17% respectively. Liver stiffness measurement ≥ 9.5 kPa was observed in 39% of patients and steatosis was identified in 50% (S1 = 7%, S2 = 28% and S3 = 15%). The variables independently associated with moderate/severe steatosis were: male gender (OR=1.35; p=0.037; 95% CI:1.01 - 1.81); systemic arterial hypertension (OR=1.57; p=0.002; 95% CI:1.17 - 2.10) and BMI (OR=1.17; p <0.01;95% CI: 1.12 - 1.22). In conclusion, when CAP was adopted as a tool to detect steatosis, genotype 1 CHC patients presented a high prevalence of moderate/advanced steatosis. In these patients, liver steatosis was associated mostly to metabolic factors (arterial hypertension and high BMI). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

HCV Ag quantification as a one-step procedure in diagnosing chronic hepatitis C infection in Cameroon: the ANRS 12336 study.

PubMed

Duchesne, Léa; Njouom, Richard; Lissock, Frédéric; Tamko-Mella, Gishlaine Flore; Rallier, Sandrine; Poiteau, Lila; Soulier, Alexandre; Chevaliez, Stéphane; Vernet, Guy; Rouveau, Nicolas; Pawlotsky, Jean-Michel; Girard, Pierre-Marie; Lacombe, Karine

2017-05-15

The diagnostic procedure for chronic hepatitis C infection (CHC) usually combines anti-HCV antibody (HCV- Ab ) and HCV-RNA measurement. Quantifying HCV core antigen (cAg) as a one-step procedure could shorten the diagnostic process. We aimed to assess the performance of cAg quantification in diagnosing CHC and how it is influenced by concomitant HIV or HBV infections. The cAg was quantified by an automated assay (Abbott Diagnostics) in 465 HCV- Ab negative serum samples and 544 HCV-RNA positive serum samples ( n  = 1009) collected in patients from the Pasteur Center in Cameroon, some of whom were infected by HBV or HIV. Its performance was evaluated in comparison to the gold standard (ELISA or PCR) by estimating its sensitivity (Se) and specificity (Sp), and by comparing the area under ROC (AUROC) curves in each patient population: HCV mono-infected, HCV-HBV and HIV-HCV co-infected. Among the 465 HCV- Ab negative patients, 51 and 79 were HIV- and HBV-infected, respectively, whereas among the 544 patients with CHC, 27 and 28 were HIV- and HBV-infected, respectively. The Spearman ρ correlation coefficient between cAg and HCV-RNA was 0.75 ( p  < 0.00001). The assay had a sensitivity of 95.7% (95% CI: 93.2-97.5) and a specificity of 99.7% (95% CI: 98.1-10) in diagnosing CHC, corresponding to an AUROC of 0.99 (95% CI: 0.98-1.0). Being HIV- or HBV-infected did not impact the performance of cAg (Se = 96.4%, Sp = 96.2% and AUROC = 0.98 (95% CI: 0.95-1.0) in the HBV group, Se = 100%, Sp = 88.2% and AUROC = 0.99 (95% CI: 0.97-1.0) in the HIV group, p between AUROC = 0.69). The cAg quantification displayed a high specificity and sensitivity for the diagnosis of CHC in Cameroon, and its performance was not significantly modified by a concomitant HIV or HBV infection. In the context of CHC elimination on a global scale, using cAg quantification as a screening tool to directly identify CHC could be a reliable tool in a "test and treat" strategy.

Impact of Hispanic or Asian ethnicity on the treatment outcomes of chronic hepatitis C: results from the WIN-R trial.

PubMed

Hu, Ke-Qin; Freilich, Bradley; Brown, Robert S; Brass, Clifford; Jacobson, Ira M

2011-09-01

African American ethnicity is a well-described negative predictor of treatment outcome for chronic hepatitis C (CHC); however, less is known about the influence of Hispanic and Asian ethnicity. The aim of this subanalysis of the Weight-based Dosing of PegINterferon α-2b and Ribavirin (WIN-R) study was to assess the impact of Asian (n=118), Hispanic (n=289), and white (n=3919) ethnicity on CHC treatment outcomes. WIN-R was an investigator-initiated trial in which patients with CHC received pegylated interferon α-2b (1.5 μg/kg/wk) plus a fixed ribavirin dose (800 mg/d) or a weight-based ribavirin dose (800 to 1400 mg/d) for 24 or 48 weeks. Sustained virologic response was higher in Asian patients than in white patients (56% vs 46%, P=0.041), and higher in Asian and white patients than in Hispanic patients (56% vs 35%, P=0.0001; and 46% vs 35%, P=0.0002, respectively). In genotype 1 patients, sustained virologic response was higher in white and Asian patients than in Hispanic patients (36% and 45% vs 25%, P<0.001 for both comparisons); however, in genotype 2/3 patients, there were no significant differences among ethnic groups. Psychiatric adverse events were less common and anemia was more common in Asians than in white or Hispanic patients. Ribavirin dose reductions were less frequent in Hispanic patients than in white patients, whereas pegylated interferonα-2b dose reductions were more common in white patients than Hispanic patients. These observations highlight the importance of ethnicity as an integral component of the tailored treatment approach to CHC.

Disparities in Diabetes Care Quality by English Language Preference in Community Health Centers.

PubMed

Leung, Lucinda B; Vargas-Bustamante, Arturo; Martinez, Ana E; Chen, Xiao; Rodriguez, Hector P

2018-02-01

To conduct a parallel analysis of disparities in diabetes care quality among Latino and Asian community health center (CHC) patients by English language preference. Clinical outcomes (2011) and patient survey data (2012) for Type 2 diabetes adults from 14 CHCs (n = 1,053). We estimated separate regression models for Latino and Asian patients by English language preference for Clinician & Group-Consumer Assessment of Healthcare Providers and System, Patient Assessment of Chronic Illness Care, hemoglobin A1c, and self-reported hypoglycemic events. We used the Blinder-Oaxaca decomposition method to parse out observed and unobserved differences in outcomes between English versus non-English language groups. After adjusting for socioeconomic and health characteristics, disparities in patient experiences by English language preference were found only among Asian patients. Unobserved factors largely accounted for linguistic disparities for most patient experience measures. There were no significant differences in glycemic control by language for either Latino or Asian patients. Given the importance of patient retention in CHCs, our findings indicate opportunities to improve CHC patients' experiences of care and to reduce disparities in patient experience by English preference for Asian diabetes patients. © Health Research and Educational Trust.

Estimation of direct medical cost related to the management of chronic hepatitis C and its complications in South Korea.

PubMed

Kim, Do Young; Yoon, Ki Tae; Kim, Won; Lee, Jung Il; Hong, Sung Hwi; Lee, Danbi; Jang, Jeong Won; Choi, Jong Won; Kim, Ilsu; Paik, Yong Han

2016-07-01

This study aimed to estimate the direct medical costs of managing chronic hepatitis C (CHC) and its complications based on health-care resources in South Korea. The study design was multicenter, retrospective, non-interventional, and observational. Between September 2013 and April 2014, health-care resource data from patients chronically infected with hepatitis C virus, regardless of genotype, were collected from 8 institutions, including data related to outpatient management, emergency care, and hospitalization. The observation period was between January 2011 and December 2012. The disease state was classified as CHC, compensated cirrhosis (CC), decompensated cirrhosis (DC), or hepatocellular carcinoma (HCC). A total of 445 patients were recruited and mean age was 60.1 ± 12.3 years. Among 155 patients with reported outcomes of antiviral therapy, 107 (69%) had sustained virologic response (SVR). The rate of patients who did not receive antiviral therapy was 52.8% (n = 235). The distribution of disease state was CHC in 307 patients (69.0%), CC in 75 (16.9%), HCC in 45 (10.1%), and DC in 18 (4.0%). All direct medical costs, whether reimbursed or nonreimbursed by the National Health Insurance System, were included. After excluding patients whose observational period was <1 month for each disease status, the mean costs per month increased as disease state progressed (CHC: 77 ± 80 USD; CC: 98 ± 94 USD; DC: 512 ± 1115 USD; HCC: 504 ± 717 USD). The mean total costs per person were 3590 ± 8783 USD, and approximately 72% of patients were reimbursed. When 44 patients with an observation period <1 month were excluded, the mean medical costs per month for patients with CHC who achieved SVR (n = 69) were significantly lower than for those (n = 215) who did not (42 ± 16 vs 79 ± 83 USD, P < 0.001). The cost also tended to be lower for patients with CC with SVR (n = 8) than for those without SVR (n = 70; 48 ± 20 vs 95 ± 96 USD, P = 0.177). The cost of antiviral therapy (pegylated interferon and ribavirin) corresponded to 19.0% of total medical costs and 53.7% of prescription/pharmacy. The direct medical costs increased as disease state progressed from CHC to cirrhosis or HCC. The achievement of SVR by antiviral therapy would decrease the costs.

Prevalence of Candida spp. in Healthy Oral Mucosa Surfaces with Higher Incidence of Chronic Hyperplastic Candidosis.

PubMed

Arruda, Claúdia; Artico, Gabriela; Freitas, Roseli; Filho, Antônio; Migliari, Dante

2016-08-01

Predisposing factors in chronic hyperplastic candidosis (CHC) have been poorly recognized. This study aimed at assessing the prevalence of Candida spp. in areas of the oral mucosa showing greater prevalent rate of CHC, such as the retrocomissural area, the lateral borders of the tongue, and the hard-palate mucosa in four groups of individuals presenting predisposing factors as follows: Smoking habits (group I); patients with low salivary flow rate (SFR) (hyposalivation - group II); patients with loss of vertical dimension of occlusion (LVDO -group III); and control subjects (group IV). A total of 44 individuals (age 4090 years, mean: 55.8 years) were divided into four groups: Group I (11 smokers); group II (10 hyposalivation patients); group III (10 LVDO patients); and group IV (control, 13 healthy subjects). All individuals were tested for Candida-pseudohyphae form by direct examination and for Candida spp. culture growth in samples obtained from the retrocomissural, tongue's lateral border, and hard-soft palatal mucosa. Direct examination showed a statistically significant prevalence rate for pseudohyphae (p < 0.05) on the retrocomissural and on tongue's lateral borders of individuals with LVDO. A statistically significant (p < 0.05) culture growth for Candida spp. was found on the retrocomissural areas of those with hyposalivation and with LVDO, and on the palate mucosa and on the tongue's lateral borders in the smokers and in the individuals with LVDO when compared with those of the control group. While direct examination is effective for detecting pseudohyphae, LVDO and tobacco smoking seem to be factors of relevance to the development of CHC. Since CHC has been linked to a high rate of malignant transformation, this study analyzes some clinical (and exogenous) factors that may contribute to the development of CHC and addresses some preventive measures to reduce its incidence.

The PAPAS index: a novel index for the prediction of hepatitis C-related fibrosis.

PubMed

Ozel, Banu D; Poyrazoğlu, Orhan K; Karaman, Ahmet; Karaman, Hatice; Altinkaya, Engin; Sevinç, Eylem; Zararsiz, Gökmen

2015-08-01

Several noninvasive tests have been developed to determine the degree of hepatic fibrosis in patients with chronic hepatitis C (CHC) without performing liver biopsy. This study aimed to determine the performance of the PAPAS (Platelet/Age/Phosphatase/AFP/AST) index in patients with CHC for the prediction of significant fibrosis and cirrhosis and to compare it with other noninvasive tests. To date, no study has evaluated the application of the PAPAS index in CHC-associated liver fibrosis. This retrospective study included 137 consecutive patients with CHC who had undergone a percutaneous liver biopsy before treatment. The aspartate aminotransferase/platelet ratio (APRI), aspartate aminotransferase/alanine transaminase ratio (AAR), age-platelet index (API), FIB4, cirrhosis discriminate score (CDS), the Göteborg University cirrhosis index (GUCI), and PAPAS were calculated and compared with the diagnostic accuracies of all fibrosis indices between the groups F0-F2 (no-mild fibrosis) versus F3-F6 (significant fibrosis) and F0-F4 (no cirrhosis) versus F5-F6 (cirrhosis). To predict significant fibrosis, the area under curve (95% confidence interval) for FIB4 was 0.727 followed by GUCI (0.721), PAPAS≈APRI≈CDS (0.716), and API (0.68). To predict cirrhosis, the area under curve (95% confidence interval) for FIB4 was calculated to be 0.735, followed by GUCI (0.723), PAPAS≈APRI≈CDS≈(0.71), and API (0.66). No statistically significant difference was observed among these predictors to exclude both significant fibrosis and cirrhosis (P>0.05). The diagnostic capability of the PAPAS index has moderate efficiency and was not superior to other fibrosis markers for the identification of fibrosis in CHC patients. There is a need for more comprehensive prospective studies to help determine the diagnostic value of PAPAS for liver fibrosis.

Stigmatization and discrimination of patients with chronic hepatitis C.

PubMed

Kostić, Marina; Kocić, Biljana; Tiodorović, Branislav

2016-12-01

Chronic hepatitis C (CHC) is often associated with injectable drug users and human immunodeficiency virus coinfection for which there is stigmatization in society. The aim of this study was to identify the presence of stigma and discrimination of patients with CHC, as well as the influence of sociodemographic factors on the occurrence of stigmatization. A cross-sectional study was performed. Patients with CHC and conducted antiviral therapy completed an anonymous structured questionnaire consisting of sociodemographic questions and Hepatitis C stigma scale. Out of 154 patients 61.7% were male and 72.1% from the city; 59.7% have completed secondary school; 61.7% were employed before the disease while 31.8% after the disease; 45.5% were unsatisfactory with financial situation; 54.5% were married; 37.7% lived with a spouse and children; 86.4% in their own house/apartment; 5.2% of the patients were abandoned by their partners, while 35.7% consumed drugs. A statistical significance of the stigma score was found in those who lived in the city (p = 0.018), unmarried (p = 0.005), abandoned by the partners after the diagnosis of CHC (p < 0.001), drug users (p = 0.002) and those living with parents (p = 0.034). Univariate regression analysis singled out as significant: residence (p = 0.018), living with their parents (p = 0.046), abandonment by a partner (p < 0.001) and drug use (p = 0.002). A multivariate regression model of independent variables singled out abandonment by partners (Beta = 5.158, p = 0.007). Men disagree significantly with the two elements inside stigma [not the same as the others (p = 0.035)] and hurt by the reaction of others (p = 0.047)). The presence of stigma in patients with CHC was proven. The results indicate the need to strengthen anti-stigma programs that will reduce their psychological and social problems and reduce stigmatization in society.

Barriers and enablers to the delivery of psychological care in the management of patients with type 2 diabetes mellitus in China: a qualitative study using the theoretical domains framework.

PubMed

Chapman, Anna; Yang, Hui; Thomas, Shane A; Searle, Kendall; Browning, Colette

2016-03-29

China has the largest number of type 2 diabetes mellitus (T2DM) cases globally and individuals with T2DM have an increased risk of developing mental health disorders and functional problems. Despite guidelines recommending that psychological care be delivered in conjunction with standard T2DM care; psychological care is not routinely delivered in China. Community Health Centre (CHC) doctors play a key role in the management of patients with T2DM in China. Understanding the behavioural determinants of CHC doctors in the implementation of psychological care recommendations allows for the design of targeted and culturally appropriate interventions. As such, this study aimed to examine barriers and enablers to the delivery of psychological care to patients with T2DM from the perspective of CHC doctors in China. Two focus groups were conducted with 23 CHC doctors from Shenzhen, China. The discussion guide applied the Theoretical Domains Framework (TDF) that examines current practice and identifies key barriers and enablers perceived to influence practice. Focus groups were conducted with an interpreter, and were digitally recorded and transcribed. Two researchers independently coded transcripts into pre-defined themes using deductive thematic analysis. Barriers and enablers perceived by doctors as being relevant to the delivery of psychological care for patients with T2DM were primarily categorised within eight TDF domains. Key barriers included: CHC doctors' knowledge and skills; time constraints; and absence of financial incentives. Other barriers included: societal perception that treating psychological aspects of health is less important than physical health; lack of opinion leaders; doctors' intentional disregard of psychological care; and doubts regarding the efficacy of psychological care. In contrast, perceived enablers included: training of CHC doctors in psychological skills; identification of afternoon/evening clinic times when recommendations could be implemented; introduction of financial incentives; and the creation of a professional role (e.g. diabetes educator), that could implement psychological care recommendations to patients with T2DM. The utilisation of the TDF allowed for the comprehensive understanding of barriers and enablers to the implementation of psychological care recommendations for patients with T2DM, and consequently, has given direction to future interventions strategies aimed at improving the implementation of such recommendations.

Determination of the Human Antibody Response to the Neutralization Epitopes Encompassing Amino Acids 313–327 and 432–443 of Hepatitis C Virus E1E2 Glycoproteins

PubMed Central

Liu, Ruyu; Rao, Huiying; Wang, Jianghua; Xie, Xingwang; Jiang, Dong; Pan, Xiaoben; Zhao, Ping; Zhang, Henghui; Wei, Lai

2013-01-01

It has been reported that monoclonal antibodies (MAbs) to the E1E2 glycoproteins may have the potential to prevent hepatitis C virus (HCV) infection. The protective epitopes targeted by these MAbs have been mapped to the regionsencompassing amino acids 313–327 and 432–443. In this study, we synthesized these two peptides and tested the reactivity of serum samples from 336 patients, 210 of whichwere from Chronic Hepatitis C (CHC) patients infected with diverse HCV genotypes.The remaining 126 samples were isolated from patients who had spontaneously clearedHCV infection.In the chronic HCV-infected group (CHC group), the prevalence of human serum antibodies reactive to epitopes 313–327 and 432–443was 24.29%(51 of 210) and4.76%(10 of 210),respectively. In thespontaneousclearance group (SC group),the prevalence was 0.79%(1 of 126) and 12.70%(16 of 126), respectively.The positive serum samples that contained antibodies reactive to epitope 313–327 neutralizedHCV pseudoparticles (HCVpp) bearing the envelope glycoproteins of genotypes 1a or 1b and/or 4, but genotypes 2a, 3a, 5 and 6 were not neutralized. The neutralizing activity of these serum samples could not be inhibited by peptide 313–327. Six samples (SC17, SC38, SC86, SC92, CHC75 and CHC198) containing antibodies reactive to epitope 432–443 had cross-genotype neutralizing activities. Theneutralizing activityof SC38, SC86, SC92 and CHC75waspartiallyinhibited by peptide 432–443. However,the neutralizing activity of sample SC17 for genotype 4HCVpp and sample CHC198 for genotype 1b HCVppwere notinhibited by the peptide.This study identifies the neutralizing ability of endogenous anti-HCV antibodies and warrants the exploration of antibodies reactive to epitope432–443as sources for future antibody therapies. PMID:23826163

Open source electronic health records and chronic disease management.

PubMed

Goldwater, Jason C; Kwon, Nancy J; Nathanson, Ashley; Muckle, Alison E; Brown, Alexa; Cornejo, Kerri

2014-02-01

To study and report on the use of open source electronic health records (EHR) to assist with chronic care management within safety net medical settings, such as community health centers (CHC). The study was conducted by NORC at the University of Chicago from April to September 2010. The NORC team undertook a comprehensive environmental scan, including a literature review, a dozen key informant interviews using a semistructured protocol, and a series of site visits to CHC that currently use an open source EHR. Two of the sites chosen by NORC were actively using an open source EHR to assist in the redesign of their care delivery system to support more effective chronic disease management. This included incorporating the chronic care model into an CHC and using the EHR to help facilitate its elements, such as care teams for patients, in addition to maintaining health records on indigent populations, such as tuberculosis status on homeless patients. The ability to modify the open-source EHR to adapt to the CHC environment and leverage the ecosystem of providers and users to assist in this process provided significant advantages in chronic care management. Improvements in diabetes management, controlled hypertension and increases in tuberculosis vaccinations were assisted through the use of these open source systems. The flexibility and adaptability of open source EHR demonstrated its utility and viability in the provision of necessary and needed chronic disease care among populations served by CHC.

Evaluating Diagnostic Accuracy of Noninvasive Tests in Assessment of Significant Liver Fibrosis in Chronic Hepatitis C Egyptian Patients.

PubMed

Omran, Dalia; Zayed, Rania A; Nabeel, Mohammed M; Mobarak, Lamiaa; Zakaria, Zeinab; Farid, Azza; Hassany, Mohamed; Saif, Sameh; Mostafa, Muhammad; Saad, Omar Khalid; Yosry, Ayman

2018-05-01

Stage of liver fibrosis is critical for treatment decision and prediction of outcomes in chronic hepatitis C (CHC) patients. We evaluated the diagnostic accuracy of transient elastography (TE)-FibroScan and noninvasive serum markers tests in the assessment of liver fibrosis in CHC patients, in reference to liver biopsy. One-hundred treatment-naive CHC patients were subjected to liver biopsy, TE-FibroScan, and eight serum biomarkers tests; AST/ALT ratio (AAR), AST to platelet ratio index (APRI), age-platelet index (AP index), fibrosis quotient (FibroQ), fibrosis 4 index (FIB-4), cirrhosis discriminant score (CDS), King score, and Goteborg University Cirrhosis Index (GUCI). Receiver operating characteristic curves were constructed to compare the diagnostic accuracy of these noninvasive methods in predicting significant fibrosis in CHC patients. TE-FibroScan predicted significant fibrosis at cutoff value 8.5 kPa with area under the receiver operating characteristic (AUROC) 0.90, sensitivity 83%, specificity 91.5%, positive predictive value (PPV) 91.2%, and negative predictive value (NPV) 84.4%. Serum biomarkers tests showed that AP index and FibroQ had the highest diagnostic accuracy in predicting significant liver fibrosis at cutoff 4.5 and 2.7, AUROC was 0.8 and 0.8 with sensitivity 73.6% and 73.6%, specificity 70.2% and 68.1%, PPV 71.1% and 69.8%, and NPV 72.9% and 72.3%, respectively. Combined AP index and FibroQ had AUROC 0.83 with sensitivity 73.6%, specificity 80.9%, PPV 79.6%, and NPV 75.7% for predicting significant liver fibrosis. APRI, FIB-4, CDS, King score, and GUCI had intermediate accuracy in predicting significant liver fibrosis with AUROC 0.68, 0.78, 0.74, 0.74, and 0.67, respectively, while AAR had low accuracy in predicting significant liver fibrosis. TE-FibroScan is the most accurate noninvasive alternative to liver biopsy. AP index and FibroQ, either as individual tests or combined, have good accuracy in predicting significant liver fibrosis, and are better combined for higher specificity.

Regulatory polymorphism of CXCL10 rs1439490 in seronegative occult hepatitis C virus infection.

PubMed

Wang, Xu; Wang, Song; Liu, Zhen-Hua; Qi, Wen-Qian; Zhang, Qian; Zhang, Yong-Gui; Sun, De-Rong; Xu, Yan; Wang, Hong-Guang; Li, Zhong-Xie; Cong, Xian-Ling; Zhao, Ping; Zhou, Chang-Yu; Wang, Jiang-Bin

2018-05-28

To examine the relationship between the single nucleotide polymorphism CXCL10 rs1439490 and seronegative occult hepatitis C virus (HCV) infection (OCI). One hundred and three cases of seronegative OCI and 155 cases of seropositive chronic HCV infection (CHC) were diagnosed at five Liver Centers in Northeastern China, from 2012 to 2016. CXCL10 rs1439490, rs1440802, and IL-28B rs12979860 were analyzed by sequencing. Serum CXCL10 was measured by ELISA. Intrahepatic CXCL10 was determined by quantitative PCR and immunohistochemical semi-quantitative scoring. Liver necroinflammation and fibrosis were scored according to the METAVIR system. CXCL10 rs1439490 G/G was more prevalent in OCI patients ( n = 93/103; 90.3%) than in CHC patients ( n = 116/155; 74.8%; P = 0.008). OCI patients had lower serum CXCL10 levels than CHC patients (192.91 ± 46.50 pg/mL vs 354.78 ± 102.91 pg/mL, P < 0.0001). Of IL-28B rs12979860 C/C patients, OCI patients with rs1439490 G/G had lower serum and liver levels of CXCL10 and lower levels of liver necroinflammation and fibrosis than non-G/G patients. OCI patients had higher alanine aminotransferase normalization rates after Peg-interferon treatment than CHC patients (P < 0.05) and serum CXCL10 decreased significantly (P < 0.0001). Liver necroinflammation and fibrosis were alleviated in 8 OCI patients after treatment. Multivariate analysis indicated that rs1439490 G/G significantly influenced the occurrence of OCI in HCV infection (OR = 0.31, 95%CI: 0.15-0.66, P = 0.002). CXCL10 rs1439490 G/G is positively associated with OCI in HCV infection and antiviral outcome.

[Cognitive disturbances observed in chronic hepatitis C patients during pegylated interferon alpha and ribavirin therapy].

PubMed

Pawełczyk, Tomasz; Pawełczyk, Agnieszka; Białkowska, Jolanta; Jabłkowski, Maciej; Strzelecki, Dominik; Dworniak, Daniela; Rabe-Jabłońska, Jolanta

2008-01-01

Chronic hepatitis C (CHC) patients treated with peg-interferon alpha and ribavirin (peg-IFNalpha/RBV) complain of irritability, attention and memory disturbances which may indicate cognitive impairment associated with treatment. Assessment of the probable connection between peg-IFNalpha/RBV treatment and the development of cognitive disturbances in CHC patients. 47 CHC patients were divided into two groups: experimental (n=26) and control (n=21). The experimental group patients were given peg-IFNalpha2a (n=18) or peg-IFNalpha2b (n=8) plus RBV in standard doses as recommended by the manufacturers. Control group patients did not receive the above treatment. Both groups underwent a neuropsychological examination consisting of R. Brickenkamp d2 test, Auditory Verbal Learning Test and Hooper Visual Organization Test at the beginning (t=0) and after 12 weeks of treatment or observation (t=1). The experimental group patients showed significant deterioration in all the measured cognitive functions in t=1 comparing to t=0. Cognitive decline was not seen in the control group. The observed cognitive performance changes could not be correlated sufficiently enough with the presence of organic affective disorders diagnosed according to ICD-10 criteria. The findings suggest that peg-IFNalpha/RBV therapy of CHC patients is connected with the deterioration in cognitive functioning including attention, auditory verbal memory and visuo-spatial skills. These changes may be the effect of peg-IFNalpha-induced neurotransmission abnormalities in the dorso-lateral prefrontal cortex, anterior cingulate cortex, hippocampus and parieto-orbital cortical regions and can impair patients' ability to drive a motor vehicle, operate machinery, or their engagement in hazardous activities requiring attention and coordination. Medical professionals should thoroughly inform patients about the possibility of cognitive decline associated with peg-IFNalpha/RBV therapy.

Comorbidities and medications of patients with chronic hepatitis C under specialist care in the UK

PubMed Central

Hudson, Benjamin; Walker, Alex J.

2017-01-01

Designing services with the capacity and expertise to meet the needs of the chronic hepatitis C (CHC) population in the era of direct acting antivirals (DAAs), and widening access to such treatments, requires detailed understanding of the characteristics and healthcare needs of the existing patient population. In this retrospective analysis of data from the National HCV Research UK Biobank between March 2012 and October 2014, the characteristics of the CHC population currently under specialist care in the UK were evaluated—with specific focus upon use of medications, adverse lifestyle choices, and comorbidities. Demographic data, risk factors for CHC acquisition, HCV genotype, liver disease status, lifestyle factors, comorbidities, and medication classes were collected. Data were analyzed by history of injecting drug use (IDU), age, and severity of liver disease. A total of 6278 patients (70.5% white; median age, 52 years) from 59 UK specialist centres were included; 59.1% of patients had acquired HCV through IDU. The prevalence of adverse lifestyle factors was significantly lower in non‐IDU compared with previous IDU or recent IDU patients. Depression was common in the previous (50.8%) and recent IDU (68.1%) groups, compared with 27.6% in non‐IDU patients. Cirrhosis was common (23.6%), and prevalence increased with age. We describe a heterogeneous, polymorbid, and aging population of CHC patients in secondary care, and demonstrate underrepresentation of injecting drug users within the current system. The implications of this present significant challenges to physicians and healthcare commissioners in designing services which are fit for purpose inthe DAA era. PMID:28480974

Use of Traditional and Complementary Medicine as Self-Care Strategies in Community Health Centers: Cross-Sectional Study in Urban Pearl River Delta Region of China.

PubMed

Chung, Vincent C H; Wong, Samuel Y S; Wang, Harry H X; Wong, Martin C S; Wei, Xiaolin; Wang, Jiaji; Liu, Siya; Ho, Robin S T; Yu, Ellen L M; Griffiths, Sian M

2016-06-01

In China, Community Health Centers (CHCs) are major providers of primary care services, but their potential in empowering patients' self-management capacity has not been assessed. This study aims to describe self-care practice patterns amongst CHC attendees in urban China.In this cross-sectional quantitative study, 3360 CHC patients from 6 cities within the Pearl Delta Region were sampled using multistage cluster sampling.Thirty-seven per cent had used with over-the-counter Chinese herbal medicines (OTC CHMs) in the past year and majority of respondents found OTC CHMs effective. OTC CHMs were more popular amongst those who needed to pay out of pocket for CHC services. Less than 10% used vitamins and minerals, and those with a lower socioeconomic background have a higher propensity to consume. Although doubts on their usefulness are expressed, their use by the vulnerable population may reflect barriers to access to conventional health care, cultural affinity, or a defense against negative consequences of illnesses. About 25% performed physical exercise, but the prevalence is lower amongst women and older people. Taiji seems to be an alternative for these populations with promising effectiveness, but overall only 6% of CHC attendees participated.These results suggest that CHCs should start initiatives in fostering appropriate use of OTC CHM, vitamins, and minerals. Engaging community pharmacists in guiding safe and effective use of OTC CHM amongst the uninsured is essential given their low accessibility to CHC services. Prescription of Taiji instead of physical exercises to women and older people could be more culturally appropriate, and the possibility of including this as part of the CHC services worth further exploration.

Effect of branched-chain amino acid supplementation on insulin resistance and quality of life in chronic hepatitis C patients

PubMed Central

Ocaña-Mondragón, Alicia; Mata-Marín, José Antonio; Uriarte-López, Mario; Bekker-Méndez, Carolina; Alcalá-Martínez, Enrique; Ribas-Aparicio, Rosa María; Uribe-Noguéz, Luis Antonio; Rodríguez-Galindo, Dulce María; Martínez-Rodríguez, María de La Luz

2018-01-01

The incidence rate of insulin resistance (IR) in patients with chronic hepatitis C (CHC) is high. Recently, branched-chain amino acids (BCAA) have been shown to attenuate IR in CHC patients; however, their effect on patient quality of life remains unclear. Therefore, the aim of the current prospective study was to determine the effects of BCAA supplement on IR and health-related quality of life (HR-QoL) in patients with CHC. In the study, 20 non-diabetic patients with CHC, who were non-responders to peginterferon-α and ribavirin, were recruited. Patients took a BCAA supplement once a day (30 g, after a minimum 10-h overnight fast) for 3 months. Serum levels of glucose, insulin, albumin, triglycerides and cholesterol were measured at 0 and 3 months. Additionally, IR was measured using the Homeostasis Model Assessment-IR, HR-QoL was assessed using the 36-item Short Form Health Survey and viral load was measured by reverse transcription polymerase chain reaction using Taqman probes. The Wilcoxon signed-rank test was used to determine statistical significance. The results indicated that 70% of the subjects were positive for IR, which decreased to 50% by the end of the study; furthermore, 85% of the subjects demonstrated some level of improvement. Overall, the BCAA treatment significantly decreased IR (P=0.006) and augmented serum albumin concentration (P=0.008) compared with basal values. Additionally, by the end of the treatment, viral load and triglycerides levels had decreased, though these results were not significant (P=0.084 and P=0.080, respectively). BCAA treatment also improved HR-QoL regarding role limitations due to physical health problems (P=0.017), role limitations due to emotional problems (P=0.026) and social function (P=0.008). In conclusion, BCAA supplementation reduced IR and improved HR-QoL in patients with CHC. These findings support the application of IR therapy as a possible therapeutic strategy for hepatitis C infection. PMID:29399341

Functional pathway analysis of genes associated with response to treatment for chronic hepatitis C.

PubMed

Birerdinc, A; Afendy, A; Stepanova, M; Younossi, I; Manyam, G; Baranova, A; Younossi, Z M

2010-10-01

Chronic hepatitis C (CH-C) is among the most common causes of chronic liver disease. Approximately 50% of patients with CH-C treated with pegylated interferon-α and ribavirin (PEG-IFN-α + RBV) achieve a sustained virological response (SVR). Several factors such as genotype 1, African American (AA) race, obesity and the absence of an early virological response (EVR) are associated with low SVR. This study elucidates molecular pathways deregulated in patients with CH-C with negative predictors of response to antiviral therapy. Sixty-eight patients with CH-C who underwent a full course of treatment with PEG-IFN-α + RBV were included in the study. Pretreatment blood samples were collected in PAXgene™ RNA tubes. EVR, complete EVR (cEVR), and SVR rates were 76%, 57% and 41%, respectively. Total RNA was extracted from pretreatment peripheral blood mononuclear cells, quantified and used for one-step RT-PCR to profile 154 mRNAs. The expression of mRNAs was normalized with six 'housekeeping' genes. Differentially expressed genes were separated into up and downregulated gene lists according to the presence or absence of a risk factor and subjected to KEGG Pathway Painter which allows high-throughput visualization of the pathway-specific changes in expression profiles. The genes were consolidated into the networks associated with known predictors of response. Before treatment, various genes associated with core components of the JAK/STAT pathway were activated in the cohorts least likely to achieve SVR. Genes related to focal adhesion and TGF-β pathways were activated in some patients with negative predictors of response. Pathway-centred analysis of gene expression profiles from treated patients with CH-C points to the Janus kinase-signal transducers and activators of transcription signalling cascade as the major pathogenetic component responsible for not achieving SVR. In addition, focal adhesion and TGF-β pathways are associated with some predictors of response. © 2009 Blackwell Publishing Ltd.

"Birth Control can Easily Take a Back Seat": Challenges Providing IUDs in Community Health Care Settings.

PubMed

Biggs, M Antonia; Kaller, Shelly; Harper, Cynthia C; Freedman, Lori; Mays, Aisha R

2018-01-01

To assess community health centers' (CHCs) capacity to offer streamlined intrauterine devices (IUDs) services. Prior to implementing a contraceptive training project, we surveyed health care staff (N=97) from 11 CHC sites that offer IUDs onsite. Twenty interviews with clinicians explored more deeply their challenges offering IUDs in the CHC setting. Most practices required multiple visits for IUD placement, most (66%) clinician survey respondents had placed an IUD and 19% had placed an IUD as emergency contraception. Need for screening tests, scheduling challenges, pressures to meet patient quotas, and lack of priority given to women's health hindered streamlined IUD provision. Although access to IUDs has increased, significant barriers to provision in CHC settings persist. Clinic policies may need to address a variety of system and provider-level barriers to meet the needs of patients.

The impact of IL28B genotype on the gene expression profile of patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin

PubMed Central

2012-01-01

Background Recent studies of CH-C patients have demonstrated a strong association between IL28B CC genotype and sustained virologic response (SVR) after PEG-IFN/RBV treatment. We aimed to assess whether IL28B alleles rs12979860 genotype influences gene expression in response to PEG-IFN/RBV in CH-C patients. Methods Clinical data and gene expression data were available for 56 patients treated with PEG-IFN/RBV. Whole blood was used to determine IL28B genotypes. Differential expression of 153 human genes was assessed for each treatment time point (Days: 0, 1, 7, 28, 56) and was correlated with IL28B genotype (IL28B C/C or non-C/C) over the course of the PEG-IFN/RBV treatment. Genes with statistically significant changes in their expression at each time point were used as an input for pathway analysis using KEGG Pathway Painter (KPP). Pathways were ranked based on number of gene involved separately per each study cohort. Results The most striking difference between the response patterns of patients with IL28B C/C and T* genotypes during treatment, across all pathways, is a sustained pattern of treatment-induced gene expression in patients carrying IL28B C/C. In the case of IL28B T* genotype, pre-activation of genes, the lack of sustained pattern of gene expression or a combination of both were observed. This observation could potentially provide an explanation for the lower rate of SVR observed in these patients. Additionally, when the lists of IL28B genotype-specific genes which were differentially expressed in patients without SVR were compared at their baseline, IRF2 and SOCS1 genes were down-regulated regardless of patients' IL28B genotype. Furthermore, our data suggest that CH-C patients who do not have the SOCS1 gene silenced have a better chance of achieving SVR. Our observations suggest that the action of SOCS1 is independent of IL28B genotype. Conclusions IL28B CC genotype patients with CH-C show a sustained treatment-induced gene expression profile which is not seen in non-CC genotype patients. Silencing of SOCS1 is a negative and independent predictor of SVR. These data may provide some mechanistic explanation for higher rate of SVR in IL28B CC patients who are treated with PEG-IFN/RBV. PMID:22313623

A validated high performance liquid chromatograph-photodiode array method for simultaneous determination of 10 bioactive components in compound hongdoushan capsule

PubMed Central

Zhu, Liancai; Yang, Xian; Tan, Jun; Wang, Bochu; Zhang, Xue

2014-01-01

Background: The compound Hongdoushan capsule (CHC) is widely known as compound herbal preparation and is often used to treat ovarian cancer and breast cancer, and to enhance the body immunity, etc., in clinical practice. Objective: To determine simultaneously 10 bioactive components from CHC, namely glycyrrhetinic acid, liquiritin, glycyrrhizin, baccatin III, 10-deacetylbaccatin III, cephalomannine, taxol, ginsenoside Rg1, ginsenoside Re, and ginsenoside Rb1. Materials and Methods: A high performance liquid chromatograph method coupled with photodiode array detector was developed and validated for the 1st time. Chromatographic analysis was performed on a SHIMADZU C18 by utilizing a gradient elution program. The mobile phase was acetonitrile (A)-water (B) at a flow rate of 0.8 mL/min. Results: The calibration curve was linear over the investigated concentration ranges with the values of r2 higher than 0.9993 for all the 10 bioactive components. The average recovery rates range from 98.4% to 100.5% with relative standard deviations ≤2.9%. The developed method was successfully applied to analyze 10 compounds in six CHC samples from different batches. In addition, the herbal sources of 32 chromatographic peaks were identified through comparative studying on chromatograms of standard, the respective extracts of Hongdoushan, RenShen, GanCao, and CHC. Conclusion: All the results imply that the accurate and reproducible method developed has high separation rate and enables the determination of 10 bioactive components in a single run for the quality control of CHC. PMID:24696551

Cerebrospinal fluid biomarkers of infantile congenital hydrocephalus

PubMed Central

Limbrick, David D.; Baksh, Brandon; Morgan, Clinton D.; Habiyaremye, Gakwaya; McAllister, James P.; Inder, Terrie E.; Mercer, Deanna; Holtzman, David M.; Strahle, Jennifer; Wallendorf, Michael J.; Morales, Diego M.

2017-01-01

Introduction Hydrocephalus is a complex neurological disorder with a pervasive impact on the central nervous system. Previous work has demonstrated derangements in the biochemical profile of cerebrospinal fluid (CSF) in hydrocephalus, particularly in infants and children, in whom neurodevelopment is progressing in parallel with concomitant neurological injury. The objective of this study was to examine the CSF of children with congenital hydrocephalus (CHC) to gain insight into the pathophysiology of hydrocephalus and identify candidate biomarkers of CHC with potential diagnostic and therapeutic value. Methods CSF levels of amyloid precursor protein (APP) and derivative isoforms (sAPPα, sAPPβ, Aβ42), tau, phosphorylated tau (pTau), L1CAM, NCAM-1, aquaporin 4 (AQP4), and total protein (TP) were measured by ELISA in 20 children with CHC. Two comparative groups were included: age-matched controls and children with other neurological diseases. Demographic parameters, ventricular frontal-occipital horn ratio, associated brain malformations, genetic alterations, and surgical treatments were recorded. Logistic regression analysis and receiver operating characteristic curves were used to examine the association of each CSF protein with CHC. Results CSF levels of APP, sAPPα, sAPPβ, Aβ42, tau, pTau, L1CAM, and NCAM-1 but not AQP4 or TP were increased in untreated CHC. CSF TP and normalized L1CAM levels were associated with FOR in CHC subjects, while normalized CSF tau levels were associated with FOR in control subjects. Predictive ability for CHC was strongest for sAPPα, especially in subjects ≤12 months of age (p<0.0001 and AUC = 0.99), followed by normalized sAPPβ (p = 0.0001, AUC = 0.95), tau, APP, and L1CAM. Among subjects ≤12 months, a normalized CSF sAPPα cut-point of 0.41 provided the best prediction of CHC (odds ratio = 528, sensitivity = 0.94, specificity = 0.97); these infants were 32 times more likely to have CHC. Conclusions CSF proteins such as sAPPα and related proteins hold promise as biomarkers of CHC in infants and young children, and provide insight into the pathophysiology of CHC during this critical period in neurodevelopment. PMID:28212403

PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease.

PubMed

Salameh, Habeeb; Masadeh, Maen; Al Hanayneh, Muhannad; Petros, Vincent; Maslonka, Matthew; Nanda, Arjun; Singal, Ashwani K

2016-12-18

To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms. Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients.

High resolution melting curve assay for detecting rs12979860 IL28B polymorphisms involved in response of Iranian patients to chronic hepatitis C treatment.

PubMed

Fateh, Abolfazl; Aghasadeghi, Mohammad Reza; Keyvani, Hossein; Mollaie, Hamid Reza; Yari, Shamsi; Hadizade Tasbiti, Ali Reza; Ghazanfari, Morteza; Monavari, Seyed Hamid Reza

2015-01-01

A recent genome-wide association study (GWAS) on patients with chronic hepatitis C (CHC) treated with peginterferon and ribavirin (pegIFN-α/RBV) identified a single nucleotide polymorphism (SNP) on chromosome 19 (rs12979860) which was strongly associated with a sustained virological response (SVR). The aim of this study was twofold: to study the relationship between IL28B rs12979860 and sustained virological response (SVR) to pegIFN-α/RVB therapy among CHC patients and to detect the rs12979860 polymorphism by high resolution melting curve (HRM) assay as a simple, fast, sensitive, and inexpensive method. The study examined outcomes in 100 patients with chronic hepatitis C in 2 provinces of Iran from December 2011 to June 2013. Two methods were applied to detect IL28B polymorphisms: PCR-sequencing as a gold standard method and HRM as a simple, fast, sensitive, and inexpensive method. The frequencies of IL28B rs12979860 CC, CT, and TT alleles in chronic hepatitis C genotype 1a patients were 10% (10/100), 35% (35/100), and 6% (6/100) and in genotype 3a were 13% (13/100), 31% (31/100), and 5% (5/100), respectively. In genotype 3a infected patients, rs12979860 (CC and CT alleles) and in genotype 1a infected patients (CC allele) were significantly associated with a sustained virological response (SVR). The SVR rates for CC, CT and TT (IL28B rs12979860) were 18%, 34% and 4%, respectively. Multiple logistic regression analysis identified two independent factors that were significantly associated with SVR: IL-28B genotype (rs 12979860 CC vs TT and CT; odds ratio [ORs], 7.86 and 4.084, respectively), and HCV subtype 1a (OR, 7.46). In the present study, an association between SVR rates and IL28B polymorphisms was observed. The HRM assay described herein is rapid, inexpensive, sensitive and accurate for detecting rs12979860 alleles in CHC patients. This method can be readily adopted by any molecular diagnostic laboratory with HRM capability and will be clinically beneficial in predicting treatment response in HCV genotype 1 and 3 infected patients. In addition, it was demonstrated that CC and CT alleles in HCV-3a and the CC allele in HCV-1a were significantly associated with response to pegIFN-α/RBV treatment. The present results may help identify subjects for whom the therapy might be successful.

Community health centers and primary care access and quality for chronically-ill patients - a case-comparison study of urban Guangdong Province, China.

PubMed

Shi, Leiyu; Lee, De-Chih; Liang, Hailun; Zhang, Luwen; Makinen, Marty; Blanchet, Nathan; Kidane, Ruth; Lindelow, Magnus; Wang, Hong; Wu, Shaolong

2015-11-30

Reform of the health care system in urban areas of China has prompted concerns about the utilization of Community Health Centers (CHC). This study examined which of the dominant primary care delivery models, i.e., the public CHC model, the 'gate-keeper' CHC model, or the hospital-owned CHC models, was most effective in enhancing access to and quality of care for patients with chronic illness. The case-comparison design was used to study nine health care organizations in Guangzhou, Dongguan, and Shenzhen cities within Guangdong province, China. 560 patients aged 50 or over with hypertension or diabetes who visited either CHCs or hospitals in these three cities were surveyed by using face-to-face interviews. Bivariate analyses were performed to compare quality and value of care indicators among subjects from the three cities. Multivariate analyses were used to assess the association between type of primary care delivery and quality as well as value of chronic care after controlling for patients' demographic and health status characteristics. Patients from all three cities chose their current health care providers primarily out of concern for quality of care (both provider expertise and adequate medical equipment), patient-centered care, and insurance plan requirement. Compared with patients from Guangzhou, those from Dongguan performed significantly better on most quality and value of care indicators. Most of these indicators remained significantly better even after controlling for patients' demographic and health status characteristics. The Shenzhen model (hospital-owned and -managed CHC) was generally effective in enhancing accessibility and continuity. However, coordination suffered due to seemingly duplicating primary care outpatients at the hospital setting. Significant associations between types of health care facilities and quality of care were also observed such that patients from CHCs were more likely to be satisfied with traveling time and follow-up care by their providers. The study suggested that the Dongguan model (based on insurance mandate and using family practice physicians as 'gate-keepers') seemed to work best in terms of improving access and quality for patients with chronic conditions. The study suggested adequately funded and well-organized primary care system can play a gatekeeping role and has the potential to provide a reasonable level of care to patients.

75 FR 11189 - Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-10

...] Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C Infection in... hepatitis C (CHC) infection in patients with unmet medical need. This public hearing is being held to obtain.... Background A. CHC In the United States, hepatitis C virus infection causes 20 percent of all cases of acute...

Depression and fatigue in chronic hepatitis C patients with and without HIV co-infection.

PubMed

Tavakkoli, Mohammad; Ferrando, Stephen J; Rabkin, Judith; Marks, Kristen; Talal, Andrew H

2013-01-01

Depression and fatigue are common in chronic hepatitis C (CHC). We report clinical predictors of these conditions in patients seen in a university clinic. A total of 167 CHC patients completed the Patient Health Questionnaire-9 (PHQ-9) and Fatigue Severity Scale (FSS). Major depressive disorder (MDD) suggested by PHQ-9 was confirmed by clinical interview. FSS scores ≥41 were considered clinically significant fatigue. Logistic and multiple regression models were employed for analysis. Thirty-three percent of patients had MDD and 52% had clinically significant fatigue. Sixty-one percent were HIV-infected, among whom both MDD and clinically significant fatigue were significantly less prevalent (OR = 0.47 and 0.46, respectively). MDD was least common in patients without a history of IV drug use (OR = 0.28), and highest in methadone users (OR = 3.57). Compared with methadone users, patients with no history of IV drug use and former IV drug users had less severe fatigue (coefficients = -31.0, -34.0, respectively). Lack of a history of hepatitis treatment was also associated with less severe fatigue (coefficient= -7.6). Our study confirms high prevalence of fatigue and depression in CHC. HIV-positivity was associated with lower rates of MDD and clinically significant fatigue, arguably due to support systems for people living with HIV. Higher rates of depression in methadone users might be due to intrinsically higher rates of psychopathology in this group. Being on hepatitis treatment was associated with higher rates of fatigue, probably due to the adverse effects of interferon. Our findings emphasize the importance of routine screening and evaluation of depression and fatigue in CHC populations. Copyright © 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

Clinical Value of Thyrotropin Receptor Antibodies for the Differential Diagnosis of Interferon Induced Thyroiditis.

PubMed

Benaiges, D; Garcia-Retortillo, M; Mas, A; Cañete, N; Broquetas, T; Puigvehi, M; Chillarón, J J; Flores-Le Roux, J A; Sagarra, E; Cabrero, B; Zaffalon, D; Solà, R; Pedro-Botet, J; Carrión, J A

2016-01-01

The clinical value of thyrotropin receptor antibodies for the differential diagnosis of thyrotoxicosis induced by pegylated interferon-alpha remains unknown. We analyzed the diagnostic accuracy of thyrotropin receptor antibodies in the differential diagnosis of thyrotoxicosis in patients with chronic hepatitis C (CHC) receiving pegylated interferon-alpha plus ribavirin. Retrospective analysis of 274 patients with CHC receiving pegylated interferon-alpha plus ribavirin. Interferon-induced thyrotoxicosis was classified according to clinical guidelines as Graves disease, autoimmune and non- autoimmune destructive thyroiditis. 48 (17.5%) patients developed hypothyroidism, 17 (6.2%) thyrotoxicosis (6 non- autoimmune destructive thyroiditis, 8 autoimmune destructive thyroiditis and 3 Graves disease) and 22 "de novo" thyrotropin receptor antibodies (all Graves disease, 2 of the 8 autoimmune destructive thyroiditis and 17 with normal thyroid function). The sensitivity and specificity of thyrotropin receptor antibodies for Graves disease diagnosis in patients with thyrotoxicosis were 100 and 85%, respectively. Patients with destructive thyroiditis developed hypothyroidism in 87.5% of autoimmune cases and in none of those with a non- autoimmune etiology (p<0.001). Thyrotropin receptor antibodies determination cannot replace thyroid scintigraphy for the differential diagnosis of thyrotoxicosis in CHC patients treated with pegylated interferon. © Georg Thieme Verlag KG Stuttgart · New York.

Chronic hepatitis C and liver fibrosis

PubMed Central

Sebastiani, Giada; Gkouvatsos, Konstantinos; Pantopoulos, Kostas

2014-01-01

Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy. PMID:25170193

Establishing ultrasound based transient elastography cutoffs for different stages of hepatic fibrosis and cirrhosis in Egyptian chronic hepatitis C patients.

PubMed

Elsharkawy, Aisha; Alboraie, Mohamed; Fouad, Rabab; Asem, Noha; Abdo, Mahmoud; Elmakhzangy, Hesham; Mehrez, Mai; Khattab, Hany; Esmat, Gamal

2017-12-01

Transient elastography is widely used to assess fibrosis stage in chronic hepatitis C (CHC). We aimed to establish and validate different transient elastography cut-off values for significant fibrosis and cirrhosis in CHC genotype 4 patients. The data of 100 treatment-naive CHC patients (training set) and 652 patients (validation set) were analysed. The patients were subjected to routine pretreatment laboratory investigations, liver biopsy and histopathological staging of hepatic fibrosis according to the METAVIR scoring system. Transient elastography was performed before and in the same week as liver biopsy using FibroScan (Echosens, Paris, France). Transient elastography results were correlated to different stages of hepatic fibrosis in both the training and validation sets. ROC curves were constructed. In the training set, the best transient elastography cut-off values for significant hepatic fibrosis (≥F2 METAVIR), advanced hepatic fibrosis (≥F3 METAVIR) and cirrhosis (F4 METAVIR) were 7.1, 9 and 12.2 kPa, with sensitivities of 87%, 87.5% and 90.9% and specificities of 100%, 99.9% and 99.9%, respectively. The application of these cut-offs in the validation set showed sensitivities of 85.5%, 82.8% and 92% and specificities of 86%, 89.4% and 99.01% for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, respectively. Transient elastography performs well for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, with validated cut-offs of 7.1, 9 and 12.2 kPa, respectively, in genotype 4 CHC patients. Copyright © 2017 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.

A Single Test Combining Blood Markers and Elastography is More Accurate Than Other Fibrosis Tests in the Main Causes of Chronic Liver Diseases.

PubMed

Ducancelle, Alexandra; Leroy, Vincent; Vergniol, Julien; Sturm, Nathalie; Le Bail, Brigitte; Zarski, Jean Pierre; Nguyen Khac, Eric; Salmon, Dominique; de Ledinghen, Victor; Calès, Paul

2017-08-01

International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases. Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis). OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD. Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.

Bilateral hippocampal atrophy in temporal lobe epilepsy: Effect of depressive symptoms and febrile seizures

PubMed Central

Finegersh, Andrey; Avedissian, Christina; Shamim, Sadat; Dustin, Irene; Thompson, Paul M.; Theodore, William H.

2011-01-01

Summary Purpose Neuroimaging studies suggest a history of febrile seizures, and depression, are associated with hippocampal volume reductions in patients with temporal lobe epilepsy (TLE). Methods We used radial atrophy mapping (RAM), a three-dimensional (3D) surface modeling tool, to measure hippocampal atrophy in 40 patients with unilateral TLE, with or without a history of febrile seizures and symptoms of depression. Multiple linear regression was used to single out the effects of covariates on local atrophy. Key Findings Subjects with a history of febrile seizures (n = 15) had atrophy in regions corresponding to the CA1 and CA3 subfields of the hippocampus contralateral to seizure focus (CHC) compared to those without a history of febrile seizures (n = 25). Subjects with Beck Depression Inventory II (BDI-II) score ≥14 (n = 11) had atrophy in the superoanterior portion of the CHC compared to subjects with BDI-II <14 (n = 29). Significance Contralateral hippocampal atrophy in TLE may be related to febrile seizures or depression. PMID:21269286

Characterization of a Gene Encoding Clathrin Heavy Chain in Maize Up-Regulated by Salicylic Acid, Abscisic Acid and High Boron Supply

PubMed Central

Zeng, Mu-Heng; Liu, Sheng-Hong; Yang, Miao-Xian; Zhang, Ya-Jun; Liang, Jia-Yong; Wan, Xiao-Rong; Liang, Hong

2013-01-01

Clathrin, a three-legged triskelion composed of three clathrin heavy chains (CHCs) and three light chains (CLCs), plays a critical role in clathrin-mediated endocytosis (CME) in eukaryotic cells. In this study, the genes ZmCHC1 and ZmCHC2 encoding clathrin heavy chain in maize were cloned and characterized for the first time in monocots. ZmCHC1 encodes a 1693-amino acid-protein including 29 exons and 28 introns, and ZmCHC2 encodes a 1746-amino acid-protein including 28 exons and 27 introns. The high similarities of gene structure, protein sequences and 3D models among ZmCHC1, and Arabidopsis AtCHC1 and AtCHC2 suggest their similar functions in CME. ZmCHC1 gene is predominantly expressed in maize roots instead of ubiquitous expression of ZmCHC2. Consistent with a typical predicted salicylic acid (SA)-responsive element and four predicted ABA-responsive elements (ABREs) in the promoter sequence of ZmCHC1, the expression of ZmCHC1 instead of ZmCHC2 in maize roots is significantly up-regulated by SA or ABA, suggesting that ZmCHC1 gene may be involved in the SA signaling pathway in maize defense responses. The expressions of ZmCHC1 and ZmCHC2 genes in maize are down-regulated by azide or cold treatment, further revealing the energy requirement of CME and suggesting that CME in plants is sensitive to low temperatures. PMID:23880865

Can integrated health services delivery have an impact on hypertension management? A cross-sectional study in two cities of China.

PubMed

Li, Haitao; Sun, Ying; Qian, Dongfu

2016-11-30

Policy makers require information regarding performance of different primary care delivery models in managing hypertension, which can be helpful for better hypertension management. This study aims to compare continuity of care among hypertensive patients between Direct Management (DM) Model of community health centers (CHCs) in Wuhan and Loose Collaboration (LC) Model in Nanjing. A cross-sectional questionnaire survey was conducted. Four CHCs in each city were randomly selected as study settings. 386 patients in Nanjing and 396 in Wuhan completed face-to-face interview surveys and were included in the final analysis. The relational continuity and coordination continuity (including both information continuity and management continuity) were measured and analyzed. Binary or multinomial logistic regression models were used for comparison between the two cities. Participants from Nanjing had better relational continuity with primary care providers as compared with those from Wuhan, including more likely to be familiar with a CHC physician (OR = 2.762; 95%CI: 1.878 to 4.061), taken care of by the same CHC physician (OR = 1.846; 95%CI: 1.262 to 2.700), and known well by a CHC physician (OR = 1.762; 95%CI: 1.206 to 2.572). Multinomial logistic regression analyses showed there were significant differences between the two cities in reported frequency of communications between hospital and CHC physicians (P = 0.001), whether hospital and CHC physicians gave same treatment suggestions (P = 0.016), as well as how treatment strategy was formulated (P < 0.001). Participants in Wuhan were less likely than those in Nanjing to consider there was continuum regarding health services provided by hospital and CHC physicians (OR = 3.932; 95%CI: 2.394 to 6.459). Our study shows that continuity of care is better for LC Model in Nanjing than DM Model in Wuhan. Our study suggests there is room for improvement regarding relational and information continuity in both cities.

Histological versus clinical cirrhosis in chronic hepatitis C: does race/ethnicity really matter?

PubMed

Kohla, Mohamed; Iwata, Shunpei; Ea, Roth; Keyhan, Sanaz; Taylor, Robert; Yu, Mimi C; Groshen, Susan; Bonacini, Maurizio

2012-03-01

Liver fibrosis progression in hepatitis C virus (HCV) infection has been in part associated with race/ethnicity. Little is known of the frequency of clinical cirrhosis in Asian patients in the US. To compare histological and clinical features of chronic hepatitis C (CHC) in a multiethnic cohort of patients. Retrospective query of an electronic medical registry for CHC patients evaluated from 1999 to 2005. Histological cirrhosis was defined as advanced METAVIR fibrosis score at biopsy. Clinical cirrhosis was defined as any of: varices, ascites, or splenomegaly. Liver cirrhosis was defined as either histological or clinical cirrhosis. Chi-square tests, t tests, and logistic regression method were used for data analysis. Six hundred and ninety-two patients were categorized into four racial-ethnic groups: 292 Caucasian (C), 145 Hispanic (H), 121 African American (AA), and 134 Asian (As) patients. Median age of AA (54 years) and As (53) was higher than C (52), or H (50) (p < 0.05). H patients had a higher percentage of alcohol abuse (60%) than AA and C (42-44%) and As (14%; p < 0.0001). Body mass index (BMI) was significantly lower in Asians compared to all other groups (p < 0.0001). Features of the metabolic syndrome were common, ranging from 28% in As to 72% in H patients. Liver cirrhosis was found in 53% H, 35% C, 29% As, and 19% AA. In multivariable analysis, only alcohol abuse, BMI, diabetes mellitus (DM), and age were significantly associated with liver cirrhosis. There was a trend for AA to have less cirrhosis, either histological or clinical (p = 0.08). Using only histology, liver cirrhosis was significantly underestimated. In our cohort, severity of CHC was not clearly affected by race when alcohol use and features of the metabolic syndrome were taken into consideration. However, there was a trend for African Americans to have lower cirrhosis rates.

Hepatic flares in chronic hepatitis C: spontaneous exacerbation vs hepatotropic viruses superinfection.

PubMed

Sagnelli, Evangelista; Sagnelli, Caterina; Pisaturo, Mariantonietta; Coppola, Nicola

2014-06-14

The hepatitis C virus (HCV) causes an acute infection that is frequently asymptomatic, but a spontaneous eradication of HCV infection occurs only in one-third of patients. The remaining two-thirds develop a chronic infection that, in most cases, shows an indolent course and a slow progression to the more advanced stages of the illness. Nearly a quarter of cases with chronic hepatitis C (CHC) develop liver cirrhosis with or without hepatocellular carcinoma. The indolent course of the illness may be troubled by the occurrence of a hepatic flare, i.e., a spontaneous acute exacerbation of CHC due to changes in the immune response, immunosuppression and subsequent restoration, and is characterized by an increase in serum aminotransferase values, a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment. A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses, namely hepatitis B virus (HBV), HBV plus hepatitis D virus, hepatitis E virus, cytomegalovirus, particularly in geographical areas with high endemicity levels. The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

Nutritional status in patients with hepatitis C.

PubMed

Ismail, Faisal Wasim; Khan, Rustam A; Kamani, Lubna; Wadalawala, Ashfaq A; Shah, Hasnain Ali; Hamid, Saeed S; Jafri, Wasim

2012-03-01

To assess the nutritional status via the SGA (subjective global assessment) screening tool of patients at all stages of hepatitis C virus (HCV) liver disease. Descriptive study. Out-patient Clinics of the Aga Khan University Hospital, Karachi, conducted from October 2009 to January 2011. Patients with hepatitis C virus infection and their HCV-negative attendants were enrolled from the outpatient clinics, and categorized into 4 groups of 100 patients each: healthy controls (HC), those with chronic hepatitis C infection (CHC), compensated cirrhotics (CC) and decompensated cirrhotics (DC). The validated subjective global assessment (SGA) tool was used to assess nutritional status. A total of 400 patients were enrolled. Most of the patients in the HC group were class 'A' (best nutritional status). In contrast, the majority (64%) in the DC group were in the class 'C' (worst status). The compensated cirrhosis (CC) group showed that 90% of patients were malnourished, while 98% of all patients were malnourished in the DC group, predominantly class 'C'. Most importantly, 14% of patients with chronic hepatitis C (CHC) also scored a 'B' on the SGA; which when compared to HC was statistically significant (p=0.005). As the groups progressed in their disease from CHC to DC, the transition in nutritional status from 'A' to 'C' between groups was statistically significant. Malnutrition occurs early in the course of HCV, and progresses relentlessly throughout the spectrum of HCVdisease.

Psoriatic patients with chronic viral hepatitis do not have an increased risk of liver cirrhosis despite long-term methotrexate use: real-world data from a nationwide cohort study in Taiwan.

PubMed

Tang, Kuo-Tung; Chen, Yi-Ming; Chang, Shih-Ni; Lin, Ching-Heng; Chen, Der-Yuan

2018-05-09

Methotrexate (MTX) is commonly used in the treatment of patients with moderate to severe psoriasis. We conducted a nationwide population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic viral hepatitis-related cirrhosis among psoriatic patients in Taiwan. This study obtained data from the National Health Insurance Research Database in Taiwan. We identified 2417 psoriatic patients with chronic hepatitis B (CHB) (370 MTX users and 2047 MTX non-users) and 1127 psoriatic patients with chronic hepatitis C (CHC) (174 MTX users and 953 MTX non-users) from January 1, 2000 to December 31, 2010. After a mean follow-up of more than 9 years since the diagnosis of chronic viral hepatitis, a total of 125 (5%) CHB patients and 120 (11%) CHC patients developed liver cirrhosis. A comparable proportion of MTX users and MTX non-users developed liver cirrhosis (4% vs. 5% in CHB patients and 11% and vs. 11% in CHC patients, both p < 0.05). There is possibly selection bias and medication nonadherence. Our real-world data show that long-term MTX use may not be associated with an increased risk of liver cirrhosis among psoriatic patients with chronic viral hepatitis. Copyright © 2018. Published by Elsevier Inc.

Abnormality of autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease.

PubMed

Fukuo, Yuka; Yamashina, Shunhei; Sonoue, Hiroshi; Arakawa, Atsushi; Nakadera, Eisuke; Aoyama, Tomonori; Uchiyama, Akira; Kon, Kazuyoshi; Ikejima, Kenichi; Watanabe, Sumio

2014-09-01

Recent evidences indicate that hepatic steatosis suppresses autophagic proteolysis. The present study evaluated the correlation between autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease (NAFLD). Liver biopsy specimens were obtained from patients with chronic liver diseases (chronic hepatitis C [CHC; n = 20], chronic hepatitis B [CHB; n = 16], primary biliary cirrhosis [PBC; n = 23], NAFLD [n = 22] and control [n = 14]). The number of autophagic vesicles in hepatocytes was counted by using transmission electron microscopy. Expression of cathepsin B, D, L and p62 in the liver section was analyzed by immunohistochemical staining. The histological severity of NAFLD is assessed by NAFLD activity score (NAS). The number of autophagic vesicles in hepatocytes was significantly increased in both CHC and NAFLD groups, but not CHB and PBC, more than control. Although hepatocytes with aggregation of p62 were observed in less than 15% of CHC, p62 aggregation was detected in approximately 65% of NAFLD. Cathepsin B, D and L expression was significantly suppressed in the liver from NAFLD patients. Suppression of cathepsin B, D and L expression was not observed in CHB, CHC and PBC. In NAFLD patients, p62 aggregation was correlated with serum alanine aminotransferase value and inflammatory activity by NAS. These results indicate that a decrease in hepatic cathepsin expression in NAFLD is associated with autophagic dysfunction. Hepatic inflammation correlates with autophagic dysfunction in NAFLD. These findings indicate that the suppression of autophagic proteolysis by hepatic steatosis is involved in the pathogenesis of NAFLD. © 2013 The Japan Society of Hepatology.

Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

PubMed Central

Sartori, Massimo; Andorno, Silvano; Rossini, Angelo; Boldorini, Renzo; Bozzola, Cristina; Carmagnola, Stefania; Piano, Mario Del; Albano, Emanuele

2010-01-01

AIM: To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C (CHC). METHODS: We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to, or unsuitable for, antiviral therapy who underwent mild iron depletion (ferritin ≤ 70 ng/mL) by long-term phlebotomy. Histological improvement, as defined by at least one point reduction in the staging score or, in case of unchanged stage, as at least two points reduction in the grading score (Knodell), was evaluated in two subsequent liver biopsies (before and at the end of phlebotomy, 48 ± 16 mo apart). RESULTS: Phlebotomy showed an excellent safety profile. Histological improvement occurred in 12/28 phlebotomized patients. Only males responded to phlebotomy. At univariate logistic analysis alcohol intake (P = 0.034), high histological grading (P = 0.01) and high hepatic iron concentration (HIC) (P = 0.04) before treatment were associated with histological improvement. Multivariate logistic analysis showed that in males high HIC was the only predictor of histological improvement following phlebotomy (OR = 1.41, 95% CI: 1.03-1.94, P = 0.031). Accordingly, 12 out of 17 (70%) patients with HIC ≥ 20 μmol/g showed histological improvements at the second biopsy. CONCLUSION: Male CHC Caucasian non-responders to antiviral therapy with low-grade iron overload can benefit from mild iron depletion by long-term phlebotomy. PMID:20128028

Cesium hafnium chloride: A high light yield, non-hygroscopic cubic crystal scintillator for gamma spectroscopy

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

Burger, Arnold, E-mail: aburger@fisk.edu; Department of Physics and Astronomy, Vanderbilt University, Nashville, Tennessee 37235; Rowe, Emmanuel

We report on the scintillation properties of Cs{sub 2}HfCl{sub 6} (cesium hafnium chloride or CHC) as an example of a little-known class of non-hygroscopic compounds having the generic cubic crystal structure of K{sub 2}PtCl{sub 6}. The crystals are easily growable from the melt using the Bridgman method with minimal precursor treatments or purification. CHC scintillation is centered at 400 nm, with a principal decay time of 4.37 μs and a light yield of up to 54 000 photons/MeV when measured using a silicon CCD photodetector. The light yield is the highest ever reported for an undoped crystal, and CHC also exhibits excellent lightmore » yield nonproportionality. These desirable properties allowed us to build and test CHC gamma-ray spectrometers providing energy resolution of 3.3% at 662 keV.« less

Communication between hospitals and isolated aboriginal community health clinics.

PubMed

Mackenzie, G; Currie, B J

1999-04-01

This study described the communication dynamics, identified problems and recommended changes to improve patient follow-up and communication between Royal Darwin Hospital (RDH) and isolated Aboriginal community health clinics (CHC) in the Northern Territory (NT). In 1995, staff interviews were conducted and an audit of isolated Aboriginal patients' RDH discharge summaries (DS). Eighteen per cent of RDH DSs never arrived in CHCs. DSs were often prepared late and more likely to be in CHC records if written on time and if the referral source was specified. Interviews revealed discontent between CHCs and RDH regarding: communication, DS documentation, the supply of discharge medication, as well as different hospital and community perceptions of Aboriginies' reliability to carry a DS and CHC desire for patients to be given DSs at discharge. Aboriginal patients should be given a DS at discharge and resident medical officers should be educated as to the function and importance of the DS. In 18 months following this study, RDH appointed unit-based Aboriginal health workers and a policy was produced for written communication between hospital and CHCs, as well as a discharge planning manual for Aboriginal communities. Projects investigating communication between hospitals and isolated Aboriginal clinics and patient follow-up may result in significant policy changes concerning these processes.

Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C.

PubMed

López-Rodríguez, Rosario; Hernández-Bartolomé, Ángel; Borque, María Jesús; Rodríguez-Muñoz, Yolanda; Martín-Vílchez, Samuel; García-Buey, Luisa; González-Moreno, Leticia; Real-Martínez, Yolanda; Muñoz de Rueda, Paloma; Salmerón, Javier; Vidal-Castiñeira, José Ramón; López-Larrea, Carlos; Rodrigo, Luis; Moreno-Otero, Ricardo; Sanz-Cameno, Paloma

2017-01-01

Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients. NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates. Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p<0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74). The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.

Noninvasive Assessment of Liver Fibrosis By Transient Elastography and FIB4/APRI for Prediction of Treatment Response in Chronic Hepatitis C-An Experience from a Tertiary Care Hospital.

PubMed

Taneja, Sunil; Tohra, Sunil; Duseja, Ajay; Dhiman, Radha Krishan; Chawla, Yogesh Kumar

2016-12-01

Liver fibrosis and its sequel cirrhosis represent a major health care burden, and assessment of fibrosis by biopsy is gradually being replaced by noninvasive methods. In clinical practice, the determination of fibrosis stage is important, since patients with advanced fibrosis have faster progression to cirrhosis and antiviral therapy is indicated in these patients. To assess the role of transient elastography (TE) and compare it with APRI and FIB4 for predicting liver fibrosis and assessing the effect of host and viral factors on fibrosis and treatment outcome in CHC patients. In a retrospective analysis, 330 CHC patients underwent liver stiffness measurement (LSM) by TE and tests needed for calculating APRI and FIB4 scores at baseline. 228 patients received a combination of Pegylated IFN-based antiviral therapy and were analyzed for therapeutic response. The study included 330 patients (median age 39 years [range 18-67]), predominantly males ( n  = 227, 68.8%) with baseline LSMs. The median liver stiffness was 7.8 kPa (range 3.2-69.1 kPa). LSMs and its thresholds for severe fibrosis progression (≥9.5 kPa) and cirrhosis (≥12.5 kPa) were significantly higher in patients with age ≥40 years, diabetes mellitus, and patients with significant alcohol intake ( P  = 0.003 to P  < 0.001). By taking TE as a reference, the diagnostic accuracy of FIB4 scores for predicting cirrhosis (AUROC 0.896) was good (+LR 13.4) compared to APRI (AUROC 0.823) with moderate likelihood ratio (+LR 6.9). Among 228 treated patients the SVR rate in genotype 3 was 70% versus 57.8% in genotype 1. Fibrosis score F4 ( P  = 0.023) and HCV genotype ( P  = 0.008) were independent predictors of SVR. The study shows that LSM by TE and fibrosis assessment by FIB4/APRI scores can be used with fair reliability to predict fibrosis and treatment response in patients with CHC infection.

Impact of etiology of chronic liver disease on hepatocellular carcinoma biomarkers.

PubMed

Ricco, Gabriele; Cavallone, Daniela; Cosma, Chiara; Caviglia, Gian Paolo; Oliveri, Filippo; Biasiolo, Alessandra; Abate, Maria Lorena; Plebani, Mario; Smedile, Antonina; Bonino, Ferruccio; Pontisso, Patrizia; Brunetto, Maurizia Rossana

2018-02-14

The role of serum biomarkers in the surveillance of hepatocellular carcinoma (HCC) is controversial. We assessed the diagnostic performances of alpha-fetoprotein (AFP) and protein-induced by vitamin-K-absence/antagonist-II (PIVKA-II) in 388 cirrhotic patients with chronic liver disease (CLD). Biomarkers were quantified by automated chemiluminescent-enzyme-immunoassays (Fujirebio, Tokyo, Japan) at HCC diagnosis in 258 patients (204 males; median age 66.9 years) and in 130 cirrhotics without HCC (104 males; median-age 60.6 years). CLD etiology in HCC/non-HCC was CHB in 48/35, CHC in 126/56 and Non-Viral in 84/39. Overall AUROC values for AFP and PIVKA-II were 0.698 (95%CI = 0.642-0.753, P< 0.001) and 0.780 (95%CI = 0.730-0.831, P< 0.001). AFP/PIVKA-II AUROC (95%CI) were: 0.822 (0.728-0.915)/0.833 (0.739-0.926) in CHB, 0.648 (0.560-0.736)/0.732 (0.650-0.814) in CHC; 0.640 (0.540-0.740)/0.806 (0.722-0.889) in Non-Viral-CLD. AFP/PIVKA-II diagnostic accuracy was 40.5-59.8%/62.7-73.5% and combining both markers 78.2% for CHB, 77% for Non-Viral-CLD and 75% for CHC. AFP correlated with ALT in HCC patients with CHC (ρ= 0.463/P< 0.001) and Non-Viral CLD (ρ= 0.359/P= 0.047), but not in CHB (treated with antivirals). PIVKA-II correlated with tumour size independently of CLD-etiology (P< 0.001) and AFP in CHB patients only (P= 0.007). The diagnostic performance of AFP and PIVKA-II is significantly influenced by the etiology and activity of CLD; their combination provides a better diagnostic accuracy.

Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets

PubMed Central

Miranda-Gonçalves, Vera; Honavar, Mrinalini; Pinheiro, Céline; Martinho, Olga; Pires, Manuel M.; Pinheiro, Célia; Cordeiro, Michelle; Bebiano, Gil; Costa, Paulo; Palmeirim, Isabel; Reis, Rui M.; Baltazar, Fátima

2013-01-01

Background Gliomas exhibit high glycolytic rates, and monocarboxylate transporters (MCTs) play a major role in the maintenance of the glycolytic metabolism through the proton-linked transmembrane transport of lactate. However, their role in gliomas is poorly studied. Thus, we aimed to characterize the expression of MCT1, MCT4, and their chaperone CD147 and to assess the therapeutic impact of MCT inhibition in gliomas. Methods MCTs and CD147 expressions were characterized by immunohistochemistry in nonneoplastic brain and glioma samples. The effect of CHC (MCT inhibitor) and MCT1 silencing was assessed in in vitro and in vivo glioblastoma models. Results MCT1, MCT4, and CD147 were overexpressed in the plasma membrane of glioblastomas, compared with diffuse astrocytomas and nonneoplastic brain. CHC decreased glycolytic metabolism, migration, and invasion and induced cell death in U251 cells (more glycolytic) but only affected proliferation in SW1088 (more oxidative). The effectiveness of CHC in glioma cells appears to be dependent on MCT membrane expression. MCT1 downregulation showed similar effects on different glioma cells, supporting CHC as an MCT1 inhibitor. There was a synergistic effect when combining CHC with temozolomide treatment in U251 cells. In the CAM in vivo model, CHC decreased the size of tumors and the number of blood vessels formed. Conclusions This is the most comprehensive study reporting the expression of MCTs and CD147 in gliomas. The MCT1 inhibitor CHC exhibited anti-tumoral and anti-angiogenic activity in gliomas and, of importance, enhanced the effect of temozolomide. Thus, our results suggest that development of therapeutic approaches targeting MCT1 may be a promising strategy in glioblastoma treatment. PMID:23258846

Chronic Conditions Among Children Investigated by Child Welfare: A National Sample

PubMed Central

Hurlburt, Michael S.; Heneghan, Amy M.; Zhang, Jinjin; Rolls-Reutz, Jennifer; Silver, Ellen J.; Fisher, Emily; Landsverk, John; Horwitz, Sarah McCue

2013-01-01

OBJECTIVE: To assess the presence of chronic health conditions (CHCs) among a nationally representative sample of children investigated by child welfare agencies. METHODS: The study included 5872 children, aged 0 to 17.5 years, whose families were investigated for maltreatment between February 2008 and April 2009. Using data from the second National Survey of Child and Adolescent Well-Being, we examined the proportion of children who had CHC. We developed 2 categorical and 2 noncategorical measures of CHC from the available data and analyzed them by using bivariate and multivariable analyses. RESULTS: Depending on the measure used, 30.6% to 49.0% of all children investigated were reported by their caregivers to have a CHC. Furthermore, the children identified by using diverse methods were not entirely overlapping. In the multivariable analyses, children with poorer health were more likely to be male, older, and receiving special educational services but not more likely to be in out-of-home placements. CONCLUSIONS: The finding that a much higher proportion of these children have CHC than in the general population underscores the substantial health problems of children investigated by child welfare agencies and the need to monitor their health carefully, regardless of their placement postinvestigation. PMID:23420907

Relationship between Hepatitis C Virus Infection and Iron Overload.

PubMed

Zou, Dong-Mei; Sun, Wan-Ling

2017-04-05

The aim of this study was to summarize the interactions between hepatitis C virus (HCV) infection and iron overload, and to understand the mechanisms of iron overload in chronic hepatitis C (CHC) and the role iron plays in HCV life cycle. This review was based on data in articles published in the PubMed databases up to January 28, 2017, with the keywords "hepatitis C virus", "iron overload", "iron metabolism", "hepcidin", "translation", and "replication". Articles related to iron metabolism, iron overload in patients with CHC, or the effects of iron on HCV life cycle were selected for the review. Iron overload is common in patients with CHC. The mechanisms involve decreased hepcidin levels caused by HCV through signal transducer and activator of transcription 3, mitogen-activated protein kinase, or bone morphogenetic protein/SMAD signaling pathways, and the altered expression of other iron-metabolism-related genes. Some studies found that iron increases HCV replication, while other studies found the opposite result. Most of the studies suggest the positive role of iron on HCV translation, the mechanisms of which involve increased expression levels of factors associated with HCV internal ribosome entry site-dependent translation, such as eukaryotic initiation factor 3 and La protein. The growing literature demonstrates that CHC leads to iron overload, and iron affects the HCV life cycle in turn. Further research should be conducted to clarify the mechanism involved in the complicated interaction between iron and HCV.

[Determination of drug resistance mutations of NS3 inhibitors in chronic hepatitis C patients infected with genotype 1].

PubMed

Şanlıdağ, Tamer; Sayan, Murat; Akçalı, Sinem; Kasap, Elmas; Buran, Tahir; Arıkan, Ayşe

2017-04-01

Direct-acting antiviral agents (DAA) such as NS3 protease inhibitors is the first class of drugs used for chronic hepatitis C (CHC) treatment. NS3 inhibitors (PI) with low genetic barrier have been approved to be used in the CHC genotype 1 infections, and in the treatment of compensated liver disease including cirrhosis together with pegile interferon and ribavirin. Consequently, the development of drug resistance during DAA treatment of CHC is a major problem. NS3 resistant variants can be detected before treatment as they can occurnaturally. The aim of this study was to investigate new and old generation NS3 inhibitors resistance mutations before DAA treatment in hepatitis C virus (HCV) that were isolated from CHC. The present study was conducted in 2015 and included 97 naive DAA patients infected with HCV genotype 1, who were diagnosed in Manisa and Kocaeli cities of Turkey. Magnetic particle based HCV RNA extraction and than RNA detection and quantification were performed using commercial real-time PCR assay QIASypmhony + Rotorgene Q/ArtusHCV QS-RGQ and COBAS Ampliprep/COBAS TaqMan HCV Tests. HCV NS3 viral protease genome region was amplified with PCR and mutation analysis was performed by Sanger dideoxy sequencing technique of NS3 protease codons (codon 32-185). HCV NS3 protease inhibitors; asunaprevir, boceprevir, faldaprevir, grazoprevir, pariteprevir, simeprevir and telaprevir were analysed for resistant mutations by Geno2pheno-HCV resistance tool. HCV was genotyped in all patients and 88 patients (n= 88/97, 91%) had genotype 1. Eight (n= 8/97, 8.2%) and 80 (n= 80/97, 82.4%) HCC patients were subgenotyped as 1a and 1b, respectively. Many aminoacid substitutions and resistance mutations were determined in 39/88 (44%) patients in the study group. Q80L, S122C/N, S138W were defined as potential substitutions (6/88 patients; 7%); R109K, R117C, S122G, I132V, I170V, N174S were described as potential resistance (34/88 patients; 39%); V36L, T54S, V55A, Q80H were characterized as resistance (7/88 patients; 8%) and Q80K, A156S were defined as high resistance (3/88 patients; 3%) mutations. Based on resistance and high resistance mutations, clinically significant mutations were defined in 10/88 (11%) of the patients. Our study shows that it is essential to analyse HCV NS3 protease inhibitors drug resistance before DAA treatment of CHC patients. On the other hand, our results pointed out that analysis of NS5A and NS5B genome region mutations may also be required in the near future.

Predictive factors for the severity of liver fibrosis in patients with chronic hepatitis C and moderate alcohol consumption.

PubMed

Vădan, Roxana; Gheorghe, Liana; Becheanu, Gabriel; Iacob, Răzvan; Iacob, Speranţa; Gheorghe, Cristian

2003-09-01

Among the histological lesions seen in chronic hepatitis C (CHC), the presence of steatosis, bile duct lesions and lymphoid aggregates are characteristic. Recent reports suggest that steatosis is an independent risk factor for liver fibrosis in CHC. The aim of our study was to determine the relative contribution of steatosis and moderate alcohol consumption to the severity of liver fibrosis in patients infected with genotype 1 hepatitis C virus. We evaluated the patients with biopsy proven CHC and no or only moderate alcohol intake (<40 g/day). The demographical parameters of the study population, the indices of alcohol consumption: erythrocyte median corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), the histological characteristics were noted and a statistical analysis was performed in order to determine the factors independently associated with severe fibrosis and with severe steatosis. From the 200 patients included in the study, 82 were males and 118 females, with a mean age of 47.75+/-10.42 years. At univariate analysis, advanced (grade 2, 3) fibrosis correlated with: the age at the time of biopsy, increased inflammatory activity (HAI), moderate/severe steatosis, alcohol intake, elevated GGT and MCV values. After multivariate logistic regression only age, HAI and steatosis were independently associated with advanced fibrosis stage. Regarding hepatic steatosis, from the factors found to correlate with severe steatosis at univariate analysis (alcohol intake, elevated GGT and MCV levels, severe fibrosis), after multivariate logistic regression only the elevated level of GGT was an independent prognostic factor for severe steatosis. Steatosis is an important risk factor for the severity of liver disease in CHC patients. Among patients with genotype 1 hepatitis C virus infection and moderate alcohol intake, those with serum levels of GGT over two times the normal value are at high risk for severe steatosis.

Association of caffeine intake and histological features of chronic hepatitis C.

PubMed

Costentin, Charlotte E; Roudot-Thoraval, Françoise; Zafrani, Elie-Serge; Medkour, Fatiha; Pawlotsky, Jean-Michel; Mallat, Ariane; Hézode, Christophe

2011-06-01

The severity of chronic hepatitis C (CHC) is modulated by host and environmental factors. Several reports suggest that caffeine intake exerts hepatoprotective effects in patients with chronic liver disease. The aim of this study was to evaluate the impact of caffeine consumption on activity grade and fibrosis stage in patients with CHC. A total of 238 treatment-naïve patients with histologically-proven CHC were included in the study. Demographic, epidemiological, environmental, virological, and metabolic data were collected, including daily consumption of alcohol, cannabis, tobacco, and caffeine during the six months preceding liver biopsy. Daily caffeine consumption was estimated as the sum of mean intakes of caffeinated coffee, tea, and caffeine-containing sodas. Histological activity grade and fibrosis stage were scored according to Metavir. Patients (154 men, 84 women, mean age: 45±11 years) were categorized according to caffeine consumption quartiles: group 1 (<225 mg/day, n=59), group 2 (225-407 mg/day, n=57), group 3 (408-678 mg/day, n=62), and group 4 (>678 mg/day, n=60). There was a significant inverse relationship between activity grade and daily caffeine consumption: activity grade>A2 was present in 78%, 61%, 52%, and 48% of patients in group 1, 2, 3, and 4, respectively (p<0.001). By multivariate analysis, daily caffeine consumption greater than 408 mg/day was associated with a lesser risk of activity grade>A2 (OR=0.32 (0.12-0.85). Caffeine intake showed no relation with fibrosis stage. Caffeine consumption greater than 408 mg/day (3 cups or more) is associated with reduced histological activity in patients with CHC. These findings support potential hepatoprotective properties of caffeine in chronic liver diseases. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Cross-sectional study of factors associated with community health centre use in a recently urbanised community in Chengdu, China.

PubMed

Liu, Danping; Meng, Hongdao; Dobbs, Debra; Conner, Kyaien O; Hyer, Kathryn; Li, Ningxiu; Ren, Xiaohui; Gao, Bo

2017-06-08

Public investment in community health centres (CHCs) has been increasing as a response to rapid urbanisation in China. The objectives of this study were: (1) to examine factors associated with CHC use among residents from a recently urbanised community in western China and (2) to describe satisfaction with CHC among users. Cross-sectional design. A community recently converted to urban status with a newly constructed CHC in Southwest China. A random sample of 2259 adults in the Hezuo community in Chengdu, China, completed the survey in 2013. Trained staff interviewed study participants in their homes using structured questionnaires. The survey included questions regarding sociodemographics, health status, access to and usage of healthcare, health behaviours and CHC use. The Andersen's behavioural model of health service use was used to guide multivariable logistic regression modelling in identifying predisposing, enabling and need factors associated with the likelihood of using CHC. Descriptive statistics were used to describe residents' satisfaction with the CHC. A total of 71.8% of the respondents reported using the CHC during the past year. Factors influencing adults' CHC use included: gender, marital status, education level and knowledge of one's blood pressure (predisposing factors); annual household per capita income and walking time to the CHC (enabling factors) and self-rated health as well as physical activities (need factors). CHC users reported modest satisfaction across various aspects of the CHC. Neighbourhood CHC in urban areas provides important services to these residents living in a recently urbanised community. All three categories of factors in the Andersen model help explain the likelihood of CHC use. There is much room for improvement in CHC to enhance customer satisfaction. Future research is needed to improve access to CHCs and promote their use in urbanised populations with low to modest education. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Enzymes involved in a novel anaerobic cyclohexane carboxylic acid degradation pathway.

PubMed

Kung, Johannes W; Meier, Anne-Katrin; Mergelsberg, Mario; Boll, Matthias

2014-10-01

The anaerobic degradation of cyclohexane carboxylic acid (CHC) has so far been studied only in Rhodopseudomonas palustris, in which CHC is activated to cyclohexanoyl coenzyme A (cyclohexanoyl-CoA [CHCoA]) and then dehydrogenated to cyclohex-1-ene-1-carboxyl-CoA (CHeneCoA). This intermediate is further degraded by reactions of the R. palustris-specific benzoyl-CoA degradation pathway of aromatic compounds. However, CHeneCoA is not an intermediate in the degradation of aromatic compounds in all other known anaerobic bacteria; consequently, degradation of CHC was mostly unknown in anaerobic bacteria. We identified a previously unknown CHC degradation pathway in the Fe(III)-reducing Geobacter metallireducens by determining the following CHC-induced in vitro activities: (i) the activation of CHC to CHCoA by a succinyl-CoA:CHC CoA transferase, (ii) the 1,2-dehydrogenation of CHCoA to CHeneCoA by CHCoA dehydrogenase, and (iii) the unusual 1,4-dehydrogenation of CHeneCoA to cyclohex-1,5-diene-1-carboxyl-CoA. This last represents a previously unknown joint intermediate of the CHC and aromatic compound degradation pathway in bacteria other than R. palustris. The enzymes catalyzing the three reactions were purified and characterized as specific enzymes after heterologous expression of the encoding genes. Quantitative reverse transcription-PCR revealed that expression of these genes was highly induced during growth with CHC but not with benzoate. The newly identified CHC degradation pathway is suggested to be present in nearly all CHC-degrading anaerobic bacteria, including denitrifying, Fe(III)-reducing, sulfate-reducing, and fermenting bacteria. Remarkably, all three CHC degradation pathways always link CHC catabolism to the catabolic pathways of aromatic compounds. We propose that the capacity to use CHC as a carbon source evolved from already-existing aromatic compound degradation pathways. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Enzymes Involved in a Novel Anaerobic Cyclohexane Carboxylic Acid Degradation Pathway

PubMed Central

Kung, Johannes W.; Meier, Anne-Katrin; Mergelsberg, Mario

2014-01-01

The anaerobic degradation of cyclohexane carboxylic acid (CHC) has so far been studied only in Rhodopseudomonas palustris, in which CHC is activated to cyclohexanoyl coenzyme A (cyclohexanoyl-CoA [CHCoA]) and then dehydrogenated to cyclohex-1-ene-1-carboxyl-CoA (CHeneCoA). This intermediate is further degraded by reactions of the R. palustris-specific benzoyl-CoA degradation pathway of aromatic compounds. However, CHeneCoA is not an intermediate in the degradation of aromatic compounds in all other known anaerobic bacteria; consequently, degradation of CHC was mostly unknown in anaerobic bacteria. We identified a previously unknown CHC degradation pathway in the Fe(III)-reducing Geobacter metallireducens by determining the following CHC-induced in vitro activities: (i) the activation of CHC to CHCoA by a succinyl-CoA:CHC CoA transferase, (ii) the 1,2-dehydrogenation of CHCoA to CHeneCoA by CHCoA dehydrogenase, and (iii) the unusual 1,4-dehydrogenation of CHeneCoA to cyclohex-1,5-diene-1-carboxyl-CoA. This last represents a previously unknown joint intermediate of the CHC and aromatic compound degradation pathway in bacteria other than R. palustris. The enzymes catalyzing the three reactions were purified and characterized as specific enzymes after heterologous expression of the encoding genes. Quantitative reverse transcription-PCR revealed that expression of these genes was highly induced during growth with CHC but not with benzoate. The newly identified CHC degradation pathway is suggested to be present in nearly all CHC-degrading anaerobic bacteria, including denitrifying, Fe(III)-reducing, sulfate-reducing, and fermenting bacteria. Remarkably, all three CHC degradation pathways always link CHC catabolism to the catabolic pathways of aromatic compounds. We propose that the capacity to use CHC as a carbon source evolved from already-existing aromatic compound degradation pathways. PMID:25112478

Healthcare Costs for Chronic Hepatitis C in South Korea from 2009 to 2013: An Analysis of the National Health Insurance Claims' Data.

PubMed

Ki, Moran; Choi, Hwa Young; Kim, Kyung-Ah; Jang, Eun Sun; Jeong, Sook-Hyang

2017-11-15

The introduction of direct-acting antivirals (DAA) in 2013 revolutionized hepatitis C virus (HCV) treatment, offering a cure rate >90%. However, this therapy is expensive, and estimations of the number of chronic HCV-infected (CHC) patients and their treatment costs pre-2013 are therefore essential for creating policies and expanding drug access. Herein, we aimed to investigate the number of HCV-related liver disease patients, their healthcare utilization, their annual direct medical costs, and the interferon-based antiviral treatment rates and costs from 2009 to 2013 in South Korea. The National Health Insurance database was reviewed, and patients diagnosed with CHC from 2009 to 2013 were extracted. Data regarding detailed healthcare utilization, prescribed drugs, and direct medical costs were obtained. For annual direct healthcare cost calculations, a prevalence-based approach was used. Overall, 181,768 CHC patients were identified. In 2013, the annual per-patient costs for chronic hepatitis, liver cirrhosis, hepatocellular carcinoma, and the first year post-liver transplant were 895, 1,873, 6,945, and 67,359 United States dollars, respectively. Interferon-based antiviral therapeutics were prescribed to 25,223 patients (13.9%). Healthcare costs have increased remarkably with increasing liver disease severity. Thus, efforts to stop disease progression are needed. Moreover, the low rate of interferon-based therapy indicates an unmet need for DAA.

Evolution of noninvasive tests of liver fibrosis is associated with prognosis in patients with chronic hepatitis C.

PubMed

Vergniol, Julien; Boursier, Jérôme; Coutzac, Clélia; Bertrais, Sandrine; Foucher, Juliette; Angel, Camille; Chermak, Faiza; Hubert, Isabelle Fouchard; Merrouche, Wassil; Oberti, Frédéric; de Lédinghen, Victor; Calès, Paul

2014-07-01

No data are available about the prediction of long-term survival using repeated noninvasive tests of liver fibrosis in chronic hepatitis C (CHC). We aimed to assess the prognostic value of 3-year liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), and fibrosis 4 (FIB-4) evolution in CHC. CHC patients with two LSM (1,000-1,500 days interval) were prospectively included. Blood fibrosis tests APRI and FIB-4 were calculated the day of baseline (bLSM) and follow-up (fLSM) LSM. Evolution of fibrosis tests was expressed as delta: (follow-up-baseline results)/duration. Date and cause of death were recorded during follow-up that started the day of fLSM. In all, 1,025 patients were included. Median follow-up after fLSM was 38.0 months (interquartile range [IQR]: 27.7-46.1) during which 35 patients died (14 liver-related death) and seven had liver transplantation. Prognostic accuracy (Harrell C-index) of multivariate models including baseline and delta results was not significantly different between LSM and FIB-4 (P ≥ 0.24), whereas FIB-4 provided more accurate prognostic models than APRI (P = 0.03). By multivariate analysis including LSM variables, overall survival was independently predicted by bLSM, delta (dLSM), and sustained virological response (SVR). Prognosis was excellent in patients having bLSM <7 kPa, SVR, or no increase (<1 kPa/year) in 7-14 kPa bLSM. Prognosis was significantly impaired in patients with an increase (≥ 1 kPa/year) in 7-14 kPa bLSM, or decrease (≤ 0 kPa/year) in ≥ 14 kPa bLSM (P = 0.949 between these two groups). Patients with an increase (>0 kPa/year) in ≥ 14 kPa bLSM had the worst prognosis. Baseline and delta FIB-4 also identified patient subgroups with significantly different prognosis. Three-year evolution of noninvasive tests of liver fibrosis has a strong prognostic value in CHC patients. These tests should be repeated to monitor patients and predict their outcome. © 2014 by the American Association for the Study of Liver Diseases.

Role of occult hepatitis B virus infection in chronic hepatitis C

PubMed Central

Coppola, Nicola; Onorato, Lorenzo; Pisaturo, Mariantonietta; Macera, Margherita; Sagnelli, Caterina; Martini, Salvatore; Sagnelli, Evangelista

2015-01-01

The development of sensitive assays to detect small amounts of hepatitis B virus (HBV) DNA has favored the identification of occult hepatitis B infection (OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV (HBsAg) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody (anti-HBc) in serum of HBsAg-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C (CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma (HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC. PMID:26576082

Hepatitis C performance measure on hepatitis A and B vaccination: missed opportunities?

PubMed

Hernandez, Bridget; Hasson, Noelle K; Cheung, Ramsey

2009-08-01

Prevention of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection in patients with chronic hepatitis C (CHC) through vaccination is endorsed by all major professional societies. This study was conducted to determine adherence to the recently adopted physician performance measure on HAV and HBV vaccination. This was a retrospective study. Hepatitis A and B serology data and immunization records between 2000 and 2007 from CHC patients with detectable hepatitis C virus (HCV) RNA were analyzed. A total of 2,968 CHC patients were included in the study. Of these, 2,143 patients (72%) were tested for susceptibility to HAV, of which 53% had immunity. Of the non-immune patients, 746 (74%) were vaccinated as well as an additional 218 without prior testing. For HBV, 2,303 patients (78%) were tested for immunity and 782 (34%) were immune. Of the susceptible patients, 1,086 (71%) were vaccinated as well as an additional 197 patients without prior testing. The overall vaccination performance measure adherence rate was 71% for HAV, 70% for HBV, and 62% for both HAV and HBV. Random review of 176 charts found the major reasons for non-adherence were missed opportunity (41%), change of health care system (31%), and documented vaccination outside our health care system (22%). Our study found a high and improved adherence to the recommendations, but missed opportunity was still the main reason of non-adherence. This study also supported the strategy of selective vaccination in the veteran population.

Uninsured Primary Care Visit Disparities Under the Affordable Care Act

PubMed Central

Angier, Heather; Hoopes, Megan; Marino, Miguel; Huguet, Nathalie; Jacobs, Elizabeth A.; Heintzman, John; Holderness, Heather; Hood, Carlyn M.; DeVoe, Jennifer E.

2017-01-01

PURPOSE Health insurance coverage affects a patient’s ability to access optimal care, the percentage of insured patients on a clinic’s panel has an impact on the clinic’s ability to provide needed health care services, and there are racial and ethnic disparities in coverage in the United States. Thus, we aimed to assess changes in insurance coverage at community health center (CHC) visits after the Patient Protection and Affordable Care Act (ACA) Medicaid expansion by race and ethnicity. METHODS We undertook a retrospective, observational study of visit payment type for CHC patients aged 19 to 64 years. We used electronic health record data from 10 states that expanded Medicaid and 6 states that did not, 359 CHCs, and 870,319 patients with more than 4 million visits. Our analyses included difference-in-difference (DD) and difference-in-difference-in-difference (DDD) estimates via generalized estimating equation models. The primary outcome was health insurance type at each visit (Medicaid-insured, uninsured, or privately insured). RESULTS After the ACA was implemented, uninsured visit rates decreased for all racial and ethnic groups. Hispanic patients experienced the greatest increases in Medicaid-insured visit rates after ACA implementation in expansion states (rate ratio [RR] = 1.77; 95% CI, 1.56–2.02) and the largest gains in privately insured visit rates in nonexpansion states (RR = 3.63; 95% CI, 2.73–4.83). In expansion states, non-Hispanic white patients had twice the magnitude of decrease in uninsured visits compared with Hispanic patients (DD = 2.03; 95% CI, 1.53–2.70), and this relative change was more than 2 times greater in expansion states compared with nonexpansion states (DDD = 2.06; 95% CI, 1.52–2.78). CONCLUSION The lower rates of uninsured visits for all racial and ethnic groups after ACA implementation suggest progress in expanding coverage to CHC patients; this progress, however, was not uniform when comparing expansion with nonexpansion states and among all racial and ethnic minority subgroups. These findings suggest the need for continued and more equitable insurance expansion efforts to eliminate health insurance disparities. PMID:28893813

Use of Traditional and Complementary Medicine as Self-Care Strategies in Community Health Centers

PubMed Central

Chung, Vincent C.H.; Wong, Samuel Y.S.; Wang, Harry H.X.; Wong, Martin C.S.; Wei, Xiaolin; Wang, Jiaji; Liu, Siya; Ho, Robin S.T.; Yu, Ellen L.M.; Griffiths, Sian M.

2016-01-01

Abstract In China, Community Health Centers (CHCs) are major providers of primary care services, but their potential in empowering patients’ self-management capacity has not been assessed. This study aims to describe self-care practice patterns amongst CHC attendees in urban China. In this cross-sectional quantitative study, 3360 CHC patients from 6 cities within the Pearl Delta Region were sampled using multistage cluster sampling. Thirty-seven per cent had used with over-the-counter Chinese herbal medicines (OTC CHMs) in the past year and majority of respondents found OTC CHMs effective. OTC CHMs were more popular amongst those who needed to pay out of pocket for CHC services. Less than 10% used vitamins and minerals, and those with a lower socioeconomic background have a higher propensity to consume. Although doubts on their usefulness are expressed, their use by the vulnerable population may reflect barriers to access to conventional health care, cultural affinity, or a defense against negative consequences of illnesses. About 25% performed physical exercise, but the prevalence is lower amongst women and older people. Taiji seems to be an alternative for these populations with promising effectiveness, but overall only 6% of CHC attendees participated. These results suggest that CHCs should start initiatives in fostering appropriate use of OTC CHM, vitamins, and minerals. Engaging community pharmacists in guiding safe and effective use of OTC CHM amongst the uninsured is essential given their low accessibility to CHC services. Prescription of Taiji instead of physical exercises to women and older people could be more culturally appropriate, and the possibility of including this as part of the CHC services worth further exploration. PMID:27281074

Variations on a theme: diversification of cuticular hydrocarbons in a clade of cactophilic Drosophila

PubMed Central

2011-01-01

Background We characterized variation and chemical composition of epicuticular hydrocarbons (CHCs) in the seven species of the Drosophila buzzatii cluster with gas chromatography/mass spectrometry. Despite the critical role of CHCs in providing resistance to desiccation and involvement in communication, such as courtship behavior, mating, and aggregation, few studies have investigated how CHC profiles evolve within and between species in a phylogenetic context. We analyzed quantitative differences in CHC profiles in populations of the D. buzzatii species cluster in order to assess the concordance of CHC differentiation with species divergence. Results Thirty-six CHC components were scored in single fly extracts with carbon chain lengths ranging from C29 to C39, including methyl-branched alkanes, n-alkenes, and alkadienes. Multivariate analysis of variance revealed that CHC amounts were significantly different among all species and canonical discriminant function (CDF) analysis resolved all species into distinct, non-overlapping groups. Significant intraspecific variation was found in different populations of D. serido suggesting that this taxon is comprised of at least two species. We summarized CHC variation using CDF analysis and mapped the first five CHC canonical variates (CVs) onto an independently derived period (per) gene + chromosome inversion + mtDNA COI gene for each sex. We found that the COI sequences were not phylogenetically informative due to introgression between some species, so only per + inversion data were used. Positive phylogenetic signal was observed mainly for CV1 when parsimony methods and the test for serial independence (TFSI) were used. These results changed when no outgroup species were included in the analysis and phylogenetic signal was then observed for female CV3 and/or CV4 and male CV4 and CV5. Finally, removal of divergent populations of D. serido significantly increased the amount of phylogenetic signal as up to four out of five CVs then displayed positive phylogenetic signal. Conclusions CHCs were conserved among species while quantitative differences in CHC profiles between populations and species were statistically significant. Most CHCs were species-, population-, and sex-specific. Mapping CHCs onto an independently derived phylogeny revealed that a significant portion of CHC variation was explained by species' systematic affinities indicating phylogenetic conservatism in the evolution of these hydrocarbon arrays, presumptive waterproofing compounds and courtship signals as in many other drosophilid species. PMID:21699713

Diagnostic performance of T lymphocyte subpopulations in assessment of liver fibrosis stages in hepatitis C virus patients: simple noninvasive score.

PubMed

Toson, El-Shatat A; Shiha, Gamal E; El-Mezayen, Hatem A; El-Sharkawy, Aml M

2016-08-01

Evaluation of liver fibrosis in patients infected with hepatitis C virus is highly useful for the diagnosis of the disease as well as therapeutic decision. Our aim was to develop and validate a simple noninvasive score for liver fibrosis staging in chronic hepatitis C (CHC) patients and compare its performance against three published simple noninvasive indexes. CHC patients were divided into two groups: an estimated group (n=70) and a validated group (n=52). Liver fibrosis was tested in biopsies using the Metavair score system. CD4 and CD8 count/percentage were assayed by fluorescence-activated cell sorting analysis. The multivariate discriminant analysis selects a function on the basis of absolute values of five biochemical markers: immune fibrosis index (IFI); score=3.07+3.06×CD4/CD8+0.02×α-fetoprotein (U/l)-0.07×alanine aminotransferase ratio-0.005×platelet count (10/l)-1.4×albumin (g/dl). The IFI score produced areas under curve of 0.949, 0.947, and 0.806 for differentiation of all patient categories [significant fibrosis (F2-F4), advanced fibrosis (F3-F4), and cirrhosis (F4)]. The IFI score, a novel noninvasive test, can be used easily for the prediction of liver fibrosis stage in CHC patients. Our score was more efficient than aspartate aminotransferase to platelet ratio index, fibrosis index, and fibroQ and more suitable for use in Egyptian hepatitis C virus patients.

PNPLA3 I148M associations with liver carcinogenesis in Japanese chronic hepatitis C patients.

PubMed

Nakaoka, Kazunori; Hashimoto, Senju; Kawabe, Naoto; Nitta, Yoshifumi; Murao, Michihito; Nakano, Takuji; Shimazaki, Hiroaki; Kan, Toshiki; Takagawa, Yuka; Ohki, Masashi; Kurashita, Takamitsu; Takamura, Tomoki; Nishikawa, Toru; Ichino, Naohiro; Osakabe, Keisuke; Yoshioka, Kentaro

2015-01-01

To investigate associations between patatin-like phospholipase domain-containing 3 (PNPLA3) genotypes and fibrosis and hepatocarcinogenesis in Japanese chronic hepatitis C (CHC) patients. Two hundred and thirty-one patients with CHC were examined for PNPLA3 genotypes, liver stiffness measurements (LSM), and hepatocellular carcinoma (HCC) from May 2010 to October 2012 at Fujita Health University Hospital. The rs738409 single nucleotide polymorphism (SNP) encoding for a functional PNPLA3 I148M protein variant was genotyped using a TaqMan predesigned SNP genotyping assay. LSM was determined as the velocity of a shear wave (Vs) with an acoustic radiation force impulse. Vs cut-off values for cirrhosis were set at 1.55 m/s. We excluded CHC patients with a sustained virological response or relapse after interferon treatment. PNPLA3 genotypes were CC, CG, and GG for 118, 72, and 41 patients, respectively. Multivariable logistic regression analysis selected older age (OR = 1.06; 95% CI: 1.03-1.09; p < 0.0001), higher body mass index (BMI) (OR= 1.12; 95% CI: 1.03-1.22; p = 0.0082), and PNPLA3 genotype GG (OR = 2.07; 95% CI: 0.97-4.42; p = 0.0599) as the factors independently associated with cirrhosis. When 137 patients without past history of interferon treatment were separately assessed, multivariable logistic regression analysis selected older age (OR = 1.05; 95% CI: 1.02-1.09; p = 0.0034), and PNPLA3 genotype GG (OR = 3.35; 95% CI: 1.13-9.91; p = 0.0291) as the factors independently associated with cirrhosis. Multivariable logistic regression analysis selected older age (OR = 1.12; 95% CI: 1.07-1.17; p < 0.0001), PNPLA3 genotype GG (OR = 2.62; 95% CI: 1.15-5.96; p = 0.0218), and male gender (OR = 1.83; 95% CI: 0.90-3.71); p = 0.0936) as the factors independently associated with HCC. PNPLA3 genotype I148M is one of risk factors for developing HCC in Japanese CHC patients, and is one of risk factors for progress to cirrhosis in the patients without past history of interferon treatment.

Identifying Successful Practices to Overcome Access to Care Challenges in Community Health Centers

PubMed Central

Toscos, Tammy; Carpenter, Maria; Flanagan, Mindy; Kunjan, Kislaya; Doebbeling, Bradley N.

2018-01-01

Background: Despite health care access challenges among underserved populations, patients, providers, and staff at community health clinics (CHCs) have developed practices to overcome limited access. These “positive deviant” practices translate into organizational policies to improve health care access and patient experience. Objective: To identify effective practices to improve access to health care for low-income, uninsured or underinsured, and minority adults and their families. Participants: Seven CHC systems, involving over 40 clinics, distributed across one midwestern state in the United States. Methods: Ninety-two key informants, comprised of CHC patients (42%) and clinic staff (53%), participated in semi-structured interviews. Interview transcripts were subjected to thematic analysis to identify patient-centered solutions for managing access challenges to primary care for underserved populations. Transcripts were coded using qualitative analytic software. Results: Practices to improve access to care included addressing illiteracy and low health literacy, identifying cost-effective resources, expanding care offerings, enhancing the patient–provider relationship, and cultivating a culture of teamwork and customer service. Helping patients find the least expensive options for transportation, insurance, and medication was the most compelling patient-centered strategy. Appointment reminders and confirmation of patient plans for transportation to appointments reduced no-show rates. Conclusion: We identified nearly 35 practices for improving health care access. These were all patient-centric, uncovered by both clinic staff and patients who had successfully navigated the health care system to improve access. PMID:29552599

Variation in prevention of child maltreatment by Dutch child healthcare professionals.

PubMed

Visscher, Simeon J A; van Stel, Henk F

2017-08-01

Child maltreatment (CM) is a common condition with a large impact on the victim and society. In the Netherlands, the preventive child healthcare (CHC) aims to protect children against such threats. However, several studies indicate that the efficacy in this area may be suboptimal for many CHC professionals. Therefore, this study aims to map the practice variation in the primary and secondary prevention of CM, by CHC physicians and nurses. This mixed-methods study used interviews to identify relevant topics and develop an online questionnaire. All CHC organizations in the Netherlands (n=45) were asked to forward this questionnaire to their professionals. Practice variation was described with domain scores and item response distributions. Multi-level analysis was used to assess case mix-corrected variance between organizations. Interview participants (n=11) expected suboptimal care in 35 topics which they considered important for prevention of CM, resulting in a 15min questionnaire. Nearly two-thirds of the organizations (n=29) agreed to forward the questionnaire to their employees. The response rate was 42% (n=1104). Suboptimal care and practice variation was found in all domains (i.e. communication, medical expertise, collaboration, involvement in prevention of CM, and improvement opportunities), mostly caused by intra-organization variance. Significant inter-organization variance was found for collaboration (variance partition coefficient 6-7%) and involvement (2-3%). Furthermore, the majority of the respondents (96%) reported fear in acting upon suspicions of CM. Substantial suboptimal care and practice variation in prevention of CM warrant action from authorities, CHC training institutes, CHC organizations, and professionals. Copyright © 2017 Elsevier Ltd. All rights reserved.

Is exposure to Agent Orange a risk factor for hepatocellular cancer?-A single-center retrospective study in the U.S. veteran population.

PubMed

Krishnamurthy, Padmini; Hazratjee, Nyla; Opris, Dan; Agrawal, Sangeeta; Markert, Ronald

2016-06-01

Approximately 15% to 35% of those with chronic hepatitis C (CHC) related cirrhosis will develop hepatocellular cancer (HCC). With this burden increasing across the globe, identification of risk factors for HCC has become imperative. Exposure to Agent Orange has been implicated as a possible risk factor for liver cancer in a study from the Republic of Korea. However, there has been no study in U.S. veterans with CHC and cirrhosis that has evaluated exposure to Agent Orange as a risk factor for HCC. We conducted a retrospective study of U.S. military veterans diagnosed with CHC and cirrhosis over a period of 14 years to evaluate potential risk factors for HCC including exposure to Agent Orange. We retrospectively reviewed 390 patients with confirmed CHC-related cirrhosis between 2000 and 2013 and identified patients with HCC. We compared demographic, laboratory, and other clinical characteristics of patients with and without HCC. The mean age of the cohort was 51 years (SD =7.5), with the majority being male (98.5%). Seventy-nine of 390 (20.2%) patients developed HCC, diagnosed on average 8 (SD =4.8) years after diagnosis of CHC. Nearly half (49.4%) were Childs A, 40.5% were Childs B, and 10.1% were Childs C. HCC patients were more likely to be African American than non-HCC patients (40.5% vs. 25.4%, P=0.009) and to be addicted to alcohol (86.1% vs. 74.3%, P=0.027). A trend toward significance was seen in the HCC group for exposure to Agent Orange (16.5% vs. 10.0%, P=0.10) and smoking addiction (88.6% vs. 80.7%, P=0.10). Consequently, race, alcohol addiction, Agent Orange exposure, and smoking addiction were included in the multivariable logistic regression (MLR) analysis. Alcohol addiction [odds ratio (OR) =2.17; 95% confidence interval (CI), 1.07-4.43] and African American race (OR =2.07; 95% CI, 1.22-3.51) were found to be the only two definitive independent risk factors for HCC in our sample. African American race and alcohol addiction were independent risk factors for HCC development in this U.S. veteran population. There was no significant association between exposure to Agent Orange and HCC, although larger studies are needed in the U.S. military veteran population to evaluate further this toxic herbicide from the Vietnam War era.

Industrial, not fruit fructose intake is associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients.

PubMed

Petta, Salvatore; Marchesini, Giulio; Caracausi, Linda; Macaluso, Fabio Salvatore; Cammà, Calogero; Ciminnisi, Stefania; Cabibi, Daniela; Porcasi, Rossana; Craxì, Antonio; Di Marco, Vito

2013-12-01

Unhealthy food intake, specifically fructose, has been associated with metabolic alterations and with the severity of liver fibrosis in patients with non-alcoholic fatty liver disease. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of fructose intake with the severity of liver histology. Anthropometric and metabolic factors, including waist circumference (WC), waist-to-hip ratio (WHR), dorso-cervical lipohypertrophy and HOMA were assessed in 147 consecutive biopsy-proven G1 CHC patients. Food intake, namely industrial and fruit fructose, was investigated by a three-day structured interview and a computed database. All biopsies were scored by an experienced pathologist for staging and grading (Scheuer classification), and graded for steatosis, which was considered moderate-severe if ≥ 20%. Features of non-alcoholic steatohepatitis (NASH) in CHC were also assessed (Bedossa classification). Mean daily intake of total, industrial and fruit fructose was 18.0±8.7g, 6.0±4.7g, and 11.9±7.2g, respectively. Intake of industrial, not fruit fructose, was independently associated with higher WHR (p=0.02) and hypercaloric diet (p<0.001). CHC patients with severe liver fibrosis (⩾F3) reported a significantly higher intake of total (20.8±10.2 vs. 17.2±8.1g/day; p=0.04) and industrial fructose (7.8±6.0 vs. 5.5±4.2; p=0.01), not fruit fructose (12.9±8.0 vs. 11.6±7.0; p=0.34). Multivariate logistic regression analysis showed that older age (OR 1.048, 95% CI 1.004-1.094, p=0.03), severe necroinflammatory activity (OR 3.325, 95% CI 1.347-8.209, p=0.009), moderate-severe steatosis (OR 2.421, 95% CI 1.017-6.415, p=0.04), and industrial fructose intake (OR 1.147, 95% CI 1.047-1.257, p=0.003) were independently linked to severe fibrosis. No association was found between fructose intake and liver necroinflammatory activity, steatosis, and the features of NASH. The daily intake of industrial, not fruit fructose is a risk factor for metabolic alterations and the severity of liver fibrosis in patients with G1 CHC. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The I148M PNPLA3 polymorphism influences serum adiponectin in patients with fatty liver and healthy controls.

PubMed

Valenti, Luca; Rametta, Raffaela; Ruscica, Massimiliano; Dongiovanni, Paola; Steffani, Liliana; Motta, Benedetta Maria; Canavesi, Elena; Fracanzani, Anna Ludovica; Mozzi, Enrico; Roviaro, Giancarlo; Magni, Paolo; Fargion, Silvia

2012-08-16

Reduced adiponectin is implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), and the I148M Patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism predisposes to NAFLD and liver damage progression in NASH and chronic hepatitis C (CHC) by still undefined mechanisms, possibly involving regulation of adipose tissue function. Aim of this study was to evaluate whether the I148M PNPLA3 polymorphism influences serum adiponectin in liver diseases and healthy controls. To this end, we considered 144 consecutive Italian patients with NAFLD, 261 with CHC, 35 severely obese subjects, and 257 healthy controls with very low probability of steatosis, all with complete clinical and genetic characterization, including adiponectin (ADIPOQ) genotype. PNPLA3 rs738409 (I148M) and ADIPOQ genotypes were evaluated by Taqman assays, serum adiponectin by ELISA. Adiponectin mRNA levels were evaluated by quantitative real-time PCR in the visceral adipose tissue (VAT) of 35 obese subjects undergoing bariatric surgery. Adiponectin levels were independently associated with the risk of NAFLD and with the histological severity of the disease. Adiponectin levels decreased with the number of 148 M PNPLA3 alleles at risk of NASH both in patients with NAFLD (p = 0.03), and in healthy subjects (p = 0.04). At multivariate analysis, PNPLA3 148 M alleles were associated with low adiponectin levels (<6 mg/ml, median value) independently of NAFLD diagnosis, age, gender, BMI, and ADIPOQ genotype (OR 1.67, 95% c.i. 1.07-2.1 for each 148 M allele). The p.148 M PNPLA3 variant was associated with decreased adiponectin mRNA levels in the VAT of obese patients (p < 0.05) even in the absence of NASH. In contrast, in CHC, characterized by adiponectin resistance, low adiponectin was associated with male gender and steatosis, but not with PNPLA3 and ADIPOQ genotypes and viral features. The I148M PNPLA3 variant is associated with adiponectin levels in patients with NAFLD and in healthy subjects, but in the presence of adiponectin resistance not in CHC patients. The I148M PNPLA3 genotype may represent a genetic determinant of serum adiponectin levels. Modulation of serum adiponectin might be involved in mediating the susceptibility to steatosis, NASH, and hepatocellular carcinoma in carriers of the 148 M PNPLA3 variant without CHC, with potential therapeutic implications.

[Detection and the production mechanism of antinuclear antibodies (ANA) and anti-liver/kidney microsomal tpe 1 antibodies (anti-LKM1) in patients with chronic hepatitis C].

PubMed

Bai, Li; Lu, Hai-Ying; Feng, Zhen-Ru; Yu, Min; Li, Wen-Gang; Gong, Wei-Bo; Zhao, Nu-en-ji-ya; Xu, Xiao-Yuan

2009-08-01

To investigate the prevalence of antinuclear antibodies (ANA) and anti-liver/ kidney microsomal type 1 antibodies (anti-LKM1) in patients with chronic hepatitis C (CHC)and to explore the mechanism of production of these autoantibodies. Serum samples were collected from 360 patients with CHC (case group), 69 patients with chronic hepatitis B (CHB) and 69 patients with autoimmune hepatitis (AIH) (control group). Serum ANA and anti-LKM1 were detected by indirect immunofluorescence (HF) technique and enzyme-linked immunosorbent assay (ELISA), respectively. Multi-factor analysis was performed to explore the correlations of the production of autoantibodies with some factors such as age, sex, viral loads, HCV genotype, biochemical parameters and clinical characteristics. Fifty-four (15%) of 360 patients infected with HCV were positive in autoantibodies. The prevalence of ANA and anti-LKM1 were 12.5% (45/360) and 2.5% (9/ 360), respectively. The positive rate of autoantibodies in patients with CHC was significantly higher than that in patients with CHB (15% vs 2.9%, P = 0.006), but significantly lower than that in patients with AIH (15% vs 47.9%, P < 0.001). Twenty-one (11.35%) of 185 male patients and 33 (18.86%) of 175 female patients were positive in autoantibodies, the difference in positive rate was significant (P < 0.05). HCV virus loads in the autoantibodies negative group were higher than that in the autoantibodies positive group (7.2 x 10(7) copies/L vs 1.23 x 10(7) copies/L, P < 0.05). There were not significant differences in age and genotype between the autoantibody positive group and the autoantibody negative group. The serum biochemical parameters of the autoantibody positive group were similar to those of the autoantibody negative group. The differences were not significant for the course of disease, clinical symptom, the incidence of cirrhosis between the autoantibody positive group and the autoantibody negative group. The prevalence of autoantibodies was not different for patients with or without interferon treatment (P > 0.05). Autoantibodies related to AIH can be detected in CHC patients; interferon may not induce the production of autoantibodies; it is very likely that HCV infection induces the autoimmune reaction and the production of autoantibodies.

The changing landscape of hepatitis C virus therapy: focus on interferon-free treatment.

PubMed

Lam, Brian P; Jeffers, Thomas; Younoszai, Zahra; Fazel, Yousef; Younossi, Zobair M

2015-09-01

Chronic hepatitis C (CHC) affects over 185 million individuals worldwide, approximately 3% of the world's population. CHC can lead to quality of life impairment, cirrhosis, hepatocellular carcinoma (HCC), liver failure and liver-related death. While CHC has been associated with increases in HCC, liver-related mortality and all-cause mortality, being cured of CHC is associated with improvement in these outcomes. Older interferon-based regimens were complex and toxic and required 6-12 months of therapy, with cure rates averaging around 40-45% for HCV genotype 1. Newer interferon-free regimens are now available in the US, Europe, Japan and in other countries. These regimens have short durations, minimal side effects, low pill burden and efficacy approaching 90-100%. We may eventually see single-tablet regimens lasting no more than 4-6 weeks. This review will summarize the data regarding these interferon-free regimens, including Gilead's Harvoni (sofosbuvir/ledipasvir), AbbVie's Viekira Pak (paritaprevir/ritonavir/ombitasvir with dasabuvir), and Janssen's Olysio (simeprevir) with sofosbuvir. Some practical considerations as we move into an interferon-free era will also be discussed, such as patient adherence and drug-drug interactions.

The changing landscape of hepatitis C virus therapy: focus on interferon-free treatment

PubMed Central

Lam, Brian P.; Jeffers, Thomas; Younoszai, Zahra; Fazel, Yousef

2015-01-01

Chronic hepatitis C (CHC) affects over 185 million individuals worldwide, approximately 3% of the world’s population. CHC can lead to quality of life impairment, cirrhosis, hepatocellular carcinoma (HCC), liver failure and liver-related death. While CHC has been associated with increases in HCC, liver-related mortality and all-cause mortality, being cured of CHC is associated with improvement in these outcomes. Older interferon-based regimens were complex and toxic and required 6–12 months of therapy, with cure rates averaging around 40–45% for HCV genotype 1. Newer interferon-free regimens are now available in the US, Europe, Japan and in other countries. These regimens have short durations, minimal side effects, low pill burden and efficacy approaching 90–100%. We may eventually see single-tablet regimens lasting no more than 4–6 weeks. This review will summarize the data regarding these interferon-free regimens, including Gilead’s Harvoni (sofosbuvir/ledipasvir), AbbVie’s Viekira Pak (paritaprevir/ritonavir/ombitasvir with dasabuvir), and Janssen’s Olysio (simeprevir) with sofosbuvir. Some practical considerations as we move into an interferon-free era will also be discussed, such as patient adherence and drug–drug interactions. PMID:26327920

Direct Acting Antiviral Agents in Korean Patients with Chronic Hepatitis C and Hemophilia Who Are Treatment-Naïve or Treatment-Experienced

PubMed Central

Lee, Hyun Woong; Yoo, Ki Young; Won, Joung Won; Kim, Hyung Joon

2017-01-01

Background/Aims Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. Methods Patients (n=30) were enrolled between September 2015 and April 2016. Twenty-six patients were genotype 1 (1b, n=21; 1a, n=5) and four patients were genotype 2a/2b. Among 21 patients with genotype 1b, Y93H resistance-associated variants (RAVs) were detected in three patients (14.3%). We evaluated sustained virologic response (SVRs) at 12 weeks, as well as relapse and safety. Results Five patients with genotype 1a and three patients with genotype 1b (RAV positive) received ledipasvir/sofosbuvir for 12 weeks. SVR12 rate was 100% (8/8). Eleven patients with genotype 1b were treatment-naïve and received daclatasvir plus asunaprevir for 24 weeks. SVR12 rate was 91% (10/11). One patient experienced viral breakthrough without RAV at 12 weeks. Seven treatment-experienced patients with genotype 1b received daclatasvir plus asunaprevir for 24 weeks. SVR12 rate was 85.7% (6/7). One patient experienced viral breakthrough with RAV (L31M, Y93H) at 12 weeks. Four patients with genotype 2a/2b received sofosbuvir plus ribavirin for 12 weeks. SVR12 rate was 100% (4/4). No serious adverse event-related discontinuations were noted. Conclusions New direct acting antiviral treatment achieved high SVRs rates at 12 weeks in CHC patients with hemophilia without serious adverse events. PMID:28874040

Specialty-care access for community health clinic patients: processes and barriers

PubMed Central

Ezeonwu, Mabel C

2018-01-01

Introduction Community health clinics/centers (CHCs) comprise the US’s core health-safety net and provide primary care to anyone who walks through their doors. However, access to specialty care for CHC patients is a big challenge. Materials and methods In this descriptive qualitative study, semistructured interviews of 37 referral coordinators of CHCs were used to describe their perspectives on processes and barriers to patients’ access to specialty care. Analysis of data was done using content analysis. Results The process of coordinating care referrals for CHC patients is complex and begins with a provider’s order for consultation and ends when the referring provider receives the specialist’s note. Poverty, specialist and referral coordinator shortages, lack of insurance, insurance acceptability by providers, transport and clinic-location factors, lack of clinic–hospital affiliations, and poor communication between primary and specialty providers constitute critical barriers to specialty-care access for patients. Conclusion Understanding the complexities of specialty-care coordination processes and access helps determine the need for comprehensive and uninterrupted access to quality health care for vulnerable populations. Guaranteed access to primary care at CHCs has not translated into improved access to specialty care. It is critical that effective policies be pursued to address the barriers and minimize interruptions in care, and to ensure continuity of care for all patients needing specialty care. PMID:29503559

Workload and casemix in Cape Town emergency departments.

PubMed

Wallis, Lee A; Twomey, Michele

2007-12-01

Little is known about the nature of patients presenting to emergency departments (EDs) in South Africa. This study aimed to provide evidence on ED usage in Cape Town by studying patients at four community health centre (CHC) EDs, with details of the severity of their presentation and their disposal. A total of 16,392 patients presented in this 8-week prospective observational study, and 15,681 were included in the descriptive data analysis. One-quarter were children. There were clear and predictable peaks in attendance after 1600 hr and at weekends, with a steady stream of patients presenting overnight. Case severity was evenly distributed between emergency, urgent and routine care. Nearly 10% of patients were referred on to a higher level of care. The data from this study present a model for staffing and resource allocation. It has implications for the provision of emergency care in CHC EDs.

Association between pre‐sarcopenia, sarcopenia, and bone mineral density in patients with chronic hepatitis C

PubMed Central

Bering, Tatiana; Diniz, Kiara G.D.; Coelho, Marta Paula P.; Vieira, Diego A.; Soares, Maria Marta S.; Kakehasi, Adriana M.; Correia, Maria Isabel T.D.; Teixeira, Rosângela; Queiroz, Dulciene M.M.; Rocha, Gifone A.

2018-01-01

Abstract Background Preserved skeletal muscle is essential for the maintenance of healthy bone. Loss of bone mineral density (BMD) and muscle strength, considered a predictor of BMD, have been demonstrated in patients with cirrhosis, but they are poorly studied in chronic hepatitis C (CHC) without cirrhosis. Thus, we aimed to evaluate the prevalence of low BMD and its association with body composition, muscle strength, and nutritional status in CHC. Methods One hundred and four subjects [mean age, 50.5 ± 11.3 years; 75.0% males; 67.3% non‐cirrhotic; and 32.7% with compensated cirrhosis] with CHC, prospectively, underwent scanning of the lean tissue, appendicular skeletal muscle mass (ASM), fat mass, lumbar spine, hip, femoral neck, and whole‐body BMD by dual‐energy X‐ray absorptiometry. Muscle strength was assessed by dynamometry. Sarcopenia was defined by the presence of both low, ASM/height2 (ASMI) and low muscle strength according to the European Working Group on Sarcopenia in Older People criteria. The cut‐off points for low ASMI and low muscle strength, for women and men, were < 5.45 and < 7.26 kg/m2 and < 20 and < 30 kg, respectively. According to the adopted World Health Organization criteria in men aged > 50 years, the T‐score of osteopenia is between −1.0 and −2.49 standard deviation (SD) below the young average value and of osteoporosis is ≥−2.5 SD below the young normal mean for men, and the Z‐score of low bone mass is ≤−2.0 SD below the expected range in men aged < 50 years and women in the menacme. Nutritional status evaluation was based on the Controlling Nutritional Status score. Results Low BMD, low muscle strength, pre‐sarcopenia, sarcopenia, and sarcopenic obesity were observed in 34.6% (36/104), 27.9% (29/104), 14.4% (15/104), 8.7% (9/104), and 3.8% (4/104) of the patients, respectively. ASMI was an independent predictor of BMD (P < 0.001). Sarcopenia was independently associated with bone mineral content (P = 0.02) and malnutrition (P = 0.01). In 88.9% of the sarcopenic patients and in all with sarcopenic obesity, BMI was normal. The mid‐arm muscle circumference was positively correlated with ASMI (r = 0.88; P < 0.001). Conclusions This is the first study to demonstrate that ASM is an independent predictor of BMD in CHC. Mid‐arm muscle circumference coupled with handgrip strength testing should be incorporated into routine clinical practice to detect low muscle mass, which may be underdiagnosed when only BMI is used. These findings may influence clinical decision‐making and contribute to the development of effective strategies to screen the musculoskeletal abnormalities in CHC patients, independently of the stage of the liver disease. PMID:29349902

Performance comparison among the major healthcare financing systems in six cities of the Pearl River Delta region, mainland China.

PubMed

Wong, Martin C S; Wang, Harry H X; Wong, Samuel Y S; Wei, Xiaolin; Yang, Nan; Zhang, Zhenzhen; Li, Haitao; Gao, Yang; Li, Donald K T; Tang, Jinling; Wang, Jiaji; Griffiths, Sian M

2012-01-01

The healthcare system of mainland China is undergoing drastic reform and the optimal models for healthcare financing for provision of primary care will need to be identified. This study compared the performance indicators of the community health centres (CHCs) under different healthcare financing systems in the six cities of the Pearl River Delta region. Approximately 300 hypertensive patients were randomly recruited from the computerized chronic disease management records provided by one CHC in each of the six cities in 2011 using a multi-stage cluster random sampling method. The major outcome measures included the treatment rate of hypertension, defined as prescription of ≥ one antihypertensive agent; and the control rate of hypertension, defined as systolic blood pressure levels <140 mmHg and diastolic blood pressure levels <90 mmHg in patients without diabetes mellitus, or <130/80 mmHg among patients with concomitant diabetes. Binary logistic regression analyses were conducted with these two measures as outcome variables, respectively, controlling for patients' socio-demographic variables. The financing system (Hospital- vs. Government- vs. private-funded) was the independent variable tested for association with the outcomes. From 1,830 patients with an average age of 65.9 years (SD 12.8), the overall treatment and control rates were 75.4% and 20.2%, respectively. When compared with hospital-funded CHCs, patients seen in the Government-funded (adjusted odds ratio [AOR] 0.462, 95% C.I. 0.325-0.656) and private-funded CHCs (AOR 0.031, 95% C.I. 0.019-0.052) were significantly less likely to be prescribed antihypertensive medication. However, the Government-funded CHC was more likely to have optimal BP control (AOR 1.628, 95% C.I. 1.157-2.291) whilst the privately-funded CHC was less likely to achieve BP control (AOR 0.146, 95% C.I. 0.069-0.310), irrespective of whether antihypertensive drugs were prescribed. Privately-funded CHCs had the lowest rates of BP treatment and control due to a variety of potential factors as discussed.

Ghrelin gene polymorphism as a genetic biomarker for prediction of therapy induced clearance in Egyptian chronic HCV patients.

PubMed

Hamdy, Marwa; Kassim, Samar Kamal; Khairy, Eman; Maher, Mohsen; Mansour, Khaled Amr; Albreedy, Ashraf M

2018-04-05

Ghrelin (GHRL) has important implications for liver disease. It has anti-inflammatory effects, regulates cell proliferation, modulates the fibrogenic response and protects liver tissue. Genetic variations in the GHRL gene may play a crucial role in the development of chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we examined the association of GHRL gene polymorphisms (rs26312 and rs27647), and its serum level to virologic responses to combined sofosbuvir and Simeprevir therapy for a course of 12 successive weeks in Egyptian chronic hepatitis C (CHC) patients. Human genomic and clinical data were collected from 100 Egyptian participants in this study, 90 HCV patients who received sofosbuvir and Simeprevir and 10 non-HCV healthy subjects. Genotyping of GHRL rs26312 and rs27647, were determined with the TaqMan qRT-PCR allele detection assay. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA). GHRL polymorphisms (rs26312 and rs27647) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. In addition, we found significant lower serum GHRL levels in CHC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26312 and rs27647 polymorphisms with GHRL levels in CHC patients. We conclude that GHRL SNPs (rs26312 and rs27647) do not affect response to combined sofosbuvir and Simeprevir treatment in chronic Egyptian HCV patients. Copyright © 2018 Elsevier B.V. All rights reserved.

A novel bubble-forming material for preparing hydrophobic-agent-loaded bubbles with theranostic functionality.

PubMed

Yang, Pei-Sin; Tung, Fu-I; Chen, Hsiao-Ping; Liu, Tse-Ying; Lin, Yi-Ying

2014-08-01

In the present study, a new bubble-forming material (carboxymethyl hexanoyl chitosan, CHC), together with superparamagnetic iron oxide (SPIO) nanoparticles, was employed to prepare image-guided bubbles for efficiently encapsulating and delivering hydrophobic agents to kill tumor cells. The results showed that CHC could be used for preparing not only micronized bubbles (CHC/SPIO MBs) to exhibit ultrasound imaging functionality but also nanosized bubbles (CHC/SPIO NBs) to exhibit magnetic resonance T2 image contrast. It was found that the amounts of SPIO nanoparticles and hexane during preparation process were the key factors to obtaining CHC/SPIO NBs. Most importantly, under in vitro cell culture conditions with the same amount of camptothecin (CPT) and therapeutic sonication, CPT-loaded CHC/SPIO NBs demonstrated more significant transcellular delivery and cytotoxicity than free CPT. Subsequently, an intratumoral injection was proposed for the in vivo administration of hydrophobic-agent-loaded CHC/SPIO NBs. After injection, the distribution of a hydrophobic dye (DiR, an agent with near-infrared (NIR) fluorescence used as a model drug) released from the CHC/SPIO NBs was tracked by an NIR imaging technique. A significant tumor-specific accumulation was observed in the mouse that received the DiR-loaded CHC/SPIO NBs; the same was not observed in the mouse that received the free dye (without incorporating with CHC/SPIO NBs). It is expected, in the future, both the dose of the therapeutic agent administered and its side effects can be significantly lowered by using novel CHC/SPIO NBs together with local delivery (intratumoral injection), targeted imaging and enhanced cellular uptake of the drug. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Chronic Hepatitis C Therapy in Liver Cirrhosis Complicated by Telaprevir-Induced DRESS.

PubMed

Mousa, Omar Y S; Khalaf, Rossa; Shannon, Rhonda L; Egwim, Chukwuma I; Zela, Scott A; Ankoma-Sey, Victor

2014-01-01

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare yet severe adverse drug-induced reaction with up to 10% mortality rate. Recent clinical trials reported an association between DRESS and telaprevir (TVR), an NS3/4A protease inhibitor of chronic hepatitis C (CHC) virus genotype 1. Its diagnosis is challenging given the variable pattern of cutaneous eruption and the myriad internal organ involvement. We present two patients who are middle-aged, obese, and white with CHC cirrhosis. They both developed a progressive diffuse, painful pruritic maculopapular rash at weeks 8 and 10 of CHC therapy with TVR, Peg-Interferon alfa-2a, and Ribavirin. They had no exposures to other medications that can cause this syndrome. Physical exam and labs and skin biopsy supported a "Definite" clinical diagnosis of DRESS, per RegiSCAR criteria. Thus Telaprevir-based triple therapy was discontinued and both patients experienced rapid resolution of the systemic symptoms with gradual improvement of eosinophilia and the skin eruption. These two cases illustrate the paramount importance of having a high index of suspicion for TVR-induced DRESS, critical for early diagnosis. Immediate discontinuation of TVR is essential in prevention of a potentially life-threatening complication. Risk factors for development of DRESS in patients receiving TVR remain to be elucidated.

A novel process for separation of hazardous poly(vinyl chloride) from mixed plastic wastes by froth flotation.

PubMed

Wang, Jianchao; Wang, Hui; Wang, Chongqing; Zhang, Lingling; Wang, Tao; Zheng, Long

2017-11-01

A novel method, calcium hypochlorite (CHC) treatment, was proposed for separation of hazardous poly(vinyl chloride) (PVC) plastic from mixed plastic wastes (MPWs) by froth flotation. Flotation behavior of single plastic indicates that PVC can be separated from poly(ethylene terephthalate) (PET), poly(acrylonitrile-co-butadiene-co-styrene) (ABS), polystyrene (PS), polycarbonate (PC) and poly(methyl methacrylate) (PMMA) by froth flotation combined with CHC treatment. Mechanism of CHC treatment was examined by contact angle measurement, scanning electron microscopy, Fourier transform infrared and X-ray photoelectron spectroscopy. Under the optimum conditions, separation of PVC from binary plastics with different particle sizes is achieved efficiently. The purity of PC, ABS, PMMA, PS and PET is greater than 96.8%, 98.5%, 98.8%, 97.4% and 96.3%, respectively. Separation of PVC from multi-plastics was further conducted by two-stage flotation. PVC can be separated efficiently from MPWs with residue content of 0.37%. Additionally, reusing CHC solution is practical. This work indicates that separation of hazardous PVC from MPWs is effective by froth flotation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of a women's counselling programme on combined hormonal contraception in Portugal--the IMAGINE Study.

PubMed

Costa, Ana Rosa R; Palma, Fátima; Sá, José Luís; Vicente, Lisa; Bombas, Teresa; Nogueira, Ana Maria; Rocha, Pedro

2011-12-01

The aim of this health education project was to measure the impact of counselling about combined hormonal contraceptive (CHC) methods on the subsequent choice of method by Portuguese women. This was a multi-centre study with a representative population, at the national and regional levels, of 2951 Portuguese women≥16 years of age visiting the gynaecologist. Counselling on available CHC methods was provided using a single leaflet, and their CHC choice was assessed before and after counselling. A combined oral contraceptive (COC) was the method preferred by the majority of the women prior to counselling. After counselling, 35% of women who initially had chosen the pill, switched to either the vaginal ring or the transdermal patch, and the difference was statistically significant. Ease of use was the major reason for choosing the COC, while a lower probability of omission was the reason for choosing the vaginal ring and the patch. The implementation of a counselling programme significantly affected contraceptive choices leading in a number of cases to the selection of alternatives better suited to women's lifestyle. Age and educational level are socio-demographic factors which play an important role.

The associations of exposure to combined hormonal contraceptive use on bone mineral content and areal bone mineral density accrual from adolescence to young adulthood: A longitudinal study.

PubMed

Jackowski, Stefan A; Baxter-Jones, Adam D G; McLardy, Ashlee J; Pierson, Roger A; Rodgers, Carol D

2016-12-01

The association of long term combined hormone based contraceptives (CHC) use on bone mineral content (BMC) and areal bone mineral density (aBMD) development remains controversial, as it appears that the relationship may be age-dependent. The purpose of this study was to investigate the long-term associations of CHC exposure on the accrual of bone parameters from adolescence into young-adulthood. 110 women (67 exposed to CHC) were drawn from the Pediatric Bone Mineral Accrual Study (PBMAS). Serial measures of total body (TB), lumbar spine (LS) and femoral neck (FN) BMC and aBMD were assessed by DXA (a total of 950 scans) and aligned by biological age (BA, years from peak height velocity [PHV]). Multilevel random effects models were constructed to assess the time dependent associations between annual CHC exposure and the development of bone parameters. After BA, height, lean tissue mass, fat mass, calcium and vitamin D intake, and physical activity were controlled, it was observed that those individuals exposed to CHC 6-years post PHV developed significantly less (-0.00986 ± 0.00422 g/cm 2 ) TB aBMD than their non CHC exposed peers. Additionally, there were significant BA by CHC exposure interactions, where CHC exposure 6-years or more post PHV resulted in developing less TB BMC (-4.94 ± 2.41 g), LS BMC (-0.29 ± 0.11 g) and LS aBMD (-0.00307 ± 0.00109 g/cm 2 ). One year after the attainment of PHV, CHC users were predicted to have 1.2% more TB BMC, 3.8% more LS BMC and 1.7% more LS aBMD than non-users. At 9-years post PHV the predicted differences showed that CHC users had 0.9% less TB BMC and 2.7% less LS BMC and 1.6% less LS BMD than those not exposed to CHC. CHC may not hinder the development of BMC or aBMD during adolescence; however, exposure 6-years or more after PHV may be detrimental.

Evolution of Cuticular Hydrocarbons in the Hymenoptera: a Meta-Analysis.

PubMed

Kather, Ricarda; Martin, Stephen J

2015-10-01

Chemical communication is the oldest form of communication, spreading across all forms of life. In insects, cuticular hydrocarbons (CHC) function as chemical cues for the recognition of mates, species, and nest-mates in social insects. Although much is known about the function of individual hydrocarbons and their biosynthesis, a phylogenetic overview is lacking. Here, we review the CHC profiles of 241 species of Hymenoptera, one of the largest and most important insect orders, which includes the Symphyta (sawflies), the polyphyletic Parasitica (parasitoid wasps), and the Aculeata (wasps, bees, and ants). We investigated whether these taxonomic groups differed in the presence and absence of CHC classes and whether the sociality of a species (solitarily vs. social) had an effect on CHC profile complexity. We found that the main CHC classes (i.e., n-alkanes, alkenes, and methylalkanes) were all present early in the evolutionary history of the Hymenoptera, as evidenced by their presence in ancient Symphyta and primitive Parasitica wasps. Throughout all groups within the Hymenoptera, the more complex a CHC the fewer species that produce it, which may reflect the Occam's razor principle that insects' only biosynthesize the most simple compound that fulfil its needs. Surprisingly, there was no difference in the complexity of CHC profiles between social and solitary species, with some of the most complex CHC profiles belonging to the Parasitica. This profile complexity has been maintained in the ants, but some specialization in biosynthetic pathways has led to a simplification of profiles in the aculeate wasps and bees. The absence of CHC classes in some taxa or species may be due to gene silencing or down-regulation rather than gene loss, as demonstrated by sister species having highly divergent CHC profiles, and cannot be predicted by their phylogenetic history. The presence of highly complex CHC profiles prior to the vast radiation of the social Hymenoptera indicates a 'spring-loaded' system where the diversity of CHC needed for the complex communication systems of social insects were already present for natural selection to act upon, rather than having evolved independently. This diversity may have aided the multiple independent evolution of sociality within the Aculeata.

INFLUENCE OF HEPATOCELLULAR CARCINOMA ETIOLOGY IN THE SURVIVAL AFTER RESECTION.

PubMed

Lopes, Felipe de Lucena Moreira; Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirolla; Fonseca, Gilton Marques; Araujo, Raphael Leonardo Cunha de; Jeismann, Vagner Birk; Herman, Paulo

2016-01-01

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and its incidence is increasing around the world in the last decades, making it the third cause of death by cancer in the world. Hepatic resection is one of the most effective treatments for HCC with five-year survival rates from 50-70%, especially for patients with a single nodule and preserved liver function. Some studies have shown a worse prognosis for HCC patients whose etiology is viral. That brings us to the question about the existence of a difference between the various causes of HCC and its prognosis. To compare the prognosis (overall and disease-free survival at five years) of patients undergoing hepatectomy for the treatment of HCC with respect to various causes of liver disease. Was performed a review of medical records of patients undergoing hepatectomy between 2000 and 2014 for the treatment of HCC. They were divided into groups according to the cause of liver disease, followed by overall and disease-free survival analysis for comparison. There was no statistically significant difference in the outcomes of the groups of patients divided according to the etiology of HCC. Overall and disease-free survival at five years of the patients in this sample were 49.9% and 40.7%, respectively. From the data of this sample, was verified that there was no prognostic differences among the groups of HCC patients of the various etiologies. O carcinoma hepatocelular (CHC) é o mais frequente tipo de câncer primário do fígado e a sua incidência vem aumentando nas últimas décadas, tornando-o hoje a terceira causa de morte por câncer no mundo. A ressecção hepática é um dos tratamentos mais eficazes para ele com taxas de sobrevida em cinco anos de 50-70%, especialmente para pacientes com nódulo único e função hepática preservada. Alguns estudos mostraram pior prognóstico para os pacientes com CHC cuja causa é a infecção por vírus B ou C. Isso leva à questão sobre a existência de possível diferença entre as diversas causas e o prognóstico. Comparar o prognóstico (sobrevida global e livre de doença em cinco anos) de pacientes submetidos à hepatectomia para o tratamento do CHC com relação às diversas causas da hepatopatia. Foi realizado levantamento de prontuários dos pacientes submetidos à hepatectomia entre 2000 e 2014 para tratamento de CHC. Eles foram divididos em grupos de acordo com a causa da hepatopatia, sendo feita análise de sobrevida para comparação. Não houve diferença estatisticamente significante de prognóstico entre os grupos de pacientes divididos conforme a causa do CHC. A sobrevida global e livre de doença em cinco anos foi de 49.9% e 40.7%, respectivamente. Pôde-se constatar que não houve diferença em relação ao prognóstico entre os grupos de pacientes das diversas causas de CHC.

[Effect of interferon and ribavirin combination therapy in sixty-two patients with chronic hepatitis C originating from a single blood donor].

PubMed

Liu, San-du; Cheng, Ming-liang; Ren, Hong; Yang, Qing-kun; Shu, De-yun

2012-08-01

To investigate the efficacy of interferon alpha 2 b plus ribavirin combination therapy in sixty-two patients with chronic hepatitis c (CHC) infection originating from a single blood donor. The 62 patients who developed CHC following blood transfusion from a known single infected donor were treated with interferon and ribavirin combination therapy for 48 weeks and followed-up for 96 weeks. The therapy regimen consisted of subcutaneous administration of 3-500 MIU interferon alpha 2 b every other day and daily oral administration of 0.6-1.0 g of ribavirin. Patients were monitored during treatment and in follow-up for sustained virological response (SVR), early virology response (EVR), treatment end virology response (ETVR), biochemical response of withdrawals, and side effects. The SVR rate was 83.9% (52/62). The EVR rate was 95.2% (59/62). The ETVR rate was 87.1% (54/62). The biochemical response rate after withdrawal of treatment was 100.0%. Eight patients developed mildly abnormal thyroid function as a result of the interferon therapy, but all were able to complete the antiviral treatment regimen under the care of endocrinologists. Younger age, relatively short course of disease, low viral load, and better compliance, but not sex, were correlated to curative effect of the combination therapy. Interferon alpha 2 b plus ribavirin combination therapy had a significant curative effect on a group of 62 CHC patients originating from a single case, with 52 of the patients showing SVR out to 96 weeks after therapy. Antiviral treatment is recommended for hepatitis C virus-positive patients to eradicate the virus and prevent disease progression.

Real-World Study on Sofosbuvir-based Therapies in Asian Americans With Chronic Hepatitis C.

PubMed

Pan, Calvin Q; Tiongson, Benjamin C; Hu, Ke-Qin; Han, Steven-Huy B; Tong, Myron; Chu, Danny; Park, James; Lee, Tai Ping; Bhamidimarri, Kalyan Ram; Ma, Xiaoli; Xiao, Pei Ying; Mohanty, Smruti R; Wang, Dan

2018-06-16

Limited data exist with regard to treatment outcomes in Asian Americans with chronic hepatitis C (CHC). We evaluated sofosbuvir (SOF)-based regimens in a national cohort of Asian Americans. Eligible Asian Americans patients with CHC who had posttreatment follow-up of 24 weeks for SOF -based therapies from December 2013 to June 2017 were enrolled from 11 sites across the United States. The primary endpoint was sustained virologic response (SVR) rates at posttreatment weeks 12 and 24. Secondary endpoints were to evaluate safety by tolerability and adverse events (AEs). Among 231 patients screened, 186 were enrolled. At baseline, 31% (57/186) patients were cirrhotic, 34% (63/186) were treatment experienced. Most of the subjects (42%, 79/186) received ledispavir/SOF therapy. The overall SVR12 was 95%, ranging from 86% in genotype (GT) 1b on SOF+ribavirin to 100% in GT 1b patients on ledipasvir/SOF at subgroup analyses. SVR12 was significantly lower in cirrhotic than in noncirrhotic patients [88% (50/57) vs. 98% (126/129), P<0.01]. Stratified by GT, SVR12 were: 96% (43/45) in GT 1a; 93% (67/72) in GT 1b; 100% (23/23) in GT 2; 90% (19/21) in GT 3; 100% (1/1) in GT 4; 83% (5/6) in GT 5; and 100% (16/16) in GT 6. Cirrhotic patients with treatment failure were primarily GT 1, (GT 1a, n=2; GT 1b, n=4) with 1 GT 5 (n=1). Patients tolerated the treatment without serious AEs. Late relapse occurred in 1 patient after achieving SVR12. In Asian Americans with CHC, SOF-based regimens were well tolerated without serious AEs and could achieve high SVR12 regardless of hepatitis C viral infection GT.

PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non-obese subjects with hepatitis C.

PubMed

Petta, S; Vanni, E; Bugianesi, E; Rosso, C; Cabibi, D; Cammà, C; Di Marco, V; Eslam, M; Grimaudo, S; Macaluso, F S; McLeod, D; Pipitone, R M; Abate, M L; Smedile, A; George, J; Craxì, A

2015-05-01

The PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC). To test in genotype 1(G1)-CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis. Four hundred and thirty-four consecutively biopsied Caucasian G1-CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of steatohepatitis in CHC were assessed using the Bedossa classification. Hepatic expression of PNPLA3 mRNA was evaluated in 63 patients. The prevalence of steatohepatitis increased from 16.5% in patients with PNPLA3 CC, to 23.2% in CG and 29.2% in the GG genotype (P = 0.02). By multiple logistic regression, PNPLA3 genotype (OR 1.54, 95% CI 1.03-2.30, P = 0.03), together with age (OR 1.03, 95% CI 1.00-1.05, P = 0.02), BMI ≥ 30 (OR 2.06, 95% CI 1.04-4.10, P = 0.03) and homoeostasis model assessment (HOMA, OR 1.18, 95% CI 1.04-1.32, P = 0.006) were independently linked to steatohepatitis. When stratifying for obesity, PNPLA3 was associated with NASH in non-obese patients only (12.0% in CC vs. 18.3% in CG vs. 27.3% in GG, P = 0.01), including after correction for metabolic confounders (OR 2.06, 95% CI 1.26-3.36, P = 0.004). We showed an independent association between steatohepatitis (OR 2.05, 95% CI 1.05-4.02, P = 0.003) and severe fibrosis. Higher liver PNPLA3 mRNA was associated both with the severity of steatosis (adjusted P = 0.03) and steatohepatitis after adjusting for gender, age, BMI and HOMA (P = 0.002). In patients with genotype 1 hepatitis C, the PNPLA3 G variant is associated with a higher risk of steatosis severity and steatohepatitis, particularly among non-obese subjects. © 2015 John Wiley & Sons Ltd.

Simple score to predict risk of hepatocellular carcinoma in chronic hepatitis C patients with advanced fibrosis after pegylated interferon and ribavirin therapy.

PubMed

Hu, Ching-Chih; Weng, Cheng-Hao; Chang, Liang-Che; Lin, Chih-Lang; Chen, Yen-Ting; Hu, Ching-Fang; Hua, Man-Chin; Chen, Li-Wei; Chien, Rong-Nan

2018-01-01

Eradication of chronic hepatitis C virus (HCV) after interferon-based therapy and its association with the reduction of risk of hepatocellular carcinoma (HCC) in HCV-infected patients with advanced fibrosis is controversial. The study is aimed to develop a simple scoring model for HCC prediction among advanced fibrotic chronic hepatitis C (CHC) patients after pegylated interferon (pegIFN) and ribavirin (RBV) therapy. We enrolled 271 biopsy-proven CHC patients with advanced fibrosis between 2003 and 2016, and divided them into non-HCC (n=211) and HCC (n=60) groups. The median observation duration was 6.0 years (range: 0.9-12.6 years). The HCC prevalence after pegIFN and RBV therapy in CHC patients with sustained virologic response (SVR) and without SVR was 14.7% and 32.2%, respectively. Multivariate Cox regression showed age ≥59.5 years old at initiation of therapy (HR: 2.542, 95% CI: 1.390-4.650, P =0.002), pretreatment total bilirubin ≥1.1 mg/dL (HR: 2.630, 95% CI: 1.420-4.871, P =0.002), pretreatment platelet counts <146.5 × 10 3 /μL (HR: 2.751, 95% CI: 1.373-5.511, P =0.004), no achievement of SVR (HR: 2.331, 95% CI: 1.277-4.253, P =0.006), and no diabetes at treatment initiation (HR: 3.085, 95% CI: 1.283-7.418, P =0.012) were significant predictors of HCC development. The scoring model consisted of the five categorical predictors and had an optimal cutoff point of 2.5. The area under receiver operating characteristic (AUROC) of the scoring model was 0.774±0.035 ( P <0.001). The sensitivity and specificity of the cutoff value to detect HCC were 81.3% and 57.5%. The 5-year and 10-year cumulative incidence of HCC was 4.9% and 10.0% in patients with simple score ≤2; and 25.9% and 44.6% in patients with simple score ≥3 ( P <0.001). The simple clinical-guided score has high discriminatory power for HCC prediction in advanced fibrotic CHC patients after pegIFN and RBV therapy.

The impact of IL28B genotype on the gene expression profile of patients with chronic hepatitis C treated with pegylated interferon alpha and ribavirin.

PubMed

Younossi, Zobair M; Birerdinc, Aybike; Estep, Mike; Stepanova, Maria; Afendy, Arian; Baranova, Ancha

2012-02-07

Recent studies of CH-C patients have demonstrated a strong association between IL28B CC genotype and sustained virologic response (SVR) after PEG-IFN/RBV treatment. We aimed to assess whether IL28B alleles rs12979860 genotype influences gene expression in response to PEG-IFN/RBV in CH-C patients. Clinical data and gene expression data were available for 56 patients treated with PEG-IFN/RBV. Whole blood was used to determine IL28B genotypes. Differential expression of 153 human genes was assessed for each treatment time point (Days: 0, 1, 7, 28, 56) and was correlated with IL28B genotype (IL28B C/C or non-C/C) over the course of the PEG-IFN/RBV treatment. Genes with statistically significant changes in their expression at each time point were used as an input for pathway analysis using KEGG Pathway Painter (KPP). Pathways were ranked based on number of gene involved separately per each study cohort. The most striking difference between the response patterns of patients with IL28B C/C and T* genotypes during treatment, across all pathways, is a sustained pattern of treatment-induced gene expression in patients carrying IL28B C/C. In the case of IL28B T* genotype, pre-activation of genes, the lack of sustained pattern of gene expression or a combination of both were observed. This observation could potentially provide an explanation for the lower rate of SVR observed in these patients. Additionally, when the lists of IL28B genotype-specific genes which were differentially expressed in patients without SVR were compared at their baseline, IRF2 and SOCS1 genes were down-regulated regardless of patients' IL28B genotype. Furthermore, our data suggest that CH-C patients who do not have the SOCS1 gene silenced have a better chance of achieving SVR. Our observations suggest that the action of SOCS1 is independent of IL28B genotype. IL28B CC genotype patients with CH-C show a sustained treatment-induced gene expression profile which is not seen in non-CC genotype patients. Silencing of SOCS1 is a negative and independent predictor of SVR. These data may provide some mechanistic explanation for higher rate of SVR in IL28B CC patients who are treated with PEG-IFN/RBV.

Relation of Insulin Resistance and Liver Fibrosis Progression in Patients with Chronic Hepatitis C Virus Infection

PubMed Central

Mohamed, Hassan R; Abdel-Azziz, Mohamed Yaqoot; Zalata, Kkaled Refaat; Abdel-Razik, Ahmed M M

2009-01-01

Background: Hepatitis C virus (HCV) infection can predispose to the development of insulin resistance before diabetes occurs. Such a potential link is particularly cogent in light of recent data indicate that diabetes may be associated with increased hepatic fibrosis progression in patients with chronic HCV infection. The aim of the study is to determine the prevalence of insulin resistance in non diabetic patients with chronic hepatitis C and its relation to liver fibrosis. Methods: Thirty eight patients with chronic liver diseases. They subdivided into 2 groups; chronic hepatitis C (CHC) with elevated liver enzymes and CHC with normal liver enzymes. Age and sex matched 12 healthy subjects as control group. All subjects were subjected to Careful history and copmlete examination with stress upon symptoms and signs of chronic liver diseases. Investigations include liver function tests; viral markers (Anti HCV antibodies & PCR for HCV). Serum fasting glucose; serum fasting insulin; homeostasis model assessment (HOMA), liver biopsy and abdominal ultrasound. Results: No correlation between viral load and hepatic fibrosis in HCV infected patients. Liver fibrosis is considerably higher among HCV patients with elevated serum transaminase levels. Insulin resistance is present in HCV infected cases compared with control group and it is positively correlated with liver fibrosis. Conclusion: The present data support the hypothesis that insulin resistance may increase the rate of fibrosis progression in non diabetic patients with chronic HCV. Follow up of hyperinsulinemia by serial measurement of HOMA test in non diabetic HCV infected patients may be a biochemical indicator for progression of liver fibrosis. PMID:21475535

CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides.

PubMed

Barathan, Muttiah; Mohamed, Rosmawati; Vadivelu, Jamuna; Chang, Li Yen; Vignesh, Ramachandran; Krishnan, Jayalakshmi; Sigamani, Panneer; Saeidi, Alireza; Ram, M Ravishankar; Velu, Vijayakumar; Larsson, Marie; Shankar, Esaki M

2017-03-01

Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray™ following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide-stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-β1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessing Research Interest and Capacity in Community Health Centers

PubMed Central

Bhuiya, Nazmim; Pernice, Joan; Khan, Sami M.; Sequist, Thomas D.; Tendulkar, Shalini A.

2013-01-01

Abstract Objective Community health centers (CHCs) have great potential to participate in the development of evidence‐based primary care but face obstacles to engagement in clinical translational research. Methods To understand factors associated with CHC interest in building research infrastructure, Harvard Catalyst and the Massachusetts League of Community Health Centers conducted an online survey of medical directors in all 50 Massachusetts CHC networks. Results Thirty‐two (64%) medical directors completed the survey representing 126 clinical sites. Over 80% reported that their primary care providers (PCPs) were slightly to very interested in future clinical research and that they were interested in building research infrastructure at their CHC. Frequently cited barriers to participation in research included financial issues, lack of research skills, and lack of research infrastructure. In bivariate analyses, PCP interest in future clinical research and a belief that involvement in research contributed to PCP retention were significantly associated with interest in building research infrastructure. Conclusion CHCs critical role in caring for vulnerable populations ideally positions them to raise relevant research questions and translate evidence into practice. Our findings suggest a high interest in engagement in research among CHC leadership. CTSAs have a unique opportunity to support local CHCs in this endeavor. PMID:24127928

African American administrators in community/migrant health centers.

PubMed

Glover, S H; Shi, L; Samuels, M E

1997-05-01

Community and migrant health centers (CHC/MHCs) play a secondary role as avenues for the development of minority and women health care professionals, groups traditionally underrepresented in administrative and managerial positions within the health care system. This paper focuses on the role of CHC/MHCs in eliminating the barriers that typically limit the professional advancement of these groups. In a survey of both rural and urban CHC/MHC administrators, it was found that CHC/MHCs have higher percentages of minorities in top management positions than general management but do not necessarily reflect the minority composition of those being served. Of the CHC/MHC administrators, 20 percent were African American, less than the population served (31 percent) but greater than the percentage of African Americans in the general U.S. population (12 percent). This suggests that CHC/MHCs have partially met the original goal of upward mobility and that there is room for improvement.

Real-life prevalence of resistance-associated variants against non-structural protein 5A inhibitors and efficiency of Daclatasvir + Asunaprevir therapy in Korean patients with genotype 1b hepatitis C.

PubMed

Yu, Jung Hwan; Lee, Jung Il; Lee, Kwan Sik; Kim, Ja Kyung

2017-08-24

Direct-acting antivirals (DAAs) for chronic hepatitis C (CHC) treatment are tolerable and highly effective in a shorter period of time than before. However, resistance-associated variants (RAVs) can affect the efficacy of DAAs. The aim of this study was to investigate the real-life prevalence of RAVs against non-structural protein 5A (NS5A) inhibitors in Korean patients with genotype 1b chronic hepatitis C. All consecutive patients with CHC genotype 1b who underwent a RAV test at a single referral hospital were enrolled. A total of 142 patients (male 53, female 89) were tested for RAVs. The average age of the patients was 58 years. Liver cirrhosis was found in 34.5% (49/142) of patients, and 19.0% (29/142) of patients had previously undergone interferon-based treatment. Twenty-nine patients (20.4%) had RAVs (Y93 or L31). Y93H, L31, or Y93H with L31 were detected in 22 (15.5%), 8 (5.6%), and 1 (0.7%) patients, respectively. The presence of RAV was not affected by previous interferon-based treatment or by the existence of liver cirrhosis. Among 113 patients without baseline NS5A RAVs, 72 patients started daclatasvir (DCV) + asunaprevir (ASV) treatment and 95% (68/72) patients achieved virologic response at week 4. Virologic response at end of treatment and sustained virologic response at 12 weeks after treatment were achieved by 94% (68/72) and 94% (68/72), respectively. In Korean patients with genotype 1b CHC, 20.4% (29 of 142) of patients showed RAVs against NS5A inhibitors. Patient without RAVs who received treatment with DCV + ASV showed high virologic response rates in Korea.

Effects of losartan on hepatic expression of nonphagocytic NADPH oxidase and fibrogenic genes in patients with chronic hepatitis C.

PubMed

Colmenero, Jordi; Bataller, Ramón; Sancho-Bru, Pau; Domínguez, Marlene; Moreno, Montserrat; Forns, Xavier; Bruguera, Miquel; Arroyo, Vicente; Brenner, David A; Ginès, Pere

2009-10-01

Angiotensin II promotes liver fibrogenesis by stimulating nonphagocytic NADPH oxidase (NOX)-induced oxidative stress. Angiotensin II type 1 (AT1) receptor blockers attenuate experimental liver fibrosis, yet their effects in human liver fibrosis are unknown. We investigated the effects of losartan on hepatic expression of fibrogenic, inflammatory, and NOX genes in patients with chronic hepatitis C (CHC). Fourteen patients with CHC and liver fibrosis received oral losartan (50 mg/day) for 18 mo. Liver biopsies were performed at baseline and after treatment. The degree of inflammation and fibrosis was evaluated by histological analysis (METAVIR). Collagen content was measured by morphometric quantification of Sirius red staining. Overall collagen content and fibrosis stage remained stable in the whole series, yet the fibrosis stage decreased in seven patients. Inflammatory activity improved in seven patients. The effect of losartan on hepatic expression of 31 profibrogenic and inflammatory genes and components of the NOX complex was assessed by quantitative PCR. Losartan treatment was associated with a significant decrease in the expression of several profibrogenic and NOX genes including procollagen alpha1(I) and alpha1(IV), urokinase-type plasminogen activator, metalloproteinase type 2, NOX activator 1 (NOXA-1) and organizer 1 (NOXO-1), and Rac-1. Losartan was well tolerated in all patients and was effective in attenuating the activity of the systemic renin-angiotensin system. No effects on serum liver tests or viral load were observed. We conclude that prolonged administration of losartan, an oral AT1 receptor blocker, is associated with downregulation of NOX components and fibrogenic genes in patients with CHC. Controlled studies are warranted to assess the effect of AT1 receptor blockers in chronic liver injury.

[Mathematic Model for Prediction of Liver Fibrosis Progression Rate in Patients with Chronic Hepatitis C Based on Combination of Genomic Markers].

PubMed

Samokhodskaia, L M; Starostina, E E; Yarovaya, E B; Krasnova, T N; Mukhin, N A; Tkachuk, V A; Sadovnichy, V A

2015-01-01

To evaluate clinical significance of different combinations of gene polymorphisms IL-1b, IL-6, IL-10, TNF, HFE, TGF-b, ATR1, N0S3894, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI and their prognostic value for prediction of liver fibrosis progression rate in patients with chronic hepatitis C (CHC). 118 patients with CHC were divided into "fast" and "slow" (fibrosis rate progression ≥ 0.13 and < 0.13 fibrosis units/yr; n = 64 and n = 54) fibrosis groups. Gene polymorphisms were determined. Statistical analysis was performed using Statistica 10. A allele (p = 0.012) and genotype AA (p = 0.024) of AGT G-6T gene, as well as T allele (p = 0.013) and MT+TT genotypes (p = 0.005) of AGT 235 M/T gene were significantly more common in "fast fibrosers" than in "slow fibrosers". Patients with genotype TT of CYBA 242 C/T had a higher fibrosis progression rate than patients with CC+CT genotype (p = 0.02). Our analysis showed a protective effect of TTgenotype of ITGA2 807 C/T on fibrosis progression rate (p = 0.03). There was a trend (p < 0.15) to higher fibrosis progression rate in patients with mutant alleles and genotypes of TGFb +915 G/C, FXIII 103 G/T, PAI-675 5G/4G genes. Other gene polymorphisms were not associated with enhanced liver fibrosis. To build a mathematical modelfor prediction of liverfibrosis progression rate we performed coding with scores for genotypes and virus genotype. Total score correlated with the fibrosis progression rate (R = 0.39, p = 0.000). Determination of genetic profile of the patient and virus genotype allows to predict the course of CHC.

Value and innovation of direct-acting antivirals: long-term health outcomes of the strategic plan for the management of hepatitis C in Spain.

PubMed

Turnes, Juan; Domínguez-Hernández, Raquel; Casado, Miguel Ángel

2017-12-01

To assess the long-term healthcare costs and health outcomes in association with the access to new direct-acting antivirals (DAAs), during the first year of the National Strategic Plan for Chronic Hepatitis C (SPCHC) in patients with chronic hepatitis C (CHC) in Spain. A decision tree and a lifetime Markov model were developed to simulate the natural history, morbidity, and mortality of a cohort of 51,900 patients with CHC before (pre-DAA strategy) and after (post-DAA strategy) access to DAAs, following SPCHC approval. The percentage of patients treated, transition probabilities, disease management costs, health state utility values, sustained virologic response rates and treatment costs were obtained from the literature and published data from Spain. The results were expressed in terms of costs (€, 2016), quality-adjusted life years (QALYs) and prevention of clinical events, with an annual discount rate of 3%. The post-DAA strategy would prevent 8,667 cases of decompensated cirrhosis, 5,471 cases of hepatocellular carcinoma, 1,137 liver transplants and 9,608 liver-related deaths. The cohort of 51,900 patients would require investments of 1,606 and 1,230 million euros with the post-DAA and pre-DAA strategies, respectively. This would produce 819,674 and 665,703 QALYs. The use of new DAA-based treatments in CHC patients during the first year after the implementation of the SPCHC significantly reduced long-term morbidity and mortality and increased quality of life; demonstrating that this plan is an efficient use of public health resources.

Nutritional education and carbohydrate counting in children with type 1 diabetes treated with continuous subcutaneous insulin infusion: the effects on dietary habits, body composition and glycometabolic control.

PubMed

Marigliano, Marco; Morandi, Anita; Maschio, Maddalena; Sabbion, Alberto; Contreas, Giovanna; Tomasselli, Francesca; Tommasi, Mara; Maffeis, Claudio

2013-12-01

Carbohydrate counting (CHC) in combination with nutritional education has been used to optimize the insulin dose in patients with type 1 diabetes (T1D). The aim of this study was to test the impact of CHC and nutritional education on changes in dietary habits, body composition and body fat distribution in children with T1D treated with insulin pumps (CSII). Twenty-five children with T1D and CSII were recruited and valuated at baseline and after 18 months of follow-up. They were trained in CHC and following standard nutrition education program (based on American Diabetes Association and International Society of Pediatric and Adolescent Diabetes guidelines); clinical, biochemical and nutritional variables were measured. In the total population, body composition, body fat distribution and biochemical variables did not change, at follow-up; HbA1c was significantly reduced (8.50 ± 0.77 vs 7.92 ± 0.74 %; p < 0.001) without changing insulin/kg/day requirement. In the sub-group of patients with a significant HbA1c reduction (ΔHbA1c ≥ 0.5 %, n = 12), the carbohydrate (CHO) intake was significantly higher at follow-up (53.0 ± 4.0 vs 57.6 ± 2.5 %; p < 0.01); on the contrary, fat (31.3 ± 3.6 vs 28.5 ± 1.6 %; p < 0.05) and protein intake (15.4 ± 1.8 vs 13.3 ± 1.6 %; p < 0.01) significantly decreased. Patients without a significant HbA1c reduction did not show any difference. CHC, in combination with nutritional education, does not affect dietary habits, body composition and body fat distribution in children with T1D treated with CSII. Moreover, the sub-group of subjects showing a significant improvement in glycometabolic control reported an increase in CHO intake and a reduction in fat and protein intake.

How do cuticular hydrocarbons evolve? Physiological constraints and climatic and biotic selection pressures act on a complex functional trait

PubMed Central

Blaimer, Bonnie B.; Schmitt, Thomas

2017-01-01

Cuticular hydrocarbons (CHCs) cover the cuticles of virtually all insects, serving as a waterproofing agent and as a communication signal. The causes for the high CHC variation between species, and the factors influencing CHC profiles, are scarcely understood. Here, we compare CHC profiles of ant species from seven biogeographic regions, searching for physiological constraints and for climatic and biotic selection pressures. Molecule length constrained CHC composition: long-chain profiles contained fewer linear alkanes, but more hydrocarbons with disruptive features in the molecule. This is probably owing to selection on the physiology to build a semi-fluid cuticular layer, which is necessary for waterproofing and communication. CHC composition also depended on the precipitation in the ants' habitats. Species from wet climates had more alkenes and fewer dimethyl alkanes than those from drier habitats, which can be explained by different waterproofing capacities of these compounds. By contrast, temperature did not affect CHC composition. Mutualistically associated (parabiotic) species possessed profiles highly distinct from non-associated species. Our study is, to our knowledge, the first to show systematic impacts of physiological, climatic and biotic factors on quantitative CHC composition across a global, multi-species dataset. We demonstrate how they jointly shape CHC profiles, and advance our understanding of the evolution of this complex functional trait in insects. PMID:28298343

The relationship between epicuticular long-chained hydrocarbons and surface area - volume ratios in insects (Diptera, Hymenoptera, Lepidoptera)

PubMed Central

Brückner, Adrian; Heethoff, Michael; Blüthgen, Nico

2017-01-01

Long-chain cuticular hydrocarbons (CHCs) are common components of the epicuticle of terrestrial arthropods. CHC serve as a protective barrier against environmental influences but also act as semiochemicals in animal communication. Regarding the latter aspect, species- or intra-functional group specific CHCs composition and variation are relatively well studied. However, comparative knowledge about the relationship of CHC quantity and their relation to surface area—volume ratios in the context of water loss and protection is fragmentary. Hence, we aim to study the taxon-specific relationship of the CHC amount and surface-area to volume ratio related to their functional role (e.g. in water loss). We focused on flower visiting insects and analyzed the CHC amounts of three insect orders (Hymenoptera, Lepidoptera and Diptera) using gas chromatography—mass spectrometry (GC-MS). We included 113 species from two grassland plots, quantified their CHCs, and measured their body mass and surface area. We found differences in the surface area, CHCs per body mass and the CHC density (= amount of CHCs per surface area) across the three insect taxa. Especially the Hymenoptera had a higher CHC density compared to Diptera and Lepidoptera. CHC density could be explained by surface area-volume ratios in Hymenoptera but not in Diptera and Lepidoptera. Unexpectedly, CHC density decreased with increasing surface area—volume ratios. PMID:28384308

Occult HCV Infection: The Current State of Knowledge

PubMed Central

Rezaee-Zavareh, Mohammad Saeid; Hadi, Reza; Karimi-Sari, Hamidreza; Hossein Khosravi, Mohammad; Ajudani, Reza; Dolatimehr, Fardin; Ramezani-Binabaj, Mahdi; Miri, Seyyed Mohammad; Alavian, Seyed Moayed

2015-01-01

Context Occult HCV infection (OCI) is defined as the presence of HCV-RNA in hepatocytes and the absence of HCV in the serum according to usual tests. We aimed to define OCI and provide information about the currently available diagnostic methods. Then we focus on specific groups that are at high risk of OCI and finally investigate immune responses to OCI and the available treatment approaches. Evidence Acquisition PubMed, Scopus and Google Scholar were comprehensively searched with combination of following keywords: “occult”, “hepatitis C virus” and “occult HCV infection”. The definition of OCI, diagnostic methods, specific groups that are at high risk and available treatment approaches were extract from literature. An analysis of available articles on OCI also was done based on Scopus search results. Results OCI has been reported in several high-risk groups, especially in hemodialysis patients and subjects with cryptogenic liver disease. Furthermore, some studies have proposed a specific immune response for OCI in comparison with chronic hepatitis C (CHC). Conclusions With a clinical history of approximately 11 years, occult HCV infection can be considered an occult type of CHC. Evidences suggest that considering OCI in these high-risk groups seems to be necessary. We suggest that alternative diagnostic tests should be applied and that there is a need for the participation of all countries to determine the epidemiology of this type of HCV infection. Additionally, evaluating OCI in blood transfusion centers and in patients who receive large amounts of blood and clotting factors, such as patients with hemophilia, should be performed in future projects. PMID:26734487

Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 in Japanese patients with chronic hepatitis.

PubMed

Nishioka, M; Morshed, S A; Parveen, S; Kono, K; Matsuoka, H; Manns, M P

1997-12-01

Auto-antibodies specific to various antigens in chronic hepatitis (CH) have been detected but their specificities and implications were uncertain. The aims of the present study were to investigate the frequency and the significance of seropositivity of antibodies to P450IID6 or liver/kidney microsome 1 (LKM1), soluble liver antigen (SLA), pyruvate dehydrogenase (PDH) and branched-chain keto acid dehydrogenase (BCKD) in 188 Japanese patients with different forms of CH by western blot or enzyme immunoassay (EIA). Anti-LKM1 was also measured by indirect immunofluorescent test. Anti-P450IID6 was found in 6/188 (3.2%) CH patients including 5/104 (4.8%) with hepatitis C virus (C) infection and 1/12 (8.3%) CH-C patients with antibodies to nuclear and smooth muscle antigens and hypergammaglobulinaemia (> 2.5 g/dL). This patient was the only one diagnosed with autoimmune hepatitis (AIH). All CH patients with hepatitis B (B), hepatitis non-B non-C (NBNC) and AIH were seronegative for anti-LKM1. Antibodies to soluble liver antigen were found in two of 188 (1%) patients, one with AIH and one with CH-B. Anti-BCKD-E2 but not anti-PDH-E2 was found in four patients (2.5%), one with AIH, two with CH-C, and one with NBNC. There was no obvious difference in age, sex ratio and laboratory findings in patients with or without anti-SLA and anti-BCKD-E2. Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 are uncommon in adult CH-C, CH-B, CH-NBNC and AIH patients in Japan. Some of these patients positive for auto-antibodies appear to have autoimmune features and might require a careful follow up. The heterogeneity of these antibodies in CH preclude further justification for subtyping of AIH by the presence of the distinct auto-antibodies.

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

PubMed Central

Chang, Ming-Ling; Kuo, Chia-Jung; Pao, Li-Heng; Hsu, Chen-Ming; Chiu, Cheng-Tang

2017-01-01

ABSTRACT Background: The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. Methods: A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri- and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Results: Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n = 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. Conclusions: During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR. PMID:28267407

Cytokine levels and histopathology in chronic hepatitis B and chronic hepatitis C.

PubMed

Akcam, Fusun Zeynep; Tigli, Arzu; Kaya, Onur; Ciris, Metin; Vural, Huseyin

2012-12-01

The changes in balance of cytokine profile may result in either recovery or persistence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. This study aims to reveal a possible correlation between cytokine levels, ie, tumor necrosis factor (TNF)-α; interferon-gamma (IFN-γ); interleukin (IL)-10, IL-18, and transforming growth factor-beta (TGF-β); and Ishak score or fibrosis in patients with chronic hepatitis B (CHB) or chronic hepatitis C (CHC). Fifty patients with CHB (n=25), CHC (n=25), and the control group of subjects with negative hepatitis B and C serology (n=30) were included in the study. Patients who did not agree to participate in the study were excluded. Serum cytokine levels were measured by ELISA. Liver biopsies from the patients were also taken for pathological analyses by the same pathologist. The serum levels of TNF-α, IL-10, and IL-18 in the hepatitis C group were significantly high compared with those of the control group (P=0.017, P=0.001, and P=0.004 respectively), but, only IL-10 levels in the hepatitis B group were significantly high (P=0.001). These groups did not show any significant difference with respect to IFN-γ or TGF-β levels. In patients with CHB or CHC, there was a significant correlation (P=0.000) between TNF-α and Ishak score or fibrosis; but no such correlation was found with IFN-γ, IL-10, IL-18, or TGF-β. Result of the current study indicated that cytokine activities were important indicators of clinical severity and progression of HBV- and HCV infections. Further investigations on possible effects of cytokines on hepatocellular damage and fibrosis should be done to arrange new immunopathological approaches to viral hepatitis.

BadR and BadM Proteins Transcriptionally Regulate Two Operons Needed for Anaerobic Benzoate Degradation by Rhodopseudomonas palustris

PubMed Central

Hirakawa, Hidetada; Hirakawa, Yuko; Greenberg, E. Peter

2015-01-01

The bacterium Rhodopseudomonas palustris grows with the aromatic acid benzoate and the alicyclic acid cyclohexanecarboxylate (CHC) as sole carbon sources. The enzymatic steps in an oxygen-independent pathway for CHC degradation have been elucidated, but it was unknown how the CHC operon (badHI aliAB badK) encoding the enzymes for CHC degradation was regulated. aliA and aliB encode enzymes for the conversion of CHC to cyclohex-1-enecarboxyl–coenzyme A (CHene-CoA). At this point, the pathway for CHC degradation merges with the pathway for anaerobic benzoate degradation, as CHene-CoA is an intermediate in both degradation pathways. Three enzymes, encoded by badK, badH, and badI, prepare and cleave the alicyclic ring of CHene-CoA to yield pimelyl-CoA. Here, we show that the MarR transcription factor family member, BadR, represses transcription of the CHC operon by binding near the transcription start site of badH. 2-Ketocyclohexane-1-carboxyl–CoA, an intermediate of CHC and benzoate degradation, interacts with BadR to abrogate repression. We also present evidence that the transcription factor BadM binds to the promoter of the badDEFGAB (Bad) operon for the anaerobic conversion of benzoate to CHene-CoA to repress its expression. Contrary to previous reports, BadR does not appear to control expression of the Bad operon. These data enhance our view of the transcriptional regulation of anaerobic benzoate degradation by R. palustris. PMID:25888170

Interaction between PNPLA3 I148M Variant and Age at Infection in Determining Fibrosis Progression in Chronic Hepatitis C

PubMed Central

Aghemo, Alessio; Cheroni, Cristina; D'Ambrosio, Roberta; Pedrazzini, Michele; Marabita, Francesco; Donnici, Lorena; Maggioni, Marco; Fargion, Silvia; Colombo, Massimo; De Francesco, Raffaele; Valenti, Luca

2014-01-01

Background and Aims The PNPLA3 I148M sequence variant favors hepatic lipid accumulation and confers susceptibility to hepatic fibrosis and hepatocellular carcinoma. The aim of this study was to estimate the effect size of homozygosity for the PNPLA3 I148M variant (148M/M) on the fibrosis progression rate (FPR) and the interaction with age at infection in chronic hepatitis C (CHC). Methods FPR was estimated in a prospective cohort of 247 CHC patients without alcohol intake and diabetes, with careful estimation of age at infection and determination of fibrosis stage by Ishak score. Results Older age at infection was the strongest determinant of FPR (p<0.0001). PNPLA3 148M/M was associated with faster FPR in individuals infected at older age (above the median, 21 years; −0.64±0.2, n = 8 vs. −0.95±0.3, n = 166 log10 FPR respectively; p = 0.001; confirmed for lower age thresholds, p<0.05), but not in those infected at younger age (p = ns). The negative impact of PNPLA3 148M/M on fibrosis progression was more marked in subjects at risk of altered hepatic lipid metabolism (those with grade 2–3 steatosis, genotype 3, and overweight; p<0.05). At multivariate analysis, PNPLA3 148M/M was associated with FPR (incremental effect 0.08±0.03 log10 fibrosis unit per year; p = 0.022), independently of several confounders, and there was a significant interaction between 148M/M and older age at infection (p = 0.025). The association between 148M/M and FPR remained significant even after adjustment for steatosis severity (p = 0.032). Conclusions We observed an interaction between homozygosity for the PNPLA3 I148M variant and age at infection in determining fibrosis progression in CHC patients. PMID:25171251

The Untold Story: Examining Ontario's Community Health Centres' Initiatives to Address Upstream Determinants of Health

PubMed Central

Collins, Patricia A.; Resendes, Sarah J.; Dunn, James R.

2014-01-01

Background: Unlike traditional primary care centres, part of the Community Health Centre (CHC) mandate is to address upstream health determinants. In Ontario, CHCs refer to these activities as Community Initiatives (CIs); yet, little is known about how CIs operate. The objective of this study was to examine the scope, resource requirements, partnerships, successes and challenges among selected Ontario CIs. Methods: We conducted qualitative interviews with 10 CHC staff members representing 11 CIs across Ontario. CIs were identified through an online inventory, recruited by e-mail and interviewed between March and June 2011. Results: Most CIs aim to increase community participation, while addressing social isolation and poverty. They draw minimal financial resources from their CHC, and employ highly skilled staff to support implementation. Most enlist support from various partners, and use numerous methods for community engagement. Successes include improved community relations, increased opportunities for education and employment and rewarding partnerships, while insufficient funding was a commonly identified challenge. Conclusions: Despite minimal attention from researchers and funders, our findings suggest that CIs play key capacity-building roles in vulnerable communities across Ontario, and warrant further investigation. PMID:25410693

Oral delivery of shRNA based on amino acid modified chitosan for improved antitumor efficacy.

PubMed

Zheng, Hao; Tang, Cui; Yin, Chunhua

2015-11-01

In this investigation, chitosan-histidine-cysteine (CHC) was engineered for oral delivery of Survivin short hairpin RNA (shRNA)-expressing plasmid DNA (shSur-pDNA) to promote hepatoma regression through integrating the advantages of histidine and cysteine to conquer serial cellular and systemic barriers. CHC could effectively encapsulate shSur-pDNA to form compact nanocomplexes (NC) at adequate weight ratios. Sequential modification with histidine and cysteine conferred CHC NC with the beneficial attributes for shRNA delivery including improved stability, facilitated internalization, promoted endosomal escape, increased nuclear localization, and GSH-responsive release, which contributed to their superior performance in terms of apoptosis promotion, proliferation inhibition, and Survivin down-regulation of tumor cells. More importantly, in hepatoma-bearing mice, orally delivered CHC NC overweighed chitosan counterparts with respect to suppressed Survivin expression, retarded tumor growth, and prolonged surviving time, owing to their above-mentioned merits in combination with enhanced intestinal permeation. Especially, rapid intracellular release of CHC NC with lower molecular weight of 30 kDa (CHC30 NC) might be responsible for the most satisfactory antitumor efficacy with tumor inhibition ratio (TIR) of 92.5%, which rendered CHC30 NC a promising vehicle for oral delivery of shRNA. This investigation would shed light on the deliberate design of oral shRNA delivery vehicles to mediate effective antitumor efficacy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Release from prey preservation behavior via prey switch allowed diversification of cuticular hydrocarbon profiles in digger wasps.

PubMed

Wurdack, Mareike; Polidori, Carlo; Keller, Alexander; Feldhaar, Heike; Schmitt, Thomas

2017-11-01

The cuticle of insects is covered by a layer of hydrocarbons (CHC), whose original function is the protection from desiccation and pathogens. However, in most insects CHC profiles are species specific. While this variability among species was largely linked to communication and recognition functions, additional selective forces may shape insect CHC profiles. Here, we show that in Philanthinae digger wasps (Crabronidae) the CHC profile coevolved with a peculiar brood-care strategy. In particular, we found that the behavior to embalm prey stored in the nest with hydrocarbons is adaptive to protect larval food from fungi in those species hunting for Hymenoptera. The prey embalming secretion is identical in composition to the alkene-dominated CHC profile in these species, suggesting that their profile is adaptively conserved for this purpose. In contrast, prey embalming is not required in those species that switched to Coleoptera as prey. Released from this chemical brood-care strategy, Coleoptera-hunting species considerably diversified their CHC profiles. Differential needs to successfully protect prey types used as larval food have thus driven the diversification of CHCs profiles of female Philanthinae wasps. To the best of our knowledge, this is the first evidence of a direct link between selection pressure for food preservation and CHC diversity. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Guillain-Barre syndrome associated with peginterferon alfa-2a for chronic hepatitis C: A case report

PubMed Central

Niazi, Mumtaz A; Azhar, Ashaur; Tufail, Kashif; Feyssa, Eyob L; Penny, Stephen F; McGregory, Marlene; Araya, Victor; Ortiz, Jorge A

2010-01-01

The recommended therapy for chronic hepatitis C (CHC) infection is the combination of a Pegylated interferon and Ribavirin. Almost all such patients on combination therapy experience one or more adverse events during the course of treatment. Significant neurological side effects are rare. A few cases of Bell’s Palsy, chronic inflammatory demyelinating polyneuropathy and even one case of acute demyelinating polyneuropathy with atypical features for Guillain-Barre syndrome (GBS) associated with Interferon therapy have been reported but no report of GBS with typical features has been published. We present a case report of typical GBS associated with Peginterferon alfa-2a and Ribavirin used for treatment of CHC infection. PMID:21160989

Presence of a Community Health Center and Uninsured Emergency Department Visit Rates in Rural Counties

PubMed Central

Rust, George; Baltrus, Peter; Ye, Jiali; Daniels, Elvan; Quarshie, Alexander; Boumbulian, Paul; Strothers, Harry

2009-01-01

CONTEXT Community health centers (CHCs) provide essential access to a primary care medical home for the uninsured, especially in rural communities with no other primary care safety net. CHCs could potentially reduce uninsured emergency department (ED) visits in rural communities. PURPOSE We compared uninsured ED visit rates between rural counties in Georgia which have a community health center clinic site vs. counties without a CHC presence. METHODS We analyzed data from 100% of ED visits occurring in 117 rural (non-metropolitan statistical area [MSA]) counties in Georgia from 2003-2005. Counties were classified as having a CHC presence if a federally funded (Section 330) community health center had a primary care delivery site in that county throughout the study period. The main outcome measure was uninsured ED visit rates among the uninsured (all-cause ED visits and visits for ambulatory care sensitive conditions). Poisson regression models were used to examine the relationship between ED rates and presence of a CHC. To assure that the effects were unique to the uninsured population, we ran similar analyses on insured ED visits. FINDINGS Counties without a community health center primary care clinic site had 33% higher rates of uninsured all-cause ED visits per 10,000 uninsured population compared with non-CHC counties (rate ratio=1.33, 95% CI=1.11-1.59). Higher ED visit rates remained significant (RR=1.21, 95% CI=1.02-1.42) after adjustment for percent of population below poverty level, percent black, and number of hospitals. Uninsured ED visit rates were also higher for various categories of diagnoses, but remained statistically significant on multivariate analysis only for ambulatory care sensitive conditions (adjusted RR=1.22, 95% CI=1.01-1.47). No such relationship was found for ED visit rates of insured patients (RR=1.06, 95% CI=0.92-1.22). CONCLUSIONS Absence of a community health center is associated with a substantial excess in uninsured ED visits in rural counties, an excess not seen for ED visit rates among the insured. PMID:19166556

Recent update of the 2017 Korean Association for the Study of the Liver (KASL) treatment guidelines of chronic hepatitis C: comparison of guidelines from other continents, 2017 AASLD/IDSA and 2016 EASL.

PubMed

Yeon, Jong Eun

2018-05-02

The paradigm for the treatment of chronic hepatitis C (CHC) has been changed due to the development of direct acting antivirals (DAAs) of hepatitis C virus (HCV). The high sustained virologic response rate and ease of administration makes the DAAs approach ideal to contribute to the complete eradication of HCV. Currently, treatment options for individual patients vary depending on the genotype or subtype of HCV, presence or absence of liver cirrhosis, previous experience of antiviral treatment or resistance associated substitutions. Because of drug avalilability, cost-effectiveness, preference, compliance and greater possibility of desirable effects and presumed patient-important outcomes may vary between countries, treatment options for individual patients are different. The review focuses on the comparing the current treatment options for CHC in other continents with the 2017 Korea Association for the Study of the Liver guidelines.

Striking cuticular hydrocarbon dimorphism in the mason wasp Odynerus spinipes and its possible evolutionary cause (Hymenoptera: Chrysididae, Vespidae)

PubMed Central

Herbertz, Sina; Kroiss, Johannes; Strohm, Erhard; Baur, Hannes; Niehuis, Oliver; Schmitt, Thomas

2015-01-01

Cleptoparasitic wasps and bees smuggle their eggs into the nest of a host organism. Here the larvae of the cleptoparasite feed upon the food provision intended for the offspring of the host. As cleptoparasitism incurs a loss of fitness for the host organism (offspring of the host fail to develop), hosts of cleptoparasites are expected to exploit cues that alert them to potential cleptoparasite infestation. Cuticular hydrocarbons (CHCs) could serve as such cues, as insects inevitably leave traces of them behind when entering a nest. By mimicking the host's CHC profile, cleptoparasites can conceal their presence and evade detection by their host. Previous studies have provided evidence of cleptoparasites mimicking their host's CHC profile. However, the impact of this strategy on the evolution of the host's CHC profile has remained unexplored. Here, we present results from our investigation of a host–cleptoparasite system consisting of a single mason wasp species that serves syntopically as the host to three cuckoo wasp species. We found that the spiny mason wasp (Odynerus spinipes) is able to express two substantially different CHC profiles, each of which is seemingly mimicked by a cleptoparasitic cuckoo wasp (i.e. Chrysis mediata and Pseudospinolia neglecta). The CHC profile of the third cuckoo wasp (Chrysis viridula), a species not expected to benefit from mimicking its host's CHC profile because of its particular oviposition strategy, differs from the two CHC profiles of its host. Our results corroborate the idea that the similarity of the CHC profiles between cleptoparasitic cuckoo wasps and their hosts are the result of chemical mimicry. They further suggest that cleptoparasites may represent a hitherto unappreciated force that drives the evolution of their hosts' CHCs. PMID:26674944

Treatment with pirfenidone for two years decreases fibrosis, cytokine levels and enhances CB2 gene expression in patients with chronic hepatitis C.

PubMed

Flores-Contreras, Lucia; Sandoval-Rodríguez, Ana S; Mena-Enriquez, Mayra G; Lucano-Landeros, Silvia; Arellano-Olivera, Inmaculada; Alvarez-Álvarez, Arnulfo; Sanchez-Parada, M Guadalupe; Armendáriz-Borunda, Juan

2014-07-27

The aim of this study was to assess whether two-years treatment with Pirfenidone influences necroinflammation, fibrosis and steatosis, serum levels of TGF-β1, IL-6, TNF-α and CB1 and CB2 gene expression, in patients with chronic hepatitis C (CHC). Twenty-eight patients out of 34 with CHC virus infection were enrolled in the study and received Pirfenidone (1200 mg/day) for 24 months. Six patients dropped out after 12 months of PFD. Liver biopsies and serum samples were obtained at the beginning and end of treatment. Modified HAI was calculated. CB1 and CB2 gene expression was correlated with fibrosis progression alongside with necroinflammation and steatosis. TGF-β1, IL-6, TNF-α and liver transaminases were measured in serum at two-months intervals. HCV genotype and viral load were also assessed. Quality of life was evaluated by SF36 questionnaires and the prognosis of disease was assessed with Child-Pugh score. The Wilcoxon test matched-pair signed ranks were used to analyze the outcomes. Intention to treat analyses were performed for biochemistry and clinical parameters. At the end of treatment, necroinflammation grading was reduced in an average of 3.2 points in 82% of patients (p < 0.05) and Ishak's fibrosis stage decreased 2-points average in 67% of patients (p < 0.05). Steatosis decreased in 61% of patients. IL-6 and TGF-β1 serum levels decreased significantly in 93% and 67% of patients (p < 0.05), respectively, while TNF-α diminished in 47% of patients. ALT and AST tended to normalize in 81% of patients; CB2 mRNA levels increased in 86% and CB1 expression diminished in 29% of patients. Both, quality of life and Child-Pugh score improvements were reported in all patients. Pirfenidone for two years benefits CHC patients and improves inflammation, fibrosis and steatosis in higher number of patients as previously shown for 12-months treatment with PFD. Additionally, PFD improved TGFβ1 and IL-6 levels and diminished liver expression of anti-fibrogenic receptor CB2. ClinicalTrials.gov identifier: NCT02161952. Protocol Registration Date: 06/11/2014.

Estimating chronic hepatitis C prognosis using transient elastography-based liver stiffness: A systematic review and meta-analysis.

PubMed

Erman, A; Sathya, A; Nam, A; Bielecki, J M; Feld, J J; Thein, H-H; Wong, W W L; Grootendorst, P; Krahn, M D

2018-05-01

Chronic hepatitis C (CHC) is a leading cause of hepatic fibrosis and cirrhosis. The level of fibrosis is traditionally established by histology, and prognosis is estimated using fibrosis progression rates (FPRs; annual probability of progressing across histological stages). However, newer noninvasive alternatives are quickly replacing biopsy. One alternative, transient elastography (TE), quantifies fibrosis by measuring liver stiffness (LSM). Given these developments, the purpose of this study was (i) to estimate prognosis in treatment-naïve CHC patients using TE-based liver stiffness progression rates (LSPR) as an alternative to FPRs and (ii) to compare consistency between LSPRs and FPRs. A systematic literature search was performed using multiple databases (January 1990 to February 2016). LSPRs were calculated using either a direct method (given the difference in serial LSMs and time elapsed) or an indirect method given a single LSM and the estimated duration of infection and pooled using random-effects meta-analyses. For validation purposes, FPRs were also estimated. Heterogeneity was explored by random-effects meta-regression. Twenty-seven studies reporting on 39 groups of patients (N = 5874) were identified with 35 groups allowing for indirect and 8 for direct estimation of LSPR. The majority (~58%) of patients were HIV/HCV-coinfected. The estimated time-to-cirrhosis based on TE vs biopsy was 39 and 38 years, respectively. In univariate meta-regressions, male sex and HIV were positively and age at assessment, negatively associated with LSPRs. Noninvasive prognosis of HCV is consistent with FPRs in predicting time-to-cirrhosis, but more longitudinal studies of liver stiffness are needed to obtain refined estimates. © 2017 John Wiley & Sons Ltd.

Heat stability of chaetoglobosins A and C.

PubMed

Fogle, M R; Douglas, D R; Jumper, C A; Straus, D C

2008-05-01

Chaetomium globosum is commonly found in water-damaged buildings and produces the mycotoxins chaetoglobosin A and chaetoglobosin C (Ch-A and Ch-C, respectively). While attempting to purify Ch-A and Ch-C, we observed that these mycotoxins were broken down after heating. The objective of this study was to determine the temperature and the amount of time necessary to break down Ch-A and Ch-C. We demonstrated that the amounts of Ch-A were significantly reduced when exposed to 75 degrees C for 24 h and 100 degrees C for 90, 120, or 150 min. Under the same conditions, the levels of Ch-C were also lower (although not significantly). At 175 degrees C, no Ch-A was detected after 15 min and Ch-C was significantly reduced after 30 min. Our findings will aid other researchers who work with these mycotoxins in the future.

The impact of pegylated interferon and ribavirin combination treatment on lipid metabolism and insulin resistance in chronic hepatitis C patients.

PubMed

Jung, Hee Jae; Kim, Young Seok; Kim, Sang Gyune; Lee, Yun Nah; Jeong, Soung Won; Jang, Jae Young; Lee, Sae Hwan; Kim, Hong Soo; Kim, Boo Sung

2014-03-01

Lipid profile and insulin resistance (IR) are associated with hepatitis C virus (HCV) and may predict the chronic hepatitis C (CHC) treatment response. The aim of this study was to determine the association between CHC treatment response and lipid profile and IR change during treatment. In total, 203 CHC patients were reviewed retrospectively between January 2005 and December 2011 at Soon Chun Hyang University Hospital. The lipid profile, homeostasis model for assessment (HOMA) of IR (HOMA-IR), and HOMA of β cells (HOMA-β) were evaluated before interferon plus ribavirin therapy (BTx), at the end of treatment (DTx), and 24 weeks after the end of treatment (ATx). A sustained virologic response (SVR) was achieved by 81% of all patients (49/60), 60% (n=36) of whom possessed genotype 1, with the remainder being non-genotype-1 (40%, n=24). Apart from age, which was significantly higher in the non-SVR group (SVR, 48.0 ± 11.2 years, mean ± SD; non-SVR, 56.6 ± 9.9 years; P<0.01), there were no significant differences in the baseline characteristics between the SVR and non-SVR groups. In the SVR group, low density lipoprotein-cholesterol (LDL-C) had significantly changed at DTx and ATx compared to BTx. In addition, HOMA-IR and HOMA-β were significantly changed at DTx in the SVR group. Among those with a high baseline insulin resistance (HOMA-IR >2.5), HOMA-IR was significantly changed at DTx in the SVR group. LDL-C appears to be associated with HCV treatment in SVR patients. Furthermore, eradication of HCV may improve whole-body IR and insulin hypersecretion, as well as high baseline insulin resistance (HOMA-IR >2.5).

The Woodcock-Johnson Tests of Cognitive Abilities III's Cognitive Performance Model: Empirical Support for Intermediate Factors within CHC Theory

ERIC Educational Resources Information Center

Taub, Gordon E.; McGrew, Kevin S.

2014-01-01

The Woodcock-Johnson Tests of Cognitive Ability Third Edition is developed using the Cattell-Horn-Carroll (CHC) measurement-theory test design as the instrument's theoretical blueprint. The instrument provides users with cognitive scores based on the Cognitive Performance Model (CPM); however, the CPM is not a part of CHC theory. Within the…

Increased soluble CD36 is linked to advanced steatosis in nonalcoholic fatty liver disease.

PubMed

García-Monzón, Carmelo; Lo Iacono, Oreste; Crespo, Javier; Romero-Gómez, Manuel; García-Samaniego, Javier; Fernández-Bermejo, Miguel; Domínguez-Díez, Agustín; Rodríguez de Cía, Javier; Sáez, Alicia; Porrero, José Luís; Vargas-Castrillón, Javier; Chávez-Jiménez, Enrique; Soto-Fernández, Susana; Díaz, Ainhoa; Gallego-Durán, Rocío; Madejón, Antonio; Miquilena-Colina, María Eugenia

2014-01-01

Soluble CD36 (sCD36) clusters with insulin resistance, but no evidence exists on its relationship with hepatic fat content. We determined sCD36 to assess its link to steatosis in nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) patients. Two hundred and twenty-seven NAFLD, eighty-seven CHC, and eighty-five patients with histologically normal liver (NL) were studied. Steatosis was graded by Kleiner's histological scoring system. Serum sCD36 and hepatic CD36 expression was assessed by immunoassay and immunohistochemistry, respectively. In NAFLD, serum sCD36 levels were significantly higher in simple steatosis than in NL (361.4 ± 286.4 vs. 173.9 ± 137.4 pg/mL, respectively; P < 0.001), but not in steatohepatitis (229.6 ± 202.5 pg/mL; P = 0.153). In CHC, serum sCD36 levels were similar regardless of the absence (428.7 ± 260.3 pg/mL) or presence of steatosis (387.2 ± 283.6 pg/mL; P = 0.173). A progressive increase in serum sCD36 values was found in NAFLD depending on the histological grade of steatosis (P < 0.001), but not in CHC (P = 0.151). Serum sCD36 concentrations were independently associated with advanced steatosis in NAFLD when adjusted by demographic and anthropometric features [odds ratio (OR), 1.001; 95% confidence interval (CI), 1.000 to 1.002; P = 0.021] and by metabolic variables (OR, 1.002; 95% CI, 1.000 to 1.003; P = 0.001). Interestingly, a significant correlation was observed between hepatic CD36 and serum sCD36 (ρ = 0.499, P < 0.001). Increased serum sCD36 is an independent factor associated with advanced steatosis in NAFLD. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

[Efficacy of combination therapy with pegylated-interferon alfa-2a plus ribavirin in autoantibody-positive chronic hepatitis C patients].

PubMed

Li, Ya-xin; Yang, Yan-jia; Yang, Mei; Chen, Li-yu; Lu, Jia-jie; Ma, Yuan-ji; Liu, Kai; Lei, Xue-zhong; Tang, Hong

2013-05-01

To evaluate the therapeutic efficacy of antiviral combination therapy with pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody-positive chronic hepatitis C (CHC) and to investigate the impact of the presence of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180 mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75 kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and 36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as HCV RNA load below the lower limit of detection at 24 weeks after EOT. Correlation between autoantibodies and treatment-induced reduced HCV RNA load was assessed by univariate analysis of variance or chi-squared tests. Autoantibodies were detected in 24 patients, which included 14 ANA-positive patients, five SMA-positive patients, three LKM1-positive patients, one patient with double-positivity for ANA and SSB, and one patient with double-positivity for ANA and LC-1. The autoantibody-positive patients and autoantibody-negative patients showed similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs. 82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively reduce the HCV RNA load in autoantibody-positive CHC patients; however, the presence of autoantibodies may not be an independent predictor of therapy outcome.

Low vitamin D levels are associated with impaired virologic response to PEGIFN + RBV therapy in HIV-hepatitis C virus coinfected patients.

PubMed

Mandorfer, Mattias; Reiberger, Thomas; Payer, Berit A; Ferlitsch, Arnulf; Breitenecker, Florian; Aichelburg, Maximilian C; Obermayer-Pietsch, Barbara; Rieger, Armin; Trauner, Michael; Peck-Radosavljevic, Markus

2013-01-14

Low 25-hydroxyvitamin D [25(OH)D] levels are commonly found in HIV-hepatitis C virus (HCV) coinfected patients and are associated with liver fibrosis. No association between 25(OH)D levels and response to pegylated interferon α-2a/2b plus ribavirin (PEGIFN + RBV) has yet been reported for HIV-HCV coinfected patients. Epidemiological characteristics, HIV and HCV infection parameters, liver biopsies, as well as data on virologic response was available in 65 patients who received chronic hepatitis C (CHC) therapy with PEGIFN + RBV within a prospective trial. 25(OH)D levels were retrospectively assessed using stored screening serum samples obtained within 35 days prior to CHC treatment. According to their 25(OH)D levels, patients were assigned to the normal (>30 ng/ml; D-NORM), the insufficiency (10-30 ng/ml; D-INSUFF), or the deficiency (<10 ng/ml; D-DEF) group. HCV-GT 1/4, high HCV-RNA load (>6 × 10 IU/ml), advanced liver fibrosis (METAVIR F3/F4), and IL28B rs12979860non-C/C were considered as established risk factors for treatment failure in HIV-HCV coinfected patients. Thirty-seven (57%) and 15 (23%) patients presented with D-INSUFF and D-DEF, respectively, whereas only 13 (20%) patients had normal 25(OH)D levels. Substantial differences in cEVR (D-NORM 92% vs. D-INSUFF 68% vs. D-DEF 47%; P = 0.008) and SVR (D-NORM 85% vs. D-INSUFF 60% vs. D-DEF 40%; P = 0.029) rates were observed between 25(OH)D subgroups. Especially in difficult-to-treat patients with multiple (three to four) established risk factors, low 25(OH)D levels were clearly associated with lower rates of SVR [patients without 25(OH)D deficiency 52% vs. D-DEF 0%; P = 0.012]. Low 25(OH)D levels may impair virologic response to PEGIFN + RBV therapy, especially in difficult-to-treat patients. Vitamin D supplementation should be considered and evaluated prospectively in HIV-HCV coinfected patients receiving CHC treatment.

DETERMINATION OF FERRITIN AND HEMOSIDERIN IRON IN PATIENTS WITH NORMAL IRON STORES AND IRON OVERLOAD BY SERUM FERRITIN KINETICS

PubMed Central

SAITO, HIROSHI; TOMITA, AKIHIRO; OHASHI, HARUHIKO; MAEDA, HIDEAKI; HAYASHI, HISAO; NAOE, TOMOKI

2012-01-01

ABSTRACT We attempted to clarify the storage iron metabolism from the change in the serum ferritin level. We assumed that the nonlinear decrease in serum ferritin was caused by serum ferritin increase in iron mobilization. Under this assumption, we determined both ferritin and hemosiderin iron levels by computer-assisted simulation of the row of decreasing assay-dots of serum ferritin in 11 patients with normal iron stores free of both iron deficiency and iron overload; chronic hepatitis C (CHC) and iron deficiency anemia after treatment, and 11 patients with iron overload; hereditary hemochromatosis (HH) and transfusion-dependent anemias (TD). We determined the iron removal rates of 20 and 17 mg/day by administering mean doses of deferasirox at 631 and 616 mg/day in 2 TD during the period of balance of iron addition and removal as indicated by the serum ferritin returned to the previous level. The ferritin-per-hemosiderin ratio was almost the same in both HH and CHC. This matched the localized hepatic hemosiderin deposition in CHC with normal iron stores. We detected the ferritin increased by utilizing the hemosiderin iron in iron removal and the ferritin reduced by transforming ferritin into hemosiderin in iron additions. The iron storing capacity of hemosiderin was limitless, while that of ferritin was suppressed when ferritin iron exceeded around 5 grams. We confirmed the pathway of iron from hemosiderin to ferritin in iron mobilization, and that from ferritin to hemosiderin in iron deposition. Thus, serum ferritin kinetics enabled us to be the first to clinically clarify storage iron metabolism. PMID:22515110

How to minimize children’s environmental tobacco smoke exposure: an intervention in a clinical setting in high risk areas

PubMed Central

2013-01-01

Background Despite the low prevalence of daily smokers in Sweden, children are still being exposed to environmental tobacco smoke (ETS), primarily by their smoking parents. A prospective intervention study using methods from Quality Improvement was performed in Child Health Care (CHC). The aim was to provide nurses with new methods for motivating and supporting parents in their efforts to protect children from ETS exposure. Method Collaborative learning was used to implement and test an intervention bundle. Twenty-two CHC nurses recruited 86 families with small children which had at least one smoking parent. Using a bundle of interventions, nurses met and had dialogues with the parents over a one-year period. A detailed questionnaire on cigarette consumption and smoking policies in the home was answered by the parents at the beginning and at the end of the intervention, when children also took urine tests to determine cotinine levels. Results Seventy-two families completed the study. Ten parents (11%) quit smoking. Thirty-two families (44%) decreased their cigarette consumption. Forty-five families (63%) were outdoor smokers at follow up. The proportion of children with urinary cotinine values of >6 ng/ml had decreased. Conclusion The intensified tobacco prevention in CHC improved smoking parents’ ability to protect their children from ETS exposure. PMID:23672646

Swedish Child Health Care nurses conceptions of overweight in children: a qualitative study.

PubMed

Isma, Gabriella E; Bramhagen, Ann-Cathrine; Ahlstrom, Gerd; Ostman, Margareta; Dykes, Anna-Karin

2012-06-14

Registered Sick Children's Nurses and District Nurses employed at Child Health Care centres are in a position to help prevent childhood overweight and obesity. Prevention of this challenging public health threat could be improved through having a better understanding of how this group of nurses perceives childhood obesity. The aim of this study was to elucidate the conceptions of childhood overweight, including obesity, among nurses working in Child Health Care. A qualitative study using a phenomenographic approach, based on open-ended interviews with 18 Child Health Care nurses (CHC-nurses) strategically selected from 17 Child Health Care Centres in the southern part of Sweden. Four categories of description emerged from the data: Perception of childhood overweight changes, Overweight in younger children a neglected concern, Overweight a delicate issue and Importance of family lifestyle. The participating CHC-nurses conceived overweight in children, primarily obesity in children to be an extensive and serious problem which affects children, families and the surrounding society. Overweight in children was further perceived as a consequence of their parent's lifestyle and their awareness of the problem, which was considered by the CHC-nurses as a sensitive and a provoking issue. It was also perceived that overweight in children is not taken seriously during the pre-school period and that concerns regarding overweight in younger children were mainly about the appearance and not the health of the child. The CHC-nurses perceived that the proportion of overweight children has increased, which Swedish society and the CHC-nurses have adapted to. This adaptation makes it difficult for CHC-nurses to define those children who are overweight. CHC-nurses provide a comprehensive and complex picture of childhood overweight, which includes several difficulties dealing with this issue. Attention to CHC-nurse's conceptions of overweight in children is important since it can affect the parent-nurse relationship and thereby the nurse's, as well as the parent's efforts to influence the children's weight. It is suggested that CHC- nurses should work with person centered counseling and empowerment concerning parent to child relations in cases involving overweight.

Predictive value of FIB-4 and APRI versus METAVIR on sustained virologic response in genotype 1 hepatitis C patients.

PubMed

Ferenci, Peter; Aires, Rodrigo; Beavers, Kimberly L; Curescu, Manuela; Abrão Ferreira, Paulo R; Gschwantler, Michael; Ion, Stefan; Larrey, Dominique; Maticic, Mojca; Puoti, Massimo; Schuller, János; Tornai, Istvan; Tusnádi, Anna; Messinger, Diethelm; Tatsch, Fernando; Horban, Andrzej

2014-01-01

Advanced liver fibrosis is a negative predictor of virologic response in genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive, costly, and carries some risk of complications. Using data from the prospective, international cohort study PROPHESYS, we assessed two alternative noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index (APRI), to predict virologic response in CHC patients. CHC genotype 1, monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40 KD)/ribavirin in accordance with country-specific legal and regulatory requirements and who had baseline METAVIR, FIB-4, and APRI scores (N = 1,592) were included in this analysis. Patients were stratified according to the baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C virus (HCV) RNA <50 IU/mL] by week 4 of treatment (rapid virologic response) and 24 weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline predictors of SVR were explored by multiple logistic regression, and the strength of the association between each fibrosis measure and SVR was evaluated. Both FIB-4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis. The association between FIB-4 and SVR (p < 0.1 × 10(-30)) was stronger than that between METAVIR (p = 3.86 × 10(-13)) or APRI (p = 5.48 × 10(-6)) and SVR. Baseline factors significantly associated with SVR included male gender, lower HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase ratio. The FIB-4 index provides a valuable, noninvasive measure of fibrosis and can be used to predict virologic response in patients treated with peginterferon alfa-2a (40  KD)/ribavirin.

Association of sustained virologic response with reduced progression to liver cirrhosis in elderly patients with chronic hepatitis C.

PubMed

Tseng, Chih-Wei; Chang, Ting-Tsung; Tzeng, Shinn-Jia; Hsieh, Yu-Hsi; Hung, Tsung-Hsing; Huang, Hsiang-Ting; Wu, Shu-Fen; Tseng, Kuo-Chih

2016-01-01

We studied the effect of sustained virologic response (SVR) after treatment with pegylated-interferon (PEG-IFN) plus ribavirin on the development of liver cirrhosis in elderly patients with chronic hepatitis C (CHC). This retrospective study enrolled 145 elderly CHC patients (aged ≥65 years) who were treatment-naïve and were treated with PEG-IFN plus ribavirin for 6 months between January 2005 and December 2011. Abdominal sonography was performed and liver biochemistry was studied at baseline, at the end of treatment, and every 3-6 months thereafter. The development of liver cirrhosis and related complications was evaluated at the follow-ups. The aspartate aminotransferase-to-platelet ratio index was used as a noninvasive maker for fibrosis. The mean patient age was 69.1±3.3 years, and the average follow-up time was 5.5 years (standard deviation: 2.5 years, range: 1.1-12.3 years). Ninety-five patients (65.5%) achieved SVR, and 26 (17.9%) discontinued treatment. Twenty-seven patients (18.6%) developed liver cirrhosis after treatment. Patients without SVR had significantly greater risk of liver cirrhosis than those with SVR (hazard ratio [HR]: 3.39, 95% confidence interval [CI]: 1.312-8.761, P=0.012). The difference in 3-year cumulative incidence of liver cirrhosis was 24.8% greater for patients without SVR (35.2%, 95% CI: 13.0-57.5, P=0.012) compared with those with SVR (10.4%, 95% CI: 3.1-17.7). There was a trend of a higher baseline aspartate aminotransferase-to-platelet ratio index score in patients who progressed to liver cirrhosis compared with those who did not progress (2.1±1.2 vs 1.6±1.3, P=0.055), but the difference failed to reach significance by Cox regression (adjusted HR: 1.285, 95% CI: 0.921-1.791, P=0.14). An SVR following PEG-IFN combination treatment can reduce the risk of liver cirrhosis in elderly CHC patients.

The availability of community health center services and access to medical care.

PubMed

Kirby, James B; Sharma, Ravi

2017-12-01

Community Health Centers (CHCs) funded by Section 330 of the Public Health Service Act are an essential part of the health care safety net in the US. The Patient Protection and Affordable Care Act expanded the program significantly, but the extent to which the availability of CHCs improve access to care in general is not clear. In this paper, we examine the associations between the availability of CHC services in communities and two key measures of ambulatory care access - having a usual source of care and having any office-based medical visits over a one year period. We pooled six years of data from the Medical Expenditure Panel Survey (2008-2013) and linked it to geographic data on CHCs from Health Resources and Services Administration's Health Center Program Uniform Data System. We also link other community characteristics from the Area Health Resource File and the Dartmouth Institute's data files. The associations between CHC availability and our access measures are estimated with logistic regression models stratified by insurance status. The availability of CHC services was positively associated with both measures of access among those with no insurance coverage. Additionally, it was positively associated with having a usual source of care among those with Medicaid and private insurance. These findings persist after controlling for key individual- and community-level characteristics. Our findings suggest that an enhanced CHC program could be an important resource for supporting the efficacy of expanded Medicaid coverage under the Affordable Care Act and, ultimately, improving access to quality primary care for underserved Americans. Published by Elsevier Inc.

Sorting nexin 9 recruits clathrin heavy chain to the mitotic spindle for chromosome alignment and segregation.

PubMed

Ma, Maggie P C; Robinson, Phillip J; Chircop, Megan

2013-01-01

Sorting nexin 9 (SNX9) and clathrin heavy chain (CHC) each have roles in mitosis during metaphase. Since the two proteins directly interact for their other cellular function in endocytosis we investigated whether they also interact for metaphase and operate on the same pathway. We report that SNX9 and CHC functionally interact during metaphase in a specific molecular pathway that contributes to stabilization of mitotic spindle kinetochore (K)-fibres for chromosome alignment and segregation. This function is independent of their endocytic role. SNX9 residues in the clathrin-binding low complexity domain are required for CHC association and for targeting both CHC and transforming acidic coiled-coil protein 3 (TACC3) to the mitotic spindle. Mutation of these sites to serine increases the metaphase plate width, indicating inefficient chromosome congression. Therefore SNX9 and CHC function in the same molecular pathway for chromosome alignment and segregation, which is dependent on their direct association.

Sorting Nexin 9 Recruits Clathrin Heavy Chain to the Mitotic Spindle for Chromosome Alignment and Segregation

PubMed Central

Ma, Maggie P. C.; Robinson, Phillip J.; Chircop, Megan

2013-01-01

Sorting nexin 9 (SNX9) and clathrin heavy chain (CHC) each have roles in mitosis during metaphase. Since the two proteins directly interact for their other cellular function in endocytosis we investigated whether they also interact for metaphase and operate on the same pathway. We report that SNX9 and CHC functionally interact during metaphase in a specific molecular pathway that contributes to stabilization of mitotic spindle kinetochore (K)-fibres for chromosome alignment and segregation. This function is independent of their endocytic role. SNX9 residues in the clathrin-binding low complexity domain are required for CHC association and for targeting both CHC and transforming acidic coiled-coil protein 3 (TACC3) to the mitotic spindle. Mutation of these sites to serine increases the metaphase plate width, indicating inefficient chromosome congression. Therefore SNX9 and CHC function in the same molecular pathway for chromosome alignment and segregation, which is dependent on their direct association. PMID:23861900

Genetic architecture of natural variation in cuticular hydrocarbon composition in Drosophila melanogaster.

PubMed

Dembeck, Lauren M; Böröczky, Katalin; Huang, Wen; Schal, Coby; Anholt, Robert R H; Mackay, Trudy F C

2015-11-14

Insect cuticular hydrocarbons (CHCs) prevent desiccation and serve as chemical signals that mediate social interactions. Drosophila melanogaster CHCs have been studied extensively, but the genetic basis for individual variation in CHC composition is largely unknown. We quantified variation in CHC profiles in the D. melanogaster Genetic Reference Panel (DGRP) and identified novel CHCs. We used principal component (PC) analysis to extract PCs that explain the majority of CHC variation and identified polymorphisms in or near 305 and 173 genes in females and males, respectively, associated with variation in these PCs. In addition, 17 DGRP lines contain the functional Desat2 allele characteristic of African and Caribbean D. melanogaster females (more 5,9-C27:2 and less 7,11-C27:2, female sex pheromone isomers). Disruption of expression of 24 candidate genes affected CHC composition in at least one sex. These genes are associated with fatty acid metabolism and represent mechanistic targets for individual variation in CHC composition.

Phenotypic Plasticity of Cuticular Hydrocarbon Profiles in Insects.

PubMed

Otte, Tobias; Hilker, Monika; Geiselhardt, Sven

2018-03-01

The insect integument is covered by cuticular hydrocarbons (CHCs) which provide protection against environmental stresses, but are also used for communication. Here we review current knowledge on environmental and insect-internal factors which shape phenotypic plasticity of solitary living insects, especially herbivorous ones. We address the dynamics of changes which may occur within minutes, but may also last weeks, depending on the species and conditions. Two different modes of changes are suggested, i.e. stepwise and gradual. A switch between two distinct environments (e.g. host plant switch by phytophagous insects) results in stepwise formation of two distinct adaptive phenotypes, while a gradual environmental change (e.g. temperature gradients) induces a gradual change of numerous adaptive CHC phenotypes. We further discuss the ecological and evolutionary consequences of phenotypic plasticity of insect CHC profiles by addressing the question at which conditions is CHC phenotypic plasticity beneficial. The high plasticity of CHC profiles might be a trade-off for insects using CHCs for communication. We discuss how insects cope with the challenge to produce and "understand" a highly plastic, environmentally dependent CHC pattern that conveys reliable and comprehensible information. Finally, we outline how phenotypic plasticity of CHC profiles may promote speciation in insects that rely on CHCs for mate recognition.

Design and optimization of a nanoprobe comprising amphiphilic chitosan colloids and Au-nanorods: Sensitive detection of human serum albumin in simulated urine

NASA Astrophysics Data System (ADS)

Jean, Ren-Der; Larsson, Mikael; Cheng, Wei-Da; Hsu, Yu-Yuan; Bow, Jong-Shing; Liu, Dean-Mo

2016-12-01

Metallic nanoparticles have been utilized as analytical tools to detect a wide range of organic analytes. In most reports, gold (Au)-based nanosensors have been modified with ligands to introduce selectivity towards a specific target molecule. However, in a recent study a new concept was presented where bare Au-nanorods on self-assembled carboxymethyl-hexanoyl chitosan (CHC) nanocarriers achieved sensitive and selective detection of human serum albumin (HSA) after manipulation of the solution pH. Here this concept was further advanced through optimization of the ratio between Au-nanorods and CHC nanocarriers to create a nanotechnology-based sensor (termed CHC-AuNR nanoprobe) with an outstanding lower detection limit (LDL) for HSA. The CHC-AuNR nanoprobe was evaluated in simulated urine solution and a LDL as low as 1.5 pM was achieved at an estimated AuNR/CHC ratio of 2. Elemental mapping and protein adsorption kinetics over three orders of magnitude in HSA concentration confirmed accumulation of HSA on the nanorods and revealed the adsorption to be completed within 15 min for all investigated concentrations. The results suggest that the CHC-AuNR nanoprobe has potential to be utilized for cost-effective detection of analytes in complex liquids.

Combined hormonal contraceptive use among women with known dyslipidemias: a systematic review of critical safety outcomes.

PubMed

Dragoman, Monica; Curtis, Kathryn M; Gaffield, Mary E

2016-09-01

Dyslipidemias represent a spectrum of lipid disorders that are important risk factors for cardiovascular disease. In addition, elevated triglycerides are known to be associated with pancreatitis. Though less clear, it is possible that dyslipidemias may also contribute to risk for venous thromboembolism (VTE). Ethinyl estradiol and progestogen, contained within combined hormonal contraception, are known to impact lipid metabolism. To evaluate from the literature whether use of combined hormonal contraception (CHC), including combined oral contraception (COC) pills, transdermal patch, vaginal ring or injectables, modifies the relative risk of acute myocardial infarction (MI), stroke, VTE or pancreatitis among women with known dyslipidemias and to determine if existing lipid abnormalities worsen with CHC use. PubMed and the Cochrane Library databases were searched for all articles in all languages published between inception and September 2014 relevant to dyslipidemia, CHC use and serious adverse events (MI, stroke, VTE or pancreatitis). The quality of each individual study was assessed using the system for grading evidence developed by the United States Preventive Services Task Force. From 306 articles identified by our search strategy, 3 articles met inclusion criteria. In a poor-quality case-control study, women with hypercholesterolemia but no COC use had an increased risk of MI (adjusted odds ratio [adj OR] 3.3, 95% confidence interval [CI] 1.6-6.8), as did women who used COCs but did not have hypercholesterolemia (adj OR 2.0, 95% CI 1.4-2.8), compared with non-COC users without hypercholesterolemia; women with both COC use and hypercholesterolemia had an adjusted OR of 24.7 (95% CI 5.6-108.5) compared with women with neither risk factor. A poor-quality cohort study examined COC users and reported that women with dyslipidemia had increased risk for VTE [crude risk ratio (RR) 1.39, 95% CI 1.04-1.85] and transient ischemic attacks or cerebrovascular accidents (CVAs) (RR 1.76, 95% CI 1.51-2.06) compared to those without dyslipidemia. Another poor-quality cohort study provided direct evidence on changes in lipid levels among COC users with dyslipidemia. A minority of women with elevated total cholesterol or triglyceride levels at baseline showed normal results (25% and 28%, respectively) after 6 cycles of COC use. No evidence regarding risks associated with use of other CHC methods was identified. No evidence was identified for the outcome of pancreatitis. Limited data from poor-quality observational studies suggest that women with known dyslipidemias using CHC may be at increased risk for MI and may experience a minimal increase in risk for CVA or VTE. No evidence was identified on risk for pancreatitis in this context. The impact of CHC exposure on the status of lipid abnormalities over time, an intermediate marker for disease, is also unclear. Given the significant limitations of this body of evidence, the importance of access to effective contraception and theoretical concerns raised about the use of CHCs by women with known dyslipidemias, additional rigorous studies are needed to best estimate true associations. Contraceptive decision making should include consideration of both the known and theoretical risks of a given CHC method, safety and acceptability of alternative contraceptive methods, and risks associated with unintended pregnancy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Neuroprotection of a Novel Cyclopeptide C*HSDGIC* from the Cyclization of PACAP (1–5) in Cellular and Rodent Models of Retinal Ganglion Cell Apoptosis

PubMed Central

Cheng, Huanhuan; Ding, Yong; Yu, Rongjie; Chen, Jiansu; Wu, Chunyun

2014-01-01

Purpose To investigate the protective effects of a novel cyclopeptide C*HSDGIC* (CHC) from the cyclization of Pituitary adenylate cyclase-activating polypeptide (PACAP) (1–5) in cellular and rodent models of retinal ganglion cell apoptosis. Methodology/Principal Findings Double-labeling immunohistochemistry was used to detect the expression of Thy-1 and PACAP receptor type 1 in a retinal ganglion cell line RGC-5. The apoptosis of RGC-5 cells was induced by 0.02 J/cm2 Ultraviolet B irradiation. MTT assay, flow cytometry, fluorescence microscopy were used to investigate the viability, the level of reactive oxygen species (ROS) and apoptosis of RGC-5 cells respectively. CHC attenuated apoptotic cell death induced by Ultraviolet B irradiation and inhibited the excessive generation of ROS. Moreover, CHC treatment resulted in decreased expression of Bax and concomitant increase of Bcl-2, as was revealed by western-blot analysis. The in vivo apoptosis of retinal ganglion cells was induced by injecting 50 mM N-methyl-D-aspartate (NMDA) (100 nmol in a 2 µL saline solution) intravitreally, and different dosages of CHC were administered. At day 7, rats in CHC+ NMDA-treated groups showed obvious aversion to light when compared to NMDA rats. Electroretinogram recordings revealed a marked decrease in the amplitudes of a-wave, b-wave, and photopic negative response due to NMDA damage. In retina receiving intravitreal NMDA and CHC co-treatment, these values were significantly increased. CHC treatment also resulted in less NMDA-induced cell loss and a decrease in the proportion of dUTP end-labeling-positive cells in ganglion cell line. Conclusions C*HSDGIC*, a novel cyclopeptide from PACAP (1–5) attenuates apoptosis in RGC-5 cells and inhibits NMDA-induced retinal neuronal death. The beneficial effects may occur via the mitochondria pathway. PACAP derivatives like CHC may serve as a promising candidate for neuroprotection in glaucoma. PMID:25286089

Differences in the reliance on cuticular hydrocarbons as sexual signaling and species discrimination cues in parasitoid wasps.

PubMed

Buellesbach, Jan; Vetter, Sebastian G; Schmitt, Thomas

2018-01-01

Cuticular hydrocarbons (CHC) have been documented to play crucial roles as species- and sex-specific cues in the chemical communication systems of a wide variety of insects. However, whether they are sufficient by themselves as the sole cue triggering sexual behavior as well as preference of con- over heterospecific mating partners is rarely assessed. We conducted behavioral assays in three representative species of parasitoid wasps (Hymenoptera: Pteromalidae) to determine their reliance on CHC as species-specific sexual signaling cues. We found a surprising degree of either unspecific or insufficient sexual signaling when CHC are singled out as recognition cues. Most strikingly, the cosmopolitan species Nasonia vitripennis , expected to experience enhanced selection pressure to discriminate against other co-occurring parasitoids, did not discriminate against CHC of a partially sympatric species from another genus, Trichomalopsis sarcophagae . Focusing on the latter species, in turn, it became apparent that CHC are even insufficient as the sole cue triggering conspecific sexual behavior, hinting at the requirement of additional, synergistic sexual cues particularly important in this species. Finally, in the phylogenetically and chemically most divergent species Muscidifurax uniraptor, we intriguingly found both CHC-based sexual signaling as well as species discrimination behavior intact although this species is naturally parthenogenetic with sexual reproduction only occurring under laboratory conditions. Our findings implicate a discrepancy in the reliance on and specificity of CHC as sexual cues in our tested parasitioid wasps. CHC profiles were not sufficient for unambiguous discrimination and preference behavior, as demonstrated by clear cross-attraction between some of our tested wasp genera. Moreover, we could show that only in T. sarcophagae , additional behavioral cues need to be present for triggering natural mating behavior, hinting at an interesting shift in signaling hierarchy in this particular species. This demonstrates the importance of integrating multiple, potentially complementary signaling modalities in future studies for a better understanding of their individual contributions to natural sexual communication behavior.

Imaging Features on Contrast-Enhanced Ultrasound and Clinical Characteristics of Hepatitis B Virus-Related Combined Hepatocellular-Cholangiocarcinoma: Comparison with Hepatitis B Virus-Related Hepatocellular Carcinoma.

PubMed

Ye, Jieyi; Xie, Xiaoyan; Liu, Baoxian; Zhang, Xiaoer; Wang, Wei; Huang, Xiaowen; Lu, Mingde; Huang, Guangliang

2017-11-01

The objective of this study was to compare the clinical characteristics and imaging features on contrast-enhanced ultrasound (CEUS) of hepatitis B virus (HBV)-related combined hepatocellular-cholangiocarcinoma (CHC) and hepatocellular carcinoma (HCC). Thirty-one pathologically proven CHCs were included and 31 HCCs were randomly selected as controls. Elevated carbohydrate antigen (CA) 19-9 alone and simultaneous elevation of α-fetoprotein and CA19-9 were more frequent in CHC than in HCC patients (p = 0.004 and 0.029, respectively). On CEUS, homogeneous, heterogeneous and peripheral irregular rim-like enhancement was illustrated in 8 (25.8%), 12 (38.7%) and 11 (35.5%) CHCs and in 6 (19.4%), 23 (74.1%) and 2 (6.5%) HCCs, respectively (p = 0.007). Multivariate logistic regression analysis revealed CA19-9 elevation (p = 0.011, odds ratio [OR] = 6.545) and peripheral irregular rim-like enhancement on CEUS (p = 0.017, OR = 7.718) were independent variables. A receiver operating characteristic curve was plotted and the area under the curve was 0.740. CHC should be watched for in HBV-infected patients with liver tumor manifesting peripheral irregular rim-like enhancement on CEUS, accompanied by CA19-9 elevation. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Regionalization of surface lipids in insects

PubMed Central

Wang, Yiwen; Yu, Zhitao; Zhang, Jianzhen; Moussian, Bernard

2016-01-01

Cuticular hydrocarbons (CHCs) play a critical role in the establishment of the waterproof barrier that prevents dehydration and wetting in insects. While rich data are available on CHC composition in different species, we know little about their distribution and organization. Here, we report on our studies of the surface barrier of the fruit fly Drosophila melanogaster applying a newly developed Eosin Y staining method. The inert Eosin Y penetrates different regions of the adult body at distinct temperatures. By contrast, the larval body takes up the dye rather uniformly and gradually with increasing temperature. Cooling down specimens to 25°C after incubation at higher temperatures restores impermeability. Eosin Y penetration is also sensitive to lipid solvents such as chloroform indicating that permeability depends on CHCs. As in D. melanogaster adult flies, Eosin Y penetration is regionalized in Tenebrio molitor larvae, whereas it is not in Locusta migratoria nymphs. Regionalization of the fly surface implies tissue-specific variation of the genetic or biochemical programmes of CHC production and deposition. The Eosin Y-based map of CHC distribution may serve to identify the respective factors that are activated to accommodate ecological needs. PMID:27170708

The Chinese medicine Kuan-Sin-Yin improves liver function in patients with chronic hepatitis C: A randomised and placebo-controlled trial.

PubMed

Liu, Chia-Yu; Ko, Pin-Hao; Yen, Hung-Rong; Cheng, Chen-Hung; Li, Yu-Hsien; Liao, Zih-Han; Hsu, Chung-Hua

2016-08-01

This study examined the effects of a traditional Chinese medicine decoction, Kuan-Sin-Yin (KSY), on patients with chronic hepatitis C (CHC) in a randomised and placebo-controlled clinical trial. This trial enrolled 70 subjects with CHC who were randomised into 2 groups each with 35 participants. In total, 29 participants in the therapeutic group took 100mL of the herbal decoction daily, whereas 28 in the control group took an herbal placebo with the same dose and frequency for the 6-week study. The primary outcomes were liver function and viral load. Secondary measurements included haematopoietic and biochemical profiles, safety parameters, and a quality of life survey. All measurements were collected at the beginning of the study and after 6 weeks. In within-group analysis, significant decreases of glutamate pyruvate transaminase (GPT) 31.7±75.2IU/L and glutamate oxaloacetate transaminase (GOT) 20.3±45.7IU/L were found in the KSY group (p=0.031 and 0.024, respectively). In the between-group analysis, KSY reduced serum GOT and GPT levels by more than 20IU/L (p=0.027 and 0.047, respectively). KSY also significantly decreased viral load by 0.3 log units (p=0.047). In addition, KSY significantly decreased serum triglyceride 16.9±27.5mg/dL (p=0.024). This study demonstrates that taking the KSY herbal decoction for 6 weeks improves liver function and serum triglyceride levels and is safe for patients with CHC. The potential long-term effects of KSY on lipid metabolism related hepatoprotection and viral clearance warrant further investigation. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Female choice for male cuticular hydrocarbon profile in decorated crickets is not based on similarity to their own profile.

PubMed

Steiger, S; Capodeanu-Nägler, A; Gershman, S N; Weddle, C B; Rapkin, J; Sakaluk, S K; Hunt, J

2015-12-01

Indirect genetic benefits derived from female mate choice comprise additive (good genes) and nonadditive genetic benefits (genetic compatibility). Although good genes can be revealed by condition-dependent display traits, the mechanism by which compatibility alleles are detected is unclear because evaluation of the genetic similarity of a prospective mate requires the female to assess the genotype of the male and compare it to her own. Cuticular hydrocarbons (CHCs), lipids coating the exoskeleton of most insects, influence female mate choice in a number of species and offer a way for females to assess genetic similarity of prospective mates. Here, we determine whether female mate choice in decorated crickets is based on male CHCs and whether it is influenced by females' own CHC profiles. We used multivariate selection analysis to estimate the strength and form of selection acting on male CHCs through female mate choice, and employed different measures of multivariate dissimilarity to determine whether a female's preference for male CHCs is based on similarity to her own CHC profile. Female mating preferences were significantly influenced by CHC profiles of males. Male CHC attractiveness was not, however, contingent on the CHC profile of the choosing female, as certain male CHC phenotypes were equally attractive to most females, evidenced by significant linear and stabilizing selection gradients. These results suggest that additive genetic benefits, rather than nonadditive genetic benefits, accrue to female mate choice, in support of earlier work showing that CHC expression of males, but not females, is condition dependent. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

Adaptive dynamics of cuticular hydrocarbons in Drosophila

PubMed Central

Rajpurohit, Subhash; Hanus, Robert; Vrkoslav, Vladimír; Behrman, Emily L.; Bergland, Alan O.; Petrov, Dmitri; Cvačka, Josef; Schmidt, Paul S.

2016-01-01

Cuticular hydrocarbons (CHCs) are hydrophobic compounds deposited on the arthropod cuticle that are of functional significance with respect to stress tolerance, social interactions, and mating dynamics. We characterized CHC profiles in natural populations of Drosophila melanogaster at five levels: across a latitudinal transect in the eastern U.S., as a function of developmental temperature during culture, across seasonal time in replicate years, and as a function of rapid evolution in experimental mesocosms in the field. Furthermore, we also characterized spatial and temporal change in allele frequencies for SNPs in genes that are associated with the production and chemical profile of CHCs. Our data demonstrate a striking degree of parallelism for clinal and seasonal variation in CHCs in this taxon; CHC profiles also demonstrate significant plasticity in response to rearing temperature, and the observed patterns of plasticity parallel the spatiotemporal patterns observed in nature. We find that these congruent shifts in CHC profiles across time and space are also mirrored by predictable shifts in allele frequencies at SNPs associated with CHC chain length. Finally, we observed rapid and predictable evolution of CHC profiles in experimental mesocosms in the field. Together, these data strongly suggest that CHC profiles respond rapidly and adaptively to environmental parameters that covary with latitude and season, and that this response reflects the process of local adaptation in natural populations of D. melanogaster. PMID:27718537

Identifying Successful Practices to Overcome Access to Care Challenges in Community Health Centers: A "Positive Deviance" Approach.

PubMed

Toscos, Tammy; Carpenter, Maria; Flanagan, Mindy; Kunjan, Kislaya; Doebbeling, Bradley N

2018-01-01

Despite health care access challenges among underserved populations, patients, providers, and staff at community health clinics (CHCs) have developed practices to overcome limited access. These "positive deviant" practices translate into organizational policies to improve health care access and patient experience. To identify effective practices to improve access to health care for low-income, uninsured or underinsured, and minority adults and their families. Seven CHC systems, involving over 40 clinics, distributed across one midwestern state in the United States. Ninety-two key informants, comprised of CHC patients (42%) and clinic staff (53%), participated in semi-structured interviews. Interview transcripts were subjected to thematic analysis to identify patient-centered solutions for managing access challenges to primary care for underserved populations. Transcripts were coded using qualitative analytic software. Practices to improve access to care included addressing illiteracy and low health literacy, identifying cost-effective resources, expanding care offerings, enhancing the patient-provider relationship, and cultivating a culture of teamwork and customer service. Helping patients find the least expensive options for transportation, insurance, and medication was the most compelling patient-centered strategy. Appointment reminders and confirmation of patient plans for transportation to appointments reduced no-show rates. We identified nearly 35 practices for improving health care access. These were all patient-centric, uncovered by both clinic staff and patients who had successfully navigated the health care system to improve access.

Specialty-care access for community health clinic patients: processes and barriers.

PubMed

Ezeonwu, Mabel C

2018-01-01

Community health clinics/centers (CHCs) comprise the US's core health-safety net and provide primary care to anyone who walks through their doors. However, access to specialty care for CHC patients is a big challenge. In this descriptive qualitative study, semistructured interviews of 37 referral coordinators of CHCs were used to describe their perspectives on processes and barriers to patients' access to specialty care. Analysis of data was done using content analysis. The process of coordinating care referrals for CHC patients is complex and begins with a provider's order for consultation and ends when the referring provider receives the specialist's note. Poverty, specialist and referral coordinator shortages, lack of insurance, insurance acceptability by providers, transport and clinic-location factors, lack of clinic-hospital affiliations, and poor communication between primary and specialty providers constitute critical barriers to specialty-care access for patients. Understanding the complexities of specialty-care coordination processes and access helps determine the need for comprehensive and uninterrupted access to quality health care for vulnerable populations. Guaranteed access to primary care at CHCs has not translated into improved access to specialty care. It is critical that effective policies be pursued to address the barriers and minimize interruptions in care, and to ensure continuity of care for all patients needing specialty care.

Association of diabetes and PNPLA3 genetic variants with disease severity of patients with chronic hepatitis C virus infection.

PubMed

Huang, Chung-Feng; Dai, Chia-Yen; Yeh, Ming-Lun; Huang, Ching-I; Tai, Chi-Ming; Hsieh, Meng-Hsuan; Liang, Po-Cheng; Lin, Yi-Hung; Hsieh, Ming-Yen; Yang, Hua-Ling; Huang, Jee-Fu; Lin, Zu-Yau; Chen, Shinn-Cherng; Yu, Ming-Lung; Chuang, Wan-Long

2015-03-01

Genetic variants of patatin-like phospholipase domain-containing 3 (PNPLA3) and diabetes are associated with liver disease severity, in patients with chronic hepatitis C (CHC) infection. We aimed at exploring their interaction in determining hepatitis C virus (HCV)-related liver fibrosis. The PNPLA3 genetic polymorphism at rs738409 was verified in 1077 biopsy-proven CHC patients. Other clinical variables, including diabetes status, were analysed for factors associated with bridging fibrosis. Patients with advanced liver fibrosis had higher proportions of the GG genotype (14.5% vs. 10.4%, p=0.06 in recessive model) and GG/GC genotype carriage (64.0% vs. 56.8%, p=0.03 in dominant model). Stepwise logistic regression analysis revealed that factors predictive of advanced liver fibrosis included age (odds ratio [OR]: 1.02, 95% confidence intervals [CI]: 1.008-1.037, p=0.002), diabetes (OR: 1.81, CI: 1.236-2.653, p=0.002), α-fetoprotein (OR: 1.006, CI: 1.001-1.01, p=0.01), platelet counts (OR: 1.009, CI: 1.006-1.012, p<0.001), and PNPLA3 rs738409 CG/GG genotype (OR: 1.34, CI: 1.006-1.785, p=0.046). When patients were grouped according to their diabetes status, the PNPLA3 genetic variants were associated with advanced liver fibrosis in diabetic patients only, but not in non-diabetic patients. The PNPLA3 gene was the most important predictive factor of bridging fibrosis in diabetic patients, using the recessive model (OR: 4.53, CI: 1.356-15.106, p=0.014) or the dominant model (OR: 2.20, CI: 1.026-4.734, p=0.04). Compared to non-diabetic patients, patients with the diabetes/GG genotype were more likely to have advanced liver fibrosis (OR: 8.79, CI: 2.889-26.719, p<0.001), followed by those with diabetes/non-GG genotype (OR: 1.55, CI: 1.048-2.286, p=0.03). The effect of PNPLA3 genetic variants in HCV-related advanced liver fibrosis was enhanced in diabetic patients. The strong genetic-environmental interaction contributed to the high risk of advanced liver disease in CHC patients. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Direct Acting Antiviral Agents in Korean Patients with Chronic Hepatitis C and Hemophilia Who Are Treatment-Naïve or Treatment-Experienced.

PubMed

Lee, Hyun Woong; Yoo, Ki Young; Won, Joung Won; Kim, Hyung Joon

2017-09-15

Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. Patients (n=30) were enrolled between September 2015 and April 2016. Twenty-six patients were genotype 1 (1b, n=21; 1a, n=5) and four patients were genotype 2a/2b. Among 21 patients with genotype 1b, Y93H resistance-associated variants (RAVs) were detected in three patients (14.3%). We evaluated sustained virologic response (SVRs) at 12 weeks, as well as relapse and safety. Five patients with genotype 1a and three patients with genotype 1b (RAV positive) received ledipasvir/sofosbuvir for 12 weeks. SVR12 rate was 100% (8/8). Eleven patients with genotype 1b were treatment-naïve and received daclatasvir plus asunaprevir for 24 weeks. SVR12 rate was 91% (10/11). One patient experienced viral breakthrough without RAV at 12 weeks. Seven treatment-experienced patients with genotype 1b received daclatasvir plus asunaprevir for 24 weeks. SVR12 rate was 85.7% (6/7). One patient experienced viral breakthrough with RAV (L31M, Y93H) at 12 weeks. Four patients with genotype 2a/2b received sofosbuvir plus ribavirin for 12 weeks. SVR12 rate was 100% (4/4). No serious adverse event-related discontinuations were noted. New direct acting antiviral treatment achieved high SVRs rates at 12 weeks in CHC patients with hemophilia without serious adverse events.

Combination of blood tests for significant fibrosis and cirrhosis improves the assessment of liver-prognosis in chronic hepatitis C.

PubMed

Boursier, J; Brochard, C; Bertrais, S; Michalak, S; Gallois, Y; Fouchard-Hubert, I; Oberti, F; Rousselet, M-C; Calès, P

2014-07-01

Recent longitudinal studies have emphasised the prognostic value of noninvasive tests of liver fibrosis and cross-sectional studies have shown their combination significantly improves diagnostic accuracy. To compare the prognostic accuracy of six blood fibrosis tests and liver biopsy, and evaluate if test combination improves the liver-prognosis assessment in chronic hepatitis C (CHC). A total of 373 patients with compensated CHC, liver biopsy (Metavir F) and blood tests targeting fibrosis (APRI, FIB4, Fibrotest, Hepascore, FibroMeter) or cirrhosis (CirrhoMeter) were included. Significant liver-related events (SLRE) and liver-related deaths were recorded during follow-up (started the day of biopsy). During the median follow-up of 9.5 years (3508 person-years), 47 patients had a SLRE and 23 patients died from liver-related causes. For the prediction of first SLRE, most blood tests allowed higher prognostication than Metavir F [Harrell C-index: 0.811 (95% CI: 0.751-0.868)] with a significant increase for FIB4: 0.879 [0.832-0.919] (P = 0.002), FibroMeter: 0.870 [0.812-0.922] (P = 0.005) and APRI: 0.861 [0.813-0.902] (P = 0.039). Multivariate analysis identified FibroMeter, CirrhoMeter and sustained viral response as independent predictors of first SLRE. CirrhoMeter was the only independent predictor of liver-related death. The combination of FibroMeter and CirrhoMeter classifications into a new FM/CM classification improved the liver-prognosis assessment compared to Metavir F staging or single tests by identifying five subgroups of patients with significantly different prognoses. Some blood fibrosis tests are more accurate than liver biopsy for determining liver prognosis in CHC. A new combination of two complementary blood tests, one targeted for fibrosis and the other for cirrhosis, optimises assessment of liver-prognosis. © 2014 John Wiley & Sons Ltd.

Assessment of liver fibrosis in chronic hepatitis: comparison of shear wave elastography and transient elastography.

PubMed

Paul, Shashi B; Das, Prasenjit; Mahanta, Mousumi; Sreenivas, Vishnubhatla; Kedia, Saurabh; Kalra, Nancy; Kaur, Harpreet; Vijayvargiya, Maneesh; Ghosh, Shouriyo; Gamanagatti, Shivanand R; Shalimar; Gupta, Siddhartha Dutta; Acharya, Subrat K

2017-12-01

To evaluate the diagnostic accuracy of shear wave elastography (SWE) and transient elastography (TE) in the evaluation of liver fibrosis in chronic hepatitis B (CHB) and C (CHC) patients taking liver biopsy as gold standard. Ethics committee approved this prospective cross-sectional study. Between October 2012 and December 2014, consecutive CHB/CHC patients fulfilling the inclusion criteria were included-age more than 18 years, informed written consent, willing and suitable for liver biopsy. SWE, TE, and biopsy were performed the same day. Liver stiffness measurement (LSM) cut-offs for various stages of fibrosis were generated for SWE and TE. AUC, sensitivity, specificity, and positive/negative predictive values were estimated individually or in combination. CH patients (n = 240, CHB 172, CHC 68), 176 males, 64 females, mean age 32.6 ± 11.6 years were enrolled. Mean LSM of patients with no histological fibrosis (F0) was 5.0 ± 0.7 and 5.1+1.4 kPa on SWE and TE, respectively. For differentiating F2 and F3-4 fibrosis on SWE, at 7.0 kPa cut-off, the sensitivity was 81.3% and specificity 77.6%. For TE, at 8.3 kPa cut-off, sensitivity was 81.8% and specificity 83.1%. For F3 vs. F4, SWE sensitivity was 83.3% and specificity 90.7%. At 14.8 kPa cut-off, TE showed similar sensitivity (83.3%) but specificity increased to 96.5%. Significant correlation between SWE and TE was observed (r = 0.33, p < 0.001). On combining SWE and TE, a drop in sensitivity with increased specificity for all stages of liver fibrosis occured. SWE is an accurate technique for evaluating liver fibrosis. SWE compares favorably with TE especially for predicting advanced fibrosis/cirrhosis. Combining SWE and TE further improves specificity.

Leptin Receptor Metabolism Disorder in Primary Chondrocytes from Adolescent Idiopathic Scoliosis Girls.

PubMed

Wang, Yun-Jia; Yu, Hong-Gui; Zhou, Zhen-Hai; Guo, Qiang; Wang, Long-Jie; Zhang, Hong-Qi

2016-07-20

To investigate the underlying mechanisms of low metabolic activity of primary chondrocytes obtained from girls with adolescent idiopathic scoliosis (AIS); AIS is a spine-deforming disease that often occurs in girls. AIS is associated with a lower bone mass than that of healthy individuals and osteopenia. Leptin was shown to play an important role in bone growth. It can also regulate the function of chondrocytes. Changes in leptin and Ob-R levels in AIS patients have been reported in several studies. The underlying mechanisms between the dysfunction of peripheral leptin signaling and abnormal chondrocytes remain unclear; The following parameters were evaluated in AIS patients and the control groups: total serum leptin levels; Ob-R expression in the plasma membrane of primary chondrocytes; JAK2 and STAT3 phosphorylation status. Then, we inhibited the lysosome and proteasome and knocked down clathrin heavy chain (CHC) expression in primary chondrocytes isolated from girls with AIS and evaluated Ob-R expression. We investigated the effects of leptin combined with a lysosome inhibitor or CHC knockdown in primary chondrocytes obtained from AIS patients; Compared with the controls, AIS patients showed similar total serum leptin levels, reduced JAK2 and STAT3 phosphorylation, and decreased cartilage matrix synthesis in the facet joint. Lower metabolic activity and lower membrane expression of Ob-R were observed in primary chondrocytes from the AIS group than in the controls. Lysosome inhibition increased the total Ob-R content but had no effect on the membrane expression of Ob-R or leptin's effects on AIS primary chondrocytes. CHC knockdown upregulated the membrane Ob-R levels and enhanced leptin's effects on AIS primary chondrocytes; The underlying mechanism of chondrocytes that are hyposensitive to leptin in some girls with AIS is low plasma membrane Ob-R expression that results from an imbalance between the rate of receptor endocytosis and the insertion of newly synthesized receptors into the membrane.

Cost-effectiveness and budget impact of interferon-free direct-acting antiviral-based regimens for hepatitis C treatment: the French case.

PubMed

Deuffic-Burban, S; Obach, D; Canva, V; Pol, S; Roudot-Thoraval, F; Dhumeaux, D; Mathurin, P; Yazdanpanah, Y

2016-10-01

We evaluated the cost-effectiveness and the budget impact of new DAA-based regimen use in France. A Markov model simulated chronic hepatitis C (CHC) treatment interventions with IFN-based and IFN-free regimens at stage of fibrosis ≥F3, ≥F2 or regardless of fibrosis stage, and treatment either with the least or the most expensive combination. It estimated quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). It also assessed the budget impact over 5 years of treating all CHC-screened patients, regardless of fibrosis, assuming ≤20 000 patients treated/year and priority to ≥F3. Sensitivity analyses were also conducted. For genotypes (G) 1-4, the initiation of IFN-free regardless of fibrosis was a cost-effective strategy compared to prior standard of care (SOC) initiated at stage F2: €40 400-88 300/QALY gained in G1; similar results were obtained for patients infected with G4. Considering G2-3, the most cost-effective strategy was IFN-based regimens regardless of fibrosis compared to prior SOC initiated at stage F2: €21 300 and €19 400/QALY gained, respectively; the strategy with IFN-free regimens being more effective but not cost-effective at current costs. The budget impact of treating all CHC-screened patients over 5 years would range between 3.5 and 7.2 billion €, depending on whether one considers the least or the most expensive combination of new DAAs and whether one treats G2-3 with IFN-based or IFN-free new DAAs. In France, treatment initiation with new DDAs regardless of fibrosis stage is cost-effective, but would add 3.5-7.2 billion € to an already overburdened medical care system. © 2016 John Wiley & Sons Ltd.

Premating isolation is determined by larval rearing substrates in cactophilic Drosophila mojavensis. IX. Host plant and population specific epicuticular hydrocarbon expression influences mate choice and sexual selection.

PubMed

Havens, J A; Etges, W J

2013-03-01

Sexual signals in cactophilic Drosophila mojavensis include cuticular hydrocarbons (CHCs), contact pheromones that mediate female discrimination of males during courtship. CHCs, along with male courtship songs, cause premating isolation between diverged populations, and are influenced by genotype × environment interactions caused by different host cacti. CHC profiles of mated and unmated adult flies from a Baja California and a mainland Mexico population of D. mojavensis reared on two host cacti were assayed to test the hypothesis that male CHCs mediate within-population female discrimination of males. In multiple choice courtship trials, mated and unmated males differed in CHC profiles, indicating that females prefer males with particular blends of CHCs. Mated and unmated females significantly differed in CHC profiles as well. Adults in the choice trials had CHC profiles that were significantly different from those in pair-mated adults from no-choice trials revealing an influence of sexual selection. Females preferred different male CHC blends in each population, but the influence of host cactus on CHC variation was significant only in the mainland population indicating population-specific plasticity in CHCs. Different groups of CHCs mediated female choice-based sexual selection in each population suggesting that geographical and ecological divergence has the potential to promote divergence in mate communication systems. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Spatial distribution of neurons innervated by chandelier cells.

PubMed

Blazquez-Llorca, Lidia; Woodruff, Alan; Inan, Melis; Anderson, Stewart A; Yuste, Rafael; DeFelipe, Javier; Merchan-Perez, Angel

2015-09-01

Chandelier (or axo-axonic) cells are a distinct group of GABAergic interneurons that innervate the axon initial segments of pyramidal cells and are thus thought to have an important role in controlling the activity of cortical circuits. To examine the circuit connectivity of chandelier cells (ChCs), we made use of a genetic targeting strategy to label neocortical ChCs in upper layers of juvenile mouse neocortex. We filled individual ChCs with biocytin in living brain slices and reconstructed their axonal arbors from serial semi-thin sections. We also reconstructed the cell somata of pyramidal neurons that were located inside the ChC axonal trees and determined the percentage of pyramidal neurons whose axon initial segments were innervated by ChC terminals. We found that the total percentage of pyramidal neurons that were innervated by a single labeled ChC was 18-22 %. Sholl analysis showed that this percentage peaked at 22-35 % for distances between 30 and 60 µm from the ChC soma, decreasing to lower percentages with increasing distances. We also studied the three-dimensional spatial distribution of the innervated neurons inside the ChC axonal arbor using spatial statistical analysis tools. We found that innervated pyramidal neurons are not distributed at random, but show a clustered distribution, with pockets where almost all cells are innervated and other regions within the ChC axonal tree that receive little or no innervation. Thus, individual ChCs may exert a strong, widespread influence on their local pyramidal neighbors in a spatially heterogeneous fashion.

Competence training in evidence-based medicine for patients, patient counsellors, consumer representatives and health care professionals in Austria: a feasibility study.

PubMed

Berger, Bettina; Gerlach, Anja; Groth, Sylvia; Sladek, Ulla; Ebner, Katharina; Mühlhauser, Ingrid; Steckelberg, Anke

2013-01-01

Informed and shared decision-making require competences for both partners - healthcare professionals and patients. There is a lack of training courses in evidence-based medicine for patients and counsellors. We investigated feasibility, acceptability and the potential effects of a 2 x 2.5 days training course on critical health competences in patients, patient counsellors, consumer representatives and healthcare professionals in Austria. We adapted a previously developed curriculum for patient and consumer representatives. The adaptation comprised the specific needs of our target group in Austria and was founded on Carl Rogers' theory of person-centred education. For the formative evaluation a questionnaire was applied to address the domains: 1) organisational conditions (time and duration of the course, location, and information given in advance, registration); 2) assistance outside the courses; 3) teaching methods (performance of lecturers, teaching materials, structure of modules and blocks) and 4) satisfaction; 5) subjective assessment of competences. Participants evaluated the course, using a 5-point Likert scale. Long-term implementation was assessed using semi-structured interviews three to six months after the course. To estimate the increase in critical health competences we used the validated Critical Health Competence Test (CHC test). Eleven training courses were conducted including 142 participants: patients (n=21); self-help group representatives (n=17); professional counsellors (n=29); healthcare professionals (n=10); psychologists (n=8); teachers (n=10) and others (n=29). 97 out of 142 (68 %) participants returned the questionnaire. On average, participants strongly agreed or agreed to 1) organisational conditions: 71 % / 23 %; 2) assistance outside the courses: 96 % / 10 %; 3) teaching methods: 60 % / 28 %; and 4) satisfaction: 78 % / 20 %, respectively. Interviews showed that the training course raised awareness, activated and empowered participants. Participants passed the CHC test with mean person parameters of 463±111 (pre-test, n=120) and 547±135 (post-test, n=91). For participants who returned both tests (n=71) person parameters were comparable: pre-test 466±121 versus post-test 574±100, p<0,001. Training in evidence-based medicine for patients, patient counsellors, consumer representatives and healthcare professionals is feasible. For a broad implementation, train-the trainer courses and further research are needed. Copyright © 2012. Published by Elsevier GmbH.

Increased hepatocyte fas expression and apoptosis in HIV and hepatitis C virus coinfection.

PubMed

Macias, Juan; Japón, Miguel A; Sáez, Carmen; Palacios, Rosa B; Mira, José A; García-García, José A; Merchante, Nicolás; Vergara, Salvador; Lozano, Fernando; Gómez-Mateos, Jesús; Pineda, Juan A

2005-11-01

Chronic hepatitis C disease (CHC) follows an accelerated course in human immunodeficiency virus (HIV) coinfection. The reasons for this are unclear. Fas-mediated hepatocyte apoptosis is involved in the pathogenesis of hepatitis C virus (HCV) infection. We sought to compare the expression of Fas on hepatocytes and irreversible apoptosis of hepatocytes among patients with CHC with and without HCV/HIV coinfection. Fas-immunostained hepatocytes were semiquantified, and apoptotic hepatocytes were detected by staining caspase-cleaved cytokeratin 18 filaments and counted across the entire section of liver-biopsy specimens from HCV-infected patients with and without HCV/HIV coinfection. One hundred thirty-four HCV/HIV-coinfected and 100 HCV-infected patients were included. HCV/HIV coinfection was associated with both diffuse distribution of Fas-stained hepatocytes (adjusted odds ratio [AOR], 7.4 [95% confidence interval {CI}, 3.8-14.4]) and with apoptotic hepatocyte counts greater than the median (AOR, 2.5 [95% CI, 1.5-4.5]). In HCV/HIV-coinfected patients, CD4+ cell nadir<200 cells/mL was associated with both Fas expression (AOR, 2.9 [95% CI, 1.3-6.8]) and hepatocyte apoptosis (AOR, 2.3 [95% CI, 1.1-4.9]). HCV/HIV-coinfected patients show higher levels of hepatocytes expressing Fas and undergoing irreversible apoptosis than do HCV-infected patients. However, low CD4+ cell nadirs in coinfected patients are associated with hepatocyte Fas expression and apoptosis.

Kinetics of OH- and Cl-initiated oxidation of CH2dbnd CHC(O)O(CH2)2CH3 and CH2dbnd CHCH2C(O)O(CH2)2CH3 and fate of the alkoxy radicals formed

NASA Astrophysics Data System (ADS)

Rivela, Cynthia; Blanco, María B.; Teruel, Mariano A.

2016-05-01

Rate coefficients of the reactions of OH and Cl radicals with vinyl and allyl butyrate were determined for the first time at 298 K and 1 atm using the relative method to be (in cm3 molecule-1 s-1): k1(OH + CH2dbnd CHC(O)O(CH2)2CH3) = (2.61 ± 0.31) × 10-11, k2(Cl + CH2dbnd CHC(O)O(CH2)2CH3) = (2.48 ± 0.89) × 10-10, k3(OH + CH2dbnd CHCH2C(O)O(CH2)2CH3) = (2.89 ± 0.31) × 10-11, and k4(Cl + CH2dbnd CHCH2C(O)O(CH2)2CH3) = (2.25 ± 0.96) × 10-10. Reactivity trends and atmospheric lifetimes of esters are presented. Additionally, a product study shown butyric acid and polifunctional products for the reactions of vinyl and allyl butyrate, respectively and general mechanism is proposed.

Regionalization of surface lipids in insects.

PubMed

Wang, Yiwen; Yu, Zhitao; Zhang, Jianzhen; Moussian, Bernard

2016-05-11

Cuticular hydrocarbons (CHCs) play a critical role in the establishment of the waterproof barrier that prevents dehydration and wetting in insects. While rich data are available on CHC composition in different species, we know little about their distribution and organization. Here, we report on our studies of the surface barrier of the fruit fly Drosophila melanogaster applying a newly developed Eosin Y staining method. The inert Eosin Y penetrates different regions of the adult body at distinct temperatures. By contrast, the larval body takes up the dye rather uniformly and gradually with increasing temperature. Cooling down specimens to 25°C after incubation at higher temperatures restores impermeability. Eosin Y penetration is also sensitive to lipid solvents such as chloroform indicating that permeability depends on CHCs. As in D. melanogaster adult flies, Eosin Y penetration is regionalized in Tenebrio molitor larvae, whereas it is not in Locusta migratoria nymphs. Regionalization of the fly surface implies tissue-specific variation of the genetic or biochemical programmes of CHC production and deposition. The Eosin Y-based map of CHC distribution may serve to identify the respective factors that are activated to accommodate ecological needs. © 2016 The Author(s).

Achieving excellence in community health centers: implications for health reform.

PubMed

Gurewich, Deborah; Capitman, John; Sirkin, Jenna; Traje, Diana

2012-02-01

Existing studies tell us little about care quality variation within the community health center (CHC) delivery system. They also tell us little about the organizational conditions associated with CHCs that deliver especially high quality care. The purpose of this study was to examine the operational practices associated with a sample of high performing CHCs. Qualitative case studies of eight CHCs identified as delivering high-quality care relative to other CHCs were used to examine operational practices, including systems to facilitate care access, manage patient care, and monitor performance. Four common themes emerged that may contribute to high performance. At the same time, important differences across health centers were observed, reflecting differences in local environments and CHC capacity. In the development of effective, community-based models of care, adapting care standards to meet the needs of local conditions may be important.

Estimating the scale of chronic hepatitis C virus infection in the EU/EEA: a focus on migrants from anti-HCV endemic countries.

PubMed

Falla, A M; Ahmad, A A; Duffell, E; Noori, T; Veldhuijzen, I K

2018-01-16

Increasing the proportion diagnosed with and on treatment for chronic hepatitis C (CHC) is key to the elimination of hepatitis C in Europe. This study contributes to secondary prevention planning in the European Union/European Economic Area (EU/EEA) by estimating the number of CHC (anti-HCV positive and viraemic) cases among migrants living in the EU/EEA and born in endemic countries, defining the most affected migrant populations, and assessing whether country of birth prevalence is a reliable proxy for migrant prevalence. Migrant country of birth and population size extracted from statistical databases and anti-HCV prevalence in countries of birth and in EU/EEA countries derived from a systematic literature search were used to estimate caseload among and most affected migrants. Reliability of country of birth prevalence as a proxy for migrant prevalence was assessed via a systematic literature search. Approximately 11% of the EU/EEA adult population is foreign-born, 79% of whom were born in endemic (anti-HCV prevalence ≥1%) countries. Anti-HCV/CHC prevalence in migrants from endemic countries residing in the EU/EEA is estimated at 2.3%/1.6%, corresponding to ~580,000 CHC infections or 14% of the CHC disease burden in the EU/EEA. The highest number of cases is found among migrants from Romania and Russia (50-60,000 cases each) and migrants from Italy, Morocco, Pakistan, Poland and Ukraine (25-35,000 cases each). Ten studies reporting prevalence in migrants in Europe were identified; in seven of these estimates, prevalence was comparable with the country of birth prevalence and in three estimates it was lower. Migrants are disproportionately affected by CHC, account for a considerable number of CHC infections in EU/EEA countries, and are an important population for targeted case finding and treatment. Limited data suggest that country of birth prevalence can be used as a proxy for the prevalence in migrants.

Chemical Discrimination and Aggressiveness via Cuticular Hydrocarbons in a Supercolony-Forming Ant, Formica yessensis

PubMed Central

Kidokoro-Kobayashi, Midori; Iwakura, Misako; Fujiwara-Tsujii, Nao; Fujiwara, Shingo; Sakura, Midori; Sakamoto, Hironori; Higashi, Seigo; Hefetz, Abraham; Ozaki, Mamiko

2012-01-01

Background Territorial boundaries between conspecific social insect colonies are maintained through nestmate recognition systems. However, in supercolony-forming ants, which have developed an extraordinary social organization style known as unicoloniality, a single supercolony extends across large geographic distance. The underlying mechanism is considered to involve less frequent occurrence of intraspecific aggressive behaviors, while maintaining interspecific competition. Thus, we examined whether the supercolony-forming species, Formica yessensis has a nestmate recognition system similar to that of the multicolonial species, Camponotus japonicus with respect to the cuticular hydrocarbon-sensitive sensillum (CHC sensillum), which responds only to non-nestmate CHCs. We further investigated whether the sensory system reflects on the apparent reduced aggression between non-nestmates typical to unicolonial species. Methodology/Principal Findings F. yessensis constructs supercolonies comprising numerous nests and constitutes the largest supercolonies in Japan. We compared the within-colony or between-colonies’ (1) similarity in CHC profiles, the nestmate recognition cues, (2) levels of the CHC sensillar response, (3) levels of aggression between workers, as correlated with geographic distances between nests, and (4) their genetic relatedness. Workers from nests within the supercolony revealed a greater similarity of CHC profiles compared to workers from colonies outside it. Total response of the active CHC sensilla stimulated with conspecific alien CHCs did not increase as much as in case of C. japonicus, suggesting that discrimination of conspecific workers at the peripheral system is limited. It was particularly limited among workers within a supercolony, but was fully expressed for allospecific workers. Conclusions/Significance We demonstrate that chemical discrimination between nestmates and non-nestmates in F. yessensis was not clear cut, probably because this species has only subtle intraspecific differences in the CHC pattern that typify within a supercolony. Such an incomplete chemical discrimination via the CHC sensilla is thus an important factor contributing to decreased occurrence of intraspecific aggressive behavior especially within a supercolony. PMID:23115632

Temperature and pressure variations of d-d luminescence band maxima of bis(pyridylalkenolato)palladium(II) complexes with different ligand substituents: opposite-signed trends.

PubMed

Poirier, Stéphanie; Czympiel, Lisa; Bélanger-Desmarais, Nicolas; Mathur, Sanjay; Reber, Christian

2016-04-21

Luminescence spectra of two d(8)-configured bis(pyridylalkenolato)palladium(ii) complexes, [Pd{PyCHC(C3F7)O}2] and [Pd{PyCHC(CH3)O}2], are presented at variable temperature and pressure. Bands are assigned as d-d transitions. The heptafluoropropyl and methyl substituents on the ligands have different steric demands, influencing luminescence spectra. Broad bands with maxima at approximately 12 700 cm(-1) (790 nm) for ligands with heptafluoropropyl substituents and 12,100 cm(-1) (830 nm) for ligands with methyl substituents and widths of approximately 2100 cm(-1) for both complexes are observed at 80 K. Quenching of the luminescence is observed as temperature increases. The maxima of [Pd{PyCHC(C3F7)O}2] show a shift of -0.9 ± 0.1 cm(-1) K(-1) due to broadening of the spectra to lower energy. The luminescence maxima of [Pd{PyCHC(CH3)O}2] shift in the opposite direction by +7.2 ± 0.7 cm(-1) K(-1). Shifts with different signs are also obtained from variable-pressure luminescence spectra, with values of +13 ± 2 cm(-1) kbar(-1) and -15 ± 7 cm(-1) kbar(-1) for [Pd{PyCHC(C3F7)O}2] and [Pd{PyCHC(CH3)O}2], respectively. The pressure-induced decrease is unusual and likely caused by intermolecular interactions involving the palladium(ii) center and a vinylic proton of a neighboring complex.

Cuticular differences associated with aridity acclimation in African malaria vectors carrying alternative arrangements of inversion 2La

PubMed Central

2014-01-01

Background Principal malaria vectors in Africa, An. gambiae and An. coluzzii, share an inversion polymorphism on the left arm of chromosome 2 (2La/2L+a) that is distributed non-randomly in the environment. Genomic sequencing studies support the role of strong natural selection in maintaining steep clines in 2La inversion frequency along environmental gradients of aridity, and physiological studies have directly implicated 2La in heat and desiccation tolerance, but the precise genetic basis and the underlying behavioral and physiological mechanisms remain unknown. As the insect cuticle is the primary barrier to water loss, differences in cuticle thickness and/or epicuticular waterproofing associated with alternative 2La arrangements might help explain differences in desiccation resistance. Methods To test that hypothesis, two subcolonies of both An. gambiae and An. coluzzii were established that were fixed for alternative 2La arrangements (2La or 2L+a) on an otherwise homosequential and shared genetic background. Adult mosquitoes reared under controlled environmental conditions (benign or arid) for eight days post-eclosion were collected and analyzed. Measurements of cuticle thickness were made based on scanning electron microscopy, and cuticular hydrocarbon (CHC) composition was evaluated by gas chromatography–mass spectrometry. Results After removing the allometric effects of body weight, differences in mean cuticle thickness were found between alternative 2La karyotypes, but not between alternative environments. Moreover, the thicker cuticle of the An. coluzzii 2La karyotype was contrary to the known higher rate of water loss of this karyotype relative to 2L+a. On the other hand, quantitative differences in individual CHCs and overall CHC profiles between alternative karyotypes and environmental conditions were consistent with expectation based on previous physiological studies. Conclusions Our results suggest that alternative arrangements of the 2La inversion are associated with differences in cuticle thickness and CHC composition, but that only CHC composition appears to be relevant for desiccation resistance. Differences in the CHC composition were consistent with previous findings of a lower rate of water loss for the 2L+a karyotype at eight days post-eclosion, suggesting that CHC composition is an important strategy for maintaining water balance in this genetic background, but not for 2La. Despite a higher rate of water loss at eight days, higher body water content of the 2La karyotype confers a level of desiccation resistance equivalent to that of the 2L+a karyotype. PMID:24721548

Synergistic degradation of chlorinated hydrocarbons with microorganisms and zero valent iron

NASA Astrophysics Data System (ADS)

Schöftner, Philipp; Summer, Dorothea; Leitner, Simon; Watzinger, Andrea; Wimmer, Bernhard; Reichenauer, Thomas

2016-04-01

Sites contaminated with chlorinated hydrocarbons (CHC) are located mainly within build-up regions. Therefore in most cases only in-situ technologies without excavation of soil material can be used for remediation. This project examines a novel in-situ remediation method, in which the biotic degradation via bacteria is combined with abiotic degradation via zero-valent iron particles (ZVI). ZVI particles are injected into the aquifer where CHC-molecules are reductively dechlorinated. However Fe0 is also oxidized by reaction with water leading to generation of H2 without any CHC degradation. To achieve biotic degradation often strictly anaerobic strains of the bacteria Dehalococcoides are used. These bacteria can dechlorinate CHC by utilizing H2. By combining these processes the H2, produced during the anaerobic corrosion of Fe0, could be used by bacteria for further CHC degradation. Therefore the amount of used Fe0 and as a consequence also remediation costs could be reduced. Additionally the continuous supply of H2 could make the bacterial degradation more controllable. Different Fe0 particles (nano- and micro-scale) were tested for their perchloroethene (PCE) degradation rate and H2 production rate in microcosms. PCE-degradation rate by different bacterial cultures was investigated in the same microcosm system. In course of these experiments the 13C enrichment factors of the PCE degradation of the different particles and cultures were determined to enable the differentiation of biotic and abiotic degradation. Preliminary results showed, that the nano-scale particles reacted faster with PCE and water than their micro-scaled counterparts. The PCE degradation via micro-scaled particles lead to 13C enrichment factors in the range of -3,6 ‰ ± 0,6 to -9,5 ‰ ± 0,2. With one of the examined bacterial cultures a fast reduction of PCE to ethene was observed. Although PCE and TCE were completely degraded by this culture the metabolites DCE and VC could still be detected. Further microcosm experiments will be implemented by the time of the EGU General Assembly 2016. In the framework of these experiments other bacterial cultures and ZVI particles as well as the combination of biotic and abiotic dehalogenation will be investigated.

The pathophysiology of chronic noncommunicating hydrocephalus: lessons from continuous intracranial pressure monitoring and ventricular infusion testing.

PubMed

Eide, Per Kristian

2017-08-11

OBJECTIVE The pathophysiology of chronic noncommunicating hydrocephalus (ncHC) is poorly understood. This present study explored whether lessons about the pathophysiology of this clinical entity might be retrieved from results of overnight monitoring of pulsatile and static intracranial pressure (ICP) and ventricular infusion testing. METHODS The study cohort included adult patients (> 20 years of age) with chronic ncHC due to aqueductal stenosis in whom symptoms had lasted a minimum of 6 months. A reference cohort consisted of age- and sex-matched patients managed for communicating HC (cHC). Information about symptoms and clinical improvement following surgery was retrieved from a quality register, and results of overnight ICP recordings and ventricular infusion testing were retrieved from the hospital ICP database. RESULTS The cohort with ncHC consisted of 61 patients of whom 6 (10%) were managed conservatively, 34 (56%) by endoscopic third ventriculostomy (ETV), and 21 (34%) using ETV and subsequent shunt surgery. In patients responding to surgery, pulsatile ICP (mean ICP wave amplitude) was significantly increased to a similar magnitude in patients with ncHC and the reference cohort (cHC). Furthermore, intracranial compliance (ICC) was reduced in clinical responders. The results of ventricular infusion testing provided evidence that patients responding to ETV have impaired ventricular CSF absorption, while those requiring shunt placement after ETV present with impaired CSF absorption both in the intraventricular and extraventricular compartments. CONCLUSIONS The study may provide some lessons about the pathophysiology of chronic ncHC. First, increased pulsatile ICP and impaired ICC characterize patients with chronic ncHC who respond clinically to CSF diversion surgery, even though static ICP is not increased. Second, in patients responding clinically to ETV, impaired ventricular CSF absorption may be a key factor. Patients requiring shunt placement for clinical response appear to have both intraventricular and extraventricular CSF absorption failure. A subgroup of patients with ncHC due to aqueductal stenosis has normal ventricular CSF absorption and normal ICC and may not be in need of surgical CSF diversion.

The Impact of Ownership on Hospice Service Use, 2005–2011

PubMed Central

Stevenson, David G.; Grabowski, David C.; Keating, Nancy L.; Huskamp, Haiden A.

2016-01-01

Background/Objectives For-profit agencies comprise the majority of all United States hospice agencies, prompting concerns about aggressive enrollment practices and deficient care. Using detailed administrative data from 2005–2011, we sought to assess differences in patient populations and service use by hospice ownership, chain status, and agency size. Design/Participants Retrospective cohort study of 5,405,526 Medicare beneficiaries age 65+ enrolled in hospice during 2005–2011. Hospice use by ownership category (for-profit non-chain and chain, not-for-profit non-chain and chain, government) and agency size (0–50 patients, 51–200, 201–400, 401+). Mean length-of-use, stays ≤3 days, stays ending with live discharge, and decedents receiving no general inpatient care (GIP) or continuous home care (CHC) level hospice in the last 7 days of life. Results After adjusting for patient and geographic differences, for-profit non-chain and chain agencies had longer mean lengths-of-use (84.5 and 91.2 days, respectively) than other agency types (66.3–72.5 days); higher rates of live discharge (21.0% and 20.2% versus 14.6%–15.9%); and lower proportions of stays of ≤3 days (13.9% and 14.7% versus 16.6%–17.5%) (all p-values<0.001). The proportion of decedents not receiving GIP/CHC level care before death was highest among for-profit chains (75.9%) and lowest among not-for-profit non-chains (63.2%). Across ownership categories, smaller agencies had longer mean lengths-of-use, higher live discharge rates, lower rates of stays ≤3 days, and higher rates of patients receiving no GIP/CHC level care. Considerable variation in patient traits and unadjusted service use existed among the nation’s largest chains. Conclusion Although for-profit and not-for-profit hospice agencies differ along key dimensions, our results convey substantial heterogeneity within these categories, highlighting the need to consider factors such as agency size and chain affiliation in understanding variations in Medicare beneficiaries’ hospice care. PMID:27131344

In Vitro and In Vivo Biocompatibility Evaluation of Polyallylamine and Macromolecular Heparin Conjugates Modified Alginate Microbeads.

PubMed

Vaithilingam, Vijayaganapathy; Steinkjer, Bjørg; Ryan, Liv; Larsson, Rolf; Tuch, Bernard Edward; Oberholzer, Jose; Rokstad, Anne Mari

2017-09-15

Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC). The PAV-CHC strategy resulted in uniform and stable coatings with increased anti-clot activity and low cytotoxicity. In human whole blood, PAV coating at high dose (100 µg/ml) induced elevated complement, leukocyte CD11b and inflammatory mediators, and in Wistar rats increased fibrotic overgrowth. Coating of high dose PAV with CHC significantly reduced these responses. Low dose PAV (10 µg/ml) ± CHC and unmodified alginate microbeads showed low responses. That the human whole blood inflammatory reactions paralleled the host response shows a link between inflammatory potential and initial fibrotic response. CHC possessed anti-inflammatory activity, but failed to improve overall biocompatibility. We conclude that the human whole blood assay is an efficient first-phase screening model for inflammation, and a guiding tool in development of new generation microspheres for cell encapsulation therapy.

Aging modulates cuticular hydrocarbons and sexual attractiveness in Drosophila melanogaster

PubMed Central

Kuo, Tsung-Han; Yew, Joanne Y.; Fedina, Tatyana Y.; Dreisewerd, Klaus; Dierick, Herman A.; Pletcher, Scott D.

2012-01-01

SUMMARY Attractiveness is a major component of sexual selection that is dependent on sexual characteristics, such as pheromone production, which often reflect an individual’s fitness and reproductive potential. Aging is a process that results in a steady decline in survival and reproductive output, yet little is known about its effect on specific aspects of attractiveness. In this report we asked how aging impacts pheromone production and sexual attractiveness in Drosophila melanogaster. Evidence suggests that key pheromones in Drosophila are produced as cuticular hydrocarbons (CHC), whose functions in attracting mates and influencing behavior have been widely studied. We employed gas chromatography/mass spectrometry and laser desorption/ionization mass spectrometry to show that the composition of D. melanogaster CHC is significantly affected by aging in both sexes and that these changes are robust to different genetic backgrounds. Aging affected the relative levels of many individual CHC, and it shifted overall hydrocarbon profiles to favor compounds with longer chain lengths. We also show that the observed aging-related changes in CHC profiles are responsible for a significant reduction in sexual attractiveness. These studies illuminate causal links among pheromones, aging and attractiveness and suggest that CHC production may be an honest indicator of animal health and fertility. PMID:22323204

Effects of lifestyle changes including specific dietary intervention and physical activity in the management of patients with chronic hepatitis C – a randomized trial

PubMed Central

2013-01-01

Background In patients with chronic hepatitis C (CHC), obesity is involved in the pathogenesis of insulin resistance, fatty liver disease and progression of fibrosis. The objective of this study was to compare a normoglucidic low-calorie diet (NGLCD) with a low-fat diet (LFD) among participants with CHC. Aimed to measure the impact of dietary changes in reduction of insulin resistance, obesity but also in steatosis and fibrosis. Methods Randomized, controlled trial in three medical centers with assessments at baseline, 6 months and 12 months. Participants were patients over 35 years with chronic hepatitis C (n = 120) with BMI over 25 kg/m2. We evaluated the effects of NGLCD vs. LFD in weight management and metabolic improvement. The primary endpoint was to measure the impact of dietary changes through nutritional intervention in reversibility of insulin resistance, obesity, steatosis, and fibrosis. We performed anthropometric measurements, fasting glucose profile, serum lipids, liver profile, blood count at baseline, 6 and 12 months. Steatosis was evaluated using ultrasonographic criteria. Liver fibrosis was non-invasively assessed. Results After 6 and 12 months of intervention, both groups had a significant decrease in caloric consumption. At 6 months, weight loss was greater in the NGLCD group (−5.02 ± 3.43 kg vs. −4.1 ± 2.6 kg; p = 0.002) compared to the LFD group. At 1-year, however, weight loss was similar in both groups (−3.9 ± 3.3 kg vs. −3.1 ± 2.6 kg; p = 0.139). At 12 months, fasting plasma glucose, fasting plasma insulin, and HOMA-IR had significant improvements in both groups. With both diets aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT) decreased with significant differences; also there were significant improvements in AST/ALT ratio, Forns fibrosis index. The two diets were associated with reduction of both the prevalence and the severity of steatosis (all p < 0.001). At 12 months, total cholesterol, HDL-cholesterol, triglycerides improved in both groups (all p < 0.05). Conclusions The present study establishes the benefits of low-calorie diet and low-fat diet in management of patients with hepatitis C regarding improvement of insulin resistance, steatosis and also fibrosis. Overweight or obese patients with CHC undergoing a lifestyle intervention (specific dietary intervention and physical activity) for 1-year had significant improvements in body weight, lipid and hepatic profile. Trial registration PNCI2-3343/41008/2007 PMID:23941362

Community health center integration: experience in the State of Ohio.

PubMed

McAlearney, John S; McAlearney, Ann Scheck

2006-02-01

In the face of severe financial challenges and demands to improve quality and service to patients, many community health centers (CHCs) have aligned or integrated with other CHCs, physician groups, or hospitals. Yet the nature of and rationale for these organizational decisions are not well understood. Our research applied an organizational theoretical framework to test whether strategic adaptation theory or institutional theory best describes the integration activity of CHCs in Ohio. We collected primary data from case studies of seven CHCs selected for geographic representation and studied December 2000-January 2001. Semi-structured interviews and a case study database supported our chain of evidence. We found that CHC integration activity was substantial (five of seven CHCs integrated) and extremely varied. Consistent with strategic adaptation theory, we determined that CHC integration actions were predominantly center-specific, rational responses to environmental challenges and were initiated to improve operations or financial performance. Rarely did CHCs initiate major organizational change merely to mimic other CHC actions, as might have been expected of highly institutionalized organizations. Understanding the basis for CHCs' strategic decisions while monitoring financial health will remain critical as lawmakers and administrators work to develop policies that both maintain progress made and improve primary care access for the poor, the uninsured, and those with special health care needs served by these important safety net providers.

Secretory carcinoma of the breast and its histopathological mimics: value of markers for differential diagnosis.

PubMed

Osako, Tomo; Takeuchi, Kengo; Horii, Rie; Iwase, Takuji; Akiyama, Futoshi

2013-10-01

Secretory carcinoma (SC) is a rare histological type of breast cancer, and ETV6-NTRK3 gene fusion is highly specific to it. The differential diagnoses of SC include acinic cell carcinoma (ACCA) and cystic hypersecretory carcinoma (CHC), as well as invasive ductal carcinoma (IDC). For patients with these rare but distinctive histological subtypes, SC and its histopathological mimics should be differentiated from each other. However, differential markers have not yet been assessed systematically, and we aimed to identify and evaluate novel and existing markers. We reviewed 19 cases diagnosed initially as SC using integrated diagnostic techniques, including morphology, immunohistochemistry and molecular pathology, and validated promising markers in 445 breast cancers. We reclassified 19 formerly diagnosed 'SCs' into nine SCs, three ACCAs, three CHCs, three IDCs and one microglandular adenosis. We confirmed that ETV6-NTRK3 gene rearrangement and amylase positivity are good diagnostic markers for SC and ACCA, respectively. Vacuolar staining for adipophilin, positivity for α-lactalbumin and negativity for ETV6 rearrangement are diagnostic markers for CHC. In this study, we propose a panel of four markers (ETV6 rearrangement, amylase, α-lactalbumin and adipophilin) for distinguishing SC, ACCA, CHC and IDC. This simple but robust panel will serve pathologists well as a practical guide for reaching an appropriate diagnosis. © 2013 John Wiley & Sons Ltd.

Societies drifting apart? Behavioural, genetic and chemical differentiation between supercolonies in the yellow crazy ant Anoplolepis gracilipes.

PubMed

Drescher, Jochen; Blüthgen, Nico; Schmitt, Thomas; Bühler, Jana; Feldhaar, Heike

2010-10-22

In populations of most social insects, gene flow is maintained through mating between reproductive individuals from different colonies in periodic nuptial flights followed by dispersal of the fertilized foundresses. Some ant species, however, form large polygynous supercolonies, in which mating takes place within the maternal nest (intranidal mating) and fertilized queens disperse within or along the boundary of the supercolony, leading to supercolony growth (colony budding). As a consequence, gene flow is largely confined within supercolonies. Over time, such supercolonies may diverge genetically and, thus, also in recognition cues (cuticular hydrocarbons, CHC's) by a combination of genetic drift and accumulation of colony-specific, neutral mutations. We tested this hypothesis for six supercolonies of the invasive ant Anoplolepis gracilipes in north-east Borneo. Within supercolonies, workers from different nests tolerated each other, were closely related and showed highly similar CHC profiles. Between supercolonies, aggression ranged from tolerance to mortal encounters and was negatively correlated with relatedness and CHC profile similarity. Supercolonies were genetically and chemically distinct, with mutually aggressive supercolony pairs sharing only 33.1%±17.5% (mean ± SD) of their alleles across six microsatellite loci and 73.8%±11.6% of the compounds in their CHC profile. Moreover, the proportion of alleles that differed between supercolony pairs was positively correlated to the proportion of qualitatively different CHC compounds. These qualitatively differing CHC compounds were found across various substance classes including alkanes, alkenes and mono-, di- and trimethyl-branched alkanes. We conclude that positive feedback between genetic, chemical and behavioural traits may further enhance supercolony differentiation through genetic drift and neutral evolution, and may drive colonies towards different evolutionary pathways, possibly including speciation.

What are the Mechanisms Behind a Parasite-Induced Decline in Nestmate Recognition in Ants?

PubMed

Beros, Sara; Foitzik, Susanne; Menzel, Florian

2017-09-01

Social insects have developed sophisticated recognition skills to defend their nests against intruders. They do this by aggressively discriminating against non-nestmates with deviant cuticular hydrocarbon (CHC) signatures. Studying nestmate recognition can be challenging as individual insects do not only vary in their discriminatory abilities, but also in their motivation to behave aggressively. To disentangle the influence of signaling and behavioral motivation on nestmate recognition, we investigated the ant Temnothorax nylanderi, where the presence of tapeworm-infected nestmates leads to reduced nestmate recognition among uninfected workers. The parasite-induced decline in nestmate recognition could be caused by higher intra-colonial cue diversity as tapeworm-infected workers are known to exhibit a modified hydrocarbon signature. This in turn may broaden the neuronal template of their nestmates, leading to a higher tolerance towards alien conspecifics. To test this hypothesis, we exchanged infected ants between colonies and analyzed their impact on CHC profiles of uninfected workers. We demonstrate that despite frequent grooming, which should promote the transfer of recognition cues, CHC profiles of uninfected workers neither changed in the presence of tapeworm-infected ants, nor did it increase cue diversity among uninfected nestmates within or between colonies. However, CHC profiles were systematically affected by the removal of nestmates and addition of non-nestmates, independently from the ants' infection status. For example, when non-nestmates were present workers expressed more dimethyl alkanes and higher overall CHC quantities, possibly to achieve a better distinction from non-nestmates. Workers showed clear task-specific profiles with tapeworm-infected workers resembling more closely young nurses than older foragers. Our results show that the parasite-induced decline in nestmate recognition is not due to increased recognition cue diversity or altered CHC profiles of uninfected workers, but behavioral changes might explain tolerance towards intruders.

Combined use of nuclear phosphoprotein c-Myc and cellular phosphoprotein p53 for hepatocellular carcinoma detection in high-risk chronic hepatitis C patients.

PubMed

Attallah, A M; El-Far, M; Abdelrazek, M A; Omran, M M; Attallah, A A; Elkhouly, A A; Elkenawy, H M; Farid, K

2017-10-01

Hepatocellular carcinoma (HCC) is a multistage process resulting from various genetic changes. We aimed to determine nuclear phosphoprotein c-Myc and cellular phosphoprotein p53 expression and to evaluate their importance in HCC diagnosis. One hundred and twenty chronic hepatitis C (CHC) patients (60 non-HCC CHC patients and 60 HCC patients who had a single small (<5 cm) tumour) were recruited. The gene products of c-Myc and p53 were identified in liver tissues and serum samples using immunostaining, western blot and ELISA. Immunohistochemical detection of c-Myc and p53 with monospecific antibodies revealed intense and diffuse cytoplasmic staining patterns. Accumulated mutant proteins, released from tumour cells into the extracellular serum, were detected at 62 KDa, for c-Myc, and 53 KDa, for p53, using western blotting. In contrast to alpha feto-protein, there was a significant increase (p < 0.0001) in the positivity rate of c-Myc (86.7% vs. 6.7%) and p53 (78.3% vs. 8.3%) in the malignant vs. non-malignant patients. The parallel combination of c-Myc and p53 reach the absolute sensitivity (100%), for more accurate and reliable HCC detection (specificity was 87%). c-Myc and p53 are potential HCC diagnostic biomarkers, and convenient combinations of them could improve diagnostic accuracy of HCC.

Theory and Research: The Nexus of Clinical Inference

ERIC Educational Resources Information Center

Claeys, Joseph

2013-01-01

The practice of individual assessment has been moving toward the empirically derived Cattell-Horn-Carroll (CHC) theory of intellectual ability, which offers a hierarchical taxonomy of cognitive abilities. Current assessment tools provide varying adherence to operationalizing CHC theory, making clinical inference difficult. Expert consensus…

Effect of soy protein supplementation in patients with chronic hepatitis C: A randomized clinical trial

PubMed Central

Oliveira, Lucivalda PM; de Jesus, Rosangela P; Boulhosa, Ramona SSB; Mendes, Carlos Mauricio C; Gnoatto, Maria Cecilia; Lemaire, Denise C; Toralles, Maria Betania P; Cavalcante, Lourianne N; Lyra, Andre C; Lyra, Luiz GC

2012-01-01

AIM: To evaluate the effects of soy supplementation on insulin resistance, fatty liver and alanine aminotransferase (ALT) levels in non-diabetic patients with chronic hepatitis C (CHC). METHODS: In a prospective, randomized and single-blinded clinical trial, we compared patients with CHC who had casein as a supplement (n = 80) (control group), with patients who consumed a soy supplement diet (n = 80) [intervention group (IG)]. Both groups received 32 g/d of protein for 12 wk. RESULTS: Patients’ baseline features showed that 48.1% were overweight, 43.7% had abdominal fat accumulation, 34.7% had hepatic steatosis and 36.3% had an homeostasis model assessment index of insulin resistance (HOMA-IR) ≥ 3.0. Descriptive analysis showed that protein supplementation diet reduced hepatic steatosis in both groups; however, significant reductions in ALT levels occurred in the soy group. Multiple regression modeling indicated that in the presence of severe fibrosis (F3/F4), γ glutamyl transferase elevation and high density lipoprotein (HDL) reduction, the intervention group had 75% less chance of developing hepatic steatosis (OR= 0.25; 95% CI: 0.06-0.82) and 55% less chance of presenting with an ALT level ≥ 1.5 × the upper limit of normal (ULN) (OR = 0.45, 95% CI: 0.22-0.89). Soy treatment did not have any effect on insulin resistance (OR = 1.92; 95% CI: 0.80-4.83), which might be attributed to the fact that the HOMA-IR values at baseline in most of our patients were in the normal range. Advanced hepatic fibrosis, an ALT level > 1.5 × ULN and visceral fat were predictors of an HOMA-IR ≥ 3. The IG group had a reduced risk of an ALT level > 1.5 × ULN. An HOMA-IR ≥ 3.0 and HDL < 35 mg/dL were also risk factors for increased ALT. CONCLUSION: Soy supplementation decreased ALT levels and thus may improve liver inflammation in hepatitis C virus (HCV) patients; it also reduced hepatic steatosis in a subgroup of patients but did not change insulin resistance. It should be considered in the nutritional care of HCV patients. PMID:22611313

Transforming the urban food desert from the grassroots up: a model for community change.

PubMed

Lewis, LaVonna Blair; Galloway-Gilliam, Lark; Flynn, Gwendolyn; Nomachi, Jonathan; Keener, LaTonya Chavis; Sloane, David C

2011-01-01

Confronted by continuing health disparities in vulnerable communities, Community Health Councils (CHC), a nonprofit community-based organization in South Los Angeles, worked with the African Americans Building a Legacy of Health Coalition and research partners to develop a community change model to address the root causes of health disparities within the community's African American population. This article discusses how the CHC Model's development and application led to public policy interventions in a "food desert." The CHC Model provided a systematic approach to engaging impacted communities in support of societal level reforms, with the goal to influence health outcomes.

Corneal repair by human corneal keratocyte-reprogrammed iPSCs and amphiphatic carboxymethyl-hexanoyl chitosan hydrogel.

PubMed

Chien, Yueh; Liao, Yi-Wen; Liu, Dean-Mo; Lin, Heng-Liang; Chen, Shih-Jen; Chen, Hen-Li; Peng, Chi-Hsien; Liang, Chang-Min; Mou, Chung-Yuan; Chiou, Shih-Hwa

2012-11-01

Induced pluripotent stem cells (iPSCs) have promising potential in regenerative medicine, but whether iPSCs can promote corneal reconstruction remains undetermined. In this study, we successfully reprogrammed human corneal keratocytes into iPSCs. To prevent feeder cell contamination, these iPSCs were cultured onto a serum- and feeder-free system in which they remained stable through 30 passages and showed ESC-like pluripotent property. To investigate the availability of iPSCs as bioengineered substitutes in corneal repair, we developed a thermo-gelling injectable amphiphatic carboxymethyl-hexanoyl chitosan (CHC) nanoscale hydrogel and found that such gel increased the viability and CD44+proportion of iPSCs, and maintained their stem-cell like gene expression, in the presence of culture media. Combined treatment of iPSC with CHC hydrogel (iPSC/CHC hydrogel) facilitated wound healing in surgical abrasion-injured corneas. In severe corneal damage induced by alkaline, iPSC/CHC hydrogel enhanced corneal reconstruction by downregulating oxidative stress and recruiting endogenous epithelial cells to restore corneal epithelial thickness. Therefore, we demonstrated that these human keratocyte-reprogrammed iPSCs, when combined with CHC hydrogel, can be used as a rapid delivery system to efficiently enhance corneal wound healing. In addition, iPSCs reprogrammed from corneal surgical residues may serve as an alternative cell source for personalized therapies for human corneal damage. Copyright © 2012 Elsevier Ltd. All rights reserved.

Can an electronic glycaemic notebook associated with an insulin calculator improve HbA1c in diabetic patients on a multiple insulin injections regimen? A 26-week observational real-life study.

PubMed

Oriot, Philippe; Ponchon, Michel; Hermans, Michel P

2016-02-01

Automated insulin calculators (AICs) with carbohydrate counting (CHC) have been shown to be effective in improving glycated haemoglobin (HbA1c) levels. By contrast, use of AICs without CHC, with predetermined prandial insulin doses modified according to a correction factor and modulated as a function of glycaemia, has not yet been investigated. This comparative, retrospective, observational and non-randomized study took place over a 6-month period of routine clinical practice. It evaluated the use of Free-style InsuLinx® and Free-style Neo® Abbott Diabetes Care (AIC) in easy mode (no CHC). All patients performed a basal-prandial insulin dosing schedule, and were not educated as to how to determine carbohydrate intake. Changes in HbA1c and capillary blood glucose levels, insulin therapy, frequency of blood glucose tests and body weight were analyzed 6 months prior to inclusion (T-6), at the time of inclusion (T0) and 6 months later (T+6). From T-6 to T0 (period A), patients used a standard blood glucose meter and adjusted their insulin doses themselves, and from T0 to T+6 (period B), each patient was provided with an AIC on easy mode function. Of the 230 patients, 221 were retained at the end of the study (126 type 1 diabetes mellitus (T1DM) and 95 type 2 diabetes mellitus (T2DM)). At T-6, average (±standard error of mean) HbA1c level was 8.3 ± 0.1%; T1DM: 8.5 ± 0.1% and T2DM: 8.0 ± 0.1%, respectively. At T0, the average HbA1c level was 8.4 ± 0.1% (p = 0.02); T1DM: 8.5 ± 0.1% (ns) and T2DM: 8.2 ± 0.1% (p = 0.004). At T+6, with AIC in easy mode, average HbA1c level decreased significantly to 7.7 ± 0.1% (p < 0.0001); T1DM: 8.0 ± 0.1% (p < 0.0001) and T2DM: 7.5 ± 0.1% (p < 0.0001). At T+6, in all diabetics, blood glucose monitoring frequency increased by 0.4/day (p < 0.0001). Insulin correction amounted to 14% of changes in predetermined prandial insulin doses. Routine clinical use of an AIC without CHC improved self-management of blood glucose and on average, decreased HbA1c levels by 0.52% in T1DM and 0.80% in T2DM after 6 months.

Human Interferon Regulatory Factor 2 Gene Expression is Induced in Chronic Hepatitis C Virus Infection—A Possible Mode of Viral Persistence

PubMed Central

Mukherjee, Rathindra M; Bansode, Budhapriyavilas; Gangwal, Puja; Jakkampudi, Aparna; Reddy, Panyala B; Rao, Padaki N; Gupta, Rajesh; Reddy, D Nageshwar

2012-01-01

Background The interferon regulatory factors (IRFs) are a family of transcription factors known to be involved in the modulation of cellular responses to interferons (IFNs) and viral infection. While IRF-1 acts as a positive regulator, IRF-2 is known to repress IFN-mediated gene expression. The increase in the IRF-1/IRF-2 ratio is considered as an important event in the transcriptional activation of IFN-α gene toward development of the cellular antiviral response. Objective This study was performed to assess the expression of IRF mRNAs along with the expression level of IFN-α, its receptor (IFNAR-1), and the signal transduction factor (STAT-1) in treatment naive hepatitis C virus (HCV)-infected subjects. Materials Thirty-five chronically infected (CHC) patients and 39 voluntary blood donors as controls were included in the study. Quantification of HCV-RNA (ribonucleic acid) and genotyping were done by real-time polymerase chain reaction (PCR) and hybridization assays, respectively, using patient's serum/plasma. In both controls and patients, the serum level of IFN-α and IFN-α was measured by flow cytometry. Target gene expressions were studied by retro-transcription of respective mRNAs extracted from peripheral blood mononuclear cells (PBMCs) followed by PCR amplification and densitometry. Minus-strand HCV-RNA as a marker of viral replication in PBMCs was detected by an inhouse PCR assay. Results Both IRF-1 and IRF-2 genes were significantly enhanced in CHC than in control subjects (P < 0.001). A significant positive correlation (r2 = 0.386, P <0.01) was obtained between higher IRF-2 gene expression and increasing level of HCV-RNA. Chronically infected subjects (13%) harboring replicating HCV in PBMCs showed no significant differences in gene expressions than the subjects without HCV in PBMCs. Conclusion Our findings indicate that HCV modulates host immunity by inducing IRF-2 gene to counteract IRF-1-mediated IFN-α gene expression. Since the IRF-2 gene is known to encode oncogenic protein, the role of IRF-2 in CHC patients developing hepatocellular carcinoma warrants further studies. PMID:25755403

On the Interpretation of the CHC Factor Gc

ERIC Educational Resources Information Center

Kan, Kees-Jan; Kievit, Rogier A.; Dolan, Conor; van der Maas, Han

2011-01-01

On the one hand, the factors Gf and Gc in the Cattell-Horn-Carroll (CHC) model of intelligence are hypothesized to represent individual differences in unique psychological or biological capacities. On the other hand, they are interpreted as representing the theoretical variables fluid and crystallized intelligence in investment theory. With…

Case-mix adjustment and the comparison of community health center performance on patient experience measures.

PubMed

Johnson, M Laura; Rodriguez, Hector P; Solorio, M Rosa

2010-06-01

To assess the effect of case-mix adjustment on community health center (CHC) performance on patient experience measures. A Medicaid-managed care plan in Washington State collected patient survey data from 33 CHCs over three fiscal quarters during 2007-2008. The survey included three composite patient experience measures (6-month reports) and two overall ratings of care. The analytic sample includes 2,247 adult patients and 2,859 adults reporting for child patients. We compared the relative importance of patient case-mix adjusters by calculating each adjuster's predictive power and variability across CHCs. We then evaluated the impact of case-mix adjustment on the relative ranking of CHCs. Important case-mix adjusters included adult self-reported health status or parent-reported child health status, adult age, and educational attainment. The effects of case-mix adjustment on patient reports and ratings were different in the adult and child samples. Adjusting for race/ethnicity and language had a greater impact on parent reports than adult reports, but it impacted ratings similarly across the samples. The impact of adjustment on composites and ratings was modest, but it affected the relative ranking of CHCs. To ensure equitable comparison of CHC performance on patient experience measures, reports and ratings should be adjusted for adult self-reported health status or parent-reported child health status, adult age, education, race/ethnicity, and survey language. Because of the differential impact of case-mix adjusters for child and adult surveys, initiatives should consider measuring and reporting adult and child scores separately.

Changes in liver stiffness measurement using acoustic radiation force impulse elastography after antiviral therapy in patients with chronic hepatitis C.

PubMed

Chen, Sheng-Hung; Lai, Hsueh-Chou; Chiang, I-Ping; Su, Wen-Pang; Lin, Chia-Hsin; Kao, Jung-Ta; Chuang, Po-Heng; Hsu, Wei-Fan; Wang, Hung-Wei; Chen, Hung-Yao; Huang, Guan-Tarn; Peng, Cheng-Yuan

2018-01-01

To compare on-treatment and off-treatment parameters acquired using acoustic radiation force impulse elastography, the Fibrosis-4 (FIB-4) index, and aspartate aminotransferase-to-platelet ratio index (APRI) in patients with chronic hepatitis C (CHC). Patients received therapies based on pegylated interferon or direct-acting antiviral agents. The changes in paired patient parameters, including liver stiffness (LS) values, the FIB-4 index, and APRI, from baseline to sustained virologic response (SVR) visit (24 weeks after the end of treatment) were compared. Multiple regression models were used to identify significant factors that explained the correlations with LS, FIB-4, and APRI values and SVR. A total of 256 patients were included, of which 219 (85.5%) achieved SVR. The paired LS values declined significantly from baseline to SVR visit in all groups and subgroups except the nonresponder subgroup (n = 10). Body mass index (P = 0.0062) and baseline LS (P < 0.0001) were identified as independent factors that explained the LS declines. Likewise, the baseline FIB-4 (P < 0.0001) and APRI (P < 0.0001) values independently explained the declines in the FIB-4 index and APRI, respectively. Moreover, interleukin-28B polymorphisms, baseline LS, and rapid virologic response were identified as independent correlates with SVR. Paired LS measurements in patients treated for CHC exhibited significant declines comparable to those in FIB-4 and APRI values. These declines may have correlated with the resolution of necroinflammation. Baseline LS values predicted SVR.

Developing Electronic Health Record (EHR) Strategies Related to Health Center Patients' Social Determinants of Health.

PubMed

Gold, Rachel; Cottrell, Erika; Bunce, Arwen; Middendorf, Mary; Hollombe, Celine; Cowburn, Stuart; Mahr, Peter; Melgar, Gerardo

2017-01-01

"Social determinants of heath" (SDHs) are nonclinical factors that profoundly affect health. Helping community health centers (CHCs) document patients' SDH data in electronic health records (EHRs) could yield substantial health benefits, but little has been reported about CHCs' development of EHR-based tools for SDH data collection and presentation. We worked with 27 diverse CHC stakeholders to develop strategies for optimizing SDH data collection and presentation in their EHR, and approaches for integrating SDH data collection and the use of those data (eg, through referrals to community resources) into CHC workflows. We iteratively developed a set of EHR-based SDH data collection, summary, and referral tools for CHCs. We describe considerations that arose while developing the tools and present some preliminary lessons learned. Standardizing SDH data collection and presentation in EHRs could lead to improved patient and population health outcomes in CHCs and other care settings. We know of no previous reports of processes used to develop similar tools. This article provides an example of 1 such process. Lessons from our process may be useful to health care organizations interested in using EHRs to collect and act on SDH data. Research is needed to empirically test the generalizability of these lessons. © Copyright 2017 by the American Board of Family Medicine.

"Smoking in Children's Environment Test": a qualitative study of experiences of a new instrument applied in preventive work in child health care

PubMed Central

2011-01-01

Background Despite knowledge of the adverse health effects of passive smoking, children are still being exposed. Children's nurses play an important role in tobacco preventive work through dialogue with parents aimed at identifying how children can be protected from environmental tobacco smoke (ETS) exposure. The study describes the experiences of Child Health Care (CHC) nurses when using the validated instrument SiCET (Smoking in Children's Environment Test) in dialogue with parents. Method In an intervention in CHC centres in south-eastern Sweden nurses were invited to use the SiCET. Eighteen nurses participated in focus group interviews. Transcripts were reviewed and their contents were coded into categories by three investigators using the method described for focus groups interviews. Results The SiCET was used in dialogue with parents in tobacco preventive work and resulted in focused discussions on smoking and support for behavioural changes among parents. The instrument had both strengths and limitations. The nurses experienced that the SiCET facilitated dialogue with parents and gave a comprehensive view of the child's ETS exposure. This gave nurses the possibility of taking on a supportive role by offering parents long-term help in protecting their child from ETS exposure and in considering smoking cessation. Conclusion Our findings indicate that the SiCET supports nurses in their dialogue with parents on children's ETS exposure at CHC. There is a need for more clinical use and evaluation of the SiCET to determine its usefulness in clinical practice under varying circumstances. PMID:22172056

Reactivation of hepatitis B in patients of chronic hepatitis C with hepatitis B virus infection treated with direct acting antivirals.

PubMed

Yeh, Ming-Lun; Huang, Chung-Feng; Hsieh, Meng-Hsuan; Ko, Yu-Min; Chen, Kuan-Yu; Liu, Ta-Wei; Lin, Yi-Hung; Liang, Po-Cheng; Hsieh, Ming-Yen; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Ching-I; Huang, Jee-Fu; Kuo, Po-Lin; Dai, Chia-Yen; Yu, Ming-Lung; Chuang, Wan-Long

2017-10-01

Hepatitis B virus (HBV) may reactivate when treating chronic hepatitis C (CHC) with direct acting antivirals (DAA). We aim to investigate the risk of HBV reactivation during DAA therapy. Chronic hepatitis C patients receiving pan-oral DAA therapy from December 2013 to August 2016 were evaluated. Fifty-seven patients that had a past HBV infection (negative hepatitis B surface antigen [HBsAg] and positive hepatitis B core antibody) and seven patients that had a current HBV infection (positive HBsAg) were enrolled. Serum HBV and hepatitis C virus (HCV) markers were regularly measured. The endpoints were the HCV sustained virological response (SVR) and the HBV virological/clinical reactivation. The overall SVR 12 rate was 96.9%, and two patients, one with positive HBsAg, had a relapse of HCV. No episodes of HBV virological reactivation were observed among the patients with a past HBV infection. For the seven patients with a current HBV infection, HBV virological reactivation was found in four (57.1%) of the seven patients. Clinical reactivation of HBV was observed in one patient with pretreatment detectable HBV DNA and recovered after entecavir administration. For the other three patients with HBV virological reactivation, the reappearance of low level HBV DNA without clinical reactivation was observed. HBsAg levels demonstrated only small fluctuations in all the patients. There was a minimal impact of hepatitis B core antibody seropositivity on HCV efficacy and safety. For CHC patients with current HBV infection, the risk of HBV reactivation was present, and monitoring the HBV DNA level during therapy is warranted. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Primary prevention of childhood obesity through counselling sessions at Swedish child health centres: design, methods and baseline sample characteristics of the PRIMROSE cluster-randomised trial.

PubMed

Döring, Nora; Hansson, Lena M; Andersson, Elina Scheers; Bohman, Benjamin; Westin, Maria; Magnusson, Margaretha; Larsson, Christel; Sundblom, Elinor; Willmer, Mikaela; Blennow, Margareta; Heitmann, Berit L; Forsberg, Lars; Wallin, Sanna; Tynelius, Per; Ghaderi, Ata; Rasmussen, Finn

2014-04-09

Childhood obesity is a growing concern in Sweden. Children with overweight and obesity run a high risk of becoming obese as adults, and are likely to develop comorbidities. Despite the immense demand, there is still a lack of evidence-based comprehensive prevention programmes targeting pre-school children and their families in primary health care settings. The aims are to describe the design and methodology of the PRIMROSE cluster-randomised controlled trial, assess the relative validity of a food frequency questionnaire, and describe the baseline characteristics of the eligible young children and their mothers. The PRIMROSE trial targets first-time parents and their children at Swedish child health centres (CHC) in eight counties in Sweden. Randomisation is conducted at the CHC unit level. CHC nurses employed at the participating CHC received training in carrying out the intervention alongside their provision of regular services. The intervention programme, starting when the child is 8-9 months of age and ending at age 4, is based on social cognitive theory and employs motivational interviewing. Primary outcomes are children's body mass index and waist circumference at four years. Secondary outcomes are children's and mothers' eating habits (assessed by a food frequency questionnaire), and children's and mothers' physical activity (measured by accelerometer and a validated questionnaire), and mothers' body mass index and waist circumference. The on-going population-based PRIMROSE trial, which targets childhood obesity, is embedded in the regular national (routine) preventive child health services that are available free-of-charge to all young families in Sweden. Of the participants (n = 1369), 489 intervention and 550 control mothers (75.9%) responded to the validated physical activity and food frequency questionnaire at baseline (i.e., before the first intervention session, or, for children in the control group, before they reached 10 months of age). The food frequency questionnaire showed acceptable relative validity when compared with an 8-day food diary. We are not aware of any previous RCT, concerned with the primary prevention of childhood obesity through sessions at CHC that addresses healthy eating habits and physical activity in the context of a routine child health services programme. ISRCTN16991919.

The Cattell-Horn-Carroll Model of Cognition for Clinical Assessment

ERIC Educational Resources Information Center

Jewsbury, Paul A.; Bowden, Stephen C.; Duff, Kevin

2017-01-01

The Cattell-Horn-Carroll (CHC) model is a comprehensive model of the major dimensions of individual differences that underlie performance on cognitive tests. Studies evaluating the generality of the CHC model across test batteries, age, gender, and culture were reviewed and found to be overwhelmingly supportive. However, less research is available…

Adolescent Linkage to Care After a Large-scale Transfer From a Hospital-based HIV Clinic to the Public Sector in South Africa.

PubMed

Ramirez-Avila, Lynn; Regan, Susan; Cloete, Christie; Crankshaw, Tamaryn; Rabideau, Dustin J; Freedberg, Kenneth A; Parker, Robert A; Walensky, Rochelle P; Losina, Elena; Bassett, Ingrid V

2017-03-01

HIV clinics formerly supported by the President's Emergency Plan for AIDS Relief are transferring patients to public-sector clinics. We evaluated adolescent linkage to care after a large-scale transfer from a President's Emergency Plan for AIDS Relief-subsidized pediatric HIV clinic in Durban, South Africa. All adolescents (11-18 years) in care at a pediatric state-subsidized, hospital-based clinic (HBC) were transferred, from May to June 2012, to government sites [primary health care (PHC) clinic; community health center (CHC); and HBCs] or private clinics. Caregivers were surveyed 7-8 months after transfer to assess their adolescents' linkage to care and their reports were validated by clinic record audits in a subset of randomly selected clinics. Of the 309 (91%) caregivers reached, only 5 (2%) reported that their adolescent did not link. Of the 304 adolescents who linked, 105 (35%) were referred to a PHC, 73 (24%) to a CHC and 106 (35%) to a HBC. A total of 146 (48%) linked adolescents attended a different clinic than that assigned. Thirty-five (20%) of the 178 who linked and were assigned to a PHC or CHC ultimately attended a HBC. Based on clinic validation, the estimated transfer success was 88% (95% confidence interval: 77%-97%). The large majority of adolescents successfully transferred to a new HIV clinic, although nearly half attended a clinic other than that assigned.

Are Isomeric Alkenes Used in Species Recognition among Neo-Tropical Stingless Bees (Melipona Spp).

PubMed

Martin, Stephen J; Shemilt, Sue; da S Lima, Cândida B; de Carvalho, Carlos A L

2017-12-01

Our understanding of the role of cuticular hydrocarbons (CHC) in recognition is based largely on temperate ant species and honey bees. The stingless bees remain relatively poorly studied, despite being the largest group of eusocial bees, comprising more than 400 species in some 60 genera. The Meliponini and Apini diverged between 80-130 Myr B.P. so the evolutionary trajectories that shaped the chemical communication systems in ants, honeybees and stingless bees may be very different. The aim of this study was to study if a unique species CHC signal existed in Neotropical stingless bees, as has been shown for many temperate species, and what compounds are involved. This was achieved by collecting CHC data from 24 colonies belonging to six species of Melipona from North-Eastern Brazil and comparing the results with previously published CHC studies on Melipona. We found that each of the eleven Melipona species studied so far each produced a unique species CHC signal based around their alkene isomer production. A remarkable number of alkene isomers, up to 25 in M. asilvai, indicated the diversification of alkene positional isomers among the stingless bees. The only other group to have really diversified in alkene isomer production are the primitively eusocial Bumblebees (Bombus spp), which are the sister group of the stingless bees. Furthermore, among the eleven Neotropical Melipona species we could detect no effect of the environment on the proportion of alkane production as has been suggested for some other species.

[Analysis of related factors for primary hepatic carcinoma caused by chronic hepatitis B and hepatitis C].

PubMed

Nie, L; Wang, X C; Niu, J Q; Shang, J; Han, Y; Xin, G J; Jia, G; Li, J L; Ding, G W; Liu, Z F

2017-06-06

Objective: To explore the related factors for primary hepatic carcinoma (PHC) caused by chronic hepatitis B (CHB) and hepatitis C (CHC). Methods: According to the principle of cross-sectional study, a cluster random sample method was used, a total of 366 chronic hepatitis patients in hospitals were recruited from three provincial tertiary hospitals in Shanxi, Henan and Jilin between July 2016 and October 2016, respectively. Using a self-designed unified questionnaire, face-to-face interviews was conducted on subjects, including sex, age, alcohol consumption, coffee consumption, green tea consumption, fish consumption, smoking, HBV/HCV diagnosis and treatment, diabetes mellitus, family history of PHC (whether PHC in first-degree relatives), etc . Multivariate unconditional logistic regression were performed to identify the related factors for PHC with CHB and CHC. According to the clinical diagnosis the patients were divided into a chronic hepatitis group (not developing to PHC) and a PHC group. Results: Among 366 cases patients, 287 (78.4%) cases were male, 79 cases were female (21.6%), average age was (52.7±9.3) years. 202 cases were chronic hepatitis group, 164 cases were PHC group. Multivariate unconditional logistics regression analysis indicated that alcohol consumption (odds ratio ( OR )=2.11, 95 %CI: 1.18-3.75), family history of PHC ( OR= 5.12, 95 %CI: 2.60-10.08) were positively correlated with the development of PHC in chronic b, green tea consumption ( OR= 0.45, 95 %CI: 0.23-0.88), antiviral treatment ( OR= 0.19, 95 %CI: 0.11-0.32) were negatively correlated. Alcohol consumption ( OR= 3.98, 95 %CI: 1.14-13.85) was positively correlated with the development of PHC in chronic c, antiviral treatment ( OR= 0.14, 95 %CI: 0.04-0.50) was negatively correlated. Conclusion: Alcohol consumption, family history of PHC, green tea consumption and antiviral treatment were the related factors for the development of PHC in chronic hepatitis b. Alcohol consumption and antiviral treatment were the related factors for the development of PHC in chronic hepatitis c.

Bio-mimetic composite scaffold from mussel shells, squid pen and crab chitosan for bone tissue engineering.

PubMed

Shavandi, Amin; Bekhit, Alaa El-Din A; Ali, M Azam; Sun, Zhifa

2015-09-01

In the present study, chitosan/hydroxyapatite (HA)/β-tircalcium phosphate (β-TCP) composites were produced using squid pen derived chitosan (CHS) and commercial crab derived chitosan (CHC). CHS was prepared from squid pens by alkaline N-deacetylation. HA and β-TCP were extracted from mussel shells using a microwave irradiation method. Two different composites were prepared by incorporating 50% (w/w) HA/(β-TCP) in CHS or CHC followed by lyophilization and cross-linking of composites by tripolyphosphate (TPP). The effect of different freezing temperatures of -20, -80 and -196 °C on the physicochemical characteristics of composites was investigated. A simulated body fluid (SBF) solution was used for preliminary in vitro study for 1, 7, 14 and 28 days and the composites were characterized by XRD, FTIR, TGA, SEM, μ-CT and ICP-MS. Porosity, pore size, water uptake; water retention abilities and in vitro degradations of the prepared composites were evaluated. The CHS composites were found to have higher porosity (62%) compared to the CHC composites (porosity 42%) and better mechanical properties. The results of this study indicated that composites produced at -20 °C had higher mechanical properties and lower degradation rate compared with -80 °C. Chitosan from the squid pen is an excellent biomaterial candidate for bone tissue engineering applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Parents’ experiences of participating in an intervention on tobacco prevention in Child Health Care

PubMed Central

2014-01-01

Background Child health care is an important arena for tobacco prevention in Sweden. The aim of this study was to describe parents’ experiences from participating in a nursebased tobacco prevention intervention. Methods Eleven parents were interviewed using semi-structured interviews. The material was analysed in a qualitative content analysis process. Results The analysis emerged four categories; Receiving support, Respectful treatment, Influence on smoking habits and Receiving information. The parents described how the CHC nurses treated them with support and respect. They described the importance of being treated with respect for their autonomy in their decisions about smoking. They also claimed that they had received little or no information about health consequences for children exposed to environmental tobacco smoke (ETS). The findings also indicate that both the questionnaire used and the urine-cotinine test had influenced parents’ smoking. Conclusion The clinical implication is that CHC is an important arena for preventive work aiming to minimize children’s tobacco smoke exposure. CHC nurses can play an important role in tobacco prevention but should be more explicit in their communication with parents about tobacco issues. The SiCET was referred to as an eye-opener and can be useful in the MI dialogues nurses perform in order to support parents in their efforts to protect their children from ETS. PMID:24612749

Profile Analysis of the Woodcock-Johnson III Tests of Cognitive Abilities with Gifted Students.

ERIC Educational Resources Information Center

Rizza, Mary G.; McIntosh, David E.; McCunn, Alice

2001-01-01

The Cattell-Horn-Carroll (CHC) factor clusters of the Woodcock-Johnson III Tests of Cognitive Abilities (WJ III COG) were studied with a group of gifted and nongifted individuals. Results found both groups display similar patterns of performance across the CHC factor clusters. Discusses clinical and educational considerations when using the WJ III…

Listening to Hyun-woo: What Can We Learn from a Korean American English Learner?

ERIC Educational Resources Information Center

Han, Keonghee Tao; Scull, W. Reed

2012-01-01

English learners (ELs) from Confucian heritage culture (CHC) are often perceived to be reserved and conforming to the authority of the classroom. But a careful look at struggles between a CHC student and the mainstream teacher reveals that the teacher's views and pedagogical approaches shape academic and social hierarchy in the classroom.…

The Impact of Cooperative Learning on CHC Students' Achievements and Its Changes over the Past Decade

ERIC Educational Resources Information Center

Chen, Qiuxian; Liu, Yuan

2017-01-01

Informed by emergent learning theories and multiple evidenced benefits, cooperative learning has developed into a widely accepted organization mode of class in the Western context. For the same reason, cooperative learning is transferred, during the past decade, into classrooms of Confucian Heritage Culture (CHC) contexts. Concerns, however, are…

Insect Cuticular Hydrocarbons as Dynamic Traits in Sexual Communication

PubMed Central

Ingleby, Fiona C.

2015-01-01

Recent research has demonstrated extensive within-species variation in pheromone expression in insect species, contrary to the view that pheromones are largely invariant within species. In fact, many studies on insect cuticular hydrocarbons (CHCs) show that pheromones can be highly dynamic traits that can express significant short-term plasticity across both abiotic and social environments. It is likely that this variability in CHC expression contributes to their important role in sexual signaling and mate choice. In this review, I discuss CHC plasticity and how this might influence sexual communication. I also highlight two important avenues for future research: examining plasticity in how individuals respond to CHC signals, and testing how sexual communication varies across abiotic and social environments. PMID:26463413

Degradation of perchloroethene by combined application of microorganisms and zero valent iron particles

NASA Astrophysics Data System (ADS)

Schöftner, Philipp; Summer, Dorothea; Wimmer, Bernhard; Reichenauer, Thomas

2017-04-01

Chlorinated hydrocarbons (CHCs) are especially toxic pollutants which are frequently found at contaminated sites in urban areas which are densely covered with buildings. In specific in such areas, in-situ technologies are favourable since conventional remediation technologies as excavation are often not applicable. This project examines a combination of two in-situ remediation methods, in which the biotic degradation via bacteria (dehalococcoides) is combined with abiotic degradation by zero-valent iron particles (ZVI). ZVI particles are injected into the aquifer where CHC-molecules are reductively dechlorinated. However Fe(0) is also oxidized by reaction with water leading to generation of H2 without any CHC degradation. To achieve biotic degradation often strictly anaerobic strains of the bacteria Dehalococcoides are used. These bacteria can dechlorinate CHC by utilizing H2. By combining these processes the H2, produced during the anaerobic corrosion of Fe(0), could be used by bacteria for further CHC degradation. Different Fe(0) particles (nano- and micro-scale) were combined with microbial dehalogenation for dehalogenation of perchloroethene (PCE) in batch experiments. PCE degradation rates and H2 production rates of the different particles and cultures were determined. Additionally an artificial aquifer (approximately 1.0 x 0.5 x 0.5 metres) was established. This aquifer was spiked with PCE and subsequently treated with Fe(0) particles and microbial. Molasses was added to facilitate microbial dehalogenation. Preliminary results showed that all H2 evolved during oxidation of Fe(0) were used by the associated microbial community. Nevertheless the overall dehalogenation of chlorinated compounds as well as the production of methane was hardly influenced by the addition of Fe(0), at least not over the experimental period of 28 days. Independent if Fe(0) was added or not all chlorinated compounds were dehalogenated whereby ethene and ethane were the only end products.

Interferon-γ-inducible protein-10 in chronic hepatitis C: Correlations with insulin resistance, histological features & sustained virological response.

PubMed

Crisan, Dana; Grigorescu, Mircea Dan; Radu, Corina; Suciu, Alina; Grigorescu, Mircea

2017-04-01

One of the multiple factors contributing to virological response in chronic hepatitis C (CHC) is interferon-gamma-inducible protein-10 (IP-10). Its level reflects the status of interferon-stimulated genes, which in turn is associated with virological response to antiviral therapy. The aim of this study was to evaluate the role of serum IP-10 levels on sustained virological response (SVR) and the association of this parameter with insulin resistance (IR) and liver histology. Two hundred and three consecutive biopsy proven CHC patients were included in the study. Serum levels of IP-10 were determined using ELISA method. IR was evaluated by homeostasis model assessment-IR (HOMA-IR). Histological features were assessed invasively by liver biopsy and noninvasively using FibroTest, ActiTest and SteatoTest. Predictive factors for SVR and their interrelations were assessed. A cut-off value for IP-10 of 392 pg/ml was obtained to discriminate between responders and non-responders. SVR was obtained in 107 patients (52.70%). Area under the receiver operating characteristic curve for SVR was 0.875 with a sensitivity of 91.6 per cent, specificity 74.7 per cent, positive predictive value 80.3 per cent and negative predictive value 88.7 per cent. Higher values of IP-10 were associated with increasing stages of fibrosis (P<0.01) and higher grades of inflammation (P=0.02, P=0.07) assessed morphologically and noninvasively through FibroTest and ActiTest. Significant steatosis and IR were also associated with increased levels of IP-10 (P=0.01 and P=0.02). In multivariate analysis, IP-10 levels and fibrosis stages were independently associated with SVR. Our findings showed that the assessment of serum IP-10 level could be a predictive factor for SVR and it was associated with fibrosis, necroinflammatory activity, significant steatosis and IR in patients with chronic HCV infection.

Cost and efficiency of a hybrid mobile multi-disease testing approach with high HIV testing coverage in East Africa

PubMed Central

Chang, Wei; Chamie, Gabriel; Mwai, Daniel; Clark, Tamara D.; Thirumurthy, Harsha; Charlebois, Edwin D.; Petersen, Maya; Kabami, Jane; Ssemmondo, Emmanuel; Kadede, Kevin; Kwarisiima, Dalsone; Sang, Norton; Bukusi, Elizabeth A.; Cohen, Craig R.; Kamya, Moses; Havlir, Diane V.; Kahn, James G.

2016-01-01

Background In 2013-14, we achieved 89% adult HIV testing coverage using a hybrid testing approach in 32 communities in Uganda and Kenya (SEARCH: NCT01864603). To inform scalability, we sought to determine: 1) overall cost and efficiency of this approach; and 2) costs associated with point-of-care (POC) CD4 testing, multi-disease services, and community mobilization. Methods We applied micro-costing methods to estimate costs of population-wide HIV testing in 12 SEARCH Trial communities. Main intervention components of the hybrid approach are census, multi-disease community health campaigns (CHC), and home-based testing (HBT) for CHC non-attendees. POC CD4 tests were provided for all HIV-infected participants. Data were extracted from expenditure records, activity registers, staff interviews, and time and motion logs. Results The mean cost per adult tested for HIV was $20.5 (range: $17.1 - $32.1) [2014 US$], including a POC CD4 test at $16 per HIV+ person identified. Cost per adult tested for HIV was $13.8 at CHC vs. $31.7 via HBT. The cost per HIV+ adult identified was $231 ($87 - $1,245), with variability due mainly to HIV prevalence among persons tested (i.e., HIV positivity rate). The marginal costs of multi-disease testing at CHCs were $1.16/person for hypertension and diabetes, and $0.90 for malaria. Community mobilization constituted 15.3% of total costs. Conclusions The hybrid testing approach achieved very high HIV testing coverage, with POC CD4, at costs similar to previously reported mobile, home-based, or venue-based HIV testing approaches in sub-Saharan Africa. By leveraging HIV infrastructure, multi-disease services were offered at low marginal costs. PMID:27741031

Cuticular Hydrocarbons of Tribolium confusum Larvae Mediate Trail Following and Host Recognition in the Ectoparasitoid Holepyris sylvanidis.

PubMed

Fürstenau, Benjamin; Hilker, Monika

2017-09-01

Parasitic wasps which attack insects infesting processed stored food need to locate their hosts hidden inside these products. Their host search is well-known to be guided by host kairomones, perceived via olfaction or contact. Among contact kairomones, host cuticular hydrocarbons (CHCs) may provide reliable information for a parasitoid. However, the chemistry of CHC profiles of hosts living in processed stored food products is largely unknown. Here we showed that the ectoparasitoid Holepyris sylvanidis uses CHCs of its host Tribolium confusum, a worldwide stored product pest, as kairomones for host location and recognition at short range. Chemical analysis of T. confusum larval extracts by gas chromatography coupled with mass spectrometry revealed a rich blend of long-chain (C25-C30) hydrocarbons, including n-alkanes, mono-, and dimethylalkanes. We further studied whether host larvae leave sufficient CHCs on a substrate where they walk along, thus allowing parasitoids to perceive a CHC trail and follow it to their host larvae. We detected 18 CHCs on a substrate that had been exposed to host larvae. These compounds were also found in crude extracts of host larvae and made up about a fifth of the CHC amount extracted. Behavioral assays showed that trails of host CHCs were followed by the parasitoids and reduced their searching time until successful host recognition. Host CHC trails deposited on different substrates were persistent for about a day. Hence, the parasitoid H. sylvanidis exploits CHCs of T. confusum larvae for host finding by following host CHC trails and for host recognition by direct contact with host larvae.

Cattell-Horn-Carroll Cognitive-Achievement Relations: What We Have Learned from the Past 20 Years of Research

ERIC Educational Resources Information Center

McGrew, Kevin S.; Wendling, Barbara J.

2010-01-01

Contemporary Cattell-Horn-Carroll (CHC) theory of cognitive abilities has evolved over the past 20 years and serves as the theoretical foundation for a number of current cognitive ability assessments. CHC theory provides a means by which we can better understand the relationships between cognitive abilities and academic achievement, an important…

Comparing Models of Intelligence in Project TALENT: The VPR Model Fits Better than the CHC and Extended Gf-Gc Models

ERIC Educational Resources Information Center

Major, Jason T.; Johnson, Wendy; Deary, Ian J.

2012-01-01

Three prominent theories of intelligence, the Cattell-Horn-Carroll (CHC), extended fluid-crystallized (Gf-Gc) and verbal-perceptual-image rotation (VPR) theories, provide differing descriptions of the structure of intelligence (McGrew, 2009; Horn & Blankson, 2005; Johnson & Bouchard, 2005b). To compare these theories, models representing them were…

Relationships between Cattell-Horn-Carroll (CHC) Cognitive Abilities and Math Achievement within a Sample of College Students with Learning Disabilities

ERIC Educational Resources Information Center

Proctor, Briley

2012-01-01

This study examined the relationship between cognitive abilities and math achievement within a sample of college students with learning disabilities (LD). The cognitive abilities were seven areas identified by Stratum II of the Cattell-Horn-Carroll (CHC) theory of cognitive abilities, in addition to the eighth area of Working Memory. Math…

Construct Validity of Fluency and Implications for the Factorial Structure of Memory

ERIC Educational Resources Information Center

Jewsbury, Paul A.; Bowden, Stephen C.

2017-01-01

Fluency is an important construct in clinical assessment and in cognitive taxonomies. In the Cattell-Horn-Carroll (CHC) model, Fluency is represented by several narrow factors that form a subset of the long-term memory encoding and retrieval (Glr) broad factor. The CHC broad classification of Fluency was evaluated in five data sets, and the CHC…

Comparison of Teachers' and School Psychologists' Accuracy in Assigning Basic Academic Tasks to Underlying CHC-Model Cognitive Abilities

ERIC Educational Resources Information Center

Petruccelli, Meredith Lohr; Fiorello, Catherine A.; Thurman, S. Kenneth

2010-01-01

Teacher perceptions of their students' cognitive abilities affect the referrals they make and intervention strategies they implement. In this study, teachers and school psychologists were asked to sort basic academic tasks into categories on the basis of the Cattell-Horn-Carroll (CHC) broad cognitive abilities, such as fluid reasoning and…

The Role of Cattell-Horn-Carroll (CHC) Cognitive Abilities in Predicting Writing Achievement during the School-Age Years

ERIC Educational Resources Information Center

Cormier, Damien C.; Bulut, Okan; McGrew, Kevin S.; Frison, Jessica

2016-01-01

Writing is a complex academic task--it involves numerous mental processes. Given the necessity for developing writing skills from elementary to secondary school, this study aimed to investigate the role of broad cognitive abilities derived from the Cattell-Horn-Carroll (CHC) theory of intelligence in predicting skills associated with writing…

Strategic questions for consumer-based health communications.

PubMed Central

Sutton, S M; Balch, G I; Lefebvre, R C

1995-01-01

Using the consumer-oriented approach of social and commercial marketers, this article presents a process for crafting messages designed to improve people's health behaviors. The process, termed consumer-based health communications (CHC), transforms scientific recommendations into message strategies that are relevant to the consumer. The core of CHC is consumer research conducted to understand the consumer's reality, and thereby allowing six strategic questions to be answered. The immediate result of the CHC process is a strategy statement--a few pages that lay out who the target consumer is, what action should be taken, what to promise and how to make the promise credible, how and when to reach him or her, and what image to convey. The strategy statement then guides the execution of all communication efforts, be they public relations, mass media, direct marketing, media advocacy, or interpersonal influence. It identifies the most important "levers" for contact with the consumer. Everyone from creative specialists through management and program personnel can use the strategy statement as a touchstone to guide and judge the effectiveness of their efforts. The article provides a step by step illustration of the CHC process using the 5 A Day campaign as an example. PMID:8570827

Evaluation of various molecular parameters as predictors of bioconcentration in fish

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

Connell, D.W.; Schueuermann G3

1988-06-01

A reliable set of data on the bioconcentration factors (KB) of a diverse range of compounds in fish was selected from the literature. Using the structures of these compounds, the following molecular parameters were calculated: molecular weight (MW), solvent accessible molecular surface area (SASA), solvent accessible molecular volume (SAV), molar refraction (MR), largest principal moment of inertia (LPMI) and several molecular connectivity indices of the Randic type (1 chi, 2 chi, 3 chi, 1 chi vr, 3 chi c). The relationships between these parameters and log KB were evaluated for all compounds and the following subgroups: chlorinated hydrocarbons (CHC), polyaromaticmore » hydrocarbons (PAH), and CHC and PAH combined. These relationships indicated that SASA, SAV, and MR were good predictors of log KB for the CHC and PAH combined or alone and the other parameters were less satisfactory with these groups. In addition with the CHC, the log of these parameters displayed an improved correlation with log KB due to apparent nonlinearity in the log to linear relationship. Thus, with these groups of compounds, calculated values of SASA, SAV, and MR provide a satisfactory means of estimating log KB without measured data.« less

Strategic questions for consumer-based health communications.

PubMed

Sutton, S M; Balch, G I; Lefebvre, R C

1995-01-01

Using the consumer-oriented approach of social and commercial marketers, this article presents a process for crafting messages designed to improve people's health behaviors. The process, termed consumer-based health communications (CHC), transforms scientific recommendations into message strategies that are relevant to the consumer. The core of CHC is consumer research conducted to understand the consumer's reality, and thereby allowing six strategic questions to be answered. The immediate result of the CHC process is a strategy statement--a few pages that lay out who the target consumer is, what action should be taken, what to promise and how to make the promise credible, how and when to reach him or her, and what image to convey. The strategy statement then guides the execution of all communication efforts, be they public relations, mass media, direct marketing, media advocacy, or interpersonal influence. It identifies the most important "levers" for contact with the consumer. Everyone from creative specialists through management and program personnel can use the strategy statement as a touchstone to guide and judge the effectiveness of their efforts. The article provides a step by step illustration of the CHC process using the 5 A Day campaign as an example.

Transfer of the high-GC cyclohexane carboxylate degradation pathway from Rhodopseudomonas palustris to Escherichia coli for production of biotin.

PubMed

Bernstein, Jeffrey R; Bulter, Thomas; Liao, James C

2008-01-01

This work demonstrates the transfer of the five-gene cyclohexane carboxylate (CHC) degradation pathway from the high-GC alphaproteobacterium Rhodopseudomonas palustris to Escherichia coli, a gammaproteobacterium. The degradation product of this pathway is pimeloyl-CoA, a key metabolite in E. coli's biotin biosynthetic pathway. This pathway is useful for biotin overproduction in E. coli; however, the expression of GC-rich genes is troublesome in this host. When the native R. palustris CHC degradation pathway is transferred to a DeltabioH pimeloyl-CoA auxotroph of E. coli, it is unable to complement growth in the presence of CHC. To overcome this expression problem we redesigned the operon with decreased GC content and removed stretches of high-GC intergenic DNA which comprise the 5' untranslated region of each gene, replacing these features with shorter low-GC sequences. We show this synthetic construct enables growth of the DeltabioH strain in the presence of CHC. When the synthetic degradation pathway is overexpressed in conjunction with the downstream genes for biotin biosynthesis, we measured significant accumulation of biotin in the growth medium, showing that the pathway transfer is successfully integrated with the host metabolism.

History of community health center affiliations with The New England College of Optometry.

PubMed

Wilson, Roger; Sharda, Vandhana

2008-10-01

Since the 1970s, The New England College of Optometry (NECO) has been a leader in community-based educational programming. This was accomplished through the development of affiliation agreements with health care facilities that care for the underserved, notably community health centers (CHCs). The college's clinical system, the New England Eye Institute (NEEI), develops CHC programs, manages professional services agreements, initiates teaching affiliation agreements, and leads staff recruitment and retention efforts. CHC collaborations, which effectively address disparities in access to health care and visual health status, represent a significant component of the college's primary care clinical training venues. Since their inception in 1972, these CHC academic-community partnerships have provided more than 650,000 eye examinations to the underserved and have trained more than 3,200 graduates in community-based eye care, interdisciplinary care management environment, clinical prevention strategies, and population health. This report describes NECO's longstanding success with CHCs, explains the scope of practice at CHCs, explains how students are involved in the CHCs' eye care services, and discusses the various management and business arrangements. The benefits and challenges of CHC affiliations with optometry schools and colleges are also discussed.

The usefulness of liver stiffness measurement using FibroScan in chronic hepatitis C in South Korea: a multicenter, prospective study.

PubMed

Kim, Seung Up; Jang, Hui Won; Cheong, Jae Youn; Kim, Ja Kyung; Lee, Myung Hee; Kim, Dong Joon; Yang, Jin Mo; Cho, Sung Won; Lee, Kwan Sik; Choi, Eun Hee; Park, Young Nyun; Han, Kwang-Hyub

2011-01-01

We investigated the accuracy of liver stiffness measurement (LSM) in chronic hepatitis C (CHC) in a multicenter, prospective study in South Korea. Between June 2005 and July 2009, 91 CHC patients without a previous history of antiviral treatment, clinical evidences of cirrhosis, coinfection with other viruses, and heavy alcohol consumption and with alanine aminotransferase (ALT) ≤5x upper limit of normal, total bilirubin ≤1.5 mg/dL, sufficient liver biopsy quality (≥15 mm and more than six portal tracts), interquartile range to median liver stiffness (LS) value ratio ≤0.21, and more than 10 valid measurements, were recruited. The Batts and Ludwig scoring system was used for histologic assessment. Age-platelet index (API), aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and age-spleen-platelet ratio index (ASPRI) were calculated. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of LSM and other noninvasive models. The mean age was 47.9 years, and the mean LS value was 7.7 kPa (44 men and 47 women). LS value was highly correlated to the fibrosis stages (r=0.835, P<0.001). The AUROCs of LSM were 0.909 for ≥F2, 0.993 for ≥F3, and 0.970 for F=4 and were superior to those of API (0.72, 0.858, and 0.948, respectively), APRI (0.780, 0.887, and 0.904, respectively), and ASPRI (0.713, 0.862, and 0.957, respectively). The optimal cutoff LS values were 6.2 kPa for ≥F2, 7.7 kPa for ≥F3, and 11.0 kPa for F=4. Our data suggest that LSM can accurately assess liver fibrosis in patients with CHC and be applied in South Korea. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Interaction between PNPLA3 I148M variant and age at infection in determining fibrosis progression in chronic hepatitis C.

PubMed

De Nicola, Stella; Dongiovanni, Paola; Aghemo, Alessio; Cheroni, Cristina; D'Ambrosio, Roberta; Pedrazzini, Michele; Marabita, Francesco; Donnici, Lorena; Maggioni, Marco; Fargion, Silvia; Colombo, Massimo; De Francesco, Raffaele; Valenti, Luca

2014-01-01

The PNPLA3 I148M sequence variant favors hepatic lipid accumulation and confers susceptibility to hepatic fibrosis and hepatocellular carcinoma. The aim of this study was to estimate the effect size of homozygosity for the PNPLA3 I148M variant (148M/M) on the fibrosis progression rate (FPR) and the interaction with age at infection in chronic hepatitis C (CHC). FPR was estimated in a prospective cohort of 247 CHC patients without alcohol intake and diabetes, with careful estimation of age at infection and determination of fibrosis stage by Ishak score. Older age at infection was the strongest determinant of FPR (p<0.0001). PNPLA3 148M/M was associated with faster FPR in individuals infected at older age (above the median, 21 years; -0.64±0.2, n = 8 vs. -0.95±0.3, n = 166 log10 FPR respectively; p = 0.001; confirmed for lower age thresholds, p<0.05), but not in those infected at younger age (p = ns). The negative impact of PNPLA3 148M/M on fibrosis progression was more marked in subjects at risk of altered hepatic lipid metabolism (those with grade 2-3 steatosis, genotype 3, and overweight; p<0.05). At multivariate analysis, PNPLA3 148M/M was associated with FPR (incremental effect 0.08±0.03 log10 fibrosis unit per year; p = 0.022), independently of several confounders, and there was a significant interaction between 148M/M and older age at infection (p = 0.025). The association between 148M/M and FPR remained significant even after adjustment for steatosis severity (p = 0.032). We observed an interaction between homozygosity for the PNPLA3 I148M variant and age at infection in determining fibrosis progression in CHC patients.

A single blood test adjusted for different liver fibrosis targets improves fibrosis staging and especially cirrhosis diagnosis.

PubMed

Calès, Paul; Boursier, Jérôme; Oberti, Frédéric; Moal, Valérie; Fouchard Hubert, Isabelle; Bertrais, Sandrine; Hunault, Gilles; Rousselet, Marie Christine

2018-04-01

Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference. FibroMeter biomarkers were targeted for different fibrosis-stage combinations into classical scores by logistic regression. Independent scores were combined into a single score reflecting Metavir stages by linear regression and called Multi-FibroMeter Version Second Generation (V2G). The primary objective was to combine the advantages of a test targeted for significant fibrosis (FibroMeter V2G ) with those of a test targeted for cirrhosis (CirrhoMeter V2G ). In the derivation CHC population, we first compared Multi-FibroMeter V2G to FibroMeter V2G and observed significant increases in the cirrhosis area under the receiver operating characteristic curve (AUROC), Obuchowski index (reflecting all fibrosis-stage AUROCs), and classification metric (six classes expressed as a correctly classified percentage) and a nonsignificant increase in significant fibrosis AUROC. Thereafter, we compared it to CirroMeter V2G and observed a nonsignificant increase in the cirrhosis AUROC. In all 3,809 patients, respective accuracies for Multi-FibroMeter V2G and FibroMeter V2G were the following: cirrhosis AUROC, 0.906 versus 0.878 ( P < 0.001; versus CirroMeter V2G , 0.897, P = 0.014); Obuchowski index, 0.795 versus 0.791 ( P = 0.059); classification, 86.0% versus 82.1% ( P < 0.001); significant fibrosis AUROC, 0.833 versus 0.832 ( P = 0.366). Multi-FibroMeter V2G had the highest correlation with the area of portoseptal fibrosis and the highest reproducibility over time. Correct classification rates of Multi-FibroMeter with hyaluronate (V2G, 86.0%) or without (V3G, 86.1%) did not differ ( P = 0.938). Conclusion: Multitargeting biomarkers significantly improves fibrosis staging and especially cirrhosis diagnosis compared to classical single-targeted blood tests. ( Hepatology Communications 2018;2:455-466).

A single blood test adjusted for different liver fibrosis targets improves fibrosis staging and especially cirrhosis diagnosis

PubMed Central

Boursier, Jérôme; Oberti, Frédéric; Moal, Valérie; Fouchard Hubert, Isabelle; Bertrais, Sandrine; Hunault, Gilles; Rousselet, Marie Christine

2018-01-01

Fibrosis blood tests are usually developed using significant fibrosis, which is a unique diagnostic target; however, these tests are employed for other diagnostic targets, such as cirrhosis. We aimed to improve fibrosis staging accuracy by simultaneously targeting biomarkers for several diagnostic targets. A total of 3,809 patients were included, comprising 1,012 individuals with chronic hepatitis C (CHC) into a derivation population and 2,797 individuals into validation populations of different etiologies (CHC, chronic hepatitis B, human immunodeficiency virus/CHC, nonalcoholic fatty liver disease, alcohol) using Metavir fibrosis stages as reference. FibroMeter biomarkers were targeted for different fibrosis‐stage combinations into classical scores by logistic regression. Independent scores were combined into a single score reflecting Metavir stages by linear regression and called Multi‐FibroMeter Version Second Generation (V2G). The primary objective was to combine the advantages of a test targeted for significant fibrosis (FibroMeterV2G) with those of a test targeted for cirrhosis (CirrhoMeterV2G). In the derivation CHC population, we first compared Multi‐FibroMeterV2G to FibroMeterV2G and observed significant increases in the cirrhosis area under the receiver operating characteristic curve (AUROC), Obuchowski index (reflecting all fibrosis‐stage AUROCs), and classification metric (six classes expressed as a correctly classified percentage) and a nonsignificant increase in significant fibrosis AUROC. Thereafter, we compared it to CirroMeterV2G and observed a nonsignificant increase in the cirrhosis AUROC. In all 3,809 patients, respective accuracies for Multi‐FibroMeterV2G and FibroMeterV2G were the following: cirrhosis AUROC, 0.906 versus 0.878 (P < 0.001; versus CirroMeterV2G, 0.897, P = 0.014); Obuchowski index, 0.795 versus 0.791 (P = 0.059); classification, 86.0% versus 82.1% (P < 0.001); significant fibrosis AUROC, 0.833 versus 0.832 (P = 0.366). Multi‐FibroMeterV2G had the highest correlation with the area of portoseptal fibrosis and the highest reproducibility over time. Correct classification rates of Multi‐FibroMeter with hyaluronate (V2G, 86.0%) or without (V3G, 86.1%) did not differ (P = 0.938). Conclusion: Multitargeting biomarkers significantly improves fibrosis staging and especially cirrhosis diagnosis compared to classical single‐targeted blood tests. (Hepatology Communications 2018;2:455‐466) PMID:29619423

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance.

PubMed

Chang, Ming-Ling; Kuo, Chia-Jung; Pao, Li-Heng; Hsu, Chen-Ming; Chiu, Cheng-Tang

2017-10-03

The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri- and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n = 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR.

Daclatasvir/peginterferon lambda-1a/ribavirin in patients with chronic HCV infection and haemophilia who are treatment naïve or prior relapsers to peginterferon alfa-2a/ribavirin.

PubMed

Santagostino, E; Pol, S; Olveira, A; Reesink, H W; van Erpecum, K; Bogomolov, P; Xu, D; Critelli, L; Srinivasan, S; Cooney, E

2016-09-01

This study explores the potential role of a novel interferon-containing regimen for treatment of patients with chronic hepatitis C (CHC) and underlying haemophilia. This trial (NCT01741545) was an open-label, non-randomized phase 3 study, which included adult haemophiliacs with hepatitis C virus (HCV). Patients with HCV genotypes (GT)-2 or -3 were treated with Lambda-IFN/ribavirin (RBV)/daclatasvir (DCV) for 12 weeks (cohort A). Patients with HCV GT-1b or -4 were treated with Lambda-IFN/RBV/DCV for 12 weeks, followed by Lambda-IFN/RBV for an additional 12 weeks (cohort B). The primary endpoint was the proportion of patients with a sustained virologic response at post-treatment follow-up week 12 (SVR12). Clinical development of Lambda-IFN was discontinued during this trial leading to study termination before a 24-week post-treatment follow-up was obtained for all participants. Overall, 51 patients were treated (cohort A, n = 12; cohort B, n = 39). The proportion of patients achieving SVR12 was 92% in cohort A and 90% in cohort B. Therapy was generally well tolerated. The most common adverse events (AEs) were related to elevations in serum transaminases and/or bilirubin. Five serious AEs, four discontinuations due to AEs, and no deaths were reported. The rate of grade 3-4 bilirubin elevations was 17-18% across cohorts. Lambda-IFN/RBV/DCV treatment demonstrated a high SVR rate and was generally well tolerated with a safety profile consistent with expectations for this special patient population. This study supports use of DCV as part of a combination treatment regimen for haemophiliacs with CHC. © 2016 John Wiley & Sons Ltd.

Temporal relations in hormone-withdrawal migraines and impact on prevention- a diary-based pilot study in combined hormonal contraceptive users.

PubMed

Merki-Feld, Gabriele S; Epple, Gina; Caveng, Nina; Imthurn, Bruno; Seifert, Burkhardt; Sandor, Peter; Gantenbein, Andreas R

2017-08-25

Menstrually related migraine (MRM) in the hormone-free interval (HFI) of combined hormonal contraceptives (CHC) are according to the ICHD definition also estrogen withdrawal migraines (EWH). MRMs are less responsive to acute medication. Therefore short-term prevention, initiated 1-2 days before onset of the anticipated bleeding and continued for 6 days, is recommended. Such a long prophylactic triptan use might increase the risk for medication overuse headache in women suffering in addition from non-menstrual migraines. In CHC users onset of hormone decline is predictable. It is however unknown, whether the EWHs are rather associated with onset of hormone withdrawal or onset of bleeding. Improved understanding of this relation might contribute to better define and shorten the time interval for prevention. For this observational diary-based pilot study we collected data from daily conducted headache diaries of CHC users with MRM in at least two of three cycles, visiting our clinic from 2009 to 2015. We analyzed frequency of migraines for each hormone free day, onset of migraine, onset of bleeding and the relation of migraine to onset of bleeding in the 7-day period following estrogen withdrawal. We identified in addition the onset of migraine attacks lasting more than 1 day (episodes). Forty patient charts met the inclusion criteria, what allowed us to analyze 103 cycles. The mean number of migraine days in the HFI was 2.2 ± 1.6. Migraine started typically on days 1-5 and bleeding on days 3-5. In relation to first day of bleeding, migraines started on days -1 to 4. Almost half of the migraine attacks lasted longer than 24 h, despite the use of rescue medication. MRM in CHC users starts on bleeding days -1 to 4, what differs from findings in the natural cycle. Referring to the HFI interval migraine started mostly on days 1-5. According to these data, it seems to be reasonable to initiate short-term prevention at the last day of pill use or the first day of the HFI and continue for 5 days.

Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US.

PubMed

Zhang, Sai; Bastian, Nathaniel D; Griffin, Paul M

2015-08-05

The standard care of treatment of interferon plus ribavirin (plus protease inhibitor for genotype 1) are effective in 50 % to 70 % of patients with CHC. Several new treatments including Harvoni, Olysio + Sovaldi, Viekira Pak, Sofosbuvir-based regimens characterized with potent inhibitors have been approved by the Food and Drug Administration (FDA) providing more options for CHC patients. Trials have shown that the new treatments increased the rate to 80% to 95%, though with a substantial increase in cost. In particular, current market pricing of a 12-week course of sofosbuvir is approximately US$84,000. We determine the cost-effectiveness of new treatments in comparison with the standard care of treatments. A Markov simulation model of CHC disease progression is used to evaluate the cost-effectiveness of different treatment strategies based on genotype. The model calculates the expected lifetime medical costs and quality adjusted life years (QALYs) of hypothetical cohorts of identical patients receiving certain treatments. For genotype 1, we compare: (1) peginterferon + ribavirin + telaprevir for 12 weeks, followed by 12 or 24 weeks treatment of peginterferon + ribavirin dependent on HCV RNA level at week 12; (2) Harvoni treatment, 12 weeks; (3) Olysio + Sovaldi, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (4) Viekira Pak + ribavirin, 12 weeks for patients without cirrhosis, 24 weeks for patients with cirrhosis; (5) sofosbuvir + peginterferon + ribavirin, 12 weeks for patients with or without cirrhosis. For genotypes 2 and 3, treatment strategies include: (1) peginterferon + ribavirin, 24 weeks for treatment-naïve patients; (2) sofosbuvir + ribavirin, 12 weeks for patients with genotype 2, 24 weeks for genotype 3; (3) peginterferon + ribavirin as initial treatment, 24 weeks for patients with genotype 2/3, follow-up treatment with sofosbuvir + ribavirin for 12/16 weeks are performed on non-responders and relapsers. Viekira Pak is cost-effective for genotype 1 patients without cirrhosis, whereas Harvoni is cost-effective for genotype 1 patients with cirrhosis. Sofosbuvir-based treatments for genotype 1 in general are not cost-effective due to its substantial high costs. Two-phase treatments with 12-week and 16-week follow-ups are cost-effective for genotype 3 patients and for genotype 2 patients with cirrhosis. The results were shown to be robust over a broad range of parameter values through sensitivity analysis. For genotype 1, sofosbuvir-based treatments are not cost-effective compared to Viekira Pak and Harvoni, although a 30% reduction in sofosbuvir price would change this result. Sofosbuvir + ribavirin are cost-effective as second-phase treatments following peginterferon + ribavirin initial treatment for genotypes 2 and 3. However, there is limited data on sofosbuvir-involved treatment, and the results obtained in this study must be interpreted within the model assumptions.

Hierarchical Exploratory Factor Analyses of the Woodcock-Johnson IV Full Test Battery: Implications for CHC Application in School Psychology

ERIC Educational Resources Information Center

Dombrowski, Stefan C.; McGill, Ryan J.; Canivez, Gary L.

2018-01-01

The Woodcock-Johnson (fourth edition; WJ IV; Schrank, McGrew, & Mather, 2014a) was recently redeveloped and retains its linkage to Cattell-Horn-Carroll theory (CHC). Independent reviews (e.g., Canivez, 2017) and investigations (Dombrowski, McGill, & Canivez, 2017) of the structure of the WJ IV full test battery and WJ IV Cognitive have…

Life and Death of a Child with Down Syndrome and a Congenital Heart Condition: Experiences of Six Couples

ERIC Educational Resources Information Center

Reilly, Deirdre; Huws, Jaci; Hastings, Richard; Vaughan, Frances

2010-01-01

Individuals with Down syndrome are at increased risk of congenital heart conditions (CHCs), and mortality is higher in people with Down syndrome and a CHC than those without (J. C. Vis et al., 2009). As a consequence, parents of children with Down syndrome and a CHC are more likely to outlive their child. In this research, semistructured…

A CHC Theory-Based Analysis of Age Differences on Cognitive Abilities and Academic Skills at Ages 22 to 90 Years

ERIC Educational Resources Information Center

Kaufman, Alan S.; Johnson, Cheryl K.; Liu, Xin

2008-01-01

Age differences for nine age groups between 22 and 25 years and 81 and 90 years were evaluated, covarying educational attainment, on five Cattell-Horn-Carroll (CHC) abilities: fluid reasoning (Gf), crystallized ability (Gc), quantitative knowledge (Gq), reading (Grw-Reading), and writing (Grw-Writing). Data were from the adult portions of the…

Association between community health center and rural health clinic presence and county-level hospitalization rates for ambulatory care sensitive conditions: an analysis across eight US states.

PubMed

Probst, Janice C; Laditka, James N; Laditka, Sarah B

2009-07-31

Federally qualified community health centers (CHCs) and rural health clinics (RHCs) are intended to provide access to care for vulnerable populations. While some research has explored the effects of CHCs on population health, little information exists regarding RHC effects. We sought to clarify the contribution that CHCs and RHCs may make to the accessibility of primary health care, as measured by county-level rates of hospitalization for ambulatory care sensitive (ACS) conditions. We conducted an ecologic analysis of the relationship between facility presence and county-level hospitalization rates, using 2002 discharge data from eight states within the US (579 counties). Counties were categorized by facility availability: CHC(s) only, RHC(s) only, both (CHC and RHC), and neither. US Agency for Healthcare Research and Quality definitions were used to identify ACS diagnoses. Discharge rates were based on the individual's county of residence and were obtained by dividing ACS hospitalizations by the relevant county population. We calculated ACS rates separately for children, working age adults, and older individuals, and for uninsured children and working age adults. To ensure stable rates, we excluded counties having fewer than 1,000 residents in the child or working age adult categories, or 500 residents among those 65 and older. Multivariate Poisson analysis was used to calculate adjusted rate ratios. Among working age adults, rate ratio (RR) comparing ACS hospitalization rates for CHC-only counties to those of counties with neither facility was 0.86 (95% Confidence Interval, CI, 0.78-0.95). Among older adults, the rate ratio for CHC-only counties compared to counties with neither facility was 0.84 (CI 0.81-0.87); for counties with both CHC and RHC present, the RR was 0.88 (CI 0.84-0.92). No CHC/RHC effects were found for children. No effects were found on estimated hospitalization rates among uninsured populations. Our results suggest that CHCs and RHCs may play a useful role in providing access to primary health care. Their presence in a county may help to limit the county's rate of hospitalization for ACS diagnoses, particularly among older people.

Epidemiology, disease burden and outcomes of cirrhosis in a large secondary care hospital in South Auckland, New Zealand.

PubMed

Hsiang, J C; Bai, W W; Raos, Z; Stableforth, W; Upton, A; Selvaratnam, S; Gane, E J; Gerred, S J

2015-02-01

Liver cirrhosis is an important cause of morbidity and mortality; however, little is known about its impact in New Zealand. We aim to determine the disease burden, epidemiology and outcomes of cirrhotic patients. This is a retrospective study of cirrhosis patients under secondary public hospital care in a geographically defined region, between the years 2000 and 2011. Cirrhosis complications and mortality was recorded. Poisson log-linear regression analysis was performed for incidence rate ratio (IRR) and Cox regression analysis was used to analyse time-related events. Seven hundred and forty-six cirrhotic patients were analysed; most were European/Other (39.9%), Pacific islanders (21.6%), Southeast Asian/Chinese (17.8%) and Maori (12.3%). 68.4% were male. The common primary aetiologies for cirrhosis were chronic hepatitis B (CHB) cirrhosis (37.3%), alcoholic liver disease (ALD) cirrhosis (24.1%), chronic hepatitis C (CHC) cirrhosis (22.3%) and non-alcoholic fatty liver disease (NAFLD) cirrhosis (16.4%). The hepatocellular carcinoma (HCC) mortality rates were highest in NAFLD and CHB cirrhosis groups (3.0 and 3.1 per 100 patient-year respectively), compared with ALD and CHC groups (2.2 and 1.4 per 100 patient-year, all P < 0.05 respectively). Patients with ALD and NAFLD cirrhosis had the highest all-cause and non-HCC mortality rate compared with viral hepatitis cirrhosis groups. The IRR for HCC incidence, liver-related mortality and HCC mortality were 1.087, 1.098 and 1.114, respectively (all P < 0.001), suggesting increasing incidence and disease burden over the study period. The number of cirrhotic patients in secondary care is increasing steadily. Cirrhosis complications and mortality rates are also rising, particularly the incidence and mortality of HCC. © 2014 Royal Australasian College of Physicians.

A Higher Correlation of HCV Core Antigen with CD4+ T Cell Counts Compared with HCV RNA in HCV/HIV-1 Coinfected Patients

PubMed Central

Zhang, Weidong; Xi, Yuanlin; Cao, Guanghua; Zhi, Yuhong; Wang, Shuiwang; Xu, Chunhui; Wei, Lai; Lu, Fengmin; Zhuang, Hui

2011-01-01

Development of HCV infection is typically followed by chronic hepatitis C (CHC) in most patients, while spontaneous HCV viral clearance (SVC) occurs in only a minority of subjects. Compared with the widespread application of HCV RNA testing by quantitative RT-PCR technique, HCV core antigen detection may be an alternative indicator in the diagnosis of hepatitis C virus infections and in monitoring the status of infectious individuals. However, the correlation and differences between these two indicators in HCV infection need more investigation, especially in patients coinfected by HIV-1. In this study, a total of 354 anti-HCV and/or anti-HIV serum positive residents from a village of central China were enrolled. Besides HCV-related hepatopathic variables including clinical status, ALT, AST, anti-HCV Abs, as well as the altered CD4+/CD8+ T cell counts, HCV core antigen and HCV viral load were also measured. The concentration of serum HCV core antigen was highly correlated with level of HCV RNA in CHC patients with or without HIV-1 coinfection. Of note, HCV core antigen concentration was negatively correlated with CD4+ T cell count, while no correlation was found between HCV RNA level and CD4+ T cell count. Our findings suggested that quantitative detection of plasma HCV core antigen may be an alternative indicator of HCV RNA qPCR assay when evaluating the association between HCV replication and host immune status in HCV/HIV-1 coinfected patients. PMID:21858166

Cost-effectiveness analysis of ledipasvir/sofosbuvir in patients with chronic hepatitis C: Treatment of patients with absence or mild fibrosis compared to patients with advanced fibrosis.

PubMed

Buti, M; Domínguez-Hernández, R; Oyagüez, I; Casado, M A; Esteban, R

2017-09-01

To evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment-naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0-F1) versus advanced fibrosis (F2-F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality-adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0-F1 compared with F2-F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load <6 million IU/mL and 12 weeks in the remaining patients. Sustained virologic response rates were obtained from real-world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0-F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2-F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0-F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver-related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2-F4 patients. In CHC treatment-naïve GT1 patients, starting treatment with LDV/SOF in patients with F0-F1 compared to those with F2-F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings. © 2017 John Wiley & Sons Ltd.

Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

PubMed Central

Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

2015-01-01

Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy. PMID:26640716

Serum Adiponectin, Vitamin D, and Alpha-Fetoprotein in Children with Chronic Hepatitis C: Can They Predict Treatment Response?

PubMed

Khedr, Mohamed Ahmed; Sira, Ahmad Mohamed; Saber, Magdy Anwar; Raia, Gamal Yousef

2015-01-01

Background & Aims. The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alpha-fetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (p < 0.0001, p = 0.071, and p = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (p < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8% sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, p < 0.0001 and p = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. In multivariate analysis, adiponectin was found to be the only independent predictor of treatment response (p = 0.044). Conclusions. The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.

Translating an Evidence-Based Behavioral Intervention for Women Living with HIV into Clinical Practice: The SMART/EST Women's Program.

PubMed

Weiss, Stephen M; Tobin, Jonathan N; Lopez, Maria; Simons, Hannah; Cook, Ryan; Jones, Deborah L

2015-06-01

The process of translating scientific findings into clinical and public health settings has only recently received priority attention within the scientific community. Fueled by "Funding Opportunity Announcements" from the National Institutes of Health and Centers for Disease Control and Prevention, scientists have begun to explore the pathways to effectively "transfer" promising research accomplishments into effective and sustainable service programs within the health care delivery system. Using Glasgow's RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) model as a guide, this research team enrolled 428 socially disadvantaged, culturally diverse women living with HIV/AIDS to test the dissemination and implementation of an evidence-based behavioral intervention designed to improve and sustain the physical and emotional health of participants into the Community Health Center (CHC) setting when conducted by trained CHC staff. Findings demonstrate the ability of trained CHC staff group leaders to attain results equivalent or superior to those achieved when conducted by research staff on the three principal study outcomes: depression, medication adherence and HIV viral load. Four of five CHCs involved in the study also identified and successfully obtained funding to continue to run intervention groups, supporting the adoption and sustainability components of the translation model. This study confirmed (a) the "translatability" of the Stress Management And Relaxation Training/Emotional Supportive Therapy (SMART/EST) Women's Program, from academic to CHC settings in two geographic regions with high HIV prevalence among women, (b) the ability of local staff (using the "train the trainer" model) to successfully achieve program fidelity and clinical outcomes, and (c) the sustainability the program beyond the auspices of research support, through supportive CHC leadership securing continued program funding.

Barriers to gene exchange in hybridizing field crickets: the role of male courtship effort and cuticular hydrocarbons.

PubMed

Maroja, Luana S; McKenzie, Zachary M; Hart, Elizabeth; Jing, Joy; Larson, Erica L; Richardson, David P

2014-03-28

Pre-zygotic barriers often involve some form of sexual selection, usually interpreted as female choice, as females are typically the choosier sex. However, males typically show some mate preferences, which are increasingly reported. Here we document previously uncharacterized male courtship behavior (effort and song) and cuticular hydrocarbon (CHC) profiles in the hybridizing crickets Gryllus firmus and G. pennsylvanicus. These two species exhibit multiple barriers to gene exchange that act throughout their life history, including a behavioral barrier that results in increased time to mate in heterospecific pairs. We demonstrated that male mate choice (as courtship effort allocation) plays a more important role in the prezygotic behavioral barrier than previously recognized. In gryllids females ultimately decide whether or not to mate, yet we found males were selective by regulating courtship effort intensity toward the preferred (conspecific) females. Females were also selective by mating with more intensely courting males, which happened to be conspecifics. We report no differences in courtship song between the two species and suggest that the mechanism that allows males to act differentially towards conspecific and heterospecific females is the cuticular hydrocarbon (CHC) composition. CHC profiles differed between males and females of both species, and there were clear differences in CHC composition between female G. firmus and G. pennsylvanicus but not between the males of each species. Although many barriers to gene exchange are known in this system, the mechanism behind the mate recognition leading to reduced heterospecific mating remains unknown. The CHC profiles might be the phenotypic cue that allow males to identify conspecifics and thus to adjust their courtship intensity accordingly, leading to differential mating between species.

Limonoid Compounds Inhibit Sphingomyelin Biosynthesis by Preventing CERT Protein-dependent Extraction of Ceramides from the Endoplasmic Reticulum*

PubMed Central

Hullin-Matsuda, Françoise; Tomishige, Nario; Sakai, Shota; Ishitsuka, Reiko; Ishii, Kumiko; Makino, Asami; Greimel, Peter; Abe, Mitsuhiro; Laviad, Elad L.; Lagarde, Michel; Vidal, Hubert; Saito, Tamio; Osada, Hiroyuki; Hanada, Kentaro; Futerman, Anthony H.; Kobayashi, Toshihide

2012-01-01

To identify novel inhibitors of sphingomyelin (SM) metabolism, a new and selective high throughput microscopy-based screening based on the toxicity of the SM-specific toxin, lysenin, was developed. Out of a library of 2011 natural compounds, the limonoid, 3-chloro-8β-hydroxycarapin-3,8-hemiacetal (CHC), rendered cells resistant to lysenin by decreasing cell surface SM. CHC treatment selectively inhibited the de novo biosynthesis of SM without affecting glycolipid and glycerophospholipid biosynthesis. Pretreatment with brefeldin A abolished the limonoid-induced inhibition of SM synthesis suggesting that the transport of ceramide (Cer) from the endoplasmic reticulum to the Golgi apparatus is affected. Unlike the Cer transporter (CERT) inhibitor HPA-12, CHC did not change the transport of a fluorescent short chain Cer analog to the Golgi apparatus or the formation of fluorescent and short chain SM from the corresponding Cer. Nevertheless, CHC inhibited the conversion of de novo synthesized Cer to SM. We show that CHC specifically inhibited the CERT-mediated extraction of Cer from the endoplasmic reticulum membranes in vitro. Subsequent biochemical screening of 21 limonoids revealed that some of them, such as 8β-hydroxycarapin-3,8-hemiacetal and gedunin, which exhibits anti-cancer activity, inhibited SM biosynthesis and CERT-mediated extraction of Cer from membranes. Model membrane studies suggest that 8β-hydroxycarapin-3,8-hemiacetal reduced the miscibility of Cer with membrane lipids and thus induced the formation of Cer-rich membrane domains. Our study shows that certain limonoids are novel inhibitors of SM biosynthesis and suggests that some biological activities of these limonoids are related to their effect on the ceramide metabolism. PMID:22605339

Fluoxetine a novel anti-hepatitis C virus agent via ROS-, JNK-, and PPARβ/γ-dependent pathways.

PubMed

Young, Kung-Chia; Bai, Chyi-Huey; Su, Hui-Chen; Tsai, Pei-Ju; Pu, Chien-Yu; Liao, Chao-Sheng; Lin, Yu-Min; Lai, Hsin-Wen; Chong, Lee-Won; Tsai, Yau-Sheng; Tsao, Chiung-Wen

2014-10-01

More than 20% of chronic hepatitis C (CHC) patients receiving interferon-alpha (IFN-α)-based anti-hepatitis C virus (HCV) therapy experienced significant depression, which was relieved by treatment with fluoxetine. However, whether and how fluoxetine affected directly the anti-HCV therapy remained unclear. Here, we demonstrated that fluoxetine inhibited HCV infection and blocked the production of reactive oxygen species (ROS) and lipid accumulation in Huh7.5 cells. Fluoxetine facilitated the IFN-α-mediated antiviral actions via activations of signal transducer and activator of transcription (STAT)-1 and c-Jun amino-terminal kinases (JNK). Alternatively, fluoxetine elevated peroxisome proliferator-activated receptor (PPAR) response element activity under HCV infection. The inhibitory effects of fluoxetine on HCV infection and lipid accumulation, but not production of ROS, were partially reversed by the PPAR-β, -γ, and JNK antagonists. Furthermore, fluoxetine intervention to the IFN-α-2b regimen facilitated to reduce HCV titer and alanine transaminase level for CHC patients. Therefore, fluoxetine intervention to the IFN-α-2b regimen improved the efficacy of anti-HCV treatment, which might be related to blockades of ROS generation and lipid accumulation and activation of host antiviral JNK/STAT-1 and PPARβ/γ signals. Copyright © 2014 Elsevier B.V. All rights reserved.

Insulin Signaling Mediates Sexual Attractiveness in Drosophila

PubMed Central

Hansen, Ingrid; Dreisewerd, Klaus; Dierick, Herman A.; Yew, Joanne Y.; Pletcher, Scott D.

2012-01-01

Sexually attractive characteristics are often thought to reflect an individual's condition or reproductive potential, but the underlying molecular mechanisms through which they do so are generally unknown. Insulin/insulin-like growth factor signaling (IIS) is known to modulate aging, reproduction, and stress resistance in several species and to contribute to variability of these traits in natural populations. Here we show that IIS determines sexual attractiveness in Drosophila through transcriptional regulation of genes involved in the production of cuticular hydrocarbons (CHC), many of which function as pheromones. Using traditional gas chromatography/mass spectrometry (GC/MS) together with newly introduced laser desorption/ionization orthogonal time-of-flight mass spectrometry (LDI-MS) we establish that CHC profiles are significantly affected by genetic manipulations that target IIS. Manipulations that reduce IIS also reduce attractiveness, while females with increased IIS are significantly more attractive than wild-type animals. IIS effects on attractiveness are mediated by changes in CHC profiles. Insulin signaling influences CHC through pathways that are likely independent of dFOXO and that may involve the nutrient-sensing Target of Rapamycin (TOR) pathway. These results suggest that the activity of conserved molecular regulators of longevity and reproductive output may manifest in different species as external characteristics that are perceived as honest indicators of fitness potential. PMID:22570625

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

PubMed Central

García-Samaniego, Javier; Romero, Miriam; Granados, Rafael; Alemán, Remedios; Jorge Juan, Miguel; Suárez, Dolores; Pérez, Ramón; Castellano, Gregorio; González-Portela, Carlos

2013-01-01

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to peginterferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d). RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventy-eight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR. PMID:23569340

The Central Role of Physician Leadership for Driving Change in Value-Based Care Environments.

PubMed

Lustig, Adam; Ogden, Michael; Brenner, Robert W; Penso, Jerry; Westrich, Kimberly D; Dubois, Robert W

2016-10-01

In 2013, it was reported that about 1 of every 3 U.S. adults has hypertension. Of these 70 million individuals, approximately 50% have their blood pressure under control. Achieving hypertension control, especially in at-risk populations, requires a multipronged approach that includes lifestyle modifications and pharmacological treatment. As provider groups, hospital systems, and integrated delivery networks optimize their care processes to promote population health activities in support of the accountable care organization (ACO) model of care, managing hypertension and other chronic diseases will be essential to their success. A critical aspect of managing populations in an ACO environment is optimization of care processes among providers to increase care efficiency and improve patient outcomes. Launched in 2013, Measure Up/Pressure Down is a 3-year campaign developed by the American Medical Group Foundation (AMGF) to reduce the burden of high blood pressure. The goal of the campaign is for participating medical groups, health systems, and other organized systems of care to achieve hypertension control for 80% of their patients with high blood pressure by 2016, according to national standards. The role of physician leadership at Cornerstone Health Care (CHC) and Summit Medical Group (SMG) in facilitating organizational change to improve hypertension management through the implementation of the Measure Up/Pressure Down national hypertension campaign is examined. Using patient stratification via its electronic health record, SMG identified 16,000 patients with hypertension. The baseline percentage of hypertension control for this patient population was 66%. Within 7 months, SMG was able to meet the 80% goal set forth by the AMGF's Measure Up/Pressure Down campaign. CHC diagnosed 25,312 patients with hypertension. The baseline percentage of hypertension control for this subgroup of patients was 51.5% when the initiative was first implemented. To date, the organization has achieved 72% hypertension control for at-risk patients and continues work towards the 80% campaign goal. The implementation of the Measure Up/Pressure Down campaign by CHC and SMG provides some valuable lessons. To further explore important aspects of successfully implementing the Measure Up/Pressure Down campaign in real-world settings, 6 key themes were identified that drove quality improvement and may be helpful to other organizations that implement similar quality improvement initiatives: (1) transitioning to value-based payments, (2) creating an environment for success, (3) leveraging program champions, (4) sharing quality data, (5) promoting care team collaboration, and (6) leveraging health information technology. The strategies employed by SMG and CHC, such as leveraging data analysis to identify at-risk patients and comparing physician performance, as well as identifying leaders to institute change, can be replicated by an ACO or a managed care organization (MCO). An MCO can provide data analysis services, sparing the provider groups the analytic burden and helping the MCO build a more meaningful relationship with their providers. No outside funding supported this project. The authors declare no conflicts of interest. The authors are members of the Working Group on Optimizing Medication Therapy in Value-Based Healthcare. Odgen is employed by Cornerstone Health Care; Brenner is employed by Summit Medical Group; and Penso is employed by American Medical Group Association. Lustig, Westrich, and Dubois are employed by the National Pharmaceutical Council, an industry-funded health policy research organization that is not involved in lobbying or advocacy. Study concept and design were contributed by Lustig, Penso, Westrich, and Dubois. Lustig, Ogden, Brenner, and Penso collected the data, and data interpretation was performed by all authors. The manuscript was written primarily by Lustig, along with the other authors, and revised by Lustig, Penso, Westrich, and Dubois, assisted by Ogden and Brenner.

Experimental and computational study of the bonding properties of mixed bis-ylides of phosphorus and sulfur.

PubMed

Serrano, Elena; Navarro, Rafael; Soler, Tatiana; Carbó, Jorge J; Lledós, Agustí; Urriolabeitia, Esteban P

2009-07-20

The reactivity of the known ylide-sulfonium salt [Ph(3)P=CHC(O)CH(2)SMe(2)]Br 1 and the new ylide-sulfide [Ph(3)P=CHC-(O)CH(2)SMe] 2 toward Pd(II) complexes has been studied. Compound 1 reacts with PdCl(2)(NCMe)(2) and NEt(3) to give cis-[PdCl(2)[Ph(3)PCHC(O)CHSMe(2)-kappa-C,C

25 years of interferon-based treatment of chronic hepatitis C: an epoch coming to an end.

PubMed

Heim, Markus H

2013-07-01

Chronic hepatitis caused by infection with hepatitis C virus C (HCV) (therefore known as chronic hepatitis C (CHC)) is a leading cause of liver disease worldwide. For the past 25 years, recombinant interferon-α (IFNα) has been the main component of treatments for HCV infection. Treatment efficacy has shown a stepwise improvement following the pegylation of IFNα and its use in combination with other antiviral drugs. However, viral escape mechanisms, refractory IFNα signalling in the liver and substantial drug toxicity still limit the efficacy of this treatment. A new generation of HCV-specific antiviral drugs will probably improve response rates and might replace IFNs in CHC treatment in the next few years. This Timeline article summarizes the history of CHC treatment using recombinant IFNα with an emphasis on the mechanisms of action and the causes of non-response.

Simultaneous identification of multi-combustion-intermediates of alkanol-air flames by femtosecond filament excitation for combustion sensing.

PubMed

Li, Helong; Chu, Wei; Xu, Huailiang; Cheng, Ya; Chin, See-Leang; Yamanouchi, Kaoru; Sun, Hong-Bo

2016-06-02

Laser filamentation produced by the propagation of intense laser pulses in flames is opening up new possibility in application to combustion diagnostics that can provide useful information on understanding combustion processes, enhancing combustion efficiency and reducing pollutant products. Here we present simultaneous identification of multiple combustion intermediates by femtosecond filament excitation for five alkanol-air flames fueled by methanol, ethanol, n-propanol, n-butanol, and n-pentanol. We experimentally demonstrate that the intensities of filament-induced photoemission signals from the combustion intermediates C, C2, CH, CN increase with the increasing number of carbons in the fuel molecules, and the signal ratios between the intermediates (CH/C, CH/C2, CN/C, CH/C2, CN/CH) are different for different alkanol combustion flames. Our observation provides a way for sensing multiple combustion components by femtosecond filament excitation in various combustion conditions that strongly depend on the fuel species.

Mission, Margin, and the Role of Consumer Governance in Decision-Making at Community Health Centers

PubMed Central

Wright, Brad; Martin, Graham P.

2017-01-01

Objective We explore the role of consumer trustees in decision-making as community health centers (CHCs) work to navigate the tension between pursuing their mission to provide primary care to all regardless of ability to pay and maintaining their limited finances. Methods We interviewed 30 trustees from 16 CHCs in 14 different states, asking extensively about decision-making processes at their CHC related to services and finances, as well as perceived advantages and disadvantages of consumer governance. Results Respondents described mission-dominant, margin-dominant, and balanced decision-making philosophies, and different decision-making pathways for service provision and finances. Consumer trustees were lauded for their role in informing the board of service quality and community needs, but criticized for being professionally unskilled and exhibiting a lack of objective decision-making. Conclusions While CHC boards do play a role in navigating the tension between mission and margin, executive directors and staff appear to be more influential. PMID:24858895

Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-alpha and ribavirin.

PubMed

Sheridan, D A; Price, D A; Schmid, M L; Toms, G L; Donaldson, P; Neely, D; Bassendine, M F

2009-06-15

Hepatitis C virus (HCV) co-opts very-low-density lipoprotein (VLDL) pathways for replication, secretion and entry into hepatocytes and associates with apolipoprotein B (apoB) in plasma. Each VLDL contains apoB-100 and variable amounts of apolipoproteins E and C, cholesterol and triglycerides. To determine whether baseline lipid levels predicted treatment outcome. Retrospective analysis was performed of 250 chronic hepatitis C (CHC) patients who had received anti-viral agents interferon-alpha and ribavirin; 165 had a sustained virological response (SVR). Pre- and post-treatment nonfasting lipid profiles were measured and non-high-density lipoprotein (non-HDL) cholesterol (i.e. apoB-associated) was calculated. Binary logistic regression analysis assessed factors independently associated with treatment outcome. There was an independent association between higher apoB-associated cholesterol (non-HDL-C) and increased odds of SVR (odds ratio 2.09, P = 0.042). In multivariate analysis, non-HDL-C was significantly lower in HCV genotype 3 (g3) than genotype 1 (P = 0.007); this was reversible upon eradication of HCVg3 (pre-treatment non-HDL-C = 2.8 mmol/L, SVR = 3.6 mmol/L, P < 0.001). Higher apoB-associated cholesterol is positively associated with treatment outcome in CHC patients receiving anti-viral therapy, possibly due to competition between apoB-containing lipoproteins and infectious low-density HCV lipo-viral particles for hepatocyte entry via shared lipoprotein receptors.

Chronic hepatitis C virus infection: Serum biomarkers in predicting liver damage

PubMed Central

Valva, Pamela; Ríos, Daniela A; De Matteo, Elena; Preciado, Maria V

2016-01-01

Currently, a major clinical challenge in the management of the increasing number of hepatitis C virus (HCV) infected patients is determining the best means for evaluating liver impairment. Prognosis and treatment of chronic hepatitis C (CHC) are partly dependent on the assessment of histological activity, namely cell necrosis and inflammation, and the degree of liver fibrosis. These parameters can be provided by liver biopsy; however, in addition to the risks related to an invasive procedure, liver biopsy has been associated with sampling error mostly due to suboptimal biopsy size. To avoid these pitfalls, several markers have been proposed as non-invasive alternatives for the diagnosis of liver damage. Distinct approaches among the currently available non-invasive methods are (1) the physical ones based on imaging techniques; and (2) the biological ones based on serum biomarkers. In this review, we discuss these approaches with special focus on currently available non-invasive serum markers. We will discuss: (1) class I serum biomarkers individually and as combined panels, particularly those that mirror the metabolism of liver extracellular matrix turnover and/or fibrogenic cell changes; (2) class II biomarkers that are indirect serum markers and are based on the evaluation of common functional alterations in the liver; and (3) biomarkers of liver cell death, since hepatocyte apoptosis plays a significant role in the pathogenesis of HCV infection. We highlight in this review the evidence behind the use of these markers and assess the diagnostic accuracy as well as advantages, limitations, and application in clinical practice of each test for predicting liver damage in CHC. PMID:26819506

Development of multiple myeloma in a patient with chronic hepatitis C: A case report and review of the literature

PubMed Central

Lakatos, Peter Laszlo; Fekete, Sandor; Horanyi, Margit; Fischer, Simon; Abonyi, Margit E

2006-01-01

An association between chronic hepatitis C virus (HCV) infection and essential mixed cryoglobulinaemia and non-Hodgkin lymphoma (NHL) has been suggested. However, a causative role of HCV in these conditions has not been established. The authors report a case of a 50 year-old woman with chronic hepatitis C (CHC) who has been followed up since 1998 due to a high viral load, genotype 1b and moderately elevated liver function tests (LFTs). Laboratory data and liver biopsy revealed moderate activity (grade: 5/18, stage: 1/6). In April 1999, one-year interferon therapy was started. HCV-RNA became negative with normalization of LFTs. However, the patient relapsed during treatment. In September 2002, the patient was admitted for chronic back pain. A CT examination demonstrated degenerative changes. In March 2003, multiple myeloma was diagnosed (IgG-kappa, bone ma-rrow biopsy: 50% plasma cell infiltration). MRI revealed a compression fracture of the 5th lumbar vertebral body and an abdominal mass in the right lower quadrant, infiltrating the canalis spinalis. Treatment with vincristine, adriamycin and dexamethasone (VAD) was started and bisphosphonate was administered regularly. In January 2004, after six cycles of VAD therapy, the multiple myeloma regressed. Thalidomide, as a second line trea-tment of refractory multiple myeloma (MM) was initiated, and followed by peginterferon-α2b and ribavirin against the HCV infection in June. In June 2005, LFTs returned to normal, while HCV-RNA was negative, demonstrating an end of treatment response. Although a pathogenic role of HCV infection in malignant lymphoproliferative disorders has not been established, NHL and possibly MM may develop in CHC patients, supporting a role of a complex follow-up in these patients. PMID:16610042

"Smoking in Children's Environment Test": a qualitative study of experiences of a new instrument applied in preventive work in child health care.

PubMed

Carlsson, Noomi; Alehagen, Siw; Andersson Gäre, Boel; Johansson, Annakarin

2011-12-15

Despite knowledge of the adverse health effects of passive smoking, children are still being exposed. Children's nurses play an important role in tobacco preventive work through dialogue with parents aimed at identifying how children can be protected from environmental tobacco smoke (ETS) exposure. The study describes the experiences of Child Health Care (CHC) nurses when using the validated instrument SiCET (Smoking in Children's Environment Test) in dialogue with parents. In an intervention in CHC centres in south-eastern Sweden nurses were invited to use the SiCET. Eighteen nurses participated in focus group interviews. Transcripts were reviewed and their contents were coded into categories by three investigators using the method described for focus groups interviews. The SiCET was used in dialogue with parents in tobacco preventive work and resulted in focused discussions on smoking and support for behavioural changes among parents. The instrument had both strengths and limitations. The nurses experienced that the SiCET facilitated dialogue with parents and gave a comprehensive view of the child's ETS exposure. This gave nurses the possibility of taking on a supportive role by offering parents long-term help in protecting their child from ETS exposure and in considering smoking cessation. Our findings indicate that the SiCET supports nurses in their dialogue with parents on children's ETS exposure at CHC. There is a need for more clinical use and evaluation of the SiCET to determine its usefulness in clinical practice under varying circumstances. © 2011 Carlsson et al; licensee BioMed Central Ltd.

Sexual selection and population divergence I: The influence of socially flexible cuticular hydrocarbon expression in male field crickets (Teleogryllus oceanicus).

PubMed

Pascoal, Sonia; Mendrok, Magdalena; Mitchell, Christopher; Wilson, Alastair J; Hunt, John; Bailey, Nathan W

2016-01-01

Debates about how coevolution of sexual traits and preferences might promote evolutionary diversification have permeated speciation research for over a century. Recent work demonstrates that the expression of such traits can be sensitive to variation in the social environment. Here, we examined social flexibility in a sexually selected male trait-cuticular hydrocarbon (CHC) profiles-in the field cricket Teleogryllus oceanicus and tested whether population genetic divergence predicts the extent or direction of social flexibility in allopatric populations. We manipulated male crickets' social environments during rearing and then characterized CHC profiles. CHC signatures varied considerably across populations and also in response to the social environment, but our prediction that increased social flexibility would be selected in more recently founded populations exposed to fluctuating demographic environments was unsupported. Furthermore, models examining the influence of drift and selection failed to support a role of sexual selection in driving population divergence in CHC profiles. Variation in social environments might alter the dynamics of sexual selection, but our results align with theoretical predictions that the role social flexibility plays in modulating evolutionary divergence depends critically on whether responses to variation in the social environment are homogeneous across populations, or whether gene by social environment interactions occur. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

The complex interplay between macronutrient intake, cuticular hydrocarbon expression and mating success in male decorated crickets.

PubMed

Rapkin, J; Jensen, K; House, C M; Sakaluk, S K; Sakaluk, J K; Hunt, J

2017-04-01

The condition dependence of male sexual traits plays a central role in sexual selection theory. Relatively little, however, is known about the condition dependence of chemical signals used in mate choice and their subsequent effects on male mating success. Furthermore, few studies have isolated the specific nutrients responsible for condition-dependent variation in male sexual traits. Here, we used nutritional geometry to determine the effect of protein (P) and carbohydrate (C) intake on male cuticular hydrocarbon (CHC) expression and mating success in male decorated crickets (Gryllodes sigillatus). We show that both traits are maximized at a moderate-to-high intake of nutrients in a P:C ratio of 1 : 1.5. We also show that female precopulatory mate choice exerts a complex pattern of linear and quadratic sexual selection on this condition-dependent variation in male CHC expression. Structural equation modelling revealed that although the effect of nutrient intake on mating success is mediated through condition-dependent CHC expression, it is not exclusively so, suggesting that other traits must also play an important role. Collectively, our results suggest that the complex interplay between nutrient intake, CHC expression and mating success plays an important role in the operation of sexual selection in G. sigillatus. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Association between Leptin and Complement in Hepatitis C Patients with Viral Clearance: Homeostasis of Metabolism and Immunity.

PubMed

Chang, Ming-Ling; Kuo, Chia-Jung; Huang, Hsin-Chih; Chu, Yin-Yi; Chiu, Cheng-Tang

2016-01-01

The association between leptin and complement in hepatitis C virus (HCV) infection remains unknown. A prospective study was conducted including 474 (250 genotype 1, 224 genotype 2) consecutive chronic hepatitis C (CHC) patients who had completed an anti-HCV therapy course and undergone pre-therapy and 24-week post-therapy assessments of interferon λ3-rs12979860 and HCV RNA/genotypes, anthropometric measurements, metabolic and liver profiles, and complement component 3 (C3), C4, and leptin levels. Of the 474 patients, 395 had a sustained virological response (SVR). Pre-therapy leptin levels did not differ between patients with and without an SVR. Univariate and multivariate analyses showed that sex (pre- and post-therapy, p<0.001), body mass index (BMI) (pre- and post-therapy, p<0.001), and C3 levels (pre-therapy, p = 0.027; post-therapy, p = 0.02) were independently associated with leptin levels with or without HCV infection. Pre-therapy BMI, total cholesterol (TC), C4 levels, and the rs12979860 genotype were independently associated with pre-therapy C3 levels in all patients. Post-therapy BMI, alanine aminotransferase, TC, C4 levels, white blood cell counts, and hepatic steatosis were independently associated with the post-therapy C3 levels of SVR patients. Compared with pre-therapy levels, SVR patients showed higher 24-week post-therapy C4 (20.32+/-7.30 vs. 21.55+/-7.07 mg/dL, p<0.001) and TC (171.68+/-32.67 vs. 186.97+/-36.09 mg/dL, p<0.001) levels; however, leptin and C3 levels remained unchanged after therapy in patients with and without an SVR. Leptin and C3 may maintain immune and metabolic homeostasis through association with C4 and TC. Positive alterations in C4 and TC levels reflect viral clearance after therapy in CHC patients.

Rapid reduction of hepatitis C virus-Core protein in the peripheral blood improve the immunological response in chronic hepatitis C patients.

PubMed

Kondo, Yasuteru; Ueno, Yoshiyuki; Wakui, Yuta; Ninomiya, Masashi; Kakazu, Eiji; Inoue, Jun; Kobayashi, Koju; Obara, Noriyuki; Shimosegawa, Tooru

2011-12-01

  The extracellular hepatitis C virus (HCV)-antigen, including HCV-Core protein, can suppress immune cells. Recently, the efficacy of double filtration plasmapheresis (DFPP) for chronic hepatitis C (CHC) was reported. However, the mechanism of efficacy of DFPP might not be only the reduction of HCV but also the effect of immune cells via direct and/or indirect mechanisms. The aim of this study is to analyze the virological and immunological parameters of difficult-to-treat HCV patients treated with DFPP combined with Peg-interferon and RBV (DFPP/Peg-IFN/RBV) therapy.   Twelve CHC patients were enrolled and treated with DFPP/Peg-IFN/RBV therapy. The immunological, virological and genetic parameters were studied.   All patients (4/4) treated with the major IL28B allele (T/T) could achieve complete early virological response (EVR). The amounts of HCV-Core antigen in the peripheral blood of EVR patients treated with DFPP/Peg-IFN/RBV rapidly declined in comparison to those of late virological response (LVR) patients treated with DFPP/Peg-IFN/RBV and EVR patients treated with Peg-IFN and RBV (Peg-IFN/RBV). The amount of IFN-γ produced from peripheral blood gradually increased. On the other hand, the amount of IL10 gradually decreased in the EVR patients. The frequencies of HCV-Core binding on CD3+ T cells rapidly declined in EVR patients treated with DFPP/Peg-IFN/RBV therapy. Moreover, the distributions of activated CD4(+) and CD8(+) T cells and CD16-CD56 high natural killer cells were significantly changed between before and after DFPP.   The rapid reduction of HCV-Core antigens and changes in the distribution of lymphoid cells could contribute to the favorable immunological response during DFPP/Peg-IFN/RBV therapy. © 2011 The Japan Society of Hepatology.

Adverse health in parents of children with disabilities and chronic health conditions: a meta-analysis using the parenting stress index's health sub-domain.

PubMed

Miodrag, N; Burke, M; Tanner-Smith, E; Hodapp, R M

2015-03-01

Compared with parents of same-aged children without disabilities, parents of children with disabilities and with chronic health conditions (CHC) show higher levels of stress and depression. Fewer studies, however, examine the physical health of these parents, and studies report mixed findings. Many studies, however, report mother's self-reported health using the Health Sub-domain of Abidin's Parenting Stress Index (PSI). We therefore conducted a meta-analysis comparing the physical health of parents of children with developmental disabilities (DD) and CHC vs. parents of children without DD/CHC in studies utilising this measure. Eligible studies used the long form of the PSI and reported results from the 5-item Health sub-domain. Group comparison effect sizes were synthesised in a meta-analysis, and we also examined the potential relations of child, parent, and study characteristics. Our search yielded 19 eligible studies. Compared with parents of children without DD/CHC, parents of children with DD/CHC reported higher PSI health problem scores, with a weighted mean effect size of 0.39 (95% CI = 0.23-0.55). Effect sizes ranged from -0.13 to 1.46 and there was evidence of heterogeneity in the effect sizes (τ2  = 0.07; Q18  = 48.64, P < 0.01; I2  = 63.0%). Studies with higher numbers of reporting quality indicators generally reported larger effects and more recent studies showed smaller effects. Although several child and parent characteristics were moderately associated with effect sizes, none reached statistical significance. Practitioners should be alerted to the need for health prevention and treatment in this at-risk parent group. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Heterogeneous hyporheic zone dechlorination of a TCE groundwater plume discharging to an urban river reach.

PubMed

Freitas, Juliana G; Rivett, Michael O; Roche, Rachel S; Durrant Neé Cleverly, Megan; Walker, Caroline; Tellam, John H

2015-02-01

The typically elevated natural attenuation capacity of riverbed-hyporheic zones is expected to decrease chlorinated hydrocarbon (CHC) groundwater plume discharges to river receptors through dechlorination reactions. The aim of this study was to assess physico-chemical processes controlling field-scale variation in riverbed-hyporheic zone dechlorination of a TCE groundwater plume discharge to an urban river reach. The 50-m long pool-riffle-glide reach of the River Tame in Birmingham (UK) studied is a heterogeneous high energy river environment. The shallow riverbed was instrumented with a detailed network of multilevel samplers. Freeze coring revealed a geologically heterogeneous and poorly sorted riverbed. A chlorine number reduction approach provided a quantitative indicator of CHC dechlorination. Three sub-reaches of contrasting behaviour were identified. Greatest dechlorination occurred in the riffle sub-reach that was characterised by hyporheic zone flows, moderate sulphate concentrations and pH, anaerobic conditions, low iron, but elevated manganese concentrations with evidence of sulphate reduction. Transient hyporheic zone flows allowing input to varying riverbed depths of organic matter are anticipated to be a key control. The glide sub-reach displayed negligible dechlorination attributed to the predominant groundwater baseflow discharge condition, absence of hyporheic zone, transition to more oxic conditions and elevated sulphate concentrations expected to locally inhibit dechlorination. The tail-of-pool-riffle sub-reach exhibited patchy dechlorination that was attributed to sub-reach complexities including significant flow bypass of a low permeability, high organic matter, silty unit of high dechlorination potential. A process-based conceptual model of reach-scale dechlorination variability was developed. Key findings of practitioner relevance were: riverbed-hyporheic zone CHC dechlorination may provide only a partial, somewhat patchy barrier to CHC groundwater plume discharges to a surface water receptor; and, monitoring requirements to assess the variability in CHC attenuation within a reach are expected to be onerous. Further research on transient hyporheic zone dechlorination is recommended. Copyright © 2014 Elsevier B.V. All rights reserved.

The funding of community health center dental programs in California.

PubMed

Hilton, Irene V

2009-05-01

The financing of dental services in community health centers, CHCs, is a mystery to most dentists in private practice, and this lack of knowledge has resulted in misconceptions that hamper mutual support. This review seeks to explain and demystify how CHC dental clinics remain financially viable. The mechanisms of financing dental care in CHCs are described including types of revenues received, financing constraints unique to CHCs and how services to indigent patients are funded.

The Youth Health Care measure-satisfaction, utilization, and needs (YHC-SUN)-development of a self-report version of the Child Health Care (CHC-SUN) proxy-measure.

PubMed

Schmidt, Silke; Thyen, Ute; Herrmann-Garitz, Carsten; Bomba, Franziska; Muehlan, Holger

2016-05-20

The transition of health care of youth (age 15-25) with chronic conditions requires the assessment of adolescents' access, use and needs as well as satisfaction with the health services they use. The aim of this study was to test the adolescent adaptation of the parent version "Child Health Care Questionnaire - Satisfaction, Utilization and Needs" (CHC-SUN) concerning its psychometric performance and appropriateness for adolescents and young adults. The Youth Health Care Measure (YHC-SUN) was designed to allow self-report of youth and it was pilot-tested in a small sample using cognitive debriefing. A cross-sectional survey in a sample of youth with chronic conditions in the transition period was carried out. One hundred eighty-two ambulatory care patients with three conditions participated in the survey. The subscales of the section on satisfaction with care showed excellent internal consistencies, uni-dimensionality and fit to the model of the parent version. There was no impact of gender and education on satisfaction with care. Associations with age, diagnosis, experiences with care and health literacy affecting the satisfaction with care indicate discriminatory and content validity. Potential applications of the new instrument are evaluations of health care services for adolescents and young adults using self-reports and evaluations of transition programs and interventions such as patient education.

Interleukin28B and inosine triphosphatase help to personalize hepatitis C treatment.

PubMed

Tanaka, Yasuhito

2011-01-01

In the therapy using a combination of pegylated interferon-α and ribavirin (PEG-IFN/RBV) for chronic hepatitis C (CHC), approximately 50% of CHC patients infected with high viremia of HCV genotype 1 reached sustained viral response. The recent discovery revealed by a genome-wide association study technology provides the unexpected role of IL28B and inosine triphosphatase (ITPA) in HCV infection. The former single nucleotide polymorphisms (SNPs) around the IL28B gene could improve the diagnostics on the prediction of spontaneous clearance and the response to anti-HCV treatment, suggesting that these findings could be strong evidence to enhance the development of a novel therapeutic strategy and the basic study of IFN-λs. Interestingly, the discovered IL28B SNPs revealed the enigma that the viral clearance rate was dependent on ethnicity. The latter functional SNP in ITPA locus was the most significant SNP associated with RBV-induced anemia as well as IFN-induced thrombocytopenia. Note that severe Hb decline, which is mainly found in ITPA-CC patients, was inversely correlated with platelet reduction, contributing to an association between severe anemia and relative reactive increase in platelet count. These data may provide a valuable pharmacogenetic diagnostic tool for tailoring PEG-IFN/RBV dosing to minimize drug-induced adverse events and for further optimization of clinical anti-HCV chemotherapeutics. Copyright © 2011 S. Karger AG, Basel.

Simultaneous identification of multi-combustion-intermediates of alkanol-air flames by femtosecond filament excitation for combustion sensing

PubMed Central

Li, Helong; Chu, Wei; Xu, Huailiang; Cheng, Ya; Chin, See-Leang; Yamanouchi, Kaoru; Sun, Hong-Bo

2016-01-01

Laser filamentation produced by the propagation of intense laser pulses in flames is opening up new possibility in application to combustion diagnostics that can provide useful information on understanding combustion processes, enhancing combustion efficiency and reducing pollutant products. Here we present simultaneous identification of multiple combustion intermediates by femtosecond filament excitation for five alkanol-air flames fueled by methanol, ethanol, n-propanol, n-butanol, and n-pentanol. We experimentally demonstrate that the intensities of filament-induced photoemission signals from the combustion intermediates C, C2, CH, CN increase with the increasing number of carbons in the fuel molecules, and the signal ratios between the intermediates (CH/C, CH/C2, CN/C, CH/C2, CN/CH) are different for different alkanol combustion flames. Our observation provides a way for sensing multiple combustion components by femtosecond filament excitation in various combustion conditions that strongly depend on the fuel species. PMID:27250021

Quantitative fluorescence measurements performed on typical matrix molecules in matrix-assisted laser desorption/ionisation

NASA Astrophysics Data System (ADS)

Allwood, D. A.; Dyer, P. E.

2000-11-01

Fundamental photophysical parameters have been determined for several molecules that are commonly used as matrices, e.g. ferulic acid, within matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Fluorescence quantum efficiencies ( φqe), singlet decay rates ( kl), vibrationless ground-singlet transition energies and average fluorescence wavelengths have been obtained from solid and solution samples by quantitative optical measurements. This new data will assist in modelling calculations of MALDI processes and in highlighting desirable characteristics of MALDI matrices. φqe may be as high as 0.59 whilst the radiative decay rate ( kf) appears to be within the (0.8-4)×10 8 s -1 range. Interestingly, α-cyano-4-hydroxycinnamic acid (α-CHC) has a very low φqe and fast non-radiative decay rate which would imply a rapid and efficient thermalisation of electronic excitation. This is in keeping with observations that α-CHC exhibits low threshold fluences for ion detection and the low fluences at which α-CHC tends to fragment.

Fabrication, characterization and antimicrobial activities of thymol-loaded zein nanoparticles stabilized by sodium caseinate-chitosan hydrochloride double layers.

PubMed

Zhang, Yaqiong; Niu, Yuge; Luo, Yangchao; Ge, Mei; Yang, Tian; Yu, Liangli Lucy; Wang, Qin

2014-01-01

Thymol-loaded zein nanoparticles stabilized with sodium caseinate (SC) and chitosan hydrochloride (CHC) were prepared and characterized. The SC stabilized nanoparticles had well-defined size range and negatively charged surface. Due to the presence of SC, the stabilized zein nanoparticles showed a shift of isoelectric point from 6.18 to 5.05, and had a desirable redispersibility in water at neutral pH after lyophilization. Coating with CHC onto the SC stabilized zein nanoparticles resulted in increased particle size, reversal of zeta potential value from negative to positive, and improved encapsulation efficiency. Both thymol-loaded zein nanoparticles and SC stabilized zein nanoparticles had a spherical shape and smooth surface, while the surfaces of CHC-SC stabilized zein nanoparticles seemed rough and had some clumps. Encapsulated thymol was more effective in suppressing gram-positive bacterium than un-encapsulated thymol for a longer time period. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact of vitamin D receptor and binding protein gene polymorphisms in clinical and laboratory data of HCV patients

PubMed Central

Scalioni, Letícia de Paula; dos Santos, Betânia Rodrigues; Spritzer, Poli Mara; Villela-Nogueira, Cristiane Alves; Laura Lewis-Ximenez, Lia; Pollo-Flores, Priscila; Bordalo Cathalá Esberard, Eliane; Brandão-Mello, Carlos Eduardo; Lampe, Elisabeth; Villar, Livia Melo

2018-01-01

Abstract Potential relationship of vitamin D, vitamin D receptor (VDR), and vitamin D binding protein (DBP) have been suggested in the pathophysiology of hepatitis C virus (HCV) infection. The aim of this observational study is to determine vitamin D levels, and VDR and DBP genetic polymorphism according demographic and laboratory data in chronic HCV patients (CHC). A total of 148 CHC patients gave serum samples for testing 25-hydroxyvitamin D (25 (OH)D) level by immunochemiluminometric assay (<20 ng/mL defined as deficient) and donated blood samples to allelic discrimination analysis using TaqMan assays. Analyzed single nucleotide polymorphisms (SNPs) were: VDR-rs7975232 (ApaI) C>A, rs731236 A>G (TaqI), rs1544410 C>T (BsmI), rs10735810 T>C (FokI) and carrier globulin/binding protein (GC)-rs4588 and rs7041 and the haplotype bAt [CCA]. Hepatic fibrosis was assessed using Fib-4 and Forns index. Eighty-two (54.40%) patients demonstrated deficiency of vitamin D and this was associated to AST (P = .019 [CI: 1.003–1.034]), total cholesterol (P = .038 [CI: 1.004–1.164]), fibrosis grade (P < .001 [CI: 0.000–0.844]), and FokI (P = .028) allele T presence. Association was found between VDR polymorphism and fibrosis (BsmI andTaqI), triglycerides (TaqI), and HDL (FokI). DBP polymorphism was associated to HCV genotype (GC rs7041), previous HCV treatment, and GGT (GC rs4588). In conclusion, low frequency of vitamin D deficiency was found, but VDR polymorphisms were frequently associated to fibrosis grade suggesting that they could be used as disease evaluation markers to understand the mechanisms underlying the virus–host interaction. PMID:29465575

Risk of hepatitis B virus reactivation with direct-acting antivirals against hepatitis C virus: A cohort study from Egypt and meta-analysis of published data.

PubMed

El Kassas, Mohamed; Shimakawa, Yusuke; Ali-Eldin, Zainab; Funk, Anna-Louise; Wifi, Mohamed Naguib; Zaky, Samy; El-Raey, Fathiya; Esmat, Gamal; Fontanet, Arnaud

2018-05-08

Hepatitis B virus (HBV) reactivation in chronic hepatitis C (CHC) patients treated with direct-acting antivirals (DAAs) became an issue. However, its frequency has been poorly estimated, because of the varying definitions used and evaluation of heterogeneous study populations, including those concurrently treated for HBV. We prospectively followed HBV surface antigen (HBsAg)-positive Egyptians undergoing interferon-free DAAs, to estimate the risk of HBV reactivation and HBV-related hepatitis. We also conducted a meta-analysis to estimate the reactivation risk using published data obtained from a systematic review of PubMed/Embase, in addition to our Egyptian data. We applied a standard definition of HBV reactivation proposed by the international liver associations (APASL and AASLD). Of 4471 CHC patients, 35 HBsAg-positive patients started interferon-free DAAs without HBV nucleos(t)ide analogues in our Egyptian cohort. Ten experienced HBV reactivation (28.6%), of whom 1 developed hepatitis (10.0%). Our systematic review identified 18 papers. The pooled reactivation risk in HBsAg-positive patients was 18.2% (95% CI: 7.9%-30.7%) without HBV therapy and 0.0% (95% CI: 0.0%-0.0%) with HBV nucleos(t)ide analogue. The pooled risk of hepatitis in those with HBV reactivation was 12.6% (95% CI: 0.0%-34.7%). The pooled reactivation risk in HBsAg-negative, antibody to HBV core antigen-positive (anti-HBc-positive) patients was negligible (0.1%, 95% CI: 0.0%-0.3%), irrespective of the presence of antibody to HBsAg (anti-HBs). We confirmed high HBV reactivation risk in HBsAg-positive patients undergoing DAAs, with only a minority developing clinically important hepatitis. The risk is negligible for HBsAg-negative anti-HBc-positive patients. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Implementation of national guidelines, incorporated within structured diabetes and hypertension records at primary level care in Cape Town, South Africa: a randomised controlled trial.

PubMed

Steyn, Krisela; Lombard, Carl; Gwebushe, Nomonde; Fourie, Jean M; Everett-Murphy, Katherine; Zwarenstein, Merrick; Levitt, Naomi S

2013-09-25

Many clinical management guidelines for chronic diseases have been published, but they have not been put into practice by busy clinicians at primary care levels. This study evaluates the implementation of national guidelines incorporated within a structured diabetes and hypertension clinical record (SR) in Cape Town in a randomised controlled trial (RCT). Eighteen public sector community health centres (CHC) were randomly selected and allocated as intervention or control CHC. At each clinic, 25 patients with diabetes and 35 patients with hypertension were enrolled at baseline. Questionnaires were completed, blood samples were collected, blood pressure (BP) and anthropometric measures were taken and patient records were audited. SR with clinical guideline prompts were introduced at the intervention clinics after training doctors in their use and suggestions to incorporate them in regular patient records. Contact was maintained during the year of intervention with the clinic staff. A follow-up survey was conducted 1 year later to assess BP and HbA1c, and the patient records were examined to ascertain the extent of use of the SR in the intervention clinics. In-depth interviews were conducted with doctors and nurses to record their response to the intervention. The intervention evaluated in this RCT had no impact on either diabetes or hypertension control. In the intervention clinics, less than 60% of the patient folders contained the SR and when present was seldom used. Although the staff were well disposed to the research team, their workload prohibited them from undertaking a true evaluation of the SR, and overall they did not perceive the SR as supporting their current process of patient care. No benefit to diabetes of hypertension care by introducing and availability of the staff in the use of the SR was shown in this RCT. The process measures suggest that the SR was not widely used by the healthcare provided in the primary care clinics.

Impacts of the Affordable Care Act on Community Health Centers: Characteristics of New Patients and Early Changes in Delivery of Care.

PubMed

Hatch, Brigit; Smith, Ning; McBurnie, Mary Ann; Quach, Thu; Mayer, Kenneth H; Dunne, Mary J; Cottrell, Erika

2018-05-15

The aim of this study was to assess the impact of the Affordable Care Act (ACA) on community health centers (CHCs). Using electronic health records from the Community Health Applied Research Network, we assessed new patient characteristics, office visit volume, and payer distribution among CHC patients before and after ACA implementation, 2011-2014 (n = 442 455). New patients post-ACA were younger, more likely to be female and have chronic health conditions, and utilized more primary care (P < .05 for each). Post-ACA, clinics delivered 19% more office visits and more visits were reimbursed by Medicaid. The support of CHCs is needed to meet increased demand post-ACA.

Clinical characteristics, healthcare costs, and resource utilization in hepatitis C vary by genotype.

PubMed

Goolsby Hunter, Alyssa; Rosenblatt, Lisa; Patel, Chad; Blauer-Peterson, Cori; Anduze-Faris, Beatrice

2017-05-01

In the United States, approximately 3 million people are infected with hepatitis C virus (HCV). Genotypes of HCV variably affect disease progression and treatment response. However, the relationships between HCV genotypes and liver disease progression, healthcare resource utilization, and healthcare costs have not been fully explored. In this retrospective study of patients with chronic hepatitis C (CHC), healthcare claims from a large US health plan were used to collect data on patient demographic and clinical characteristics. Main outcome measures include healthcare resource utilization (HCRU) and healthcare costs. Linked laboratory data provided genotype and select measures to determine liver disease severity. The sample (mean age 50.6 years, 63.5% male) included 10,331 patients, of whom 79.1% had genotype (GT)1, 12.8% had GT2, and 8.1% had GT3. Descriptive analyses demonstrated variation by HCV genotype in liver and non-liver related comorbidities, liver disease severity, and healthcare costs. The highest percentage of patients with liver-related comorbidities and advanced liver disease was found among those with GT3. Meanwhile, patients with GT2 had lower HCRU and the lowest costs, and patients with GT1 had the highest total all-cause costs. These differences may reflect differing rates of non-liver-related comorbidities and all-cause care. Multivariable analyses showed that genotype was a significant predictor of costs and liver disease severity: compared with patients having GT1, those with GT3 were significantly more likely to have advanced liver disease. Patients with GT2 were significantly less likely to have advanced disease and more likely to have lower all-cause costs. Results may not be generalizable to patients outside the represented commercial insurance plans, and analysis of a prevalent population may underestimate HCRU and costs relative to a sample of treated patients. These results suggest that liver disease progression varies by genotype and that CHC patients with GT3 appear to have more severe liver disease. These findings highlight the importance of effective HCV treatment for all patients and support guidelines for treatment of high-risk patients, including those with GT3.

FTIR gas-phase kinetic study on the reactions of some acrylate esters with OH radicals and Cl atoms.

PubMed

Moreno, A; Gallego-Iniesta, M P; Taccone, R; Martín, M P; Cabañas, B; Salgado, M S

2014-10-01

Acrylate esters are α,β-unsaturated esters that contain vinyl groups directly attached to the carbonyl carbon. These compounds are widely used in the production of plastics and resins. Atmospheric degradation processes of these compounds are currently not well understood. The kinetics of the gas phase reactions of OH radicals with methyl 3-methylacrylate and methyl 3,3-dimethylacrylate were determined using the relative rate technique in a 50 L Pyrex photoreactor using in situ FTIR spectroscopy at room temperature (298 ± 2 K) and atmospheric pressure (708 ± 8 Torr) with air as the bath gas. Rate coefficients obtained were (in units cm(3) molecule(-1) s(-1)): (3.27 ± 0.33) × 10(-11) and (4.43 ± 0.42) × 10(-11), for CH3CH═CHC(O)OCH3 and (CH3)2CH═CHC(O)OCH3, respectively. The same technique was used to study the gas phase reactions of hexyl acrylate and ethyl hexyl acrylate with OH radicals and Cl atoms. In the experiments with Cl, N2 and air were used as the bath gases. The following rate coefficients were obtained (in cm(3) molecule(-1) s(-1)): k3 (CH2═CHC(O)O(CH2)5CH3 + Cl) = (3.31 ± 0.31) × 10(-10), k4(CH2═CHC(O)OCH2CH(CH2CH3)(CH2)3CH3 + Cl) = (3.46 ± 0.31) × 10(-10), k5(CH2═CHC(O)O(CH2)5CH3 + OH) = (2.28 ± 0.23) × 10(-11), and k6(CH2═CHC(O)OCH2CH(CH2CH3)(CH2)3CH3 + OH) = (2.74 ± 0.26) × 10(-11). The reactivity increased with the number of methyl substituents on the double bond and with the chain length of the alkyl group in -C(O)OR. Estimations of the atmospheric lifetimes clearly indicate that the dominant atmospheric loss process for these compounds is their daytime reaction with the hydroxyl radical. In coastal areas and in some polluted environments, Cl atom-initiated degradation of these compounds can be significant, if not dominant. Maximum Incremental Reactivity (MIR) index and global warming potential (GWP) were also calculated, and it was concluded that these compounds have significant MIR values, but they do not influence global warming.

Cuticular differences associated with aridity acclimation in African malaria vectors carrying alternative arrangements of inversion 2La.

PubMed

Reidenbach, Kyanne R; Cheng, Changde; Liu, Fang; Liu, Cheng; Besansky, Nora J; Syed, Zainulabeuddin

2014-04-10

Principal malaria vectors in Africa, An. gambiae and An. coluzzii, share an inversion polymorphism on the left arm of chromosome 2 (2La/2L+a) that is distributed non-randomly in the environment. Genomic sequencing studies support the role of strong natural selection in maintaining steep clines in 2La inversion frequency along environmental gradients of aridity, and physiological studies have directly implicated 2La in heat and desiccation tolerance, but the precise genetic basis and the underlying behavioral and physiological mechanisms remain unknown. As the insect cuticle is the primary barrier to water loss, differences in cuticle thickness and/or epicuticular waterproofing associated with alternative 2La arrangements might help explain differences in desiccation resistance. To test that hypothesis, two subcolonies of both An. gambiae and An. coluzzii were established that were fixed for alternative 2La arrangements (2La or 2L+a) on an otherwise homosequential and shared genetic background. Adult mosquitoes reared under controlled environmental conditions (benign or arid) for eight days post-eclosion were collected and analyzed. Measurements of cuticle thickness were made based on scanning electron microscopy, and cuticular hydrocarbon (CHC) composition was evaluated by gas chromatography-mass spectrometry. After removing the allometric effects of body weight, differences in mean cuticle thickness were found between alternative 2La karyotypes, but not between alternative environments. Moreover, the thicker cuticle of the An. coluzzii 2La karyotype was contrary to the known higher rate of water loss of this karyotype relative to 2L+a. On the other hand, quantitative differences in individual CHCs and overall CHC profiles between alternative karyotypes and environmental conditions were consistent with expectation based on previous physiological studies. Our results suggest that alternative arrangements of the 2La inversion are associated with differences in cuticle thickness and CHC composition, but that only CHC composition appears to be relevant for desiccation resistance. Differences in the CHC composition were consistent with previous findings of a lower rate of water loss for the 2L+a karyotype at eight days post-eclosion, suggesting that CHC composition is an important strategy for maintaining water balance in this genetic background, but not for 2La. Despite a higher rate of water loss at eight days, higher body water content of the 2La karyotype confers a level of desiccation resistance equivalent to that of the 2L+a karyotype.

A study of structural and functional connectivity in early Alzheimer's disease using rest fMRI and diffusion tensor imaging.

PubMed

Balachandar, R; John, J P; Saini, J; Kumar, K J; Joshi, H; Sadanand, S; Aiyappan, S; Sivakumar, P T; Loganathan, S; Varghese, M; Bharath, S

2015-05-01

Alzheimer's disease (AD) is a progressive neurodegenerative condition where in early diagnosis and interventions are key policy priorities in dementia services and research. We studied the functional and structural connectivity in mild AD to determine the nature of connectivity changes that coexist with neurocognitive deficits in the early stages of AD. Fifteen mild AD subjects and 15 cognitively healthy controls (CHc) matched for age and gender, underwent detailed neurocognitive assessment and magnetic resonance imaging (MRI) of resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Rest fMRI was analyzed using dual regression approach and DTI by voxel wise statistics. Patients with mild AD had significantly lower functional connectivity (FC) within the default mode network and increased FC within the executive network. The mild AD group scored significantly lower in all domains of cognition compared with CHc. But fractional anisotropy did not significantly (p < 0.05) differ between the groups. Resting state functional connectivity alterations are noted during initial stages of cognitive decline in AD, even when there are no significant white matter microstructural changes. Copyright © 2014 John Wiley & Sons, Ltd.

Implementation and Operational Research: Cost and Efficiency of a Hybrid Mobile Multidisease Testing Approach With High HIV Testing Coverage in East Africa.

PubMed

Chang, Wei; Chamie, Gabriel; Mwai, Daniel; Clark, Tamara D; Thirumurthy, Harsha; Charlebois, Edwin D; Petersen, Maya; Kabami, Jane; Ssemmondo, Emmanuel; Kadede, Kevin; Kwarisiima, Dalsone; Sang, Norton; Bukusi, Elizabeth A; Cohen, Craig R; Kamya, Moses; Havlir, Diane V; Kahn, James G

2016-11-01

In 2013-2014, we achieved 89% adult HIV testing coverage using a hybrid testing approach in 32 communities in Uganda and Kenya (SEARCH: NCT01864603). To inform scalability, we sought to determine: (1) overall cost and efficiency of this approach; and (2) costs associated with point-of-care (POC) CD4 testing, multidisease services, and community mobilization. We applied microcosting methods to estimate costs of population-wide HIV testing in 12 SEARCH trial communities. Main intervention components of the hybrid approach are census, multidisease community health campaigns (CHC), and home-based testing for CHC nonattendees. POC CD4 tests were provided for all HIV-infected participants. Data were extracted from expenditure records, activity registers, staff interviews, and time and motion logs. The mean cost per adult tested for HIV was $20.5 (range: $17.1-$32.1) (2014 US$), including a POC CD4 test at $16 per HIV+ person identified. Cost per adult tested for HIV was $13.8 at CHC vs. $31.7 by home-based testing. The cost per HIV+ adult identified was $231 ($87-$1245), with variability due mainly to HIV prevalence among persons tested (ie, HIV positivity rate). The marginal costs of multidisease testing at CHCs were $1.16/person for hypertension and diabetes, and $0.90 for malaria. Community mobilization constituted 15.3% of total costs. The hybrid testing approach achieved very high HIV testing coverage, with POC CD4, at costs similar to previously reported mobile, home-based, or venue-based HIV testing approaches in sub-Saharan Africa. By leveraging HIV infrastructure, multidisease services were offered at low marginal costs.

Isolation and determination of absolute configurations of insect-produced methyl-branched hydrocarbons

PubMed Central

Bello, Jan E.; McElfresh, J. Steven; Millar, Jocelyn G.

2015-01-01

Although the effects of stereochemistry have been studied extensively for volatile insect pheromones, little is known about the effects of chirality in the nonvolatile methyl-branched hydrocarbons (MBCHs) used by many insects as contact pheromones. MBCHs generally contain one or more chiral centers and so two or more stereoisomeric forms are possible for each structure. However, it is not known whether insects biosynthesize these molecules in high stereoisomeric purity, nor is it known whether insects can distinguish the different stereoisomeric forms of MBCHs. This knowledge gap is due in part to the lack of methods for isolating individual MBCHs from the complex cuticular hydrocarbon (CHC) blends of insects, as well as the difficulty in determining the absolute configurations of the isolated MBCHs. To address these deficiencies, we report a straightforward method for the isolation of individual cuticular hydrocarbons from the complex CHC blend. The method was used to isolate 36 pure MBCHs from 20 species in nine insect orders. The absolute stereochemistries of the purified MBCHs then were determined by digital polarimetry. The absolute configurations of all of the isolated MBCHs were determined to be (R) by comparison with a library of synthesized, enantiomerically pure standards, suggesting that the biosynthetic pathways used to construct MBCHs are highly conserved within the Insecta. The development of a straightforward method for isolation of specific CHCs will enable determination of their functional roles by providing pure compounds for bioassays. PMID:25583471

Is HCV core antigen a reliable marker of viral load? An evaluation of HCV core antigen automated immunoassay

PubMed Central

Hadziyannis, Emilia; Minopetrou, Martha; Georgiou, Anastasia; Spanou, Fotini; Koskinas, John

2013-01-01

Background Hepatitis C viral (HCV) load detection and quantification is routinely accomplished by HCV RNA measurement, an expensive but essential test, both for the diagnosis and treatment of chronic hepatitis C (CHC). HCV core antigen (Ag) testing has been suggested as an attractive alternative to molecular diagnostics. The aim of the study was to evaluate an automated chemiluminescent immunoassay (CLIA) for HCV core Ag measurement in comparison to quantitative HCV RNA determination. Methods HCV Ag was measured in 105 anti-HCV positive patients, from which 89 were HCV RNA positive with CHC and 16 HCV RNA negative after spontaneous HCV clearance. Viral load was quantified with branched DNA (bDNA, Versant, Siemens). Sera were stored at -70°C and then tested with the Architect HCV Ag test (Abbott Laboratories), a two-step CLIA assay, with high throughput and minimal handling of the specimens. Statistical analysis was performed on logarithmically transformed values. Results HCV-Ag was detectable and quantifiable in 83/89 and in grey zone in 4/89 HCV RNA positive sera. HCV-Ag was undetectable in all 16 HCV RNA negative samples. The sample with the lowest viral load that tested positive for HCV-Ag contained 1200 IU/mL HCV RNA. There was a positive correlation between HCV RNA and HCV-Ag (r=0.89). The HCV RNA/ HCV Ag ratio varied from 1.5 to 3.25. Conclusion The HCV core Ag is an easy test with comparable sensitivity (>90%) and satisfactory correlation with the HCV RNA bDNA assay. Its role in diagnostics and other clinical applications has to be determined based on cost effectiveness. PMID:24714621

A parallel domain decomposition-based implicit method for the Cahn–Hilliard–Cook phase-field equation in 3D

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

Zheng, Xiang; Yang, Chao; State Key Laboratory of Computer Science, Chinese Academy of Sciences, Beijing 100190

2015-03-15

We present a numerical algorithm for simulating the spinodal decomposition described by the three dimensional Cahn–Hilliard–Cook (CHC) equation, which is a fourth-order stochastic partial differential equation with a noise term. The equation is discretized in space and time based on a fully implicit, cell-centered finite difference scheme, with an adaptive time-stepping strategy designed to accelerate the progress to equilibrium. At each time step, a parallel Newton–Krylov–Schwarz algorithm is used to solve the nonlinear system. We discuss various numerical and computational challenges associated with the method. The numerical scheme is validated by a comparison with an explicit scheme of high accuracymore » (and unreasonably high cost). We present steady state solutions of the CHC equation in two and three dimensions. The effect of the thermal fluctuation on the spinodal decomposition process is studied. We show that the existence of the thermal fluctuation accelerates the spinodal decomposition process and that the final steady morphology is sensitive to the stochastic noise. We also show the evolution of the energies and statistical moments. In terms of the parallel performance, it is found that the implicit domain decomposition approach scales well on supercomputers with a large number of processors.« less

An Alternative Approach for Supportive Supervision and Skill Measurements of Health Workers for Integrated Management of Neonatal and Childhood Illnesses Program in 10 Districts of Haryana.

PubMed

Aggarwal, Arun K; Gupta, Rakesh; Das, Dhritiman; Dhakar, Anar S; Sharma, Gourav; Anand, Himani; Kaur, Kamalpreet; Sheoran, Kiran; Dalpath, Suresh; Khatri, Jaidev; Gupta, Madhu

2018-01-01

"Integrated Management of Neonatal and Childhood Illnesses" (IMNCI) needs regular supportive supervision (SS). The aim of this study was to find suitable SS model for implementing IMNCI. This was a prospective interventional study in 10 high-focus districts of Haryana. Two methods of SS were used: (a) visit to subcenters and home visits (model 1) and (b) organization of IMNCI clinics/camps at primary health center (PHC) and community health center (CHC) (model 2). Skill scores were measured at different time points. Routine IMNCI data from study block and randomly selected control block of each district were retrieved for 4 months before and after the training and supervision. Change in percentage mean skill score difference and percentage difference in median number of children were assessed in two areas. Mean skill scores increased significantly from 2.1 (pretest) to 7.0 (posttest 1). Supportive supervisory visits sustained and improved skill scores. While model 2 of SS could positively involve health system officials, model 1 was not well received. Outcome indicator in terms of number of children assessed showed a significant improvement in intervention areas. SS in IMNCI clinics/camps at PHC/CHC level and innovative skill scoring method is a promising approach.

On the hydration and conformation of cocaine in solution

NASA Astrophysics Data System (ADS)

Gillams, Richard J.; Lorenz, Christian D.; McLain, Sylvia E.

2017-05-01

In order to develop theories relating to the mechanism through which cocaine can diffuse across the blood-brain barrier, it is important to understand the interplay between the hydration of the molecule and the adopted conformation. Here key differences in the hydration of cocaine hydrochloride (CHC) and freebase cocaine (CFB) are highlighted on the atomic scale in solution, through the use of molecular dynamics simulations. By adopting different conformations, CHC and CFB experience differing hydration environments. The interplay between these two factors may account for the vast difference in solubility of these two molecules.

The effect of temperature on the stability of compounds used as UV-MALDI-MS matrix: 2,5-dihydroxybenzoic acid, 2,4,6-trihydroxyacetophenone, alpha-cyano-4-hydroxycinnamic acid, 3,5-dimethoxy-4-hydroxycinnamic acid, nor-harmane and harmane.

PubMed

Tarzi, Olga I; Nonami, Hiroshi; Erra-Balsells, Rosa

2009-02-01

The thermal stability of several commonly used crystalline matrix-assisted ultraviolet laser desorption/ionization mass spectrometry (UV-MALDI-MS) matrices, 2,5-dihydroxybenzoic acid (gentisic acid; GA), 2,4,6-trihydroxyacetophenone (THA), alpha-cyano-4-hydroxycinnamic acid (CHC), 3,5-dimethoxy-4-hydroxycinnamic acid (sinapinic acid; SA), 9H-pirido[3,4-b]indole (nor-harmane; nor-Ho), 1-methyl-9H-pirido[3,4-b]indole (harmane; Ho), perchlorate of nor-harmanonium ([nor-Ho+H]+) and perchlorate of harmanonium ([Ho+H]+) was studied by heating them at their melting point and characterizing the remaining material by using different MS techniques [electron ionization mass spectrometry (EI-MS), ultraviolet laserdesorption/ionization-time-of-flight-mass spectrometry (UV-LDI-TOF-MS) and electrospray ionization-time-of-flight-mass spectrometry (ESI-TOF-MS)] as well as by thin layer chromatography analysis (TLC), electronic spectroscopy (UV-absorption, fluorescence emission and excitation spectroscopy) and 1H nuclear magnetic resonance spectroscopy (1H-NMR). In general, all compounds, except for CHC and SA, remained unchanged after fusion. CHC showed loss of CO2, yielding the trans-/cis-4-hydroxyphenylacrilonitrile mixture. This mixture was unambiguously characterized by MS and 1H-NMR spectroscopy, and its sublimation capability was demonstrated. These results explain the well-known cluster formation, fading (vanishing) and further recovering of CHC when used as a matrix in UV-MALDI-MS. Commercial SA (SA 98%; trans-SA/cis-SA 5:1) showed mainly cis- to-trans thermal isomerization and, with very poor yield, loss of CO2, yielding (3',5'-dimethoxy-4'-hydroxyphenyl)-1-ethene as the decarboxilated product. These thermal conversions would not drastically affect its behavior as a UV-MALDI matrix as happens in the case of CHC. Complementary studies of the photochemical stability of these matrices in solid state were also conducted. Copyright (c) 2008 John Wiley & Sons, Ltd.

Efficacy and safety profile of boceprevir- or telaprevir-based triple therapy or dual peginterferon alfa-2a or alfa-2b plus ribavirin therapy in chronic hepatitis C: the real-world PegBase observational study.

PubMed

Mangia, Alessandra; Foster, Graham R; Berg, Christoph P; Curescu, Manuela; Ledinghen, Victor De; Habersetzer, François; Manolakopoulos, Spilios; Negri, Elisa; Papatheodoridis, George; Ahlers, Silke; Castillo, Marco; Bakalos, Georgios; Mauss, Stefan

2017-01-01

The aim of the study was to determine the efficacy and safety of triple therapy with a first-generation protease inhibitor (PI; boceprevir, telaprevir) plus peginterferon alfa-2a or -2b plus ribavirin, and dual therapy (peginterferon alfa-2a or -2b plus ribavirin) in patients with chronic hepatitis C (CHC) in routine clinical practice. PegBase was an international, prospective, observational study in which 4441 patients with CHC were enrolled in 27 countries. This analysis focuses on results in 4100 treatment-naïve and previously treated patients treated with PI-based triple therapy or dual therapy, according to the discretion of the investigator and local standards of practice. The primary efficacy outcome was sustained virological response after 12-week follow up (SVR12). SVR12 rates in treatment-naïve genotype (G) 1 patients were 56.6% and 62.9% for recipients of boceprevir plus peginterferon alfa-2a/ribavirin and boceprevir plus peginterferon alfa-2b/ribavirin, respectively, and 65.3% and 58.6% for recipients of telaprevir plus peginterferon alfa-2a/ribavirin and telaprevir plus peginterferon alfa-2b/ribavirin, respectively. In previously treated patients assigned to these four regimens, SVR12 rates were 43.6%, 48.3%, 60.3% and 56.1%, respectively. Among treatment-naïve patients assigned to peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin, respectively, SVR12 rates were 49.2% and 41.9% in G1 patients, 75.7% and 83.3% in G2 patients, 65.9% and 65.9% in G3 patients, and 49.7%, and 51.1% in G4 patients. The safety and tolerability of dual and triple therapy were consistent with previous reports. The efficacy and safety of first-generation PI-based triple-therapy and dual-therapy regimens in this real-world cohort were broadly comparable to those of previous studies.

Meta-Analysis of the Effects of Computerized Cognitive Training on Executive Functions: a Cross-Disciplinary Taxonomy for Classifying Outcome Cognitive Factors.

PubMed

Webb, Shannon L; Loh, Vanessa; Lampit, Amit; Bateman, Joel E; Birney, Damian P

2018-06-01

The growing prevalence of neurodegenerative disorders associated with aging and cognitive decline has generated increasing cross-disciplinary interest in non-pharmacological interventions, such as computerized cognitive training (CCT), which may prevent or slow cognitive decline. However, inconsistent findings across meta-analytic reviews in the field suggest a lack of cross-disciplinary consensus and on-going debate regarding the benefits of CCT. We posit that a contributing factor is the lack of a theoretically-based taxonomy of constructs and representative tasks typically used. An integration of the Cattell-Horn-Carroll (CHC) taxonomy of broad and narrow cognitive factors and the Miyake unity-diversity theory of executive functions (EF) is proposed (CHC-M) as an attempt to clarify this issue through representing and integrating the disciplines contributing to CCT research. The present study assessed the utility of this taxonomy by reanalyzing the Lampit et al. (2014) meta-analysis of CCT in healthy older adults using the CHC-M framework. Results suggest that: 1) substantively different statistical effects are observed when CHC-M is applied to the Lampit et al. meta-analytic review, leading to importantly different interpretations of the data; 2) typically-used classification practices conflate Executive Function (EF) tasks with fluid reasoning (Gf) and retrieval fluency (Gr), and Attention with sensory perception; and 3) there is theoretical and practical advantage in differentiating attention and working-memory tasks into the narrow shifting, inhibition, and updating EF domains. Implications for clinical practice, particularly for our understanding of EF are discussed.

Replicated evolutionary divergence in the cuticular hydrocarbon profile of male crickets associated with the loss of song in the Hawaiian archipelago.

PubMed

Simmons, L W; Thomas, M L; Gray, B; Zuk, M

2014-10-01

Female choice based on male secondary sexual traits is well documented, although the extent to which this selection can drive an evolutionary divergence in male traits among populations is less clear. Male field crickets Teleogryllus oceanicus attract females using a calling song and once contacted switch to courtship song to persuade them to mate. These crickets also secrete onto their cuticle a cocktail of long-chained fatty acids or cuticular hydrocarbons (CHCs). Females choose among potential mates based on the structure of male acoustic signals and on the composition of male CHC profiles. Here, we utilize two naturally occurring mutations that have arisen independently on two Hawaiian islands and render the male silent to ask whether the evolutionary loss of acoustic signalling can drive an evolutionary divergence in the alternative signalling modality, male CHC profiles. QST -FST comparisons revealed strong patterns of CHC divergence among three populations of crickets on the islands of Hawaii, Oahu and Kauai. Contrasts between wild-type and flatwing males on the islands of Oahu and Kauai indicated that variation in male CHC profiles within populations is associated with the loss of acoustic signalling; flatwing males had a relatively low abundance of long-chained CHCs relative to the short-chained CHCs that females find attractive. Given their dual functions in desiccation resistance and sexual signalling, insect CHCs may be particularly important traits for reproductive isolation and ultimately speciation. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

What factors increase Dutch child health care professionals' adherence to a national guideline on preventing child abuse and neglect?

PubMed

Konijnendijk, Annemieke A J; Boere-Boonekamp, Magda M; Fleuren, Margot A H; Haasnoot, Maria E; Need, Ariana

2016-03-01

Guidelines to support health care professionals in early detection of, and responses to, suspected Child Abuse and Neglect (CAN) have become increasingly widely available. Yet little is known about professionals' adherence to these guidelines or the determinants that affect their uptake. This study used a cross-sectional design to assess the adherence of Dutch Child Health Care (CHC) professionals to seven key activities described in a national guideline on preventing CAN. This study also examined the presence and strengths of determinants of guideline adherence. Online questionnaires were filled in between May and July 2013 by 164 CHC professionals. Adherence was defined as the extent to which professionals performed each of seven key activities when they suspected CAN. Thirty-three determinants were measured in relation to the guideline, the health professional, the organisational context and the socio-political context. Bivariate and multivariate regression analyses tested associations between determinants and guideline adherence. Most of the responding CHC professionals were aware of the guideline and its content (83.7%). Self-reported rates of full adherence varied between 19.5% and 42.7%. Stronger habit to use the guideline was the only determinant associated with higher adherence rates in the multivariate analysis. Understanding guideline adherence and associated determinants is essential for developing implementation strategies that can stimulate adherence. Although CHC professionals in this sample were aware of the guideline, they did not always adhere to its key recommended activities. To increase adherence, tailored interventions should primarily focus on enhancing habit strength. Copyright © 2015 Elsevier Ltd. All rights reserved.

Independent examination of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV): what does the WAIS-IV measure?

PubMed

Benson, Nicholas; Hulac, David M; Kranzler, John H

2010-03-01

Published empirical evidence for the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) does not address some essential questions pertaining to the applied practice of intellectual assessment. In this study, the structure and cross-age invariance of the latest WAIS-IV revision were examined to (a) elucidate the nature of the constructs measured and (b) determine whether the same constructs are measured across ages. Results suggest that a Cattell-Horn-Carroll (CHC)-inspired structure provides a better description of test performance than the published scoring structure does. Broad CHC abilities measured by the WAIS-IV include crystallized ability (Gc), fluid reasoning (Gf), visual processing (Gv), short-term memory (Gsm), and processing speed (Gs), although some of these abilities are measured more comprehensively than are others. Additionally, the WAIS-IV provides a measure of quantitative reasoning (QR). Results also suggest a lack of cross-age invariance resulting from age-related differences in factor loadings. Formulas for calculating CHC indexes and suggestions for interpretation are provided. PsycINFO Database Record (c) 2010 APA, all rights reserved.

Life and death of a child with down syndrome and a congenital heart condition: experiences of six couples.

PubMed

Reilly, Deirdre; Huws, Jaci; Hastings, Richard; Vaughan, Frances

2010-12-01

Individuals with Down syndrome are at increased risk of congenital heart conditions (CHCs), and mortality is higher in people with Down syndrome and a CHC than those without (J. C. Vis et al., 2009). As a consequence, parents of children with Down syndrome and a CHC are more likely to outlive their child. In this research, semistructured interviews were used to explore the experiences of 6 couples whose child with Down syndrome and a CHC had died. The interviews were analyzed qualitatively using interpretative phenomenological analysis (IPA), and 4 themes emerged: dilemmas associated with the dual diagnosis; treatment decisions during the life and the death of their child ("We had to make a decision"); ways couples coped when bereaved ("We weren't really going through it together"); and ripples from the child's life. There was a high degree of similarity of experience within couples. Differences between couples existed in their experiences of coping and supporting each other. Practical implications include the importance of considering the specific needs of couples, individuals, and fathers within partnerships.

Factor Structure of the Wechsler Intelligence Scale for Children: Fourth Edition in Children with ADHD.

PubMed

Thaler, Nicholas S; Barchard, Kimberly A; Parke, Elyse; Jones, W Paul; Etcoff, Lewis M; Allen, Daniel N

2015-12-01

Recent evidence suggests that the factor structure of the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) is better explained by a five-factor model rather than the four-factor model in the standardization sample. The current study examined the WISC-IV's factor structure in a sample of children with ADHD. Participants included 314 children and adolescents who were diagnosed with ADHD. Confirmatory factor analysis was conducted on the 10 core subtests of the WISC-IV, and three models were examined including two based on Cattell-Horn-Carroll (CHC) theory. A five-factor model consisting of Gc, Gf, Gv, Gsm, and Gs factors provided the best fit for the data. The Perceptual Reasoning factor identified in the original four-factor model split into the two CHC factors, Gf and Gv, and cross-loaded the Symbol Search subtest onto the Gv factor. A five-factor model based on CHC theory provided superior fit for the WISC-IV in children with ADHD, as has been found with the standardization sample. © The Author(s) 2012.

Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database.

PubMed

Tsai, Pei-Chien; Liu, Ta-Wei; Tsai, Yi-Shan; Ko, Yu-Min; Chen, Kuan-Yu; Lin, Ching-Chih; Huang, Ching-I; Liang, Po-Cheng; Lin, Yi-Hung; Hsieh, Ming-Yen; Hou, Nai-Jen; Huang, Chung-Feng; Yeh, Ming-Lun; Lin, Zu-Yau; Chen, Shinn-Cherng; Dai, Chia-Yen; Chuang, Wan-Long; Huang, Jee-Fu; Yu, Ming-Lung

2017-06-01

For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P < .001). Treatment-naïve G1 patients of old ages, those with advanced fibrosis, high viral loads, or interleukin-28B unfavorable genotypes, or those without a rapid virological response (RVR: undetectable HCV RNA at week 4), or those with complete early virological response (cEVR: undetectable HCV RNA at week 12). Treatment-naïve G2 patients with high viral loads or without RVR or cEVR incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful, informative evidence for making decisions regarding future therapeutic strategies comprising costly direct-acting antivirals.

Geographical distribution of HCV genotypes in Mexico.

PubMed

Sánchez-Avila, Juan Francisco; González, Elizabeth; Vázquez, Victoria; Suárez, Susana; Uribe, Misael

2007-01-01

Chronic hepatitis C (CHC) is the second cause of endstage liver disease in our country and one of the main indications of liver transplantation. Hepatitis C virus (HCV) genotype is the principal prognostic factor and the determinant of the therapeutic scheme. In our country few data exist regarding the prevalence of HCV infection and genotype distribution in the Mexican Republic has not been determined. The aim of this study was to characterize the prevalence of the different HCV genotypes and to explore their geographical distribution. Mexican patients with hepatitis C infection, detected throughout the country between 2003 and 2006, were included. All samples were analyzed by a central laboratory and Hepatitis C genotype was identified by Line Immuno Probe Assay in PCR positive samples (Versant Line Probe Assay Quest Diagnostics Nichols Institute, San Juan Capistrano CA). Data were analyzed according to the four geographical areas in Mexico. One thousand three hundred and ninety CHC patients were included. The most frequent genotype detected was genotype 1 (69%) followed by genotype 2 (21.4%) and genotype 3 (9.2%). Genotype 4 and 5 were infrequent. There was no subject infected with genotype 6. Genotype 1 and 2 exhibit very similar distribution in all geographical areas. Genotype 3 infected patients were more frequent in the North region (52%) compared with other areas:center-western (30%), center (17%), South-South east (1%) (p < 0.001). The most prevalent HCV genotype in Mexico is genotype 1. Geographical distribution of HCV genotypes in the four geographical areas in Mexico is not homogenous with a greater frequency of genotype3 in the north region. This difference could be related to the global changes of risk factors for HCV infection.

How to manage organisational change and create practice teams: experiences of a South African primary care health centre.

PubMed

Mash, B J; Mayers, P; Conradie, H; Orayn, A; Kuiper, M; Marais, J

2008-07-01

In South Africa, first-contact primary care is delivered by nurses in small clinics and larger community health centres (CHC). CHCs also employ doctors, who often work in isolation from the nurses, with poor differentiation of roles and little effective teamwork or communication. Worcester CHC, a typical public sector CHC in rural South Africa, decided to explore how to create more successful practice teams of doctors and nurses. This paper is based on their experience of both unsuccessful and successful attempts to introduce practice teams and reports on their learning regarding organisational change. An emergent action research study design utilised a co-operative inquiry group. The first nine months of inquiry focused on understanding the initial unsuccessful attempt to create practice teams. This paper reports primarily on the subsequent nine months (four cycles of planning, action, observation and reflection) during which practice teams were re-introduced. The central question was how more effective practice teams of doctors and nurses could be created. The group utilised outcome mapping to assist with planning, monitoring and evaluation. Outcome mapping defined a vision, mission, boundary partners, outcome challenges, progress markers and strategies for the desired changes and supported quantitative monitoring of the process. Qualitative data were derived from the co-operative inquiry group (CIG) meetings and interviews with doctors, nurses, practice teams and patients. The CIG engaged effectively with 68% of the planned strategies, and more than 60% of the progress markers were achieved for clinical nurse practitioners, doctors, support staff and managers, but not for patients. Key themes that emerged from the inquiry group's reflection on their experience of the change process dealt with the amount of interaction, type of communication, team resilience, staff satisfaction, leadership style, reflective capacity, experimentation and evolution of new structures. The group's learning supported a view of change that sees the organisation as a living system in which information flow, participation and the development of resilience are key aspects. These themes fit well into an understanding of change based on complexity theory. If managers of the health system wish to enhance organisational change, then their goal may need to shift from optimising health care delivery in a mechanistic model to optimising health care workers in a living system.

Combined hormonal contraceptive (CHC) use among obese women and contraceptive effectiveness: a systematic review.

PubMed

Dragoman, Monica V; Simmons, Katharine B; Paulen, Melissa E; Curtis, Kathryn M

2017-02-01

To evaluate from the literature whether combined hormonal contraception (CHC), including combined oral contraception pills (COCs), transdermal patch, vaginal ring or combined injectables, have different effectiveness or failure rates by body weight or body mass index (BMI). We searched PubMed and the Cochrane Library databases for all articles in all languages published between inception and February 2016, for evidence relevant to body weight or BMI, CHC use and contraceptive effectiveness. The quality of each individual study was assessed using the system for evaluating evidence developed by the United States Preventive Services Task Force. From 2874 articles, we identified 15 reports for inclusion, all of fair to poor quality. Fourteen studies measured the association of obesity status and contraceptive failure among COC users. Three fair quality and one poor quality study reported increased COC failure among a heterogeneous population of overweight and obese women compared with normal weight women, while eight fair quality and two poor quality studies did not find an association. Two fair quality studies reported on contraceptive transdermal patches. One pooled analysis described a higher proportion of pregnancies among women using the patch who weighed ≥90 kg; another secondary analysis suggested BMI>30 was associated with increased failure. No studies directly compared contraceptive effectiveness using the combined vaginal ring or combined injectable. Current available evidence addressing the risk of CHC failure in obese compared to normal weight women is limited to fair and poor quality studies. Studies of COCs show mixed results, though absolute differences in COC failure by body weight and BMI are small. Based on limited evidence, it appears that increasing body weight and BMI may contribute to decreasing contraceptive patch effectiveness. Copyright © 2017. Published by Elsevier Inc.

From suspicion to action: the chemical conjunctivitis and silver nitrate connexion example in Brazilian hospitals.

PubMed

Napchan, Berta-Monica; Morales, Raquel Pinheiro; Carvalho, Marisa Lima; Cunha, Keliane Vasconcellos; Figueras, Albert

2005-08-01

During the 20th century, silver nitrate (SN) eye drops instillation to newborns had been the best prophylaxis against ophthalmia neonatorum (ON) caused by Neisseria gonorrheae, the most frequent cause of ocular infections leading to blindness. At present, this treatment has been questioned because there is a growing prevalence of other pathogens such as Chlamydia trachomatis, and SN is associated with chemical conjunctivitis (ChC). In addition, SN could present some conservation problems in tropical climates. Among other alternative drugs, 2.5% povidone-iodine has a proven efficacy, not only against Neisseria, but also against Chlamydia, has no conservation problems, has not been associated with ChC and is cheap. The recently created Setor de Farmacovigilãncia (SF) of the São Paulo State in Brazil has created a pharmacovigilance network of 11 big public hospitals. During a periodical signal searching process, the SF found a cluster of 33 ChC reports from one of the network hospitals. The problem was discussed with the remaining participant hospitals and this signal was used as a way to strengthen the network. Thirteen months later, 622 ChC reports were received from six hospitals. Thus, this well-known side-effect in the literature was highlighted as a 'real' problem in Brazil, and some participant hospitals began a discussion period together with the delivery and newborn care professionals in order to switch SN by povidone-iodine. This is an example of both, how a simple pharmacovigilance exercise could improve the implication of health professionals with their own therapeutic problems and how a pharmacovigilance network could be strengthened. Copyright (c) 2004 John Wiley & Sons, Ltd.

Eradicating hepatitis C virus ameliorates insulin resistance without change in adipose depots.

PubMed

Milner, K-L; Jenkins, A B; Trenell, M; Tid-Ang, J; Samocha-Bonet, D; Weltman, M; Xu, A; George, J; Chisholm, D J

2014-05-01

Chronic hepatitis C (CHC) is associated with lipid-related changes and insulin resistance; the latter predicts response to antiviral therapy, liver disease progression and the risk of diabetes. We sought to determine whether insulin sensitivity improves following CHC viral eradication after antiviral therapy and whether this is accompanied by changes in fat depots or adipokine levels. We compared 8 normoglycaemic men with CHC (genotype 1 or 3) before and at least 6 months post viral eradication and 15 hepatitis C antibody negative controls using an intravenous glucose tolerance test and two-step hyperinsulinaemic-euglycaemic clamp with [6,6-(2) H2 ] glucose to assess peripheral and hepatic insulin sensitivity. Magnetic resonance imaging and spectroscopy quantified abdominal fat compartments, liver and intramyocellular lipid. Peripheral insulin sensitivity improved (glucose infusion rate during high-dose insulin increased from 10.1 ± 1.6 to 12 ± 2.1 mg/kg/min/, P = 0.025), with no change in hepatic insulin response following successful viral eradication, without any accompanying change in muscle, liver or abdominal fat depots. There was corresponding improvement in incremental glycaemic response to intravenous glucose (pretreatment: 62.1 ± 8.3 vs post-treatment: 56.1 ± 8.5 mm, P = 0.008). Insulin sensitivity after viral clearance was comparable to matched controls without CHC. Post therapy, liver enzyme levels decreased but, interestingly, levels of glucagon, fatty acid-binding protein and lipocalin-2 remained elevated. Eradication of the hepatitis C virus improves insulin sensitivity without alteration in fat depots, adipokine or glucagon levels, consistent with a direct link of the virus with insulin resistance. © 2013 John Wiley & Sons Ltd.

Alterations in a Unique Class of Cortical Chandelier Cell Axon Cartridges in Schizophrenia.

PubMed

Rocco, Brad R; DeDionisio, Adam M; Lewis, David A; Fish, Kenneth N

2017-07-01

The axons of chandelier cells (ChCs) target the axon initial segment of pyramidal neurons, forming an array of boutons termed a cartridge. In schizophrenia, the density of cartridges detectable by gamma-aminobutyric acid (GABA) membrane transporter 1 immunoreactivity is lower, whereas the density of axon initial segments detectable by immunoreactivity for the α2 subunit of the GABA A receptor is higher in layers 2/superficial 3 of the prefrontal cortex. These findings were interpreted as compensatory responses to lower GABA levels in ChCs. However, we recently found that in schizophrenia, ChC cartridge boutons contain normal levels of the 67 kDa isoform of glutamic acid decarboxylase (GAD67) protein, the enzyme responsible for GABA synthesis in these boutons. To understand these findings we quantified the densities of ChC cartridges immunoreactive for vesicular GABA transporter (vGAT+), which is present in all cartridge boutons, and the subset of cartridges that contain calbindin (CB+). Prefrontal cortex tissue sections from 20 matched pairs of schizophrenia and unaffected comparison subjects were immunolabeled for vGAT, GAD67, and CB. The mean density of vGAT+/CB+ cartridges was 2.7-fold higher, exclusively in layer 2 of schizophrenia subjects, whereas the density of vGAT+/CB- cartridges did not differ between subject groups. Neither vGAT, CB, or GAD67 protein levels per ChC bouton nor the number of boutons per cartridge differed between subject groups. Our findings of a greater density of CB+ ChC cartridges in prefrontal cortex layer 2 from schizophrenia subjects suggests that the normal developmental pruning of these cartridges is blunted in the illness. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Woodcock-Johnson-III, Kaufman Adolescent and Adult Intelligence Test (KAIT), Kaufman Assessment Battery for Children (KABC), and Differential Ability Scales (DAS) support Carroll but not Cattell-Horn.

PubMed

Cucina, Jeffrey M; Howardson, Garett N

2017-08-01

Recently emerging evidence suggests that the dominant structural model of mental abilities-the Cattell-Horn-Carroll (CHC) model-may not adequately account for observed scores for mental abilities batteries, leading scholars to call into question the model's validity. Establishing the robustness of these findings is important since CHC is the foundation for several contemporary mental abilities test batteries, such as the Woodcock-Johnson III (WJ-III). Using confirmatory factor analysis, we investigated CHC's robustness across 4 archival samples of mental abilities test battery data, including the WJ-III, the Kaufman Adolescent & Adult Intelligence Test (KAIT), the Kaufman Assessment Battery for Children (KABC), and the Differential Ability Scales (DAS). We computed omega hierarchical (ωH) and omega subscale (ωS) coefficients for g and the broad factors, which estimated the relationship of composite scores to g and the broad factors, respectively. Across all 4 samples, we found strong evidence for a general ability, g. We additionally found evidence for 3 to 9 residualized, orthogonal broad abilities existing independently of g, many of which also explained reliable variance in test battery scores that cannot be accounted for by g alone. The reliabilities of these broad factors, however, were less than desirable (i.e., <.80) and achieving desirable reliabilities would be practically infeasible (e.g., requiring excessively large numbers of subtests). Our results, and those of CHC critics, are wholly consistent with Carroll's model. Essentially, both g and orthogonal broad abilities are required to explain variance in mental abilities test battery scores, which is consistent with Carroll but not Cattell-Horn. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Community Health Center Utilization Following the 2008 Medicaid Expansion in Oregon: Implications for the Affordable Care Act

PubMed Central

Bailey, Steffani R.; Cowburn, Stuart; Marino, Miguel; Angier, Heather; DeVoe, Jennifer E.

2016-01-01

Objectives. To assess longitudinal patterns of community health center (CHC) utilization and the effect of insurance discontinuity after Oregon’s 2008 Medicaid expansion (the Oregon Experiment). Methods. We conducted a retrospective cohort study with electronic health records and Medicaid data. We divided individuals who gained Medicaid in the Oregon Experiment into those who maintained (n = 788) or lost (n = 944) insurance coverage. We compared these groups with continuously insured (n = 921) and continuously uninsured (n = 5416) reference groups for community health center utilization rates over a 36-month period. Results. Both newly insured groups increased utilization in the first 6 months. After 6 months, use among those who maintained coverage stabilized at a level consistent with the continuously insured, whereas it returned to baseline for those who lost coverage. Conclusions. Individuals who maintained coverage through Oregon’s Medicaid expansion increased long-term utilization of CHCs, whereas those with unstable coverage did not. Policy implications. This study predicts long-term increase in CHC utilization following Affordable Care Act Medicaid expansion and emphasizes the need for policies that support insurance retention. PMID:26890164

Isolation, characterization and phylogenetic analysis of halophilic archaea from a salt mine in central Anatolia (Turkey).

PubMed

Yildiz, Evrim; Ozcan, Birgul; Caliskan, Mahmut

2012-01-01

The haloarchaeal diversity of a salt mine, a natural cave in central Anatolia, was investigated using convential microbiological and molecular biology methods. Eight halophilic archaeal isolates selected based on their colony morphology and whole cell protein profiles were taxonomically classified on the basis of their morphological, physiological, biochemical properties, polar lipid and protein profiles and 16S rDNA sequences. From the 16S rDNA sequences comparisons it was established that the isolates CH2, CH3 and CHC resembled Halorubrum saccharovorum by 98.8%, 98.9% and 99.5%, respectively. There was a 99.7% similarity between the isolate CH11 and Halobacterium noricense and 99.2% between the isolate CHA1 and Haloarcula argentinensis. The isolate CH8K and CH8B revealed a similarity rate of 99.8% and 99.3% to Halococcus dombrowskii, respectively. It was concluded that the isolates named CH2, CH3 and CHC were clustered in the genus Halorubrum and that CHA1 and CH7 in the genus Haloarcula, CH8K and CH8B in the genus Halococcus and CH11 in the genus Halobacterium.

Complex coacervation of collagen hydrolysate extracted from leather solid wastes and chitosan for controlled release of lavender oil.

PubMed

Ocak, Buğra

2012-06-15

In the world, approximately 600,000 metric tonnes of chromium-containing solid wastes are generated by the leather industry each year. Environmental concerns and escalating landfill costs are becoming increasingly serious problems to the leather industry and seeking solutions to these problems is a prime concern in much research today. In this study, solid collagen-based protein hydrolysate was isolated from chromium-tanned leather wastes and its chemical properties were determined. Microcapsules of collagen hydrolysate (CH) - chitosan (C) crosslinked with glutaraldehyde (GA) containing Lavender oil (LO) were prepared by complex coacervation method. The effects of various processing parameters, including the CH to C ratio, LO content, and GA, on the oil load (%), oil content (%), encapsulation efficiency (%) and release rate of LO from microcapsules were investigated. As the ratio of C present in the CH/C mixture and crosslinking density increased, the release rate of LO from microcapsules slowed down. Optical and scanning electron microscopy images illustrated that the LO microcapsules were spherical in shape. Fourier transform infrared spectroscopy (FTIR) studies confirmed that there was no significant interaction between CH/C complex and LO. Copyright © 2012 Elsevier Ltd. All rights reserved.

Differences in prevalence of community-associated MRSA and MSSA among U.S. and non-U.S. born populations in Six New York Community Health Centers

PubMed Central

Piper Jenks, N.; Pardos de la Gandara, M.; D’Orazio, B.M.; Correa da Rosa, J.; Kost, R.G.; Khalida, C.; Vasquez, K.S.; Coffran, C.; Pastagia, M.; Evering, T.H.; Parola, C.; Urban, T.; Salvato, S.; Barsanti, F.; Coller, B.S.; Tobin, J.N.

2016-01-01

Background Staphylococcus aureus is the most common cause of Skin and Soft Tissue Infections (SSTIs) in the community in the United States of America. Community Health Centers (CHC) serve as primary care providers for thousands of immigrants in New York. Methods As part of a research collaborative, 6 New York City-area CHCs recruited patients with SSTIs. Characterization was performed in all S. aureus isolates from wounds and nasal swabs collected from patients. Statistical analysis examined the differences in wound and nasal cultures among immigrant compared to native-born patients. Results Wound and nasal specimens were recovered from 129 patients and tested for antibiotic susceptibility. 40 patients were immigrants from 15 different countries. Although not statistically significant, immigrants had lower rates of MRSA infections (n=15) than did native-born participants, and immigrants showed significantly higher rates of MSSA wound cultures (n=11) (OR=3.5, 95% CI: 1.3, 9.7). Conclusions In our study, immigrants were more likely to present with SSTIs caused by MSSA than US-born patients. This suggests that antibiotic resistance may vary regionally and that immigrants presenting with SSTIs may benefit from a broader range of antibiotics. Immigrants also reported lower frequencies of antibiotic prescription or consumption in the months prior to SSTI infection. PMID:27773780

Combined hormonal contraceptive trials: variable data collection and bleeding assessment methodologies influence study outcomes and physician perception.

PubMed

Mishell, Daniel R; Guillebaud, John; Westhoff, Carolyn; Nelson, Anita L; Kaunitz, Andrew M; Trussell, James; Davis, Ann Jeanette

2007-01-01

Initially approved for use in the United States nearly 50 years ago, oral hormonal contraceptives containing both estrogen and progestin have undergone steady improvements in safety and convenience. Concurrent with improvements in safety associated with decreasing doses of both steroids, there has been an increased incidence of unscheduled bleeding and spotting. There exist no standards regarding data collection techniques and methods, and reporting and analysis of bleeding and spotting events during combined hormonal contraceptive (CHC) trials. For the regulatory review of hormonal contraceptives, data regarding the incidence of bleeding and spotting events are not included in either of the traditional categories of efficacy and safety. Standardization of methods for collecting and analyzing data about cycle control in all clinical trials of CHCs is long overdue. Until such standards are developed and implemented, clinicians need to familiarize themselves with the techniques used in each study in order to provide correct information to their patients about the frequency of bleeding and spotting associated with different formulations and delivery systems.

Accuracy of real-time shear wave elastography for assessing liver fibrosis in chronic hepatitis C: a pilot study.

PubMed

Ferraioli, Giovanna; Tinelli, Carmine; Dal Bello, Barbara; Zicchetti, Mabel; Filice, Gaetano; Filice, Carlo

2012-12-01

Real-time shear wave elastography (SWE) is a novel, noninvasive method to assess liver fibrosis by measuring liver stiffness. This single-center study was conducted to assess the accuracy of SWE in patients with chronic hepatitis C (CHC), in comparison with transient elastography (TE), by using liver biopsy (LB) as the reference standard. Consecutive patients with CHC scheduled for LB by referring physicians were studied. One hundred and twenty-one patients met inclusion criteria. On the same day, real-time SWE using the ultrasound (US) system, Aixplorer (SuperSonic Imagine S.A., Aix-en-Provence, France), TE using FibroScan (Echosens, Paris, France), and US-assisted LB were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic (ROC) curve were performed to calculate optimal area under the ROC curve (AUROC) for F0-F1 versus F2-F4, F0- F2 versus F3-F4, and F0-F3 versus F4 for both real-time SWE and TE. Liver stiffness values increased in parallel with degree of liver fibrosis, both with SWE and TE. AUROCs were 0.92 (95% confidence interval [CI]: 0.85-0.96) for SWE and 0.84 (95% CI: 0.76-0.90) for TE (P = 0.002), 0.98 (95% CI: 0.94-1.00) for SWE and 0.96 (95% CI: 0.90-0.99) for TE (P = 0.14), and 0.98 (95% CI: 0.93-1.00) for SWE and 0.96 (95% CI: 0.91-0.99) for TE (P = 0.48), when comparing F0-F1 versus F2- F4, F0- F2 versus F3-F4, and F0 -F3 versus F4, respectively. The results of this study show that real-time SWE is more accurate than TE in assessing significant fibrosis (≥ F2). With respect to TE, SWE has the advantage of imaging liver stiffness in real time while guided by a B-mode image. Thus, the region of measurement can be guided with both anatomical and tissue stiffness information. Copyright © 2012 American Association for the Study of Liver Diseases.

Protein pathway activation associated with sustained virologic response in patients with chronic hepatitis C treated with pegylated interferon (PEG-IFN) and ribavirin (RBV).

PubMed

Younossi, Zobair M; Limongi, Dolores; Stepanova, Maria; Pierobon, Mariaelena; Afendy, Arian; Mehta, Rohini; Baranova, Ancha; Liotta, Lance; Petricoin, Emanuel

2011-02-04

Only half of chronic hepatitis C (CH-C) patients treated with pegylated interferon and ribavirin (PEG-IFN+RBV) achieve sustained virologic response) SVR. In addition to known factors, we postulated that activation of key protein signaling networks in the peripheral blood mononuclear cells (PBMCs) may contribute to SVR due to inherent patient-specific basal immune cell signaling architecture. In this study, we included 92 patients with CH-C. PBMCs were collected while patients were not receiving treatment and used for phosphoprotein-based network profiling. Patients received a full course of PEG-IFN+RBV with overall SVR of 55%. From PBMC, protein lysates were extracted and then used for Reverse Phase Protein Microarray (RPMA) analysis, which quantitatively measured the levels of cytokines and activation levels of 25 key protein signaling molecules involved in immune cell regulation and interferon alpha signaling. Regression models for predicting SVR were generated by stepwise bidirectional selection. Both clinical-laboratory and RPMA parameters were used as predictor variables. Model accuracies were estimated using 10-fold cross-validation. Our results show that by comparing patients who achieved SVR to those who did not, phosphorylation levels of 6 proteins [AKT(T308), JAK1(Y1022/1023), p70 S6 Kinase (S371), PKC zeta/lambda(T410/403), TYK2(Y1054/1055), ZAP-70(Y319)/Syk(Y352)] and overall levels of 6 unmodified proteins [IL2, IL10, IL4, IL5, TNF-alpha, CD5L] were significantly different (P < 0.05). For SVR, the model based on a combination of clinical and proteome parameters was developed, with an AUC = 0.914, sensitivity of 92.16%, and specificity of 85.0%. This model included the following parameters: viral genotype, previous treatment status, BMI, phosphorylated states of STAT2, AKT, LCK, and TYK2 kinases as well as steady state levels of IL4, IL5, and TNF-alpha. In conclusion, SVR could be predicted by a combination of clinical, cytokine, and protein signaling activation profiles. Signaling events elucidated in the study may shed some light into molecular mechanisms of response to anti-HCV treatment.

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

Nippert, Felix, E-mail: felix@physik.tu-berlin.de; Callsen, Gordon; Westerkamp, Steffen

We investigate industrial-grade InGaN/GaN quantum wells (QWs) emitting in the green spectral region under high, resonant pumping conditions. Consequently, an ubiquitous high energy luminescence is observed that we assign to a polarization field Confined Hole Continuum (CHC). Our finding is supported by a unique combination of experimental techniques, including transmission electron microscopy, (time-resolved) photoluminescence under various excitation conditions, and electroluminescence, which confirm an extended out-of-plane localization of the CHC-states. The larger width of this localization volume surpasses the QW thickness, yielding enhanced non-radiative losses due to point defects and interfaces, whereas the energetic proximity to the bulk valence band statesmore » promotes carrier leakage.« less

[Treatment of advanced hepatocellular carcinoma : Novel agents and role of local therapy].

PubMed

Parisod, Louis; Duran, Rafael; Denys, Alban; Digklia, Antonia

2017-05-17

The incidence of hepatocellular carcinoma (HCC) is increasing in Switzerland and its treatment is a challenge. The purpose of this article is to summarize the different therapeutic approaches in the metastatic stage, as well as the perspectives of targeted treatments and immunotherapy. Until recently, the only recognized therapeutic standard for these patients with metastatic CHC was sorafenib, a tyrosine kinase inhibitor. If the patient was to progress under sorafenib, no other recognized therapeutic option was available as second line. We present in this article the recent data on regorafenib, also an inhibitor of tyrosine kinases, the first systemic therapy showing an increase in survival for patients progressing under sorafenib. Then we will discuss promising data and progress made in treatments checkpoints inhibitors and therapies combining local and systematic approaches.

Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region.

PubMed

Zhu, Ran Xu; Seto, Wai-Kay; Lai, Ching-Lung; Yuen, Man-Fung

2016-05-23

Hepatocellular carcinoma (HCC) is the predominant primary liver cancer in many countries and is the third most common cause of cancer-related death in the Asia-Pacific region. The incidence of HCC is higher in men and in those over 40 years old. In the Asia-Pacific region, chronic hepatitis B virus and hepatitis C virus infections are the main etiological agents; in particular, chronic hepatitis B infection (CHB) is still the major cause in all Asia-Pacific countries except for Japan. Over the past two decades, the incidence of HCC has remained stable in countries in the region except for Singapore and Hong Kong, where the incidence for both sexes is currently decreasing. Chronic hepatitis C infection (CHC) is an important cause of HCC in Japan, representing 70% of HCCs. Over the past several decades, the prevalence of CHC has been increasing in many Asia-Pacific countries, including Australia, New Zealand, and India. Despite advancements in treatment, HCC is still an important health problem because of the associated substantial mortality. An effective surveillance program could offer early diagnosis and hence better treatment options. Antiviral treatment for both CHB and CHC is effective in reducing the incidence of HCC.

Physical and physicochemical factors effecting transport of chlorohydrocarbon gases from lung alveolar air to blood as measured by the causation of narcosis.

PubMed

Holder, James W

2012-01-01

This systematic investigation examines gas transport in the lung for two sets of chlorohydrocarbons (CHCs): the chloromethanes (C1) and chloroethanes (C2). The C1 series includes chloromethane, methylene chloride, chloroform, and carbon tetrachloride, and the C2 series includes chloroethane, 1,2-dichloroethane, 1, 1, 2-trichloroethane, and 1, 1, 2, 2-tetrachloroethane. Most CHC gases cause narcosis. The comprehensive narcosis work of Lehmann and colleagues on CHCs was used as a basis for the narcosis endpoint in the present examination. The sites for narcosis are located in the brain (midline cortex and posterior parietal area), the spine, and at many peripheral nerve sites. Central nervous system (CNS) exposure executes a multisite, neural transmission set of inhibitions that promotes rapid loss of consciousness, sensory feeling, and current and stored memory while providing temporary amnesia. Absorption into the system requires dissolution into many lipid membranes and binding to lipoproteins. Lipophilicity is a CHC property shared with many anesthetics according to the Meyer-Overton Rule. Many structurally different lipid chemicals produce the narcosis response when the lipid concentration exceeds -67 mM. This suggests narcotic or anesthetic dissolution into CNS membranes until the lipid organization is disrupted or perturbed. This perturbation includes loading of Na(+)- and K(+)-channel transmembrane lipoprotein complexes and disrupting their respective channel functional organizations. The channel functions become attenuated or abrogated until the CHC exposure ceases and CHC loading reverses. This investigation demonstrates how the CHC physical and chemical properties influence the absorption of these CHCs via the lung and the alveolar system on route to the blood. Narcosis in test animals was used here as an objective biological endpoint to study the effects of the physical factors Bp, Vp, Kd (oil: gas) partition, Henry's constant (HK), and water solubility (S%) on gas transport. Narcosis is immediate after gas exposure and requires no chemical activation only absorption into the blood and circulation to CNS narcotic sites. The three physical factors Bp, K(d) (oil: air), and S% vary directly with unitary narcosis (UN) whereas Vp and HK vary inversely with UN in linear log-log relationships for the C2 series but not for the C1 series. Physicochemical properties of C1 series gases indicate why they depart from what is usually assumed to be an Ideal Gas. An essential discriminating process in the distal lung is the limiting alveolar film layer (AFL) and the membrane layer of the alveolar acini. The AFL step influences gas uptake by physically limiting the absorption process. Interaction with and dissolution into aqueous solvent of the AFL is required for transport and narcotic activity. Narcotics or anesthetics must engage the aqueous AFL with sufficient strength to allow transport and absorption for downstream CNS binding. CHCs that do not engage well with the AFL are not narcotic. Lipophilicity and amphipathicity are also essential solvency properties driving narcotics' transport through the alveolar layer, delivery to the blood fats and lipoproteins, and into critical CNS lipids, lipoproteins, and receptor sites that actuate narcosis. AFL disruption is thought to be strongly related to a number of serious pulmonary diseases such acute respiratory distress syndrome, infant respiratory distress syndrome, emphysema, chronic obstructive pulmonary disease, asthma, chronic bronchitis, pneumonia, pulmonary infections, and idiopathic pulmonary fibrosis. The physical factors (Bp, Vp, Kd [oil: gas] partition, Henry's constant, and water solubility [S%]) combine to affect a specific transport through the AFL if lung C > C(0) (threshold concentration for narcosis). The degree of blood CHC absorption depends on dose, lipophilicity, and lung residence time. AFL passage can be manipulated by physical factors of increased pressure (kPa) or increased gas exposure (moles). Molecular lipophilicity facilitates narcosis but lipophilicity alone does not explain narcosis. Vapor pressure is also required for narcosis. Narcotic activity apparently requires stereospecific processing in the AFL and/or down-stream inhibition at stereospecific lipoproteins at CNS inhibitory sites. It is proposed that CHCs likely cannot proceed through the AFL without perturbation or disruption of the integrity of the AFL at the alveoli. CHC physicochemical properties are not expected to allow their transport through the AFL as physiological CO(2) and O(2) naturally do in respiration. This work considers CHC inspiration and systemic absorption into the blood with special emphasis on the CHC potential perturbation effects on the lipid, protein liquid layer supra to the alveolar membrane (AFL). A heuristic gas transport model for the CHCs is presented as guidance for this examination. The gas transport model can be used to study absorption for other gas delivery endpoints of environmental concern such as carcinogens.

[Cost-effectiveness analysis of sofosbuvir, peginterferon and ribavirin in patients with chronic hepatitis C: Early treatment in the initial stage of fibrosis vs. delayed treatment in advanced fibrosis].

PubMed

Buti, María; Domínguez-Hernández, Raquel; Oyagüez, Itziar; Casado, Miguel Ángel

2016-01-01

Cost-effectiveness analysis of sofosbuvir combined with peginterferon alpha-2a and ribavirin (SOF/Peg-IFN/RBV) in early versus advanced fibrosis in previously untreated patients with chronic hepatitis C genotype 1 (CHC-GT1), from the perspective of the Spanish National Health System (NHS). A Markov model was developed to compare lifetime costs and outcomes (life years gained [LYGs] and quality-adjusted life years [QALYs]) of 2 treatment strategies: SOF/Peg-IFN/RBV administered during early fibrosis (mild-moderate fibrosis; F2-F3) or advanced fibrosis (cirrhosis; F4). Efficacy (sustained virologic response), annual transition probabilities, disease management costs and utilities were obtained from the literature. Costs and outcomes were discounted annually at 3%. Direct costs were considered, expressed in Euros (€, 2014). Probabilistic sensitivity analysis (PSA) was also performed. SOF/Peg-IFN/RBV therapy at F2-F3 was more effective (19.12 LYGs and 14.14 QALYs) compared to F4. In a cohort of 1,000 patients, SOF/Peg-IFN/RBV prevented 66 cases of decompensated cirrhosis, 60 hepatocellular carcinomas and 4 liver transplantations compared with therapy in advanced fibrosis. The total lifetime cost of early therapy (€43,263) was less than the cost of treatment in the advanced stage (€49,018). Early therapy was a dominant strategy, more effective and less costly in all simulations. In the PSA analysis, administration of SOF/PEG-IFN/RBV at F2-F3 was dominant in all simulations. Starting SOF/Peg-IFN/RBV therapy at F2-F3, compared with therapy at F4, reduced the incidence of liver disease complications and was associated with cost savings for the Spanish NHS in CHC-GT1 patients. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

Impact of Title VII Training Programs on Community Health Center Staffing and National Health Service Corps Participation

PubMed Central

Rittenhouse, Diane R.; Fryer, George E.; Phillips, Robert L.; Miyoshi, Thomas; Nielsen, Christine; Goodman, David C.; Grumbach, Kevin

2008-01-01

PURPOSE Community health centers (CHCs) are a critical component of the health care safety net. President Bush’s recent effort to expand CHC capacity coincides with difficulty recruiting primary care physicians and substantial cuts in federal grant programs designed to prepare and motivate physicians to practice in underserved settings. This article examines the association between physicians’ attendance in training programs funded by Health Resources and Services Administration (HRSA) Title VII Section 747 Primary Care Training Grants and 2 outcome variables: work in a CHC and participation in the National Health Service Corps Loan Repayment Program (NHSC LRP). METHODS We linked the 2004 American Medical Association Physician Master-file to HRSA Title VII grants files, Medicare claims data, and data from the NHSC. We then conducted retrospective analyses to compare the proportions of physicians working in CHCs among physicians who either had or had not attended Title VII–funded medical schools or residency programs and to determine the association between having attended Title VII–funded residency programs and subsequent NHSC LRP participation. RESULTS Three percent (5,934) of physicians who had attended Title VII–funded medical schools worked in CHCs in 2001–2003, compared with 1.9% of physicians who attended medical schools without Title VII funding (P<.001). We found a similar association between Title VII funding during residency and subsequent work in CHCs. These associations remained significant (P<.001) in logistic regression models controlling for NHSC participation, public vs private medical school, residency completion date, and physician sex. A strong association was also found between attending Title VII–funded residency programs and participation in the NHSC LRP, controlling for year completed training, physician sex, and private vs public medical school. CONCLUSIONS Continued federal support of Title VII training grant programs is consistent with federal efforts to increase participation in the NHSC and improve access to quality health care for underserved populations through expanded CHC capacity. PMID:18779543

Women's status and experiences of mistreatment during childbirth in Uttar Pradesh: a mixed methods study using cultural health capital theory.

PubMed

Sudhinaraset, May; Treleaven, Emily; Melo, Jason; Singh, Kanksha; Diamond-Smith, Nadia

2016-10-28

Mistreatment of women in healthcare settings during childbirth has been gaining attention globally. Mistreatment during childbirth directly and indirectly affects health outcomes, patient satisfaction, and the likelihood of delivering in a facility currently or in the future. It is important that we study patients' reports of mistreatment and abuse to develop a deeper understanding of how it is perpetrated, its consequences, and to identify potential points of intervention. Patients' perception of the quality of care is dependent, not only on the content of care, but importantly, on women's expectations of care. This study uses rich, mixed-methods data to explore women's characteristics and experiences of mistreatment during childbirth among slum-resident women in Uttar Pradesh, India. To understand the ways in which women's social and cultural factors influence their expectations of care and consequently their perceptions of respectful care, we adopt a Cultural Health Capital (CHC) framework. The quantitative sample includes 392 women, and the qualitative sample includes 26 women. Quantitative results suggest high levels of mistreatment (over 57 % of women reported any form of mistreatment). Qualitative findings suggest that lack of cultural health capital disadvantages patients in their patient-provider relationships, and that women use resources to improve care they receive. Participants articulated how providers set expectations and norms regarding behaviors in facilities; patients with lower social standing may not always understand standard practices and are likely to suffer poor health outcomes as a result. Of importance, however, patients also blame themselves for their own lack of knowledge. Lack of cultural health capital disadvantages women during delivery care in India. Providers set expectations and norms around behaviors during delivery, while women are often misinformed and may have low expectations of care.

Interaction of IFNL3 with insulin resistance, steatosis and lipid metabolism in chronic hepatitis C virus infection.

PubMed

Eslam, Mohammed; Booth, David R; George, Jacob; Ahlenstiel, Golo

2013-11-07

Metabolic changes are inextricably linked to chronic hepatitis C (CHC). Recently polymorphisms in the IFNL3 (IL28B) region have been shown to be strongly associated with spontaneous and treatment induced recovery from hepatitis C virus (HCV) infection. Further, circumstantial evidence suggests a link between IFNL3 single nucleotide polymorphisms and lipid metabolism, steatosis and insulin resistance in CHC. The emerging picture suggests that the responder genotypes of IFNL3 polymorphisms are associated with a higher serum lipid profile, and less frequent steatosis and insulin resistance. This review analyzes the current data regarding this interaction and its meaning for HCV pathogenesis and disease progression.

Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C.

PubMed

Takata, Kazuhide; Shakado, Satoshi; Sakamoto, Keiko; Fukuda, Hiromi; Yamauchi, Ryo; Fukuda, Sho; Kunimoto, Hideo; Umeda, Kaoru; Tanaka, Takashi; Yokoyama, Keiji; Morihara, Daisuke; Takeyama, Yasuaki; Irie, Makoto; Sakisaka, Shotaro

2017-10-01

Ultrasonography in a 60-year-old man with chronic hepatitis C (CHC) demonstrated multiple hyperechoic nodules. Radiological investigations did not reveal any signs of malignancy. However, magnetic resonance chemical shift imaging showed multiple focal fatty changes in the liver. Urinary levels of uroporphyrin and coproporphyrin were elevated, and we made a diagnosis of porphyria cutanea tarda. Direct-acting antivirals, ledipasvir/sofosbuvir, were initiated for CHC, which led to sustained viral response, resolution of the liver nodules, and normalization of urinary porphyrin. Hepatitis C virus infection can cause porphyria cutanea tarda with multiple hyperechoic liver nodules, which might be cured by direct-acting antivirals.

Remediation of a uranium-contamination in ground water

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

Woerner, Joerg; Margraf, Sonja; Hackel, Walter

2007-07-01

The former production site of NUKEM where nuclear fuel-elements were developed and handled from 1958 to 1988 was situated in the centre of an industrial park for various activities of the chemical and metallurgical industry. The size of the industrially used part is about 300.000 m{sup 2}. Regulatory routine controls showed elevated CHC (Chlorinated Hydro-Carbons) values of the ground water at the beginning of the 1990's in an area which represented about 80.000 m{sup 2} down-gradient of locations where CHC compounds were stored and handled. Further investigations until 1998 proved that former activities on the NUKEM site, like the UF{submore » 6} conversion process, were of certain relevance. The fact that several measured values were above the threshold values made the remediation of the ground water mandatory. This was addressed in the permission given by the Ministry for Nuclear Installations and Environment of Hesse according to chap. 7 of the German atomic law in October 2000. Ground water samples taken in an area of about 5.000 m{sup 2} showed elevated values of total Uranium activity up to between 50 and 75 Bq/l in 2002. Furthermore in an area of another 20.000 m{sup 2} the samples were above threshold value. In this paper results of the remediation are presented. The actual alpha-activities of the ground waters of the remediation wells show values of 3 to 9 Bq/l which are dominated by 80 to 90 % U-234 activity. The mass-share of total Uranium for this nuclide amounts to 0,05% on average. The authority responsible for conventional water utilisation defined target values for remediation: 20 {mu}g/l for dissolved Uranium and 10 {mu}g/l for CHC. Both values have not yet been reached for an area of about 10.000 m{sup 2}. The remediation process by extracting water from four remediation wells has proved its efficiency by reduction of the starting concentrations by a factor of 3 to 6. Further pumping will be necessary especially in that area of the site where the contaminations were found later during soil remediation activities. Only two wells have been in operation since July 2002 when the remediation technique was installed and an apparatus for direct gamma-spectroscopic measurement of the accumulated activities on the adsorbers was qualified. Two further remediation wells have been in operation since August 2006, when the installed remediation technique was about to be doubled from a throughput of 5 m{sup 3}/h to 10 m{sup 3}/h. About 20.000 m{sup 3} of ground water have been extracted since from these two wells and the decrease of their Uranium concentrations behaves similar to that of the two other wells being extracted since the beginning of remediation. Both, total Uranium-concentrations and the weight-share of the nuclides U-234, U-235 and U-238 are measured by ICP-MS (Inductively Coupled Plasma - Mass Spectrometry) besides measurements of Uranium-Alpha-Activities in addition to the measurement of CHC components of which PCE (Per-chlor-Ethene) is dominant in the contaminated area. CHC compounds are measured by GC (Gas Chromatography). Down-gradient naturally attenuated products are detected in various compositions. Overall 183.000 m{sup 3} of ground water have been extracted. Using a pump and treat method 11 kg Uranium have been collected on an ion-exchange material based on cellulose, containing almost 100 MBq U-235 activity, and almost 15 kg of CHC, essentially PCE, were collected on GAC (Granules of Activated Carbon). Less than 3% of the extracted Uranium have passed the adsorber-system of the remediation plant and were adsorbed by the sewage sludge of the industrial site's waste water treatment. The monthly monitoring of 19 monitoring wells shows that an efficient artificial barrier was built up by the water extraction. The Uranium contamination of two ground water plumes has drastically been reduced by the used technique dependent on the amounts of extracted water. The concentration of the CHC contamination has changed depending on the location of temporal pumping. Thereby maximum availability of this contaminant for the remediation process is ensured. If locations with unchanged water quality are detected electrochemical parameters of the water or hydro-geologic data of the aquifer have to be taken into further consideration to improve the process of remediation. (authors)« less

A comparative study via Monte Carlo simulation of new inorganic scintillator Cs2HfCl6 for applications in nuclear medicine, security and defense, and astrophysics

NASA Astrophysics Data System (ADS)

Chen, Henry; Raby, Paul

2016-09-01

Cs2HfCl6 (CHC) is one of the most promising recently discovered new inorganic single crystal scintillator that has high light output, non-hygroscopic, no self-activity, having energy resolution significantly better than NaI(Tl), even approaching that of LaBr3 yet can also potentially be at a much lower cost than LaBr3. This study attempts to use Monte Carlo simulation to examine the great potential offered by this new scintillator. CHC's detector performance is compared via simulation with that of 4 typical existing scintillators of the same size and same PMT readout. Two halide-scintillators: NaI(Tl) and LaBr3 and two oxide-scintillators: GSO and LSO were used in this simulation to compare their 122 keV and 511 keV gamma responses with that of CHC with both spectroscopy application and imaging applications in mind. Initial simulation results are very promising and consistent with reported experimental measurements. Beside detector energy resolution, image-quality measurement parameters commonly used to characterize imaging detectors as in nuclear medicine such as Light Response Function (LRF) which goes in parallel with spatial resolution and simulated position spectra will also be presented and discussed.

Abnormal threshold voltage shift under hot carrier stress in Ti1-xNx/HfO2 p-channel metal-oxide-semiconductor field-effect transistors

NASA Astrophysics Data System (ADS)

Tsai, Jyun-Yu; Chang, Ting-Chang; Lo, Wen-Hung; Ho, Szu-Han; Chen, Ching-En; Chen, Hua-Mao; Tseng, Tseung-Yuen; Tai, Ya-Hsiang; Cheng, Osbert; Huang, Cheng-Tung

2013-09-01

This work investigates the channel hot carrier (CHC) effect in HfO2/Ti1-xNx p-channel metal oxide semiconductor field effect transistors (p-MOSFETs). Generally, the subthreshold swing (S.S.) should increase during CHC stress (CHCS), since interface states will be generated near the drain side under high electric field due to drain voltage (Vd). However, our experimental data indicate that S.S. has no evident change under CHCS, but threshold voltage (Vth) shifts positively. This result can be attributed to hot carrier injected into high-k dielectric near the drain side. Meanwhile, it is surprising that such Vth degradation is not observed in the saturation region during stress. Therefore, drain-induced-barrier-lowering (DIBL) as a result of CHC-induced electron trapping is proposed to explain the different Vth behaviors in the linear and saturation regions. Additionally, the influence of different nitrogen concentrations in HfO2/Ti1-xNx p-MOSFETs on CHCS is also investigated in this work. Since nitrogen diffuses to SiO2/Si interface induced pre-Nit occurring to degrades channel mobility during the annealing process, a device with more nitrogen shows slightly less impact ionization, leading to insignificant charge trapping-induced DIBL behavior.

Multi-Disciplinary Research for High Energy Chemical Lasers, Closed-Cycle ElectricOIL Technology

DTIC Science & Technology

2007-10-31

flow iodine from one reservoir and trap it in another. The principal advantage of the hybrid EOIL system is trading a small fixed mass in electrical...rapidly modulate the production of the 02(a) which have motivated investigations into methods to produce significant amounts of 02(a) using flowing...RF power is used for the production of ChC’Ag) in a cylindrical tube (R=2.54 cm and length of 10 cm) with a volume of 200 cm3 at 4.2 torr of pure O2

Student Preferences in Typography.

ERIC Educational Resources Information Center

Bell, Richard C.; Sullivan, James L. F.

1981-01-01

Describes a study in which 245 university students ranked their preferences among typographical variants of typeface, size, emphasis, and interline space in 16 paragraphs. Six references are listed. (CHC)

[HOMA-IR in patients with chronic hepatitis C].

PubMed

Botshorishvili, T; Vashakidze, E

2012-02-01

The aim of investigation was to study the frequency of IR in type of viral hepatitis C, correlation with the degree of hepatic lesion and liver cirrhosis. 130 patients were investigated: 20 with acute hepatitis C; 38 with chronic hepatitis C; 72 with cirrhosis: among them 10 with Stage A, 14 with Stage B and 48 with Stage C. Also we used 30 healthy people as the controls. The study demonstrates significant changes of insulin, glucose, HOMA-IR type of viral hepatitis C, correlation with the degree of hepatic lesion and liver cirrhosis. In patients with liver cirrhosis levels of HOMA-IR is higher than in patients with chronic hepatitis C. In patients with acute hepatitis C levels of HOMA-IR was normal as in the control group. The results showed that various types of chronic viral hepatitis C and stages of cirrhosis set to increase HOMA-IR versus the controls., which were the most prominent in cases of severe hepatic lesion, which indicates that insulin resistance is a frequent companion of CHC.

Fabrication and in vitro evaluation of the collagen/hyaluronic acid PEM coating crosslinked with functionalized RGD peptide on titanium.

PubMed

Huang, Ying; Luo, Qiaojie; Li, Xiaodong; Zhang, Feng; Zhao, Shifang

2012-02-01

Surface modification of titanium (Ti) using biomolecules has attracted much attention recently. In this study, a new strategy has been employed to construct a stable and bioactive coating on Ti. To this end, a derivative of hyaluronic acid (HA), i.e. HA-GRGDSPC-(SH), was synthesized. The disulfide-crosslinked Arg-Gly-Asp (RGD)-containing collagen/hyaluronic acid polyelectrolyte membrane (PEM) coating was then fabricated on Ti through the alternate deposition of collagen and HA-GRGDSPC-(SH) with five assembly cycles and subsequent crosslinking via converting free sulphydryl groups into disulfide linkages (RGD-CHC-Ti group). The assembly processes for PEM coating and the physicochemical properties of the coating were carefully characterized. The stability of PEM coating in phosphate-buffered saline solution could be adjusted by the crosslinking degree, while its degradation behaviors in the presence of glutathione were glutathione concentration dependent. The adhesion and proliferation of MC3T3-E1 cells were significantly enhanced in the RGD-CHC-Ti group. Up-regulated bone specific genes, enhanced alkaline phosphatase activity and osteocalcin production, the increased areas of mineralization were also observed in the RGD-CHC-Ti group. These results indicate that the strategy employed herein may function as an effective way to construct stable, RGD-containing bioactive coatings on Ti. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Atmospheric degradation of industrial fluorinated acrylates and methacrylates with Cl atoms at atmospheric pressure and 298 K

NASA Astrophysics Data System (ADS)

Rivela, Cynthia B.; Blanco, María B.; Teruel, Mariano A.

2018-04-01

The gas-phase reaction of Cl atom with 2,2,2-trifluoroethylacrylate (k1), 1,1,1,3,3,3-hexafluoroisopropylacrylate (k2), 2,2,2-trifluoroethylmethacrylate (k3) and 1,1,1,3,3,3-hexafluoroisopropylmethacrylate (k4), have been investigated at 298 K and 1 atm using the relative method by gas chromatography coupled with flame ionization detection (GC-FID). The values obtained are (in cm3 molecule-1 s-1): k1(Cl+CH2=CHC(O)OCH2CF3) = (2.41 ± 0.57) × 10-10, k2(Cl+CH2=CHC(O)OCH(CF3)2) = (1.39 ± 0.34) × 10-10, k3(Cl+CH2=C(CH3)C(O)OCH2CF3) = (2.22 ± 0.45) × 10-10, and k4(Cl +CH2=C(CH3)C(O)OCH(CF3)2 = (2.44 ± 0.52) × 10-10. Products identification studies were performed by solid-phase microextraction (SPME) method, with on-fiber products derivatization using o-(2,3,4,5,6-pentafluorobenzyl) hydroxylamine hydrochloride, coupled with gas chromatography with mass spectrometry detection (GC-MS). Chloroacetone, trifluoroacetaldehyde and formaldehyde were observed as degradation products and a general mechanism is proposed. Additionally, reactivity trends and atmospheric implications are discussed. Significant ozone photochemical potentials (POCP) and acidification potentials lead to local and or regional impact of the esters under study although is expected to a have a minor impact on global warming and climate change.

Effectiveness of a tinnitus management programme: a 2-year follow-up study

PubMed Central

Gudex, Claire; Skellgaard, Preben H; West, Torben; Sørensen, Jan

2009-01-01

Background Tinnitus impairs the possibility of leading a normal life in 0.5–1% of the population. While neither medical nor surgical treatment appears effective, counselling may offer some relief. An intervention combining counselling and hearing devices is offered to clients referred to the Centre for Help Aids and Communication (CHC) in southern Denmark. The aims of this exploratory study were to examine i) the characteristics of CHC's clients and their tinnitus, ii) the effectiveness of the treatment, and iii) whether particular client groups benefit more than others. Methods One hundred new clients presenting with tinnitus completed the Tinnitus Handicap Inventory (THI) three times – before their first consultation, after one month and after 1–2 years. The scores were tested for significant differences over time using tests for paired data. Logistic regression was used to examine factors associated with a clinically important difference (i.e. THI score improvement of at least 20 points). Results At final follow-up, total THI score was significantly lower than baseline, i.e. 29.8 (CI 25.5–34.2) vs. 37.2 (CI 33.1–37.2), p < 0.01. The programme achieved a clinically important difference for 27% and 24% of the clients one month and 1–2 years after the first consultation, respectively. It appeared that greater improvement in THI score was related to higher baseline THI score and possibly also to treatment by a particular CHC therapist. The absolute reduction in mean THI score after 1–2 years for clients with moderate and severe handicap was 14 and 20 points, respectively, i.e. similar to that previously reported for TRT (14–28 points). The cost of the current programme was approximately 200 EUR per client. Conclusion The tinnitus management programme appeared to provide significant benefit to many clients at a relatively low cost. It would be useful to conduct a randomised controlled study comparing the current programme with alternative forms of combination counselling/sound therapy approaches. PMID:19558680

Comparison of antibody responses against Mycobacterium tuberculosis antigen Rv0679c in tuberculosis patients from the endemic and non-endemic regions of the Beijing genotype: a case control study.

PubMed

Zhao, Jingge; Matsuba, Takashi; Zhang, Xiaoyan; Leano, Susan; Nakajima, Chie; Chagan-Yasutan, Haorile; Telan, Elizabeth Freda; Suzuki, Yasuhiko; Hattori, Toshio

2017-05-15

Strains of the Beijing genotype of Mycobacterium tuberculosis (MTB) are reportedly associated with the virulence of tuberculosis (TB) infection, unfavorable outcomes of anti-TB treatment, and the global TB pandemic. Rv0679c, a hypothetical membrane protein related to host cell invasion, has a Beijing genotype-specific mutation at residue 142 (Asn142Lys). Antigenicity differences between Rv0679c-Asn142 (N-type) and Rv0679c-Lys142 (K-type) have been previously observed in mice antigen-antibody responses. However, the immune response to Rv0679c in humans remains unknown. Therefore, we aimed to investigate the anti-Rv0679c immune response in TB patients from the endemic and non-endemic regions of the Beijing MTB genotype. We analyzed the Rv0679c-specific antibody responses in 84 subjects from the endemic region of the Beijing genotype MTB in China, including 45 pulmonary TB patients (C-PTB) and 39 healthy controls (C-HC), and 81 subjects from the Philippines (the endemic region of the non-Beijing genotype), including 51 pulmonary TB patients (P-PTB) and 30 healthy controls (P-HC). Anti-tuberculous-glycolipid (TBGL) antigen was used as the control antibody. TBGL IgG titers were higher in both C-PTB and P-PTB than those in their corresponding HC (C-PTB median 4.2, P-PTB median 11.2; C-PTB vs. P-PTB, p > 0.05), suggesting immune response comparability in PTB from two different countries. C-PTB showed a higher response compared to C-HC for anti-K-type IgG (53.3%) than anti-N-type IgG (6.67%); this response was not observed in P-PTB (both N-type and K-type 9.80%). Dimorphic antigen Rv0679c was found to be associated with distinct immune response patterns, indicating the role of Beijing/non-Beijing genotype of MTB in stimulating specific responses in TB patients from the endemic region of Beijing MTB. Meanwhile, reactions to Rv0679c in patients and HC from non-endemic regions of the Beijing MTB may be caused by the response to the common epitope of Rv0679c N/K-type.

Growth and luminescent properties of Ce and Eu doped Cesium Hafnium Iodide single crystalline scintillators

NASA Astrophysics Data System (ADS)

Kodama, Shohei; Kurosawa, Shunsuke; Yamaji, Akihiro; Pejchal, Jan; Král, Robert; Ohashi, Yuji; Kamada, Kei; Yokota, Yuui; Nikl, Martin; Yoshikawa, Akira

2018-06-01

In order to obtain new scintillators with high light output and high effective atomic number (Zeff), we performed anion-substitution for Cs2HfCl6 (CHC) scintillator, and then, we succeeded in growing Cs2HfI6 (CHI) single crystalline scintillator. It had Zeff of 58, which is the same as that of CHC, and had high light output of ∼70,000 photons/MeV with 700 nm emission. However, its scintillation decay time of ∼2.5 μs was slow for practical use as gamma-ray monitor. In this study, we performed Ce3+/Eu2+ doping to Hf4+ site to improve decay time of CHI, introducing the fast 5d-4f luminescence. Ce:CHI and Eu:CHI single crystals were finally obtained by the vertical Bridgman-Stockbarger method. The luminescence spectra of the Ce:CHI and Eu:CHI were very similar to that of the non-doped CHI, which would mean that no 5d-4f luminescence of Ce3+/Eu2+ was observed. The measured light output and decay time of Ce:CHI were ∼48,000 photon/MeV and 2.3 ± 0.1 μs, respectively. As for Eu:CHI, light output and decay time were ∼69,000 photon/MeV and 2.8 ± 0.1 μs, respectively.

Comprehensive highway corridor planning with sustainability indicators.

DOT National Transportation Integrated Search

2011-10-01

"The Maryland State Highway Administration (SHA) has initiated major planning efforts to improve transportation : efficiency, safety, and sustainability on critical highway corridors through its Comprehensive Highway Corridor : (CHC) program. This pr...

Comprehensive highway corridor planning with sustainability indicators.

DOT National Transportation Integrated Search

2013-04-01

The Maryland State Highway Administration (SHA) has initiated major planning efforts to improve transportation : efficiency, safety, and sustainability on critical highway corridors through its Comprehensive Highway Corridor : (CHC) program. This pro...

Alkali metal complexes of sterically demanding amino-functionalized secondary phosphanide ligands.

PubMed

Izod, Keith; Stewart, John C; Clegg, William; Harrington, Ross W

2007-01-14

The reaction between {(Me(3)Si)(2)CH}PCl(2) (4) and one equivalent of either [C(6)H(4)-2-NMe(2)]Li or [2-C(5)H(4)N]ZnCl, followed by in situ reduction with LiAlH(4) gives the secondary phosphanes {(Me(3)Si)(2)CH}(C(6)H(4)-2-NMe(2))PH (5) and {(Me(3)Si)(2)CH}(2-C(5)H(4)N)PH (6) in good yields as colourless oils. Metalation of 5 with Bu(n)Li in THF gives the lithium phosphanide [[{(Me(3)Si)(2)CH}(C(6)H(4)-2-NMe(2))P]Li(THF)(2)] (7), which undergoes metathesis with either NaOBu(t) or KOBu(t) to give the heavier alkali metal derivatives [[{(Me(3)Si)(2)CH}(C(6)H(4)-2-NMe(2))P]Na(tmeda)] (8) and [[{(Me(3)Si)(2)CH}(C(6)H(4)-2-NMe(2))P]K(pmdeta)] (9) after recrystallization in the presence of the corresponding amine co-ligand [tmeda = N,N,N',N'-tetramethylethylenediamine, pmdeta = N,N,N',N'',N''-pentamethyldiethylenetriamine]. The pyridyl-functionalized phosphane 6 undergoes deprotonation on treatment with Bu(n)Li to give a red oil corresponding to the lithium compound [{(Me(3)Si)(2)CH}(2-C(5)H(4)N)P]Li (10) which could not be crystallized. Treatment of this oil with NaOBu(t) gives the sodium derivative [{[{(Me(3)Si)(2)CH}(2-C(5)H(4)N)P]Na}(2) x (Et(2)O)](2) (11), whilst treatment of with KOBu(t), followed by recrystallization in the presence of pmdeta gives the complex [[{(Me(3)Si)(2)CH}(2-C(5)H(4)N)P]K(pmdeta)](2) (12). Compounds 5-12 have been characterised by (1)H, (13)C{(1)H} and (31)P{(1)H} NMR spectroscopy and elemental analyses; compounds 7-9, and 12 have additionally been characterised by X-ray crystallography. Compounds 7-9 crystallize as discrete monomers, whereas 11 crystallizes as an unusual dimer of dimers and 12 crystallizes as a dimer with bridging pyridyl-phosphanide ligands.

Construct validity of the Wechsler Intelligence Scale for Children - Fourth UK Edition with a referred Irish sample: Wechsler and Cattell-Horn-Carroll model comparisons with 15 subtests.

PubMed

Canivez, Gary L; Watkins, Marley W; Good, Rebecca; James, Kate; James, Trevor

2017-09-01

Irish educational psychologists frequently use the Wechsler Intelligence Scale for Children - Fourth UK Edition (WISC-IV UK ; Wechsler, 2004, Wechsler Intelligence Scale for Children-Fourth UK Edition, London, UK, Harcourt Assessment) in clinical assessments of children with learning difficulties. Unfortunately, reliability and validity studies of the WISC-IV UK standardization sample have not yet been reported. Watkins et al. (2013, International Journal of School and Educational Psychology, 1, 102) found support for a bifactor structure with a large sample (N = 794) of Irish children who were administered the 10 WISC-IV UK core subtests in clinical assessments of learning difficulties and dominance of general intelligence. Because only 10 subtests were available, Cattell-Horn-Carroll (CHC; McGrew, 1997, 2005, Contemporary intellectual assessment: Theories, tests, and issues, New York, NY: Guilford; Schneider & McGrew, 2012, Contemporary intellectual assessment: Theories, tests, and issues, New York, NY, Guilford Press) models could not be tested and compared. The present study utilized confirmatory factor analyses to test the latent factor structure of the WISC-IV UK with a sample of 245 Irish children administered all 15 WISC-IV UK subtests in evaluations assessing learning difficulties in order to examine CHC- and Wechsler-based models. One through five, oblique first-order factor models and higher order versus bifactor models were examined and compared using CFA. Meaningful differences in fit statistics were not observed between the Wechsler and CHC representations of higher-order or bifactor models. In all four structures, general intelligence accounted for the largest portions of explained common variance, whereas group factors accounted for small to miniscule portions of explained common variance. Omega-hierarchical subscale coefficients indicated that unit-weighted composites that would be generated by WISC-IV UK group factors (Wechsler or CHC) would contain little unique variance and thus be of little value. These results were similar to those from other investigations, further demonstrating the replication of the WISC-IV factor structure across cultures and the importance of focusing primary interpretation on the FSIQ. © 2017 The British Psychological Society.

Illustrations in Text: A Retentional Role.

ERIC Educational Resources Information Center

Duchastel, Philippe C.

1981-01-01

Describes the results of a study of the retentional role of illustrations in a text and their effect on enhancing long-term memory with 15-year-old secondary school students. Seven references are listed. (CHC)

A Programming Language Environment for the Unassisted Learner.

ERIC Educational Resources Information Center

Thomas, P. G.; Ince, D. C.

1982-01-01

Describes the computing environment and command language for a new programing language called OUSBASIC which is designed to enable naive users to interact usefully, with little assistance, with a computer system. (Author/CHC)

Comprehensive highway corridor planning with sustainability indicators : [research summary].

DOT National Transportation Integrated Search

2013-04-01

The Maryland State Highway Administration (SHA) has initiated major planning : efforts to improve transportation efficiency, safety and sustainability on critical : highway corridors through its Comprehensive Highway Corridor (CHC) program. : It is i...

Cognitive ability influences on written expression: Evidence for developmental and sex-based differences in school-age children.

PubMed

Hajovsky, Daniel B; Villeneuve, Ethan F; Reynolds, Matthew R; Niileksela, Christopher R; Mason, Benjamin A; Shudak, Nicholas J

2018-04-01

Some studies have demonstrated that the Cattell-Horn-Carroll (CHC) cognitive abilities influence writing; however, little research has investigated whether CHC cognitive abilities influence writing the same way for males and females across grades. We used multiple group structural equation models to investigate whether CHC cognitive ability influences on written expression differed between grades or sex using the Kaufman Assessment Battery for Children, Second Edition and the Kaufman Tests of Educational Achievement, Second Edition co-normed standardization sample data (N=2117). After testing for consistent measurement of cognitive abilities across grades and sex, we tested whether the cognitive ability influences on written expression were moderated by grade level or sex. An important developmental shift was observed equally across sex groups: Learning Efficiency (Gl) influences decreased whereas Crystallized Ability (Gc) influences increased after fourth grade. Further, Short-Term Memory (Gsm) and Retrieval Fluency (Gr) influences on written expression depended on sex at grades 1-4, with larger Gr influences for females and larger Gsm influences for males. We internally replicated our main findings using two different cognitive explanatory models, adding further support for the developmental and sex-based differential cognitive ability influences on writing. Explanatory cognitive models of writing need to incorporate development, and possibly, sex to provide an expanded understanding of writing development and guard against potential generalizability issues characteristic of special population (i.e., male-female) studies. Copyright © 2017 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

A novel non-imaging optics based Raman spectroscopy device for transdermal blood analyte measurement

PubMed Central

Kong, Chae-Ryon; Barman, Ishan; Dingari, Narahara Chari; Kang, Jeon Woong; Galindo, Luis; Dasari, Ramachandra R.; Feld, Michael S.

2011-01-01

Due to its high chemical specificity, Raman spectroscopy has been considered to be a promising technique for non-invasive disease diagnosis. However, during Raman excitation, less than one out of a million photons undergo spontaneous Raman scattering and such weakness in Raman scattered light often require highly efficient collection of Raman scattered light for the analysis of biological tissues. We present a novel non-imaging optics based portable Raman spectroscopy instrument designed for enhanced light collection. While the instrument was demonstrated on transdermal blood glucose measurement, it can also be used for detection of other clinically relevant blood analytes such as creatinine, urea and cholesterol, as well as other tissue diagnosis applications. For enhanced light collection, a non-imaging optical element called compound hyperbolic concentrator (CHC) converts the wide angular range of scattered photons (numerical aperture (NA) of 1.0) from the tissue into a limited range of angles accommodated by the acceptance angles of the collection system (e.g., an optical fiber with NA of 0.22). A CHC enables collimation of scattered light directions to within extremely narrow range of angles while also maintaining practical physical dimensions. Such a design allows for the development of a very efficient and compact spectroscopy system for analyzing highly scattering biological tissues. Using the CHC-based portable Raman instrument in a clinical research setting, we demonstrate successful transdermal blood glucose predictions in human subjects undergoing oral glucose tolerance tests. PMID:22125761

Orthogonal higher order structure and confirmatory factor analysis of the French Wechsler Adult Intelligence Scale (WAIS-III).

PubMed

Golay, Philippe; Lecerf, Thierry

2011-03-01

According to the most widely accepted Cattell-Horn-Carroll (CHC) model of intelligence measurement, each subtest score of the Wechsler Intelligence Scale for Adults (3rd ed.; WAIS-III) should reflect both 1st- and 2nd-order factors (i.e., 4 or 5 broad abilities and 1 general factor). To disentangle the contribution of each factor, we applied a Schmid-Leiman orthogonalization transformation (SLT) to the standardization data published in the French technical manual for the WAIS-III. Results showed that the general factor accounted for 63% of the common variance and that the specific contributions of the 1st-order factors were weak (4.7%-15.9%). We also addressed this issue by using confirmatory factor analysis. Results indicated that the bifactor model (with 1st-order group and general factors) better fit the data than did the traditional higher order structure. Models based on the CHC framework were also tested. Results indicated that a higher order CHC model showed a better fit than did the classical 4-factor model; however, the WAIS bifactor structure was the most adequate. We recommend that users do not discount the Full Scale IQ when interpreting the index scores of the WAIS-III because the general factor accounts for the bulk of the common variance in the French WAIS-III. The 4 index scores cannot be considered to reflect only broad ability because they include a strong contribution of the general factor.

Effective Use of Existing Space in Libraries.

ERIC Educational Resources Information Center

Brown, Nancy A.

1981-01-01

Discusses the effective use of stack space through weeding, storage, microfilm, and selection; study space based on student population; and service space by reorganization of staff, collections, and study space. Three references are noted. (CHC)

Educational Technology in Argentina.

ERIC Educational Resources Information Center

Ronchi, Robert

1980-01-01

This description of the status of educational technology and trends in the development of the field in Argentina is based on article documents, reports, and a survey of projects operating in that country. Sixteen references are listed. (Author/CHC)

The Role of Microcomputers in Libraries.

ERIC Educational Resources Information Center

Lundeen, Gerald

1980-01-01

Describes the functions and characteristics of the microcomputer and discusses library applications including cataloging, circulation, acquisitions, serials control, reference and database systems, administration, current and future trends, and computers as media. Twenty references are listed. (CHC)

Perceptions of Cancer Care and Clinical Trials in the Black Community: Implications for Care Coordination Between Oncology and Primary Care Teams.

PubMed

Sprague Martinez, Linda; Freeman, Elmer R; Winkfield, Karen M

2017-09-01

Despite efforts to ameliorate disparities in cancer care and clinical trials, barriers persist. As part of a multiphase community-engaged assessment, an exploratory community-engaged research partnership, forged between an academic hospital and a community-based organization, set out to explore perceptions of cancer care and cancer clinical trials by black Bostonians. Key informant interviews with health care providers and patient advocates in community health centers (CHCs), organizers from grassroots coalitions focused on cancer, informed the development of a focus group protocol. Six focus groups were conducted with black residents in Boston, including groups of cancer survivors and family members. Transcripts were coded thematically and a code-based report was generated and analyzed by community and academic stakeholders. While some participants identified clinical trials as beneficial, overall perceptions conjured feelings of fear and exploitation. Participants describe barriers to clinical trial participation in the context of cancer care experiences, which included negative interactions with providers and mistrust. Primary care physicians (PCPs) reported being levied as a trusted resource for patients undergoing care, but lamented the absence of a mechanism by which to gain information about cancer care and clinical trials. Confusion about cancer care and clinical trials persists, even among individuals who have undergone treatment for cancer. Greater coordination between PCPs and CHC care teams and oncology care teams may improve patient experiences with cancer care, while also serving as a mechanism to disseminate information about treatment options and clinical trials. Inequities in cancer care and clinical trial participation persist. The findings of this study indicate that greater coordination with primary care physicians (PCPs) and community health center (CHC) providers may be an important step for both improving the quality of cancer care in communities and increasing awareness of clinical trials. However, PCPs and CHCs are often stretched to capacity with caring for their communities. This leaves the oncology community well positioned to create programs to bridge the communication gaps and provide resources necessary to support oncologic care along the cancer continuum, from prevention through survivorship. © AlphaMed Press 2017.

Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes.

PubMed

Barathan, Muttiah; Gopal, Kaliappan; Mohamed, Rosmawati; Ellegård, Rada; Saeidi, Alireza; Vadivelu, Jamuna; Ansari, Abdul W; Rothan, Hussin A; Ravishankar Ram, M; Zandi, Keivan; Chang, Li Y; Vignesh, Ramachandran; Che, Karlhans F; Kamarulzaman, Adeeba; Velu, Vijayakumar; Larsson, Marie; Kamarul, Tunku; Shankar, Esaki M

2015-04-01

Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(®) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.

Team composition and chronic disease management within primary healthcare practices in eastern Ontario: an application of the Measuring Organizational Attributes of Primary Health Care Survey.

PubMed

Lukewich, Julia; Edge, Dana S; VanDenKerkhof, Elizabeth; Williamson, Tyler; Tranmer, Joan

2018-04-15

Various organizational-level attributes are being implemented in primary healthcare to improve healthcare delivery. There is a need to describe the distribution and nature of these attributes and explore differences across practices.AimThe aim of this study was to better understand organizational attributes of primary care teams, focusing specifically on team composition, nursing roles, and strategies that support chronic disease management. We employed a cross-sectional survey design. Team composition, nursing roles, availability of health services, and chronic disease management activities were described using the 'Measuring Organizational Attributes of Primary Health Care Survey.'FindingsA total of 76% (n=26 out of 34) of practice locations completed the survey, including family health teams (FHT; n=21) and community health centers (CHC; n=4). Nurse practitioners (NPs) and registered nurses (RNs) were the most common non-physician providers, and CHCs had a greater proportion of non-physician providers than FHTs. There was overlap in roles performed by NPs and RNs, and registered practical nurses engaged in fewer roles compared with NPs and RNs. A greater proportion of FHTs had systematic chronic disease management services for hypertension, depression and Alzheimer's disease compared with CHC practices. The 'Measuring Organizational Attributes of Primary Health Care Survey' was a useful tool to highlight variability in organizational attributes across PHC practices. Nurses are prominent within PHC practices, engaging in a wide range of roles related to chronic disease management, suggesting a need to better understand their contributions to patient care to optimize their roles.

The role of ITPA and ribavirin transporter genes polymorphisms in prediction of ribavirin-induced anaemia in chronic hepatitis C Egyptian patients.

PubMed

El Desoky, Ehab S; Abdelhafez, Alaa T; Cusato, Jessica; Kamel, Sherif I; Hussein, Abeer Mr; De Nicolo, Amedeo; Di Perri, Giovanni; D'Avolio, Antonio

2017-09-01

Few data are available concerning the roles of polymorphisms of inosine triphosphatase (ITPA) gene and ribavirin (RBV) transporter genes in the prediction of RBV-induced anaemia among Egyptians with chronic hepatitis C (CHC). Genotyping of three ITPA gene variants and two variants of RBV transporter genes has been performed in 123 patients under pegylated interferon-α/ribavirin treatment. The baseline haemoglobin and ITPA rs1127354 CA/AA have been found as predictors of anaemia at 4, 8 and 12 weeks of RBV therapy. In addition, ITPA rs7270101 AC/CC and age predicted anaemia after 12 weeks of therapy. In conclusion, the ITPA variant rs1127354C>A significantly predict RBV-induced anaemia during the first 3 months of treatment and it is recommended to be assessed before RBV administration. © 2017 John Wiley & Sons Australia, Ltd.

Energy: Add Power to Your Collection.

ERIC Educational Resources Information Center

Rholes, Julia M.

1981-01-01

An annotated bibliography of 34 children's books on different types of energy at various reading levels includes general titles, as well as books on coal, geothermal energy, nuclear energy, ocean engineering, petroleum, solar energy, and wind energy. (CHC)

Modularization: An Attempt at Collegiate Level in India.

ERIC Educational Resources Information Center

Gabriel, J.; Pillai, J. K.

1981-01-01

The effectiveness of a modular approach to learning in a botany unit as compared to the traditional teaching approach in terms of learning efficiency, learning time, and mastery level is reported. Three references are cited. (Author/CHC)

Education by Television in the Ivory Coast.

ERIC Educational Resources Information Center

Valerien, Jean

1981-01-01

The management, administration, production, and broadcasting of educational television are discussed and evaluated with respect to its use in elementary education, training of teachers, and out-of-school education in the Ivory Coast during the 1970s. (CHC)

Private Use, Public Policy: Copyright and Home Recording.

ERIC Educational Resources Information Center

Ladd, David

1981-01-01

Discusses the relationship between copyright and the new technologies. The legal responses to copyright violations and to cases regarding fair use, as well as international efforts to protect copyright with respect to noncommercial use are considered. (CHC)

Application of ion chromatography to the study of hydrolysis of some halogenated hydrocarbons at ambient temperatures

NASA Technical Reports Server (NTRS)

Otterson, D. A.

1978-01-01

The application of ion chromatography to the study of very slow rates of hydrolysis of some halogenated hydrocarbons was investigated. The halide concentrations in the aqueous phase of mixtures of a carbonate buffer (pH = 10.3) and either chloroform (CHC13) or fluorotrichloromethane (CFC13) after aging for various lengths of time at room temperature, were determined by ion chromatography. Hydrolysis of CHC13 caused the C1(-) concentration to increase by about 1500 ppb per day. On the other hand neither the F(-) or C1(-) concentration in the CFC13 mixture increased by as much as 1 ppb per day. The magnitude of errors in the determination of halides prevented any firm conclusions regarding hydrolysis in this mixture. However, these results were used to show how ion chromatography could expedite identification of the hydrolyzing substance as well as investigations of hydrolysis mechanisms.

Improving access to health care for undocumented immigrants in the United States.

PubMed

Wallace, Steven P; Rodriguez, Michael; Padilla-Frausto, Imelda; Arredondo, Armando; Orozco, Emanuel

2013-01-01

To identify policies that increase access to health care for undocumented Mexican immigrants. Four focus groups (n=34 participants) were conducted with uninsured Mexican immigrants in Los Angeles, California. The feasibility and desirability of different policy proposals for increasing access were discussed by each group. Respondents raised significant problems with policies including binational health insurance, expanded employer-provided health insurance, and telemedicine. The only solution with a consensus that the change would be feasible, result in improved access, and they had confidence in was expanded access to community health centers (CHC's). Given the limited access to most specialists at CHC's and the continued barriers to hospital care for those without health insurance, the most effective way of improving the complete range of health services to undocumented immigrants is through immigration reform that will bring these workers under the other health care reform provisions.

A Sense of Obligation: Cultural Differences in the Experience of Obligation.

PubMed

Buchtel, Emma E; Ng, Leo C Y; Norenzayan, Ara; Heine, Steven J; Biesanz, Jeremy C; Chen, Sylvia Xiaohua; Bond, Michael Harris; Peng, Qin; Su, Yanjie

2018-05-01

In this investigation of cultural differences in the experience of obligation, we distinguish between Confucian Role Ethics versus Relative Autonomy lay theories of motivation and illustrate them with data showing relevant cultural differences in both social judgments and intrapersonal experience. First, when judging others, Western European heritage culture (WEHC) participants (relative to Confucian heritage culture [CHC] participants) judged obligation-motivated actors more negatively than those motivated by agency (Study 1, N = 529). Second, in daily diary and situation sampling studies, CHC participants (relative to WEHC participants) perceived more congruency between their own agentic and obligated motivations, and more positive emotional associations with obligated motivations (Study 2, N = 200 and Study 3, N = 244). Agentic motivation, however, was universally associated with positive emotions. More research on a Role Ethics rather than Relative Autonomy conception of agency may improve our understanding of human motivation, especially across cultures.

Combating Obesity at Community Health Centers (COACH): A Quality Improvement Collaborative for Weight Management Programs

PubMed Central

Wilkes, Abigail E.; John, Priya M.; Vable, Anusha M.; Campbell, Amanda; Heuer, Loretta; Schaefer, Cynthia; Vinci, Lisa; Drum, Melinda L.; Chin, Marshall H.; Quinn, Michael T.; Burnet, Deborah L.

2013-01-01

Community health centers (CHCs) seek effective strategies to address obesity. MidWest Clinicians’ Network partnered with [an academic medical center] to test feasibility of a weight management quality improvement (QI) collaborative. MidWest Clinicians’ Network members expressed interest in an obesity QI program. This pilot study aimed to determine whether the QI model can be feasibly implemented with limited resources at CHCs to improve weight management programs. Five health centers with weight management programs enrolled with CHC staff as primary study participants; this study did not attempt to measure patient outcomes. Participants attended learning sessions and monthly conference calls to build QI skills and share best practices. Tailored coaching addressed local needs. Topics rated most valuable were patient recruitment/retention strategies, QI techniques, evidence-based weight management, motivational interviewing. Challenges included garnering provider support, high staff turnover, and difficulty tracking patient-level data. This paper reports practical lessons about implementing a weight management QI collaborative in CHCs. PMID:23727964

Dual degradation of gaseous 1,2-dichlorobenzene and PCDD/Fs using Ce doped VxOy/TiO2 immobilized on cordierite.

PubMed

Chen, Yan; Wu, Qiong; Liu, Kuiren

2016-07-01

The photocatalytic film Ce doped VxOy/TiO2 was loaded on cordierite honeycomb (CHC), and this composite was prepared by sol-gel and dipping method, with Ce, oxides of V and TiO2 as dopant and key substances, respectively. Using gaseous 1,2-dichlorobenzene to replace dioxin as target pollutant, dual degradation experiments at 140-280 °C were carried out (thermal decomposition and photodegradation), and the effects of preparation conditions on catalytic activity were investigated: doping amount of Ce, dipping time in the gel, the concentration of ammonium metavanadate (NH4VO3) solution, dipping time in NH4VO3 solution, sintering temperature. The gaseous samples were taken before and after the reactor and analyzed by gas chromatography. According to the results, the optimal preparation conditions were determined, and the corresponding removal rate was above 95% after 90 min of degradation at 280 °C. The composite was examined by ultrasonic to analyze the adhesive strength between the film and CHC, and further characterized by XRD and SEM. Furthermore, flue gas from waste incinerator was chosen as target pollutant, which contained PCDD/Fs, the industrial sidestream degradation experiment was carried out and showed excellent removal efficiency of the composite, the removal rate of PCDD/Fs reached ca. 90% after 90 min of degradation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantitative assessment of hepatic fibrosis in chronic hepatitis B and C: T1 mapping on Gd-EOB-DTPA-enhanced liver magnetic resonance imaging.

PubMed

Pan, Shen; Wang, Xiao-Qi; Guo, Qi-Yong

2018-05-14

To assess the accuracy of Look-Locker on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for staging liver fibrosis in chronic hepatitis B/C (CHB/C). We prospectively included 109 patients with CHB or CHC who underwent a 3.0-Tesla MRI examination, including T1-weighted and Look-Locker sequences for T1 mapping. Hepatocyte fractions (HeF) and relaxation time reduction rate (RE) were measured for staging liver fibrosis. A receiver operating characteristic analysis using the area under the receiver operating characteristic curve (AUC) was used to compare the diagnostic performance in predicting liver fibrosis between HeF and RE. A total of 73 patients had both pathological results and MRI information. The number of patients in each fibrosis stage was evaluated semiquantitatively according to the METAVIR scoring system: F0, n = 23 (31.5%); F1, n = 19 (26.0%); F2, n = 13 (17.8%); F3, n = 6 (8.2%), and F4, n = 12 (16.4%). HeF by EOB enhancement imaging was significantly correlated with fibrosis stage ( r = -0.808, P < 0.05). AUC values for diagnosis of any (≥ F1), significant (≥ F2) or advanced (≥ F3) fibrosis, and cirrhosis (F4) using HeF were 0.837 (0.733-0.913), 0.890 (0.795-0.951), 0.957 (0.881-0.990), and 0.957 (0.882-0.991), respectively. HeF measurement was more accurate than use of RE in establishing liver fibrosis staging, suggesting that calculation of HeF is a superior noninvasive liver fibrosis staging method. A T1 mapping-based HeF method is an efficient diagnostic tool for the staging of liver fibrosis.

Comparison of nine blood tests and transient elastography for liver fibrosis in chronic hepatitis C: the ANRS HCEP-23 study.

PubMed

Zarski, Jean-Pierre; Sturm, Nathalie; Guechot, Jérôme; Paris, Adeline; Zafrani, Elie-Serge; Asselah, Tarik; Boisson, Renée-Claude; Bosson, Jean-Luc; Guyader, Dominique; Renversez, Jean-Charles; Bronowicki, Jean-Pierre; Gelineau, Marie-Christine; Tran, Albert; Trocme, Candice; De Ledinghen, Victor; Lasnier, Elisabeth; Poujol-Robert, Armelle; Ziegler, Frédéric; Bourliere, Marc; Voitot, Hélène; Larrey, Dominique; Rosenthal-Allieri, Maria Alessandra; Fouchard Hubert, Isabelle; Bailly, François; Vaubourdolle, Michel

2012-01-01

Blood tests and transient elastography (Fibroscan™) have been developed as alternatives to liver biopsy. This ANRS HCEP-23 study compared the diagnostic accuracy of nine blood tests and transient elastography (Fibroscan™) to assess liver fibrosis, vs. liver biopsy, in untreated patients with chronic hepatitis C (CHC). This was a multicentre prospective independent study in 19 French University hospitals of consecutive adult patients having simultaneous liver biopsy, biochemical blood tests (performed in a centralized laboratory) and Fibroscan™. Two experienced pathologists independently reviewed the liver biopsies (mean length=25±8.4 mm). Performance was assessed using ROC curves corrected by Obuchowski's method. Fibroscan™ was not interpretable in 113 (22%) patients. In the 382 patients having both blood tests and interpretable Fibroscan™, Fibroscan™ performed similarly to the best blood tests for the diagnosis of significant fibrosis and cirrhosis. Obuchowski's measure showed Fibrometer® (0.86), Fibrotest® (0.84), Hepascore® (0.84), and interpretable Fibroscan™ (0.84) to be the most accurate tests. The combination of Fibrotest®, Fibrometer®, or Hepascore® with Fibroscan™ or Apri increases the percentage of well classified patients from 70-73% to 80-83% for significant fibrosis, but for cirrhosis a combination offers no improvement. For the 436 patients having all the blood tests, AUROC's ranged from 0.82 (Fibrometer®) to 0.75 (Hyaluronate) for significant fibrosis, and from 0.89 (Fibrometer® and Hepascore®) to 0.83 (FIB-4) for cirrhosis. Contrarily to blood tests, performance of Fibroscan™ was reduced due to uninterpretable results. Fibrotest®, interpretable Fibroscan™, Fibrometer®, and Hepascore® perform best and similarly for diagnosis of significant fibrosis and cirrhosis. Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Job Sharing for the 80's.

ERIC Educational Resources Information Center

Notowitz, Carol

1982-01-01

Discusses the advantages and disadvantages of job-sharing as an alternative to part-time employment in libraries and describes a job-sharing experiment at the Parson Branch of the Public Library of Columbus and Franklin County. Six references are included. (CHC)

CHILD HEALTH CHAMPION AIR QUALITY MONITORING AND EDUCATION PROJECT

EPA Science Inventory

In response to two presidential directives, EPA has created the Child Health Champion (CHC) Environmental Monitoring for Public Access and Community Tracking (EMPACT) pilot program in communities where environmental data are not widely available and significant environmental heal...

Lessons Learned from Developing a Patient Engagement Panel: An OCHIN Report.

PubMed

Arkind, Jill; Likumahuwa-Ackman, Sonja; Warren, Nate; Dickerson, Kay; Robbins, Lynn; Norman, Kathy; DeVoe, Jennifer E

2015-01-01

There is renewed interest in patient engagement in clinical and research settings, creating a need for documenting and publishing lessons learned from efforts to meaningfully engage patients. This article describes early lessons learned from the development of OCHIN's Patient Engagement Panel (PEP). OCHIN supports a national network of more than 300 community health centers (CHCs) and other primary care settings that serve over 1.5 million patients annually across nearly 20 states. The PEP was conceived in 2009 to harness the CHC tradition of patient engagement in this new era of patient-centered outcomes research and to ensure that patients were engaged throughout the life cycle of our research projects, from conception to dissemination. Developed by clinicians and researchers within our practice-based research network, recruitment of patients to serve as PEP members began in early 2012. The PEP currently has a membership of 18 patients from 3 states. Over the past 24 months, the PEP has been involved with 12 projects. We describe developing the PEP and challenges and lessons learned (eg, recruitment, funding model, creating value for patient partners, compensation). These lessons learned are relevant not only for research but also for patient engagement in quality improvement efforts and other clinical initiatives. © Copyright 2015 by the American Board of Family Medicine.

The role of the NLRP3 inflammasome and the activation of IL-1β in the pathogenesis of chronic viral hepatic inflammation.

PubMed

Molyvdas, Adam; Georgopoulou, Urania; Lazaridis, Nikolaos; Hytiroglou, Prodromos; Dimitriadis, Alexios; Foka, Pelagia; Vassiliadis, Themistoklis; Loli, Georgia; Phillipidis, Athanasios; Zebekakis, Pantelis; Germenis, Anastasios E; Speletas, Matthaios; Germanidis, Georgios

2018-05-23

Chronic viral hepatitis is a prevalent disease with major health implications. Its underlying pathophysiological mechanisms are not fully understood. IL-1β and the NLRP3 inflammasome involvement has been suggested in recent years, from in vitro data and data from peripheral blood samples. Therefore, we investigated IL-1β and the NLRP3 inflammasome in liver tissues in an effort to clarify their role in the pathophysiology of chronic viral hepatitis. We studied liver biopsies from patients with a new diagnosis of either chronic hepatitis B (CHB) and chronic hepatitis C (CHC) or patients with chronic hepatitis B in remission (CHB-rem). The biopsies were separated in two parts. The first part was sent to histology to determine the grade of inflammation and fibrosis. From the second part, RNA was extracted and converted to cDNA used in semi-quantitative Real-Time PCR to measure the levels of IL1B, CASP1, NLRP3, ASC and IL1RA. The cell lines used in the in vitro experiments were Huh7.5, LX2 and THP-1 in variety of combinations of monocultures, co-cultures and triple cultures with one of the cell lines infected with the JFH-1 HCV clone. From the cell cultures RNA was extracted and converted to cDNA. For cell lines, we focused in the expression of IL1B and NLRP3. The expression of IL1B, CASP1 and NLRP3 were found significantly different between our groups (p = 0.001, p = 0.001 and p = 0.038, respectively). CHB patients displayed significantly higher IL1B and CASP1 mRNA levels compared to both CHB-rem and CHC patients. IL1B expression significantly correlates with liver biochemical data in CHB patients (AST: p = 0.006, r = 0.457; ALT p = 0.002, r = 0.497). Finally, mRNA levels of IL1B in CHB patients significantly correlate with the degree of inflammation (p = 0.016) but not the stage of fibrosis (p = 0.362). Interestingly, the relative expression of IL1B in triple culture experiments in vitro was below of 1.5-fold, suggesting no activation of IL1B. Moreover, no activation of NLRP3 was demonstrated in all investigated in vitro conditions. IL-1β might play an important role in the pathogenesis of chronic hepatic inflammation from HBV, but not from HCV. Copyright © 2018 Elsevier Ltd. All rights reserved.

Potential Diagnostic and Prognostic Value of Lymphocytic Mitochondrial DNA Deletion in Relation to Folic Acid Status in HCV-Related Hepatocellular Carcinoma

PubMed Central

Zekri, Abdel Rahman N; Salama, Hosny; Medhat, Eman; Hamdy, Sherif; Hassan, Zeinab K; Bakr, Yasser Mabrouk; Youssef, Amira Salah El - Din; Saleh, Doaa; Saeed, Ramy; Omran, Dalia

2017-01-01

Objective: We assessed the possibility of using mitochondrial (mt) DNA deletion as a molecular biomarker for disease progression in HCV-related hepatocellular carcinoma (HCC) and to identify its association with folic acid status. Methods: Serum folic acid and lymphocytic mtDNA deletions were assessed in 90 patients; 50 with HCC, 20 with liver cirrhosis (LC), and 20 with chronic hepatitis C (CHC) compared to 10 healthy control subjects. The diagnostic accuracy of mtDNA deletions frequency was evaluated using receiver-operating characteristic (ROC) curve analysis Survival analysis was performed using the Kaplan-Meier method. Differences in the survival rates were compared using log-rank test. Result: Our data revealed a significant elevation of mtDNA deletions frequency in the HCC group compared to the other groups (P-value <0.01). Also, our data showed a significant correlation between folate deficiency and high frequency of mtDNA deletions in patients with HCV-related HCC when compared to the other groups (r= -0.094 and P-value <0.05). Moreover, the size of the hepatic focal lesion in the HCC patients was positively correlated with mtDNA deletions (r= 0.09 and P-value <0.01). The median survival time for the HCC patients with high frequency of mtDNA deletions (∆Ct ≥3.9; 5.7+ 0.6 months) was significantly shorter than those with low mtDNA deletions frequency (∆Ct < 3.9; 11.9+ 0.04 months, P-value <0.01). Conclusion: Our data provided an evidence that lymphocytic mtDNA deletion could be used as non-invasive biomarker for disease progression and patients’ survival in HCV-related HCC. Also, our findings implied a causal relationship between the folate deficiency and the high mtDNA deletions frequency among Egyptian patients with HCV related HCC. PMID:28952275

Systems Analysis in Small Educational Systems: A Case Study.

ERIC Educational Resources Information Center

Vazquez-Abad, Jesus; And Others

1982-01-01

The use of systems analysis in transforming a graduate program in educational technology from a lecture-based system to a self-instructional one is described. Several operational research techniques are illustrated. A bibliography of 10 items is included. (CHC)

Library Architecture: The Cleveland Experience.

ERIC Educational Resources Information Center

Gaines, Ervin; And Others

1982-01-01

Discusses the importance of a well-designed library building as an important factor in creating social benefits and positive political responses in the community. The creation and implementation of design criteria for the Cleveland Public Library and the public response are described. (CHC)

Canadian Reference Sources 1980--A Selection.

ERIC Educational Resources Information Center

Ryder, Dorothy E.

1981-01-01

Provides a bibliography of 52 reference sources and 24 new editions and supplements, excluding annuals. Topics include science and technology, art, history, university courses, regional information, native languages, museums, law, geography, Canadian culture, dissertations, sports, antiques, botany, and a variety of directories. (CHC)

MOSAIC : Model Of Sustainability And Integrated Corridors, phase 3 : comprehensive model calibration and validation and additional model enhancement.

DOT National Transportation Integrated Search

2015-02-01

The Maryland State Highway Administration (SHA) has initiated major planning efforts to improve transportation : efficiency, safety, and sustainability on critical highway corridors through its Comprehensive Highway Corridor : (CHC) program. This pro...

Infotel 1981: The Future of Telecommunications.

ERIC Educational Resources Information Center

Nelson, Milo

1981-01-01

Summarizes the presentations of more than 30 leaders in the field of communications who met recently to discuss how telecommunications are going to affect our lives in the 1980s with particular regard to publishing, advertising, retailing, broadcasting, and cable television. (CHC)

Millennial-scale ocean current intensity changes off southernmost Chile and implications for Drake Passage throughflow

NASA Astrophysics Data System (ADS)

Lamy, F.; Arz, H. W.; Kilian, R.; Baeza Urrea, O.; Caniupan, M.; Kissel, C.; Lange, C.

2012-04-01

The Antarctic Circumpolar Current (ACC) plays an essential role in the thermohaline circulation and global climate. Today a large volume of ACC water passes through the Drake Passage, a major geographic constrain for the circumpolar flow. Satellite tracked surface drifters have shown that Subantarctic Surface water of the ACC is transported northeastward across the Southeast Pacific from ~53°S/100°W towards the Chilean coast at ~40°S/75°W where surface waters bifurcate and flow northward into the Peru Chile Current (PCC) finally reaching the Eastern Tropical Pacific, and southwards into the Cape Horn Current (CHC). The CHC thus transports a significant amount of northern ACC water towards the Drake Passage and reaches surface current velocities of up to 35 cm/s within a narrow belt of ~100-150 km width off the coast. Also at deeper water levels, an accelerated southward flow occurs along the continental slope off southernmost South America that likewise substantially contributes to the Drake Passage throughflow. Here we report on high resolution geochemical and grain-size records from core MD07-3128 (53°S; 1032 m water depth) which has been retrieved from the upper continental slope off the Pacific entrance of the Magellan Strait beneath the CHC. Magnetic grain-sizes and grain-size distributions of the terrigenous fraction reveal large amplitude changes between the Holocene and the last glacial, as well as millennial-scale variability (most pronounced during Marine Isotope Stage). Magnetic grain-sizes, silt/clay ratios, fine sand contents, sortable silt contents, and sortable silt mean grain-sizes are substantially higher during the Holocene suggesting strongly enhanced current activity. The high absolute values imply flow speeds larger than 25 cm/s as currently observed in the CHC surface current. Furthermore, winnowing processes through bottom current activity and changes in the availability of terrigenous material (ice-sheet extension and related supply of silt/clay, efficiency of the fjords in trapping sediment) might have contributed to the observed grain-size variations. Assuming that surface and bottom current strength changes are the major controlling factors, our data suggest a strongly enhanced CHC and deeper flow during the Holocene compared to the mean of the last glacial. During MIS 3, several phases of stronger current flow mostly correlate with warm sea surface temperatures at the site and, within age uncertainties, with millennial-scale warm phases in Antarctic ice cores. Taken together our data can be interpreted in terms of strongly reduced contributions of northern ACC water to the Drake Passage throughflow during the glacial in general and during millennial-scale cold phases in particular. At the same time, advection of northern ACC water into the PCC was probably enhanced. These results are consistent with model runs showing largely reduced volume transport through the Drake Passage during the last glacial maximum and an increasing throughflow during the last deglaciation that might have affected the strengthening of the Atlantic Meridional Overturning Circulation.

A Comparison of Quality of Community Health Services Between Public and Private Community Health Centers in Urban China.

PubMed

Yin, Xiaoxv; Gong, Yanhong; Yang, Chen; Tu, Xiaochen; Liu, Wei; Cao, Shiyi; Yang, Huajie; Lu, Zuxun

2015-10-01

This study was the first of its kind to evaluate and compare the quality of private and public community health centers (CHCs) in urban China. A total of 2501 CHCs in 35 cities were chosen in 2011 using a multistage sampling method, and data on human resources, medical equipment and drug inventory were collected. A subset of 422 CHCs was randomly selected and 100 prescriptions from each CHCs were reviewed to evaluate prescribing practice. In total, 12,386 patients who visited the selected 422 CHCs were interviewed to assess patient satisfaction and payments. Controlling for population covered per CHC and geographic regions, private CHCs were higher than public CHCs in average building area (2310.96 vs. 2000.92 square meters), average number of medical equipment (6.42 vs. 6.14), average number of physicians and nurses per 10,000 population (4.86 vs. 3.81 and 3.38 vs. 2.62), and average number of medicines in stock (435.08 vs. 375.83), but lower in average percentage of medicines on the national essential medicines list (67.29% vs. 77.55%). Prescriptions from private CHCs had significantly higher number of drugs per prescription (2.38 vs. 2.24), higher percentage of prescriptions with injections (36.44% vs. 30.50%), and higher percentage of prescriptions with antibiotics (37.17% vs. 30.14%). Patient satisfaction was similar between the 2 groups, and patient payments per visit were lower in private CHCs after controlling for patients' sociodemographic characteristics. Private CHCs are better equipped and better staffed than public CHCs but are less compliant with national policy on essential medicines and have poorer prescribing quality in China, warranting more rigorous government supervision.

An Innovative Project in Educational Technology: The Panama-Venezuela Project.

ERIC Educational Resources Information Center

Rojas, Alicia Mabel

1980-01-01

Describes a project which is being implemented in the field of educational technology in Panama and Venezuela. The project emphasizes inservice training of a cadre of professionals who will direct efforts to identify and resolve significant problems in education. (Author/CHC)

Sex-specific genotype-by-environment interactions for cuticular hydrocarbon expression in decorated crickets, Gryllodes sigillatus: implications for the evolution of signal reliability.

PubMed

Weddle, C B; Mitchell, C; Bay, S K; Sakaluk, S K; Hunt, J

2012-10-01

Phenotypic traits that convey information about individual identity or quality are important in animal social interactions, and the degree to which such traits are influenced by environmental variation can have profound effects on the reliability of these cues. Using inbred genetic lines of the decorated cricket, Gryllodes sigillatus, we manipulated diet quality to test how the cuticular hydrocarbon (CHC) profiles of males and females respond across two different nutritional rearing environments. There were significant differences between lines in the CHC profiles of females, but the effect of diet was not quite statistically significant. There was no significant genotype-by-environment interaction (GEI), suggesting that environmental effects on phenotypic variation in female CHCs are independent of genotype. There was, however, a significant effect of GEI for males, with changes in both signal quantity and content, suggesting that environmental effects on phenotypic expression of male CHCs are dependent on genotype. The differential response of male and female CHC expression to variation in the nutritional environment suggests that these chemical cues may be under sex-specific selection for signal reliability. Female CHCs show the characteristics of reliable cues of identity: high genetic variability, low condition dependence and a high degree of genetic determination. This supports earlier work showing that female CHCs are used in self-recognition to identify previous mates and facilitate polyandry. In contrast, male CHCs show the characteristics of reliable cues of quality: condition dependence and a relatively higher degree of environmental determination. This suggests that male CHCs are likely to function as cues of underlying quality during mate choice and/or male dominance interactions. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

Further insights on the French WISC-IV factor structure through Bayesian structural equation modeling.

PubMed

Golay, Philippe; Reverte, Isabelle; Rossier, Jérôme; Favez, Nicolas; Lecerf, Thierry

2013-06-01

The interpretation of the Wechsler Intelligence Scale for Children--Fourth Edition (WISC-IV) is based on a 4-factor model, which is only partially compatible with the mainstream Cattell-Horn-Carroll (CHC) model of intelligence measurement. The structure of cognitive batteries is frequently analyzed via exploratory factor analysis and/or confirmatory factor analysis. With classical confirmatory factor analysis, almost all cross-loadings between latent variables and measures are fixed to zero in order to allow the model to be identified. However, inappropriate zero cross-loadings can contribute to poor model fit, distorted factors, and biased factor correlations; most important, they do not necessarily faithfully reflect theory. To deal with these methodological and theoretical limitations, we used a new statistical approach, Bayesian structural equation modeling (BSEM), among a sample of 249 French-speaking Swiss children (8-12 years). With BSEM, zero-fixed cross-loadings between latent variables and measures are replaced by approximate zeros, based on informative, small-variance priors. Results indicated that a direct hierarchical CHC-based model with 5 factors plus a general intelligence factor better represented the structure of the WISC-IV than did the 4-factor structure and the higher order models. Because a direct hierarchical CHC model was more adequate, it was concluded that the general factor should be considered as a breadth rather than a superordinate factor. Because it was possible for us to estimate the influence of each of the latent variables on the 15 subtest scores, BSEM allowed improvement of the understanding of the structure of intelligence tests and the clinical interpretation of the subtest scores. PsycINFO Database Record (c) 2013 APA, all rights reserved.

A cluster-randomized trial of a college health center-based alcohol and sexual violence intervention (GIFTSS): Design, rationale, and baseline sample.

PubMed

Abebe, Kaleab Z; Jones, Kelley A; Rofey, Dana; McCauley, Heather L; Clark, Duncan B; Dick, Rebecca; Gmelin, Theresa; Talis, Janine; Anderson, Jocelyn; Chugani, Carla; Algarroba, Gabriela; Antonio, Ashley; Bee, Courtney; Edwards, Clare; Lethihet, Nadia; Macak, Justin; Paley, Joshua; Torres, Irving; Van Dusen, Courtney; Miller, Elizabeth

2018-02-01

Sexual violence (SV) on college campuses is common, especially alcohol-related SV. This is a 2-arm cluster randomized controlled trial to test a brief intervention to reduce risk for alcohol-related sexual violence (SV) among students receiving care from college health centers (CHCs). Intervention CHC staff are trained to deliver universal SV education to all students seeking care, to facilitate patient and provider comfort in discussing SV and related abusive experiences (including the role of alcohol). Control sites provide participants with information about drinking responsibly. Across 28 participating campuses (12 randomized to intervention and 16 to control), 2292 students seeking care at CHCs complete surveys prior to their appointment (baseline), immediately after (exit), 4months later (T2) and one year later (T3). The primary outcome is change in recognition of SV and sexual risk. Among those reporting SV exposure at baseline, changes in SV victimization, disclosure, and use of SV services are additional outcomes. Intervention effects will be assessed using generalized linear mixed models that account for clustering of repeated observations both within CHCs and within students. Slightly more than half of the participating colleges have undergraduate enrollment of ≥3000 students; two-thirds are public and almost half are urban. Among participants there were relatively more Asian (10 v 1%) and Black/African American (13 v 7%) and fewer White (58 v 74%) participants in the intervention compared to control. This study will offer the first formal assessment for SV prevention in the CHC setting. Clinical Trials #: NCT02355470. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Nurse Practitioner Independent Practice Authority and Mental Health Service Delivery in U.S. Community Health Centers.

PubMed

Yang, Bo Kyum; Trinkoff, Alison M; Zito, Julie Magno; Burcu, Mehmet; Safer, Daniel J; Storr, Carla L; Johantgen, Mary E; Idzik, Shannon

2017-10-01

Little is known about how nurse practitioner independent practice authority (NP-IPA) influences patient care. This study examined the effect of NP-IPA on patterns of mental health-related visits provided by NPs in U.S. community health centers (CHCs). State NP regulatory information was linked to National Ambulatory Medical Care Survey data on NP- and physician-provided visits (N=61,457) in CHCs from 2006 through 2011. The proportion of NP-provided versus physician-provided mental health-related visits in states with NP-IPA was compared with the proportion in states without NP-IPA. The adjusted odds of mental health-related visits in CHCs provided by NPs in states with and without NP-IPA were compared by using multiple logistic regression models while accounting for the complex survey design. Between 2006 and 2011, the odds of NP- versus physician-provided mental health-related visits in CHCs were more than two times greater in states with NP-IPA than in states with no NP-IPA (adjusted odds ratio [OR]= 2.43, 95% confidence interval [CI]=1.12-4.60). In contrast, no significant difference between states with and without NP-IPA was noted in non-mental health-related CHC visits provided by NPs. Among all mental health-related visits, the odds of visits in which psychotropic medications were prescribed by an NP were more than three times higher in states with NP-IPA than in those without NP-IPA (adjusted OR=3.14, CI=1.50-6.54). Compared with physicians, NPs provided proportionally more CHC mental health-related visits in states with NP-IPA than in states without NP-IPA.

GAK, a regulator of clathrin-mediated membrane traffic, also controls centrosome integrity and chromosome congression.

PubMed

Shimizu, Hiroyuki; Nagamori, Ippei; Yabuta, Norikazu; Nojima, Hiroshi

2009-09-01

Cyclin G-associated kinase (GAK) is an association partner of clathrin heavy chain (CHC) and is essential for clathrin-mediated membrane trafficking. Here, we report two novel functions of GAK: maintenance of proper centrosome maturation and of mitotic chromosome congression. Indeed, GAK knockdown by siRNA caused cell-cycle arrest at metaphase, which indicates that GAK is required for proper mitotic progression. We found that this impaired mitotic progression was due to activation of the spindle-assembly checkpoint, which senses protruded, misaligned or abnormally condensed chromosomes in GAK-siRNA-treated cells. GAK knockdown also caused multi-aster formation, which was due to abnormal fragmentation of pericentriolar material, but not of the centrioles. Moreover, GAK and CHC cooperated in the same pathway and interacted in mitosis to regulate the formation of a functional spindle. Taken together, we conclude that GAK and clathrin function cooperatively not only in endocytosis, but also in mitotic progression.

Combination of inclusive and differential t\\overline{t} charge asymmetry measurements using ATLAS and CMS data at √{s}=7 and 8 TeV

NASA Astrophysics Data System (ADS)

Aaboud, M.; Aad, G.; Abbott, B.; Abdinov, O.; Abeloos, B.; Abidi, S. H.; AbouZeid, O. S.; Abraham, N. L.; Abramowicz, H.; Abreu, H.; Abulaiti, Y.; Acharya, B. S.; Adachi, S.; Adamczyk, L.; Adelman, J.; Adersberger, M.; Adye, T.; Affolder, A. A.; Afik, Y.; Agheorghiesei, C.; Aguilar-Saavedra, J. A.; Ahlen, S. P.; Ahmadov, F.; Aielli, G.; Akatsuka, S.; Åkesson, T. P. A.; Akilli, E.; Akimov, A. V.; Alberghi, G. L.; Albert, J.; Albicocco, P.; Alconada Verzini, M. J.; Alderweireldt, S. C.; Aleksa, M.; Aleksandrov, I. N.; Alexa, C.; Alexander, G.; Alexopoulos, T.; Alhroob, M.; Ali, B.; Aliev, M.; Alimonti, G.; Alison, J.; Alkire, S. P.; Allbrooke, B. M. M.; Allen, B. W.; Allport, P. P.; Aloisio, A.; Alonso, A.; Alonso, F.; Alpigiani, C.; Alshehri, A. A.; Alstaty, M. I.; Alvarez Gonzalez, B.; Álvarez Piqueras, D.; Alviggi, M. G.; Amadio, B. T.; Amaral Coutinho, Y.; Amelung, C.; Amidei, D.; Amor Dos Santos, S. P.; Amoroso, S.; Anastopoulos, C.; Ancu, L. S.; Andari, N.; Andeen, T.; Anders, C. F.; Anders, J. K.; Anderson, K. J.; Andreazza, A.; Andrei, V.; Angelidakis, S.; Angelozzi, I.; Angerami, A.; Anisenkov, A. V.; Annovi, A.; Antel, C.; Antonelli, M.; Antonov, A.; Antrim, D. J.; Anulli, F.; Aoki, M.; Aperio Bella, L.; Arabidze, G.; Arai, Y.; Araque, J. P.; Araujo Ferraz, V.; Arce, A. T. H.; Ardell, R. E.; Arduh, F. A.; Arguin, J.-F.; Argyropoulos, S.; Armbruster, A. J.; Armitage, L. J.; Arnaez, O.; Arnold, H.; Arratia, M.; Arslan, O.; Artamonov, A.; Artoni, G.; Artz, S.; Asai, S.; Asbah, N.; Ashkenazi, A.; Asquith, L.; Assamagan, K.; Astalos, R.; Atkinson, M.; Atlay, N. B.; Augsten, K.; Avolio, G.; Axen, B.; Ayoub, M. K.; Azuelos, G.; Baas, A. E.; Baca, M. J.; Bachacou, H.; Bachas, K.; Backes, M.; Bagnaia, P.; Bahmani, M.; Bahrasemani, H.; Baines, J. T.; Bajic, M.; Baker, O. K.; Bakker, P. J.; Bakshi Gupta, D.; Baldin, E. M.; Balek, P.; Balli, F.; Balunas, W. K.; Banas, E.; Bandyopadhyay, A.; Banerjee, Sw.; Bannoura, A. A. E.; Barak, L.; Barberio, E. L.; Barberis, D.; Barbero, M.; Barillari, T.; Barisits, M.-S.; Barkeloo, J. T.; Barklow, T.; Barlow, N.; Barnes, S. L.; Barnett, B. M.; Barnett, R. M.; Barnovska-Blenessy, Z.; Baroncelli, A.; Barone, G.; Barr, A. J.; Barranco Navarro, L.; Barreiro, F.; Barreiro Guimarães da Costa, J.; Bartoldus, R.; Barton, A. E.; Bartos, P.; Basalaev, A.; Bassalat, A.; Bates, R. L.; Batista, S. J.; Batley, J. R.; Battaglia, M.; Bauce, M.; Bauer, F.; Bauer, K. T.; Bawa, H. S.; Beacham, J. B.; Beattie, M. D.; Beau, T.; Beauchemin, P. H.; Bechtle, P.; Beck, H. P.; Beck, H. C.; Becker, K.; Becker, M.; Becot, C.; Beddall, A. J.; Beddall, A.; Bednyakov, V. A.; Bedognetti, M.; Bee, C. P.; Beermann, T. A.; Begalli, M.; Begel, M.; Behr, J. K.; Bell, A. S.; Bella, G.; Bellagamba, L.; Bellerive, A.; Bellomo, M.; Belotskiy, K.; Belyaev, N. L.; Benary, O.; Benchekroun, D.; Bender, M.; Benekos, N.; Benhammou, Y.; Benhar Noccioli, E.; Benitez, J.; Benjamin, D. P.; Benoit, M.; Bensinger, J. R.; Bentvelsen, S.; Beresford, L.; Beretta, M.; Berge, D.; Bergeaas Kuutmann, E.; Berger, N.; Bergsten, L. J.; Beringer, J.; Berlendis, S.; Bernard, N. R.; Bernardi, G.; Bernius, C.; Bernlochner, F. U.; Berry, T.; Berta, P.; Bertella, C.; Bertoli, G.; Bertram, I. A.; Bertsche, C.; Besjes, G. J.; Bessidskaia Bylund, O.; Bessner, M.; Besson, N.; Bethani, A.; Bethke, S.; Betti, A.; Bevan, A. J.; Beyer, J.; Bianchi, R. M.; Biebel, O.; Biedermann, D.; Bielski, R.; Bierwagen, K.; Biesuz, N. V.; Biglietti, M.; Billoud, T. R. V.; Bindi, M.; Bingul, A.; Bini, C.; Biondi, S.; Bisanz, T.; Bittrich, C.; Bjergaard, D. M.; Black, J. E.; Black, K. M.; Blair, R. E.; Blazek, T.; Bloch, I.; Blocker, C.; Blue, A.; Blumenschein, U.; Blunier, S.; Bobbink, G. J.; Bobrovnikov, V. S.; Bocchetta, S. S.; Bocci, A.; Bock, C.; Boerner, D.; Bogavac, D.; Bogdanchikov, A. G.; Bohm, C.; Boisvert, V.; Bokan, P.; Bold, T.; Boldyrev, A. S.; Bolz, A. E.; Bomben, M.; Bona, M.; Boonekamp, M.; Borisov, A.; Borissov, G.; Bortfeldt, J.; Bortoletto, D.; Bortolotto, V.; Boscherini, D.; Bosman, M.; Bossio Sola, J. D.; Boudreau, J.; Bouhova-Thacker, E. V.; Boumediene, D.; Bourdarios, C.; Boutle, S. K.; Boveia, A.; Boyd, J.; Boyko, I. R.; Bozson, A. J.; Bracinik, J.; Brandt, A.; Brandt, G.; Brandt, O.; Braren, F.; Bratzler, U.; Brau, B.; Brau, J. E.; Breaden Madden, W. D.; Brendlinger, K.; Brennan, A. J.; Brenner, L.; Brenner, R.; Bressler, S.; Briglin, D. L.; Bristow, T. M.; Britton, D.; Britzger, D.; Brochu, F. M.; Brock, I.; Brock, R.; Brooijmans, G.; Brooks, T.; Brooks, W. K.; Brost, E.; Broughton, J. H.; Bruckman de Renstrom, P. A.; Bruncko, D.; Bruni, A.; Bruni, G.; Bruni, L. S.; Bruno, S.; Brunt, B. H.; Bruschi, M.; Bruscino, N.; Bryant, P.; Bryngemark, L.; Buanes, T.; Buat, Q.; Buchholz, P.; Buckley, A. G.; Budagov, I. A.; Buehrer, F.; Bugge, M. K.; Bulekov, O.; Bullock, D.; Burch, T. J.; Burdin, S.; Burgard, C. D.; Burger, A. M.; Burghgrave, B.; Burka, K.; Burke, S.; Burmeister, I.; Burr, J. T. P.; Büscher, D.; Büscher, V.; Buschmann, E.; Bussey, P.; Butler, J. M.; Buttar, C. M.; Butterworth, J. M.; Butti, P.; Buttinger, W.; Buzatu, A.; Buzykaev, A. R.; Changqiao, C.-Q.; Cabrera Urbán, S.; Caforio, D.; Cai, H.; Cairo, V. M.; Cakir, O.; Calace, N.; Calafiura, P.; Calandri, A.; Calderini, G.; Calfayan, P.; Callea, G.; Caloba, L. P.; Calvente Lopez, S.; Calvet, D.; Calvet, S.; Calvet, T. P.; Camacho Toro, R.; Camarda, S.; Camarri, P.; Cameron, D.; Caminal Armadans, R.; Camincher, C.; Campana, S.; Campanelli, M.; Camplani, A.; Campoverde, A.; Canale, V.; Cano Bret, M.; Cantero, J.; Cao, T.; Capeans Garrido, M. D. M.; Caprini, I.; Caprini, M.; Capua, M.; Carbone, R. M.; Cardarelli, R.; Cardillo, F.; Carli, I.; Carli, T.; Carlino, G.; Carlson, B. T.; Carminati, L.; Carney, R. M. D.; Caron, S.; Carquin, E.; Carrá, S.; Carrillo-Montoya, G. D.; Casadei, D.; Casado, M. P.; Casha, A. F.; Casolino, M.; Casper, D. W.; Castelijn, R.; Castillo Gimenez, V.; Castro, N. F.; Catinaccio, A.; Catmore, J. R.; Cattai, A.; Caudron, J.; Cavaliere, V.; Cavallaro, E.; Cavalli-Sforza, M.; Cavasinni, V.; Celebi, E.; Ceradini, F.; Cerda Alberich, L.; Cerqueira, A. S.; Cerri, A.; Cerrito, L.; Cerutti, F.; Cervelli, A.; Cetin, S. A.; Chafaq, A.; Chakraborty, D.; Chan, S. K.; Chan, W. S.; Chan, Y. L.; Chang, P.; Chapman, J. D.; Charlton, D. G.; Chau, C. C.; Chavez Barajas, C. A.; Che, S.; Chegwidden, A.; Chekanov, S.; Chekulaev, S. V.; Chelkov, G. A.; Chelstowska, M. A.; Chen, C.; Chen, C.; Chen, H.; Chen, J.; Chen, J.; Chen, S.; Chen, S.; Chen, X.; Chen, Y.; Cheng, H. C.; Cheng, H. J.; Cheplakov, A.; Cheremushkina, E.; Cherkaoui El Moursli, R.; Cheu, E.; Cheung, K.; Chevalier, L.; Chiarella, V.; Chiarelli, G.; Chiodini, G.; Chisholm, A. S.; Chitan, A.; Chiu, Y. H.; Chizhov, M. V.; Choi, K.; Chomont, A. R.; Chouridou, S.; Chow, Y. S.; Christodoulou, V.; Chu, M. C.; Chudoba, J.; Chuinard, A. J.; Chwastowski, J. J.; Chytka, L.; Cinca, D.; Cindro, V.; Cioara, I. A.; Ciocio, A.; Cirotto, F.; Citron, Z. H.; Citterio, M.; Clark, A.; Clark, M. R.; Clark, P. J.; Clarke, R. N.; Clement, C.; Coadou, Y.; Cobal, M.; Coccaro, A.; Cochran, J.; Colasurdo, L.; Cole, B.; Colijn, A. P.; Collot, J.; Conde Muiño, P.; Coniavitis, E.; Connell, S. H.; Connelly, I. A.; Constantinescu, S.; Conti, G.; Conventi, F.; Cooper-Sarkar, A. M.; Cormier, F.; Cormier, K. J. R.; Corradi, M.; Corrigan, E. E.; Corriveau, F.; Cortes-Gonzalez, A.; Costa, M. J.; Costanzo, D.; Cottin, G.; Cowan, G.; Cox, B. E.; Cranmer, K.; Crawley, S. J.; Creager, R. A.; Cree, G.; Crépé-Renaudin, S.; Crescioli, F.; Cristinziani, M.; Croft, V.; Crosetti, G.; Cueto, A.; Cuhadar Donszelmann, T.; Cukierman, A. R.; Cummings, J.; Curatolo, M.; Cúth, J.; Czekierda, S.; Czodrowski, P.; D'amen, G.; D'Auria, S.; D'eramo, L.; D'Onofrio, M.; Da Cunha Sargedas De Sousa, M. J.; Da Via, C.; Dabrowski, W.; Dado, T.; Dai, T.; Dale, O.; Dallaire, F.; Dallapiccola, C.; Dam, M.; Dandoy, J. R.; Daneri, M. F.; Dang, N. P.; Dann, N. S.; Danninger, M.; Dano Hoffmann, M.; Dao, V.; Darbo, G.; Darmora, S.; Dassoulas, J.; Dattagupta, A.; Daubney, T.; Davey, W.; David, C.; Davidek, T.; Davis, D. R.; Davison, P.; Dawe, E.; Dawson, I.; De, K.; de Asmundis, R.; De Benedetti, A.; De Castro, S.; De Cecco, S.; De Groot, N.; de Jong, P.; De la Torre, H.; De Lorenzi, F.; De Maria, A.; De Pedis, D.; De Salvo, A.; De Sanctis, U.; De Santo, A.; De Vasconcelos Corga, K.; De Vivie De Regie, J. B.; Debenedetti, C.; Dedovich, D. V.; Dehghanian, N.; Deigaard, I.; Del Gaudio, M.; Del Peso, J.; Delgove, D.; Deliot, F.; Delitzsch, C. M.; Dell'Acqua, A.; Dell'Asta, L.; Della Pietra, M.; della Volpe, D.; Delmastro, M.; Delporte, C.; Delsart, P. A.; DeMarco, D. A.; Demers, S.; Demichev, M.; Demilly, A.; Denisov, S. P.; Denysiuk, D.; Derendarz, D.; Derkaoui, J. E.; Derue, F.; Dervan, P.; Desch, K.; Deterre, C.; Dette, K.; Devesa, M. R.; Deviveiros, P. O.; Dewhurst, A.; Dhaliwal, S.; Di Bello, F. A.; Di Ciaccio, A.; Di Ciaccio, L.; Di Clemente, W. K.; Di Donato, C.; Di Girolamo, A.; Di Micco, B.; Di Nardo, R.; Di Petrillo, K. F.; Di Simone, A.; Di Sipio, R.; Di Valentino, D.; Diaconu, C.; Diamond, M.; Dias, F. A.; Diaz, M. A.; Dickinson, J.; Diehl, E. B.; Dietrich, J.; Díez Cornell, S.; Dimitrievska, A.; Dingfelder, J.; Dita, P.; Dita, S.; Dittus, F.; Djama, F.; Djobava, T.; Djuvsland, J. I.; do Vale, M. A. B.; Dobre, M.; Dodsworth, D.; Doglioni, C.; Dolejsi, J.; Dolezal, Z.; Donadelli, M.; Donati, S.; Donini, J.; Dopke, J.; Doria, A.; Dova, M. T.; Doyle, A. T.; Drechsler, E.; Dris, M.; Du, Y.; Duarte-Campderros, J.; Dubinin, F.; Dubreuil, A.; Duchovni, E.; Duckeck, G.; Ducourthial, A.; Ducu, O. A.; Duda, D.; Dudarev, A.; Dudder, A. Chr.; Duffield, E. M.; Duflot, L.; Dührssen, M.; Dulsen, C.; Dumancic, M.; Dumitriu, A. E.; Duncan, A. K.; Dunford, M.; Duperrin, A.; Duran Yildiz, H.; Düren, M.; Durglishvili, A.; Duschinger, D.; Dutta, B.; Duvnjak, D.; Dyndal, M.; Dziedzic, B. S.; Eckardt, C.; Ecker, K. M.; Edgar, R. C.; Eifert, T.; Eigen, G.; Einsweiler, K.; Ekelof, T.; El Kacimi, M.; El Kosseifi, R.; Ellajosyula, V.; Ellert, M.; Ellinghaus, F.; Elliot, A. A.; Ellis, N.; Elmsheuser, J.; Elsing, M.; Emeliyanov, D.; Enari, Y.; Ennis, J. S.; Epland, M. B.; Erdmann, J.; Ereditato, A.; Errede, S.; Escalier, M.; Escobar, C.; Esposito, B.; Estrada Pastor, O.; Etienvre, A. I.; Etzion, E.; Evans, H.; Ezhilov, A.; Ezzi, M.; Fabbri, F.; Fabbri, L.; Fabiani, V.; Facini, G.; Fakhrutdinov, R. M.; Falciano, S.; Falla, R. J.; Faltova, J.; Fang, Y.; Fanti, M.; Farbin, A.; Farilla, A.; Farina, E. M.; Farooque, T.; Farrell, S.; Farrington, S. M.; Farthouat, P.; Fassi, F.; Fassnacht, P.; Fassouliotis, D.; Faucci Giannelli, M.; Favareto, A.; Fawcett, W. J.; Fayard, L.; Fedin, O. L.; Fedorko, W.; Feigl, S.; Feligioni, L.; Feng, C.; Feng, E. J.; Feng, M.; Fenton, M. J.; Fenyuk, A. B.; Feremenga, L.; Fernandez Martinez, P.; Ferrando, J.; Ferrari, A.; Ferrari, P.; Ferrari, R.; Ferreira de Lima, D. E.; Ferrer, A.; Ferrere, D.; Ferretti, C.; Fiedler, F.; Filipčič, A.; Filthaut, F.; Fincke-Keeler, M.; Finelli, K. D.; Fiolhais, M. C. N.; Fiorini, L.; Fischer, C.; Fischer, J.; Fisher, W. C.; Flaschel, N.; Fleck, I.; Fleischmann, P.; Fletcher, R. R. M.; Flick, T.; Flierl, B. M.; Flores Castillo, L. R.; Forcolin, G. T.; Formica, A.; Förster, F. A.; Forti, A.; Foster, A. G.; Fournier, D.; Fox, H.; Fracchia, S.; Francavilla, P.; Franchini, M.; Franchino, S.; Francis, D.; Franconi, L.; Franklin, M.; Frate, M.; Fraternali, M.; Freeborn, D.; Fressard-Batraneanu, S. M.; Freund, B.; Freund, W. S.; Froidevaux, D.; Frost, J. A.; Fukunaga, C.; Fusayasu, T.; Fuster, J.; Gabizon, O.; Gabrielli, A.; Gabrielli, A.; Gach, G. P.; Gadatsch, S.; Gadomski, S.; Gagliardi, G.; Gagnon, L. G.; Galea, C.; Galhardo, B.; Gallas, E. J.; Gallop, B. J.; Gallus, P.; Galster, G.; Gan, K. K.; Ganguly, S.; Gao, Y.; Gao, Y. S.; Garay Walls, F. M.; García, C.; García Navarro, J. E.; García Pascual, J. A.; Garcia-Sciveres, M.; Gardner, R. W.; Garelli, N.; Garonne, V.; Gasnikova, K.; Gaudiello, A.; Gaudio, G.; Gavrilenko, I. L.; Gay, C.; Gaycken, G.; Gazis, E. N.; Gee, C. N. P.; Geisen, J.; Geisen, M.; Geisler, M. P.; Gellerstedt, K.; Gemme, C.; Genest, M. H.; Geng, C.; Gentile, S.; Gentsos, C.; George, S.; Gerbaudo, D.; Geßner, G.; Ghasemi, S.; Ghneimat, M.; Giacobbe, B.; Giagu, S.; Giangiacomi, N.; Giannetti, P.; Gibson, S. M.; Gignac, M.; Gilchriese, M.; Gillberg, D.; Gilles, G.; Gingrich, D. M.; Giordani, M. P.; Giorgi, F. M.; Giraud, P. F.; Giromini, P.; Giugliarelli, G.; Giugni, D.; Giuli, F.; Giulini, M.; Gjelsten, B. K.; Gkaitatzis, S.; Gkialas, I.; Gkougkousis, E. L.; Gkountoumis, P.; Gladilin, L. K.; Glasman, C.; Glatzer, J.; Glaysher, P. C. F.; Glazov, A.; Goblirsch-Kolb, M.; Godlewski, J.; Goldfarb, S.; Golling, T.; Golubkov, D.; Gomes, A.; Gonçalo, R.; Goncalves Gama, R.; Goncalves Pinto Firmino Da Costa, J.; Gonella, G.; Gonella, L.; Gongadze, A.; Gonnella, F.; Gonski, J. L.; González de la Hoz, S.; Gonzalez-Sevilla, S.; Goossens, L.; Gorbounov, P. A.; Gordon, H. A.; Gorini, B.; Gorini, E.; Gorišek, A.; Goshaw, A. T.; Gössling, C.; Gostkin, M. I.; Gottardo, C. A.; Goudet, C. R.; Goujdami, D.; Goussiou, A. G.; Govender, N.; Goy, C.; Gozani, E.; Grabowska-Bold, I.; Gradin, P. O. J.; Graham, E. C.; Gramling, J.; Gramstad, E.; Grancagnolo, S.; Gratchev, V.; Gravila, P. M.; Gray, C.; Gray, H. M.; Greenwood, Z. D.; Grefe, C.; Gregersen, K.; Gregor, I. M.; Grenier, P.; Grevtsov, K.; Griffiths, J.; Grillo, A. A.; Grimm, K.; Grinstein, S.; Gris, Ph.; Grivaz, J.-F.; Groh, S.; Gross, E.; Grosse-Knetter, J.; Grossi, G. C.; Grout, Z. J.; Grummer, A.; Guan, L.; Guan, W.; Guenther, J.; Guescini, F.; Guest, D.; Gueta, O.; Gui, B.; Guillemin, T.; Guindon, S.; Gul, U.; Gumpert, C.; Guo, J.; Guo, W.; Guo, Y.; Gupta, R.; Gurbuz, S.; Gustavino, G.; Gutelman, B. J.; Gutierrez, P.; Gutierrez Ortiz, N. G.; Gutschow, C.; Guyot, C.; Guzik, M. P.; Gwenlan, C.; Gwilliam, C. B.; Haas, A.; Haber, C.; Hadavand, H. K.; Haddad, N.; Hadef, A.; Hageböck, S.; Hagihara, M.; Hakobyan, H.; Haleem, M.; Haley, J.; Halladjian, G.; Hallewell, G. D.; Hamacher, K.; Hamal, P.; Hamano, K.; Hamilton, A.; Hamity, G. N.; Han, K.; Han, L.; Han, S.; Hanagaki, K.; Hance, M.; Handl, D. M.; Haney, B.; Hanke, P.; Hansen, J. B.; Hansen, J. D.; Hansen, M. C.; Hansen, P. H.; Hara, K.; Hard, A. S.; Harenberg, T.; Hariri, F.; Harkusha, S.; Harrison, P. F.; Hartmann, N. M.; Hasegawa, Y.; Hasib, A.; Hassani, S.; Haug, S.; Hauser, R.; Hauswald, L.; Havener, L. B.; Havranek, M.; Hawkes, C. M.; Hawkings, R. J.; Hayden, D.; Hays, C. P.; Hays, J. M.; Hayward, H. S.; Haywood, S. J.; Heck, T.; Hedberg, V.; Heelan, L.; Heer, S.; Heidegger, K. K.; Heim, S.; Heim, T.; Heinemann, B.; Heinrich, J. J.; Heinrich, L.; Heinz, C.; Hejbal, J.; Helary, L.; Held, A.; Hellman, S.; Helsens, C.; Henderson, R. C. W.; Heng, Y.; Henkelmann, S.; Henriques Correia, A. M.; Herbert, G. H.; Herde, H.; Herget, V.; Hernández Jiménez, Y.; Herr, H.; Herten, G.; Hertenberger, R.; Hervas, L.; Herwig, T. C.; Hesketh, G. G.; Hessey, N. P.; Hetherly, J. W.; Higashino, S.; Higón-Rodriguez, E.; Hildebrand, K.; Hill, E.; Hill, J. C.; Hiller, K. H.; Hillier, S. J.; Hils, M.; Hinchliffe, I.; Hirose, M.; Hirschbuehl, D.; Hiti, B.; Hladik, O.; Hlaluku, D. R.; Hoad, X.; Hobbs, J.; Hod, N.; Hodgkinson, M. C.; Hoecker, A.; Hoeferkamp, M. R.; Hoenig, F.; Hohn, D.; Holmes, T. R.; Holzbock, M.; Homann, M.; Honda, S.; Honda, T.; Hong, T. M.; Hooberman, B. H.; Hopkins, W. H.; Horii, Y.; Horton, A. J.; Hostachy, J.-Y.; Hostiuc, A.; Hou, S.; Hoummada, A.; Howarth, J.; Hoya, J.; Hrabovsky, M.; Hrdinka, J.; Hristova, I.; Hrivnac, J.; Hryn'ova, T.; Hrynevich, A.; Hsu, P. J.; Hsu, S.-C.; Hu, Q.; Hu, S.; Huang, Y.; Hubacek, Z.; Hubaut, F.; Huegging, F.; Huffman, T. B.; Hughes, E. W.; Huhtinen, M.; Hunter, R. F. H.; Huo, P.; Huseynov, N.; Huston, J.; Huth, J.; Hyneman, R.; Iacobucci, G.; Iakovidis, G.; Ibragimov, I.; Iconomidou-Fayard, L.; Idrissi, Z.; Iengo, P.; Igonkina, O.; Iizawa, T.; Ikegami, Y.; Ikeno, M.; Iliadis, D.; Ilic, N.; Iltzsche, F.; Introzzi, G.; Ioannou, P.; Iodice, M.; Iordanidou, K.; Ippolito, V.; Isacson, M. F.; Ishijima, N.; Ishino, M.; Ishitsuka, M.; Issever, C.; Istin, S.; Ito, F.; Iturbe Ponce, J. M.; Iuppa, R.; Iwasaki, H.; Izen, J. M.; Izzo, V.; Jabbar, S.; Jackson, P.; Jacobs, R. M.; Jain, V.; Jakobi, K. B.; Jakobs, K.; Jakobsen, S.; Jakoubek, T.; Jamin, D. O.; Jana, D. K.; Jansky, R.; Janssen, J.; Janus, M.; Janus, P. A.; Jarlskog, G.; Javadov, N.; Javůrek, T.; Javurkova, M.; Jeanneau, F.; Jeanty, L.; Jejelava, J.; Jelinskas, A.; Jenni, P.; Jeske, C.; Jézéquel, S.; Ji, H.; Jia, J.; Jiang, H.; Jiang, Y.; Jiang, Z.; Jiggins, S.; Jimenez Pena, J.; Jin, S.; Jinaru, A.; Jinnouchi, O.; Jivan, H.; Johansson, P.; Johns, K. A.; Johnson, C. A.; Johnson, W. J.; Jon-And, K.; Jones, R. W. L.; Jones, S. D.; Jones, S.; Jones, T. J.; Jongmanns, J.; Jorge, P. M.; Jovicevic, J.; Ju, X.; Juste Rozas, A.; Kaczmarska, A.; Kado, M.; Kagan, H.; Kagan, M.; Kahn, S. J.; Kaji, T.; Kajomovitz, E.; Kalderon, C. W.; Kaluza, A.; Kama, S.; Kamenshchikov, A.; Kanjir, L.; Kantserov, V. A.; Kanzaki, J.; Kaplan, B.; Kaplan, L. S.; Kar, D.; Karakostas, K.; Karastathis, N.; Kareem, M. J.; Karentzos, E.; Karpov, S. N.; Karpova, Z. M.; Kartvelishvili, V.; Karyukhin, A. N.; Kasahara, K.; Kashif, L.; Kass, R. D.; Kastanas, A.; Kataoka, Y.; Kato, C.; Katre, A.; Katzy, J.; Kawade, K.; Kawagoe, K.; Kawamoto, T.; Kawamura, G.; Kay, E. F.; Kazanin, V. F.; Keeler, R.; Kehoe, R.; Keller, J. S.; Kellermann, E.; Kempster, J. J.; Kendrick, J.; Keoshkerian, H.; Kepka, O.; Kerševan, B. P.; Kersten, S.; Keyes, R. A.; Khader, M.; Khalil-zada, F.; Khanov, A.; Kharlamov, A. G.; Kharlamova, T.; Khodinov, A.; Khoo, T. J.; Khovanskiy, V.; Khramov, E.; Khubua, J.; Kido, S.; Kiehn, M.; Kilby, C. R.; Kim, H. Y.; Kim, S. H.; Kim, Y. K.; Kimura, N.; Kind, O. M.; King, B. T.; Kirchmeier, D.; Kirk, J.; Kiryunin, A. E.; Kishimoto, T.; Kisielewska, D.; Kitali, V.; Kivernyk, O.; Kladiva, E.; Klapdor-Kleingrothaus, T.; Klein, M. H.; Klein, M.; Klein, U.; Kleinknecht, K.; Klimek, P.; Klimentov, A.; Klingenberg, R.; Klingl, T.; Klioutchnikova, T.; Klitzner, F. F.; Kluge, E.-E.; Kluit, P.; Kluth, S.; Kneringer, E.; Knoops, E. B. F. G.; Knue, A.; Kobayashi, A.; Kobayashi, D.; Kobayashi, T.; Kobel, M.; Kocian, M.; Kodys, P.; Koffas, T.; Koffeman, E.; Köhler, N. M.; Koi, T.; Kolb, M.; Koletsou, I.; Kondo, T.; Kondrashova, N.; Köneke, K.; König, A. C.; Kono, T.; Konoplich, R.; Konstantinidis, N.; Konya, B.; Kopeliansky, R.; Koperny, S.; Korcyl, K.; Kordas, K.; Korn, A.; Korolkov, I.; Korolkova, E. V.; Kortner, O.; Kortner, S.; Kosek, T.; Kostyukhin, V. V.; Kotwal, A.; Koulouris, A.; Kourkoumeli-Charalampidi, A.; Kourkoumelis, C.; Kourlitis, E.; Kouskoura, V.; Kowalewska, A. B.; Kowalewski, R.; Kowalski, T. Z.; Kozakai, C.; Kozanecki, W.; Kozhin, A. S.; Kramarenko, V. A.; Kramberger, G.; Krasnopevtsev, D.; Krasny, M. W.; Krasznahorkay, A.; Krauss, D.; Kremer, J. A.; Kretzschmar, J.; Kreutzfeldt, K.; Krieger, P.; Krizka, K.; Kroeninger, K.; Kroha, H.; Kroll, J.; Kroll, J.; Kroseberg, J.; Krstic, J.; Kruchonak, U.; Krüger, H.; Krumnack, N.; Kruse, M. C.; Kubota, T.; Kuday, S.; Kuechler, J. T.; Kuehn, S.; Kugel, A.; Kuger, F.; Kuhl, T.; Kukhtin, V.; Kukla, R.; Kulchitsky, Y.; Kuleshov, S.; Kulinich, Y. P.; Kuna, M.; Kunigo, T.; Kupco, A.; Kupfer, T.; Kuprash, O.; Kurashige, H.; Kurchaninov, L. L.; Kurochkin, Y. A.; Kurth, M. G.; Kuwertz, E. S.; Kuze, M.; Kvita, J.; Kwan, T.; La Rosa, A.; La Rosa Navarro, J. L.; La Rotonda, L.; La Ruffa, F.; Lacasta, C.; Lacava, F.; Lacey, J.; Lack, D. P. J.; Lacker, H.; Lacour, D.; Ladygin, E.; Lafaye, R.; Laforge, B.; Lai, S.; Lammers, S.; Lampl, W.; Lançon, E.; Landgraf, U.; Landon, M. P. J.; Lanfermann, M. C.; Lang, V. S.; Lange, J. C.; Langenberg, R. J.; Lankford, A. J.; Lanni, F.; Lantzsch, K.; Lanza, A.; Lapertosa, A.; Laplace, S.; Laporte, J. F.; Lari, T.; Lasagni Manghi, F.; Lassnig, M.; Lau, T. S.; Law, A. T.; Laycock, P.; Lazzaroni, M.; Le, B.; Le Dortz, O.; Le Guirriec, E.; Le Quilleuc, E. P.; LeBlanc, M.; LeCompte, T.; Ledroit-Guillon, F.; Lee, C. A.; Lee, G. R.; Lee, S. C.; Lee, L.; Lefebvre, B.; Lefebvre, G.; Lefebvre, M.; Legger, F.; Leggett, C.; Lehmann Miotto, G.; Lei, X.; Leight, W. A.; Leisos, A.; Leite, M. A. L.; Leitner, R.; Lellouch, D.; Lemmer, B.; Leney, K. J. C.; Lenz, T.; Lenzi, B.; Leone, R.; Leone, S.; Leonidopoulos, C.; Lerner, G.; Leroy, C.; Les, R.; Lesage, A. A. J.; Lester, C. G.; Levchenko, M.; Levêque, J.; Levin, D.; Levinson, L. J.; Levy, M.; Lewis, D.; Li, B.; Li, H.; Li, L.; Li, Q.; Li, Q.; Li, S.; Li, X.; Li, Y.; Liang, Z.; Liberti, B.; Liblong, A.; Lie, K.; Limosani, A.; Lin, C. Y.; Lin, K.; Lin, S. C.; Lin, T. H.; Linck, R. A.; Lindquist, B. E.; Lionti, A. E.; Lipeles, E.; Lipniacka, A.; Lisovyi, M.; Liss, T. M.; Lister, A.; Litke, A. M.; Liu, B.; Liu, H.; Liu, H.; Liu, J. K. K.; Liu, J. B.; Liu, K.; Liu, M.; Liu, Y. L.; Liu, Y.; Livan, M.; Lleres, A.; Llorente Merino, J.; Lloyd, S. L.; Lo, C. Y.; Lo Sterzo, F.; Lobodzinska, E. M.; Loch, P.; Loebinger, F. K.; Loesle, A.; Loew, K. M.; Lohse, T.; Lohwasser, K.; Lokajicek, M.; Long, B. A.; Long, J. D.; Long, R. E.; Longo, L.; Looper, K. A.; Lopez, J. A.; Lopez Paz, I.; Lopez Solis, A.; Lorenz, J.; Lorenzo Martinez, N.; Losada, M.; Lösel, P. J.; Lou, X.; Lounis, A.; Love, J.; Love, P. A.; Lu, H.; Lu, N.; Lu, Y. J.; Lubatti, H. J.; Luci, C.; Lucotte, A.; Luedtke, C.; Luehring, F.; Lukas, W.; Luminari, L.; Lund-Jensen, B.; Lutz, M. S.; Luzi, P. M.; Lynn, D.; Lysak, R.; Lytken, E.; Lyu, F.; Lyubushkin, V.; Ma, H.; Ma, L. L.; Ma, Y.; Maccarrone, G.; Macchiolo, A.; Macdonald, C. M.; Maček, B.; Machado Miguens, J.; Madaffari, D.; Madar, R.; Mader, W. F.; Madsen, A.; Madysa, N.; Maeda, J.; Maeland, S.; Maeno, T.; Maevskiy, A. S.; Magerl, V.; Maidantchik, C.; Maier, T.; Maio, A.; Majersky, O.; Majewski, S.; Makida, Y.; Makovec, N.; Malaescu, B.; Malecki, Pa.; Maleev, V. P.; Malek, F.; Mallik, U.; Malon, D.; Malone, C.; Maltezos, S.; Malyukov, S.; Mamuzic, J.; Mancini, G.; Mandić, I.; Maneira, J.; Manhaes de Andrade Filho, L.; Manjarres Ramos, J.; Mankinen, K. H.; Mann, A.; Manousos, A.; Mansoulie, B.; Mansour, J. D.; Mantifel, R.; Mantoani, M.; Manzoni, S.; Marceca, G.; March, L.; Marchese, L.; Marchiori, G.; Marcisovsky, M.; Marin Tobon, C. A.; Marjanovic, M.; Marley, D. E.; Marroquim, F.; Marshall, Z.; Martensson, M. U. F.; Marti-Garcia, S.; Martin, C. B.; Martin, T. A.; Martin, V. J.; Martin dit Latour, B.; Martinez, M.; Martinez Outschoorn, V. I.; Martin-Haugh, S.; Martoiu, V. S.; Martyniuk, A. C.; Marzin, A.; Masetti, L.; Mashimo, T.; Mashinistov, R.; Masik, J.; Maslennikov, A. L.; Mason, L. H.; Massa, L.; Mastrandrea, P.; Mastroberardino, A.; Masubuchi, T.; Mättig, P.; Maurer, J.; Maxfield, S. J.; Maximov, D. A.; Mazini, R.; Maznas, I.; Mazza, S. M.; Mc Fadden, N. C.; Mc Goldrick, G.; Mc Kee, S. P.; McCarn, A.; McCarthy, T. G.; McClymont, L. I.; McDonald, E. F.; Mcfayden, J. A.; Mchedlidze, G.; McMahon, S. J.; McNamara, P. C.; McNicol, C. J.; McPherson, R. A.; Meehan, S.; Megy, T. J.; Mehlhase, S.; Mehta, A.; Meideck, T.; Meier, K.; Meirose, B.; Melini, D.; Mellado Garcia, B. R.; Mellenthin, J. D.; Melo, M.; Meloni, F.; Melzer, A.; Menary, S. B.; Meng, L.; Meng, X. T.; Mengarelli, A.; Menke, S.; Meoni, E.; Mergelmeyer, S.; Merlassino, C.; Mermod, P.; Merola, L.; Meroni, C.; Merritt, F. S.; Messina, A.; Metcalfe, J.; Mete, A. S.; Meyer, C.; Meyer, J.-P.; Meyer, J.; Meyer Zu Theenhausen, H.; Miano, F.; Middleton, R. P.; Miglioranzi, S.; Mijović, L.; Mikenberg, G.; Mikestikova, M.; Mikuž, M.; Milesi, M.; Milic, A.; Millar, D. A.; Miller, D. W.; Milov, A.; Milstead, D. A.; Minaenko, A. A.; Minashvili, I. A.; Mincer, A. I.; Mindur, B.; Mineev, M.; Minegishi, Y.; Ming, Y.; Mir, L. M.; Mirto, A.; Mistry, K. P.; Mitani, T.; Mitrevski, J.; Mitsou, V. A.; Miucci, A.; Miyagawa, P. S.; Mizukami, A.; Mjörnmark, J. U.; Mkrtchyan, T.; Mlynarikova, M.; Moa, T.; Mochizuki, K.; Mogg, P.; Mohapatra, S.; Molander, S.; Moles-Valls, R.; Mondragon, M. C.; Mönig, K.; Monk, J.; Monnier, E.; Montalbano, A.; Montejo Berlingen, J.; Monticelli, F.; Monzani, S.; Moore, R. W.; Morange, N.; Moreno, D.; Moreno Llácer, M.; Morettini, P.; Morgenstern, M.; Morgenstern, S.; Mori, D.; Mori, T.; Morii, M.; Morinaga, M.; Morisbak, V.; Morley, A. K.; Mornacchi, G.; Morris, J. D.; Morvaj, L.; Moschovakos, P.; Mosidze, M.; Moss, H. J.; Moss, J.; Motohashi, K.; Mount, R.; Mountricha, E.; Moyse, E. J. W.; Muanza, S.; Mueller, F.; Mueller, J.; Mueller, R. S. P.; Muenstermann, D.; Mullen, P.; Mullier, G. A.; Munoz Sanchez, F. J.; Murray, W. J.; Muškinja, M.; Mwewa, C.; Myagkov, A. G.; Myers, J.; Myska, M.; Nachman, B. P.; Nackenhorst, O.; Nagai, K.; Nagai, R.; Nagano, K.; Nagasaka, Y.; Nagata, K.; Nagel, M.; Nagy, E.; Nairz, A. M.; Nakahama, Y.; Nakamura, K.; Nakamura, T.; Nakano, I.; Naranjo Garcia, R. F.; Narayan, R.; Narrias Villar, D. I.; Naryshkin, I.; Naumann, T.; Navarro, G.; Nayyar, R.; Neal, H. A.; Nechaeva, P. Yu.; Neep, T. J.; Negri, A.; Negrini, M.; Nektarijevic, S.; Nellist, C.; Nelson, M. E.; Nemecek, S.; Nemethy, P.; Nessi, M.; Neubauer, M. S.; Neumann, M.; Newman, P. R.; Ng, T. Y.; Ng, Y. S.; Nguyen Manh, T.; Nickerson, R. B.; Nicolaidou, R.; Nielsen, J.; Nikiforou, N.; Nikolaenko, V.; Nikolic-Audit, I.; Nikolopoulos, K.; Nilsson, P.; Ninomiya, Y.; Nisati, A.; Nishu, N.; Nisius, R.; Nitsche, I.; Nitta, T.; Nobe, T.; Noguchi, Y.; Nomachi, M.; Nomidis, I.; Nomura, M. A.; Nooney, T.; Nordberg, M.; Norjoharuddeen, N.; Novgorodova, O.; Novotny, R.; Nozaki, M.; Nozka, L.; Ntekas, K.; Nurse, E.; Nuti, F.; O'connor, K.; O'Neil, D. C.; O'Rourke, A. A.; O'Shea, V.; Oakham, F. G.; Oberlack, H.; Obermann, T.; Ocariz, J.; Ochi, A.; Ochoa, I.; Ochoa-Ricoux, J. P.; Oda, S.; Odaka, S.; Oh, A.; Oh, S. H.; Ohm, C. C.; Ohman, H.; Oide, H.; Okawa, H.; Okumura, Y.; Okuyama, T.; Olariu, A.; Oleiro Seabra, L. F.; Olivares Pino, S. A.; Oliveira Damazio, D.; Olsson, M. J. R.; Olszewski, A.; Olszowska, J.; Onofre, A.; Onogi, K.; Onyisi, P. U. E.; Oppen, H.; Oreglia, M. J.; Oren, Y.; Orestano, D.; Orgill, E. C.; Orlando, N.; Orr, R. S.; Osculati, B.; Ospanov, R.; Otero y Garzon, G.; Otono, H.; Ouchrif, M.; Ould-Saada, F.; Ouraou, A.; Oussoren, K. P.; Ouyang, Q.; Owen, M.; Owen, R. E.; Ozcan, V. E.; Ozturk, N.; Pachal, K.; Pacheco Pages, A.; Pacheco Rodriguez, L.; Padilla Aranda, C.; Pagan Griso, S.; Paganini, M.; Paige, F.; Palacino, G.; Palazzo, S.; Palestini, S.; Palka, M.; Pallin, D.; Panagiotopoulou, E. St.; Panagoulias, I.; Pandini, C. E.; Panduro Vazquez, J. G.; Pani, P.; Pantea, D.; Paolozzi, L.; Papadopoulou, Th. D.; Papageorgiou, K.; Paramonov, A.; Paredes Hernandez, D.; Parker, A. J.; Parker, M. A.; Parker, K. A.; Parodi, F.; Parsons, J. A.; Parzefall, U.; Pascuzzi, V. R.; Pasner, J. M.; Pasqualucci, E.; Passaggio, S.; Pastore, Fr.; Pataraia, S.; Pater, J. R.; Pauly, T.; Pearson, B.; Pedraza Lopez, S.; Pedro, R.; Peleganchuk, S. V.; Penc, O.; Peng, C.; Peng, H.; Penwell, J.; Peralva, B. S.; Perego, M. M.; Perepelitsa, D. V.; Peri, F.; Perini, L.; Pernegger, H.; Perrella, S.; Peshekhonov, V. D.; Peters, K.; Peters, R. F. Y.; Petersen, B. A.; Petersen, T. C.; Petit, E.; Petridis, A.; Petridou, C.; Petroff, P.; Petrolo, E.; Petrov, M.; Petrucci, F.; Pettersson, N. E.; Peyaud, A.; Pezoa, R.; Phillips, F. H.; Phillips, P. W.; Piacquadio, G.; Pianori, E.; Picazio, A.; Pickering, M. A.; Piegaia, R.; Pilcher, J. E.; Pilkington, A. D.; Pinamonti, M.; Pinfold, J. L.; Pitt, M.; Pleier, M.-A.; Pleskot, V.; Plotnikova, E.; Pluth, D.; Podberezko, P.; Poettgen, R.; Poggi, R.; Poggioli, L.; Pogrebnyak, I.; Pohl, D.; Pokharel, I.; Polesello, G.; Poley, A.; Policicchio, A.; Polifka, R.; Polini, A.; Pollard, C. S.; Polychronakos, V.; Ponomarenko, D.; Pontecorvo, L.; Popeneciu, G. A.; Portillo Quintero, D. M.; Pospisil, S.; Potamianos, K.; Potrap, I. N.; Potter, C. J.; Potti, H.; Poulsen, T.; Poveda, J.; Pozo Astigarraga, M. E.; Pralavorio, P.; Prell, S.; Price, D.; Primavera, M.; Prince, S.; Proklova, N.; Prokofiev, K.; Prokoshin, F.; Protopopescu, S.; Proudfoot, J.; Przybycien, M.; Puri, A.; Puzo, P.; Qian, J.; Qin, Y.; Quadt, A.; Queitsch-Maitland, M.; Radeka, V.; Radhakrishnan, S. K.; Rados, P.; Ragusa, F.; Rahal, G.; Raine, J. A.; Rajagopalan, S.; Rashid, T.; Raspopov, S.; Ratti, M. G.; Rauch, D. M.; Rauscher, F.; Rave, S.; Ravinovich, I.; Rawling, J. H.; Raymond, M.; Read, A. L.; Readioff, N. P.; Reale, M.; Rebuzzi, D. M.; Redelbach, A.; Redlinger, G.; Reece, R.; Reed, R. G.; Reeves, K.; Rehnisch, L.; Reichert, J.; Reiss, A.; Rembser, C.; Ren, H.; Rescigno, M.; Resconi, S.; Resseguie, E. D.; Rettie, S.; Reynolds, E.; Rezanova, O. L.; Reznicek, P.; Richter, R.; Richter, S.; Richter-Was, E.; Ricken, O.; Ridel, M.; Rieck, P.; Riegel, C. J.; Rifki, O.; Rijssenbeek, M.; Rimoldi, A.; Rimoldi, M.; Rinaldi, L.; Ripellino, G.; Ristić, B.; Ritsch, E.; Riu, I.; Rizatdinova, F.; Rizvi, E.; Rizzi, C.; Roberts, R. T.; Robertson, S. H.; Robichaud-Veronneau, A.; Robinson, D.; Robinson, J. E. M.; Robson, A.; Rocco, E.; Roda, C.; Rodina, Y.; Rodriguez Bosca, S.; Rodriguez Perez, A.; Rodriguez Rodriguez, D.; Roe, S.; Rogan, C. S.; Røhne, O.; Roloff, J.; Romaniouk, A.; Romano, M.; Romano Saez, S. M.; Romero Adam, E.; Rompotis, N.; Ronzani, M.; Roos, L.; Rosati, S.; Rosbach, K.; Rose, P.; Rosien, N.-A.; Rossi, E.; Rossi, L. P.; Rosten, J. H. N.; Rosten, R.; Rotaru, M.; Rothberg, J.; Rousseau, D.; Roy, D.; Rozanov, A.; Rozen, Y.; Ruan, X.; Rubbo, F.; Rühr, F.; Ruiz-Martinez, A.; Rurikova, Z.; Rusakovich, N. A.; Russell, H. L.; Rutherfoord, J. P.; Ruthmann, N.; Rüttinger, E. M.; Ryabov, Y. F.; Rybar, M.; Rybkin, G.; Ryu, S.; Ryzhov, A.; Rzehorz, G. F.; Saavedra, A. F.; Sabato, G.; Sacerdoti, S.; Sadrozinski, H. F.-W.; Sadykov, R.; Safai Tehrani, F.; Saha, P.; Sahinsoy, M.; Saimpert, M.; Saito, M.; Saito, T.; Sakamoto, H.; Salamanna, G.; Salazar Loyola, J. E.; Salek, D.; Sales De Bruin, P. H.; Salihagic, D.; Salnikov, A.; Salt, J.; Salvatore, D.; Salvatore, F.; Salvucci, A.; Salzburger, A.; Sammel, D.; Sampsonidis, D.; Sampsonidou, D.; Sánchez, J.; Sanchez Pineda, A.; Sandaker, H.; Sandbach, R. L.; Sander, C. O.; Sandhoff, M.; Sandoval, C.; Sankey, D. P. C.; Sannino, M.; Sano, Y.; Sansoni, A.; Santoni, C.; Santos, H.; Santoyo Castillo, I.; Sapronov, A.; Saraiva, J. G.; Sasaki, O.; Sato, K.; Sauvan, E.; Savage, G.; Savard, P.; Savic, N.; Sawyer, C.; Sawyer, L.; Sbarra, C.; Sbrizzi, A.; Scanlon, T.; Scannicchio, D. A.; Schaarschmidt, J.; Schacht, P.; Schachtner, B. M.; Schaefer, D.; Schaefer, L.; Schaeffer, J.; Schaepe, S.; Schäfer, U.; Schaffer, A. C.; Schaile, D.; Schamberger, R. D.; Schegelsky, V. A.; Scheirich, D.; Schenck, F.; Schernau, M.; Schiavi, C.; Schier, S.; Schildgen, L. K.; Schillo, C.; Schioppa, E. J.; Schioppa, M.; Schleicher, K. E.; Schlenker, S.; Schmidt-Sommerfeld, K. R.; Schmieden, K.; Schmitt, C.; Schmitt, S.; Schmitz, S.; Schnoor, U.; Schoeffel, L.; Schoening, A.; Schopf, E.; Schott, M.; Schouwenberg, J. F. P.; Schovancova, J.; Schramm, S.; Schuh, N.; Schulte, A.; Schultz-Coulon, H.-C.; Schumacher, M.; Schumm, B. A.; Schune, Ph.; Schwartzman, A.; Schwarz, T. A.; Schweiger, H.; Schwemling, Ph.; Schwienhorst, R.; Schwindling, J.; Sciandra, A.; Sciolla, G.; Scornajenghi, M.; Scuri, F.; Scutti, F.; Searcy, J.; Seema, P.; Seidel, S. C.; Seiden, A.; Seixas, J. M.; Sekhniaidze, G.; Sekhon, K.; Sekula, S. J.; Semprini-Cesari, N.; Senkin, S.; Serfon, C.; Serin, L.; Serkin, L.; Sessa, M.; Severini, H.; Šfiligoj, T.; Sforza, F.; Sfyrla, A.; Shabalina, E.; Shaikh, N. W.; Shan, L. Y.; Shang, R.; Shank, J. T.; Shapiro, M.; Shatalov, P. B.; Shaw, K.; Shaw, S. M.; Shcherbakova, A.; Shehu, C. Y.; Shen, Y.; Sherafati, N.; Sherman, A. D.; Sherwood, P.; Shi, L.; Shimizu, S.; Shimmin, C. O.; Shimojima, M.; Shipsey, I. P. J.; Shirabe, S.; Shiyakova, M.; Shlomi, J.; Shmeleva, A.; Shoaleh Saadi, D.; Shochet, M. J.; Shojaii, S.; Shope, D. R.; Shrestha, S.; Shulga, E.; Sicho, P.; Sickles, A. M.; Sidebo, P. E.; Sideras Haddad, E.; Sidiropoulou, O.; Sidoti, A.; Siegert, F.; Sijacki, Dj.; Silva, J.; Silva, M.; Silverstein, S. B.; Simic, L.; Simion, S.; Simioni, E.; Simmons, B.; Simon, M.; Sinervo, P.; Sinev, N. B.; Sioli, M.; Siragusa, G.; Siral, I.; Sivoklokov, S. Yu.; Sjölin, J.; Skinner, M. B.; Skubic, P.; Slater, M.; Slavicek, T.; Slawinska, M.; Sliwa, K.; Slovak, R.; Smakhtin, V.; Smart, B. H.; Smiesko, J.; Smirnov, N.; Smirnov, S. Yu.; Smirnov, Y.; Smirnova, L. N.; Smirnova, O.; Smith, J. W.; Smith, M. N. K.; Smith, R. W.; Smizanska, M.; Smolek, K.; Snesarev, A. A.; Snyder, I. M.; Snyder, S.; Sobie, R.; Socher, F.; Soffer, A.; Søgaard, A.; Soh, D. A.; Sokhrannyi, G.; Solans Sanchez, C. A.; Solar, M.; Soldatov, E. Yu.; Soldevila, U.; Solodkov, A. A.; Soloshenko, A.; Solovyanov, O. V.; Solovyev, V.; Sommer, P.; Son, H.; Song, W.; Sopczak, A.; Sosa, D.; Sotiropoulou, C. L.; Sottocornola, S.; Soualah, R.; Soukharev, A. M.; South, D.; Sowden, B. C.; Spagnolo, S.; Spalla, M.; Spangenberg, M.; Spanò, F.; Sperlich, D.; Spettel, F.; Spieker, T. M.; Spighi, R.; Spigo, G.; Spiller, L. A.; Spousta, M.; St. Denis, R. D.; Stabile, A.; Stamen, R.; Stamm, S.; Stanecka, E.; Stanek, R. W.; Stanescu, C.; Stanitzki, M. M.; Stapf, B. S.; Stapnes, S.; Starchenko, E. A.; Stark, G. H.; Stark, J.; Stark, S. H.; Staroba, P.; Starovoitov, P.; Stärz, S.; Staszewski, R.; Stegler, M.; Steinberg, P.; Stelzer, B.; Stelzer, H. J.; Stelzer-Chilton, O.; Stenzel, H.; Stevenson, T. J.; Stewart, G. A.; Stockton, M. C.; Stoicea, G.; Stolte, P.; Stonjek, S.; Straessner, A.; Stramaglia, M. E.; Strandberg, J.; Strandberg, S.; Strauss, M.; Strizenec, P.; Ströhmer, R.; Strom, D. M.; Stroynowski, R.; Strubig, A.; Stucci, S. A.; Stugu, B.; Styles, N. A.; Su, D.; Su, J.; Suchek, S.; Sugaya, Y.; Suk, M.; Sulin, V. V.; Sultan, D. M. S.; Sultansoy, S.; Sumida, T.; Sun, S.; Sun, X.; Suruliz, K.; Suster, C. J. E.; Sutton, M. R.; Suzuki, S.; Svatos, M.; Swiatlowski, M.; Swift, S. P.; Sykora, I.; Sykora, T.; Ta, D.; Tackmann, K.; Taenzer, J.; Taffard, A.; Tafirout, R.; Tahirovic, E.; Taiblum, N.; Takai, H.; Takashima, R.; Takasugi, E. H.; Takeda, K.; Takeshita, T.; Takubo, Y.; Talby, M.; Talyshev, A. A.; Tanaka, J.; Tanaka, M.; Tanaka, R.; Tanioka, R.; Tannenwald, B. B.; Araya, S. Tapia; Tapprogge, S.; Tarem, S.; Tartarelli, G. F.; Tas, P.; Tasevsky, M.; Tashiro, T.; Tassi, E.; Delgado, A. Tavares; Tayalati, Y.; Taylor, A. C.; Taylor, A. J.; Taylor, G. N.; Taylor, P. T. E.; Taylor, W.; Teixeira-Dias, P.; Temple, D.; Ten Kate, H.; Teng, P. K.; Teoh, J. J.; Tepel, F.; Terada, S.; Terashi, K.; Terron, J.; Terzo, S.; Testa, M.; Teuscher, R. J.; Thais, S. J.; Theveneaux-Pelzer, T.; Thiele, F.; Thomas, J. P.; Thomas-Wilsker, J.; Thompson, P. D.; Thompson, A. S.; Thomsen, L. A.; Thomson, E.; Tian, Y.; Torres, R. E. Ticse; Tikhomirov, V. O.; Tikhonov, Yu. A.; Timoshenko, S.; Tipton, P.; Tisserant, S.; Todome, K.; Todorova-Nova, S.; Todt, S.; Tojo, J.; Tokár, S.; Tokushuku, K.; Tolley, E.; Tomoto, M.; Tompkins, L.; Toms, K.; Tong, B.; Tornambe, P.; Torrence, E.; Torres, H.; Pastor, E. Torró; Toth, J.; Touchard, F.; Tovey, D. R.; Treado, C. J.; Trefzger, T.; Tresoldi, F.; Tricoli, A.; Trigger, I. M.; Trincaz-Duvoid, S.; Tripiana, M. F.; Trischuk, W.; Trocmé, B.; Trofymov, A.; Troncon, C.; Trovatelli, M.; Truong, L.; Trzebinski, M.; Trzupek, A.; Tsang, K. W.; Tseng, J. C.-L.; Tsiareshka, P. V.; Tsirintanis, N.; Tsiskaridze, S.; Tsiskaridze, V.; Tskhadadze, E. G.; Tsukerman, I. I.; Tsulaia, V.; Tsuno, S.; Tsybychev, D.; Tu, Y.; Tudorache, A.; Tudorache, V.; Tulbure, T. T.; Tuna, A. N.; Turchikhin, S.; Turgeman, D.; Cakir, I. Turk; Turra, R.; Tuts, P. M.; Ucchielli, G.; Ueda, I.; Ughetto, M.; Ukegawa, F.; Unal, G.; Undrus, A.; Unel, G.; Ungaro, F. C.; Unno, Y.; Uno, K.; Urban, J.; Urquijo, P.; Urrejola, P.; Usai, G.; Usui, J.; Vacavant, L.; Vacek, V.; Vachon, B.; Vadla, K. O. H.; Vaidya, A.; Valderanis, C.; Santurio, E. Valdes; Valente, M.; Valentinetti, S.; Valero, A.; Valéry, L.; Vallier, A.; Ferrer, J. A. Valls; Van Den Wollenberg, W.; van der Graaf, H.; van Gemmeren, P.; Van Nieuwkoop, J.; van Vulpen, I.; van Woerden, M. C.; Vanadia, M.; Vandelli, W.; Vaniachine, A.; Vankov, P.; Vari, R.; Varnes, E. W.; Varni, C.; Varol, T.; Varouchas, D.; Vartapetian, A.; Varvell, K. E.; Vasquez, J. G.; Vasquez, G. A.; Vazeille, F.; Furelos, D. Vazquez; Schroeder, T. Vazquez; Veatch, J.; Veloce, L. M.; Veloso, F.; Veneziano, S.; Ventura, A.; Venturi, M.; Venturi, N.; Vercesi, V.; Verducci, M.; Verkerke, W.; Vermeulen, A. T.; Vermeulen, J. C.; Vetterli, M. C.; Maira, N. Viaux; Viazlo, O.; Vichou, I.; Vickey, T.; Boeriu, O. E. Vickey; Viehhauser, G. H. A.; Viel, S.; Vigani, L.; Villa, M.; Perez, M. Villaplana; Vilucchi, E.; Vincter, M. G.; Vinogradov, V. B.; Vishwakarma, A.; Vittori, C.; Vivarelli, I.; Vlachos, S.; Vogel, M.; Vokac, P.; Volpi, G.; von Buddenbrock, S. E.; von Toerne, E.; Vorobel, V.; Vorobev, K.; Vos, M.; Vossebeld, J. H.; Vranjes, N.; Milosavljevic, M. Vranjes; Vrba, V.; Vreeswijk, M.; Vuillermet, R.; Vukotic, I.; Wagner, P.; Wagner, W.; Wagner-Kuhr, J.; Wahlberg, H.; Wahrmund, S.; Wakamiya, K.; Walder, J.; Walker, R.; Walkowiak, W.; Wallangen, V.; Wang, A. M.; Wang, C.; Wang, F.; Wang, H.; Wang, H.; Wang, J.; Wang, J.; Wang, Q.; Wang, R.-J.; Wang, R.; Wang, S. M.; Wang, T.; Wang, W.; Wang, W.; Wang, Z.; Wanotayaroj, C.; Warburton, A.; Ward, C. P.; Wardrope, D. R.; Washbrook, A.; Watkins, P. M.; Watson, A. T.; Watson, M. F.; Watts, G.; Watts, S.; Waugh, B. M.; Webb, A. F.; Webb, S.; Weber, M. S.; Weber, S. M.; Weber, S. A.; Webster, J. S.; Weidberg, A. R.; Weinert, B.; Weingarten, J.; Weirich, M.; Weiser, C.; Wells, P. S.; Wenaus, T.; Wengler, T.; Wenig, S.; Wermes, N.; Werner, M. D.; Werner, P.; Wessels, M.; Weston, T. D.; Whalen, K.; Whallon, N. L.; Wharton, A. M.; White, A. S.; White, A.; White, M. J.; White, R.; Whiteson, D.; Whitmore, B. W.; Wickens, F. J.; Wiedenmann, W.; Wielers, M.; Wiglesworth, C.; Wiik-Fuchs, L. A. M.; Wildauer, A.; Wilk, F.; Wilkens, H. G.; Williams, H. H.; Williams, S.; Willis, C.; Willocq, S.; Wilson, J. A.; Wingerter-Seez, I.; Winkels, E.; Winklmeier, F.; Winston, O. J.; Winter, B. T.; Wittgen, M.; Wobisch, M.; Wolf, A.; Wolf, T. M. H.; Wolff, R.; Wolter, M. W.; Wolters, H.; Wong, V. W. S.; Woods, N. L.; Worm, S. D.; Wosiek, B. K.; Wozniak, K. W.; Wu, M.; Wu, S. L.; Wu, X.; Wu, Y.; Wyatt, T. R.; Wynne, B. M.; Xella, S.; Xi, Z.; Xia, L.; Xu, D.; Xu, L.; Xu, T.; Xu, W.; Yabsley, B.; Yacoob, S.; Yajima, K.; Yamaguchi, D.; Yamaguchi, Y.; Yamamoto, A.; Yamanaka, T.; Yamane, F.; Yamatani, M.; Yamazaki, T.; Yamazaki, Y.; Yan, Z.; Yang, H.; Yang, H.; Yang, S.; Yang, Y.; Yang, Z.; Yao, W.-M.; Yap, Y. C.; Yasu, Y.; Yatsenko, E.; Wong, K. H. Yau; Ye, J.; Ye, S.; Yeletskikh, I.; Yigitbasi, E.; Yildirim, E.; Yorita, K.; Yoshihara, K.; Young, C.; Young, C. J. S.; Yu, J.; Yu, J.; Yuen, S. P. Y.; Yusuff, I.; Zabinski, B.; Zacharis, G.; Zaidan, R.; Zaitsev, A. M.; Zakharchuk, N.; Zalieckas, J.; Zaman, A.; Zambito, S.; Zanzi, D.; Zeitnitz, C.; Zemaityte, G.; Zeng, J. C.; Zeng, Q.; Zenin, O.; Ženiš, T.; Zerwas, D.; Zhang, D.; Zhang, D.; Zhang, F.; Zhang, G.; Zhang, H.; Zhang, J.; Zhang, L.; Zhang, L.; Zhang, M.; Zhang, P.; Zhang, R.; Zhang, R.; Zhang, X.; Zhang, Y.; Zhang, Z.; Zhao, X.; Zhao, Y.; Zhao, Z.; Zhemchugov, A.; Zhou, B.; Zhou, C.; Zhou, L.; Zhou, M.; Zhou, M.; Zhou, N.; Zhou, Y.; Zhu, C. G.; Zhu, H.; Zhu, J.; Zhu, Y.; Zhuang, X.; Zhukov, K.; Zibell, A.; Zieminska, D.; Zimine, N. I.; Zimmermann, S.; Zinonos, Z.; Zinser, M.; Ziolkowski, M.; Živković, L.; Zobernig, G.; Zoccoli, A.; Zou, R.; zur Nedden, M.; Zwalinski, L.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Ambrogi, F.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Escalante Del Valle, A.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Grossmann, J.; Hrubec, J.; Jeitler, M.; König, A.; Krammer, N.; Krätschmer, I.; Liko, D.; Madlener, T.; Mikulec, I.; Pree, E.; Rad, N.; Rohringer, H.; Schieck, J.; Schöfbeck, R.; Spanring, M.; Spitzbart, D.; Taurok, A.; Waltenberger, W.; Wittmann, J.; Wulz, C.-E.; Zarucki, M.; Chekhovsky, V.; Mossolov, V.; Suarez Gonzalez, J.; De Wolf, E. A.; Di Croce, D.; Janssen, X.; Lauwers, J.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; De Bruyn, I.; De Clercq, J.; Deroover, K.; Flouris, G.; Lontkovskyi, D.; Lowette, S.; Marchesini, I.; Moortgat, S.; Moreels, L.; Python, Q.; Skovpen, K.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Beghin, D.; Bilin, B.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Dorney, B.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Kalsi, A. K.; Lenzi, T.; Luetic, J.; Maerschalk, T.; Marinov, A.; Seva, T.; Starling, E.; Vander Velde, C.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Zenoni, F.; Cornelis, T.; Dobur, D.; Fagot, A.; Gul, M.; Khvastunov, I.; Poyraz, D.; Roskas, C.; Salva, S.; Tytgat, M.; Verbeke, W.; Zaganidis, N.; Bakhshiansohi, H.; Bondu, O.; Brochet, S.; Bruno, G.; Caputo, C.; Caudron, A.; David, P.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Saggio, A.; Vidal Marono, M.; Wertz, S.; Zobec, J.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Correia Silva, G.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Coelho, E.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Melo De Almeida, M.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Sanchez Rosas, L. J.; Santoro, A.; Sznajder, A.; Thiel, M.; Tonelli Manganote, E. J.; Torres Da Silva De Araujo, F.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Misheva, M.; Rodozov, M.; Shopova, M.; Sultanov, G.; Dimitrov, A.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Gao, X.; Yuan, L.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Jiang, C. H.; Leggat, D.; Liao, H.; Liu, Z.; Romeo, F.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Yazgan, E.; Yu, T.; Zhang, H.; Zhang, S.; Zhao, J.; Ban, Y.; Chen, G.; Li, J.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Zhang, F.; Wang, Y.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; González Hernández, C. F.; Ruiz Alvarez, J. D.; Segura Delgado, M. A.; Courbon, B.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Starodumov, A.; Susa, T.; Ather, M. W.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; Assran, Y.; Elgammal, S.; Mahrous, A.; Bhowmik, S.; Dewanjee, R. K.; Kadastik, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Kirschenmann, H.; Pekkanen, J.; Voutilainen, M.; Havukainen, J.; Heikkilä, J. K.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Laurila, S.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Siikonen, H.; Tuominen, E.; Tuominiemi, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Faure, J. L.; Ferri, F.; Ganjour, S.; Ghosh, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Kucher, I.; Leloup, C.; Locci, E.; Machet, M.; Malcles, J.; Negro, G.; Rander, J.; Rosowsky, A.; Sahin, M. Ö.; Titov, M.; Abdulsalam, A.; Amendola, C.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Charlot, C.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Lobanov, A.; Martin Blanco, J.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Stahl Leiton, A. G.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Drouhin, F.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Jansová, M.; Juillot, P.; Le Bihan, A.-C.; Tonon, N.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fay, J.; Finco, L.; Gascon, S.; Gouzevitch, M.; Grenier, G.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Sordini, V.; Vander Donckt, M.; Viret, S.; Toriashvili, T.; Tsamalaidze, Z.; Autermann, C.; Feld, L.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Preuten, M.; Schomakers, C.; Schulz, J.; Teroerde, M.; Wittmer, B.; Zhukov, V.; Albert, A.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hamer, M.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Teyssier, D.; Thüer, S.; Flügge, G.; Kargoll, B.; Kress, T.; Künsken, A.; Müller, T.; Nehrkorn, A.; Nowack, A.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Arndt, T.; Asawatangtrakuldee, C.; Beernaert, K.; Behnke, O.; Behrens, U.; Bermúdez Martínez, A.; Bin Anuar, A. A.; Borras, K.; Botta, V.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Eren, E.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Grados Luyando, J. M.; Grohsjean, A.; Gunnellini, P.; Guthoff, M.; Harb, A.; Hauk, J.; Hempel, M.; Jung, H.; Kasemann, M.; Keaveney, J.; Kleinwort, C.; Korol, I.; Krücker, D.; Lange, W.; Lelek, A.; Lenz, T.; Leonard, J.; Lipka, K.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Ntomari, E.; Pitzl, D.; Raspereza, A.; Savitskyi, M.; Saxena, P.; Shevchenko, R.; Stefaniuk, N.; Van Onsem, G. P.; Walsh, R.; Wen, Y.; Wichmann, K.; Wissing, C.; Zenaiev, O.; Aggleton, R.; Bein, S.; Blobel, V.; Centis Vignali, M.; Dreyer, T.; Garutti, E.; Gonzalez, D.; Haller, J.; Hinzmann, A.; Hoffmann, M.; Karavdina, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Kurz, S.; Lapsien, T.; Marconi, D.; Meyer, M.; Niedziela, M.; Nowatschin, D.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Scharf, C.; Schleper, P.; Schmidt, A.; Schumann, S.; Schwandt, J.; Sonneveld, J.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Stöver, M.; Tholen, H.; Troendle, D.; Usai, E.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baselga, M.; Baur, S.; Butz, E.; Caspart, R.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Faltermann, N.; Freund, B.; Friese, R.; Giffels, M.; Harrendorf, M. A.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Kassel, F.; Kudella, S.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Karathanasis, G.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Kousouris, K.; Evangelou, I.; Foudas, C.; Gianneios, P.; Katsoulis, P.; Kokkas, P.; Mallios, S.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Strologas, J.; Triantis, F. A.; Tsitsonis, D.; Csanad, M.; Filipovic, N.; Pasztor, G.; Surányi, O.; Veres, G. I.; Bencze, G.; Hajdu, C.; Horvath, D.; Hunyadi, Á.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Beni, N.; Czellar, S.; Karancsi, J.; Makovec, A.; Molnar, J.; Szillasi, Z.; Bartók, M.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Choudhury, S.; Komaragiri, J. R.; Bahinipati, S.; Mal, P.; Mandal, K.; Nayak, A.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Chawla, R.; Dhingra, N.; Kaur, A.; Kaur, M.; Kaur, S.; Kumar, R.; Kumari, P.; Mehta, A.; Singh, J. B.; Walia, G.; Kumar, Ashok; Shah, Aashaq; Bhardwaj, A.; Chauhan, S.; Choudhary, B. C.; Garg, R. B.; Keshri, S.; Kumar, A.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Sharma, R.; Bhardwaj, R.; Bhattacharya, R.; Bhattacharya, S.; Bhawandeep, U.; Dey, S.; Dutt, S.; Dutta, S.; Ghosh, S.; Majumdar, N.; Modak, A.; Mondal, K.; Mukhopadhyay, S.; Nandan, S.; Purohit, A.; Roy, A.; Roy Chowdhury, S.; Sarkar, S.; Sharan, M.; Thakur, S.; Behera, P. K.; Chudasama, R.; Dutta, D.; Jha, V.; Kumar, V.; Mohanty, A. K.; Netrakanti, P. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Dugad, S.; Mahakud, B.; Mitra, S.; Mohanty, G. B.; Sur, N.; Sutar, B.; Banerjee, S.; Bhattacharya, S.; Chatterjee, S.; Das, P.; Guchait, M.; Jain, Sa.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Sarkar, T.; Wickramage, N.; Chauhan, S.; Dube, S.; Hegde, V.; Kapoor, A.; Kothekar, K.; Pandey, S.; Rane, A.; Sharma, S.; Chenarani, S.; Eskandari Tadavani, E.; Etesami, S. M.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Errico, F.; Fiore, L.; Iaselli, G.; Lezki, S.; Maggi, G.; Maggi, M.; Marangelli, B.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Sharma, A.; Silvestris, L.; Venditti, R.; Verwilligen, P.; Zito, G.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Borgonovi, L.; Braibant-Giacomelli, S.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Albergo, S.; Costa, S.; Di Mattia, A.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Chatterjee, K.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Lenzi, P.; Meschini, M.; Paoletti, S.; Russo, L.; Sguazzoni, G.; Strom, D.; Viliani, L.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Primavera, F.; Calvelli, V.; Ferro, F.; Ravera, F.; Robutti, E.; Tosi, S.; Benaglia, A.; Beschi, A.; Brianza, L.; Brivio, F.; Ciriolo, V.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Ghezzi, A.; Govoni, P.; Malberti, M.; Malvezzi, S.; Manzoni, R. A.; Menasce, D.; Moroni, L.; Paganoni, M.; Pauwels, K.; Pedrini, D.; Pigazzini, S.; Ragazzi, S.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; Di Guida, S.; Fabozzi, F.; Fienga, F.; Iorio, A. O. M.; Khan, W. A.; Lista, L.; Meola, S.; Paolucci, P.; Sciacca, C.; Thyssen, F.; Azzi, P.; Bacchetta, N.; Benato, L.; Bisello, D.; Boletti, A.; Carlin, R.; Carvalho Antunes De Oliveira, A.; Checchia, P.; Dall'Osso, M.; De Castro Manzano, P.; Dorigo, T.; Dosselli, U.; Gasparini, U.; Gozzelino, A.; Lacaprara, S.; Lujan, P.; Margoni, M.; Meneguzzo, A. T.; Pozzobon, N.; Ronchese, P.; Rossin, R.; Simonetto, F.; Torassa, E.; Ventura, S.; Zanetti, M.; Zumerle, G.; Braghieri, A.; Magnani, A.; Montagna, P.; Ratti, S. P.; Re, V.; Ressegotti, M.; Riccardi, C.; Salvini, P.; Vai, I.; Vitulo, P.; Alunni Solestizi, L.; Biasini, M.; Bilei, G. M.; Cecchi, C.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Leonardi, R.; Manoni, E.; Mantovani, G.; Mariani, V.; Menichelli, M.; Rossi, A.; Santocchia, A.; Spiga, D.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Boccali, T.; Borrello, L.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Fedi, G.; Giannini, L.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Manca, E.; Mandorli, G.; Messineo, A.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Cipriani, M.; Daci, N.; Del Re, D.; Di Marco, E.; Diemoz, M.; Gelli, S.; Longo, E.; Margaroli, F.; Marzocchi, B.; Meridiani, P.; Organtini, G.; Paramatti, R.; Preiato, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bartosik, N.; Bellan, R.; Biino, C.; Cartiglia, N.; Cenna, F.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Kiani, B.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Monteil, E.; Monteno, M.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Romero, A.; Ruspa, M.; Sacchi, R.; Shchelina, K.; Sola, V.; Solano, A.; Staiano, A.; Traczyk, P.; Belforte, S.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Zanetti, A.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Lee, J.; Lee, S.; Lee, S. W.; Moon, C. S.; Oh, Y. D.; Sekmen, S.; Son, D. C.; Yang, Y. C.; Lee, A.; Kim, H.; Moon, D. H.; Oh, G.; Brochero Cifuentes, J. A.; Goh, J.; Kim, T. J.; Cho, S.; Choi, S.; Go, Y.; Gyun, D.; Ha, S.; Hong, B.; Jo, Y.; Kim, Y.; Lee, K.; Lee, K. S.; Lee, S.; Lim, J.; Park, S. K.; Roh, Y.; Almond, J.; Kim, J.; Kim, J. S.; Lee, H.; Lee, K.; Nam, K.; Oh, S. B.; Radburn-Smith, B. C.; Seo, S. h.; Yang, U. K.; Yoo, H. D.; Yu, G. B.; Kim, H.; Kim, J. H.; Lee, J. S. H.; Park, I. C.; Choi, Y.; Hwang, C.; Lee, J.; Yu, I.; Dudenas, V.; Juodagalvis, A.; Vaitkus, J.; Ahmed, I.; Ibrahim, Z. A.; Md Ali, M. A. B.; Mohamad Idris, F.; Wan Abdullah, W. A. T.; Yusli, M. N.; Zolkapli, Z.; Reyes-Almanza, R.; Ramirez-Sanchez, G.; Duran-Osuna, M. C.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-De La Cruz, I.; Rabadan-Trejo, R. I.; Lopez-Fernandez, R.; Mejia Guisao, J.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Oropeza Barrera, C.; Vazquez Valencia, F.; Eysermans, J.; Pedraza, I.; Salazar Ibarguen, H. A.; Uribe Estrada, C.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Saddique, A.; Shah, M. A.; Shoaib, M.; Waqas, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Szleper, M.; Zalewski, P.; Bunkowski, K.; Byszuk, A.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Pyskir, A.; Walczak, M.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Di Francesco, A.; Faccioli, P.; Galinhas, B.; Gallinaro, M.; Hollar, J.; Leonardo, N.; Lloret Iglesias, L.; Nemallapudi, M. V.; Seixas, J.; Strong, G.; Toldaiev, O.; Vadruccio, D.; Varela, J.; Afanasiev, S.; Bunin, P.; Gavrilenko, M.; Golutvin, I.; Gorbunov, I.; Kamenev, A.; Karjavin, V.; Lanev, A.; Malakhov, A.; Matveev, V.; Moisenz, P.; Palichik, V.; Perelygin, V.; Shmatov, S.; Shulha, S.; Skatchkov, N.; Smirnov, V.; Voytishin, N.; Zarubin, A.; Ivanov, Y.; Kim, V.; Kuznetsova, E.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sosnov, D.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Karneyeu, A.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Pozdnyakov, I.; Safronov, G.; Spiridonov, A.; Stepennov, A.; Stolin, V.; Toms, M.; Vlasov, E.; Zhokin, A.; Aushev, T.; Bylinkin, A.; Chadeeva, M.; Parygin, P.; Philippov, D.; Polikarpov, S.; Popova, E.; Rusinov, V.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Rusakov, S. V.; Terkulov, A.; Baskakov, A.; Belyaev, A.; Boos, E.; Bunichev, V.; Dubinin, M.; Dudko, L.; Ershov, A.; Klyukhin, V.; Korneeva, N.; Lokhtin, I.; Miagkov, I.; Obraztsov, S.; Perfilov, M.; Savrin, V.; Volkov, P.; Blinov, V.; Shtol, D.; Skovpen, Y.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Elumakhov, D.; Godizov, A.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Mandrik, P.; Petrov, V.; Ryutin, R.; Sobol, A.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Cirkovic, P.; Devetak, D.; Dordevic, M.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Bachiller, I.; Barrio Luna, M.; Cerrada, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Moran, D.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; Álvarez Fernández, A.; Albajar, C.; de Trocóniz, J. F.; Missiroli, M.; Cuevas, J.; Erice, C.; Fernandez Menendez, J.; Gonzalez Caballero, I.; González Fernández, J. R.; Palencia Cortezon, E.; Sanchez Cruz, S.; Vischia, P.; Vizan Garcia, J. M.; Cabrillo, I. J.; Calderon, A.; Chazin Quero, B.; Curras, E.; Duarte Campderros, J.; Fernandez, M.; Garcia-Ferrero, J.; Gomez, G.; Lopez Virto, A.; Marco, J.; Martinez Rivero, C.; Martinez Ruiz del Arbol, P.; Matorras, F.; Piedra Gomez, J.; Rodrigo, T.; Ruiz-Jimeno, A.; Scodellaro, L.; Trevisani, N.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Akgun, B.; Auffray, E.; Baillon, P.; Ball, A. H.; Barney, D.; Bendavid, J.; Bianco, M.; Bloch, P.; Bocci, A.; Botta, C.; Camporesi, T.; Castello, R.; Cepeda, M.; Cerminara, G.; Chapon, E.; Chen, Y.; d'Enterria, D.; Dabrowski, A.; Daponte, V.; David, A.; De Gruttola, M.; De Roeck, A.; Deelen, N.; Dobson, M.; du Pree, T.; Dünser, M.; Dupont, N.; Elliott-Peisert, A.; Everaerts, P.; Fallavollita, F.; Franzoni, G.; Fulcher, J.; Funk, W.; Gigi, D.; Gilbert, A.; Gill, K.; Glege, F.; Gulhan, D.; Harris, P.; Hegeman, J.; Innocente, V.; Jafari, A.; Janot, P.; Karacheban, O.; Kieseler, J.; Knünz, V.; Kornmayer, A.; Kortelainen, M. J.; Krammer, M.; Lange, C.; Lecoq, P.; Lourenço, C.; Lucchini, M. T.; Malgeri, L.; Mannelli, M.; Martelli, A.; Meijers, F.; Merlin, J. A.; Mersi, S.; Meschi, E.; Milenovic, P.; Moortgat, F.; Mulders, M.; Neugebauer, H.; Ngadiuba, J.; Orfanelli, S.; Orsini, L.; Pape, L.; Perez, E.; Peruzzi, M.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Rabady, D.; Racz, A.; Reis, T.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Seidel, M.; Selvaggi, M.; Sharma, A.; Silva, P.; Sphicas, P.; Stakia, A.; Steggemann, J.; Stoye, M.; Tosi, M.; Treille, D.; Triossi, A.; Tsirou, A.; Veckalns, V.; Verweij, M.; Zeuner, W. D.; Bertl, W.; Caminada, L.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Rohe, T.; Wiederkehr, S. A.; Backhaus, M.; Bäni, L.; Berger, P.; Bianchini, L.; Casal, B.; Dissertori, G.; Dittmar, M.; Donegà, M.; Dorfer, C.; Grab, C.; Heidegger, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Klijnsma, T.; Lustermann, W.; Mangano, B.; Marionneau, M.; Meinhard, M. T.; Meister, D.; Micheli, F.; Musella, P.; Nessi-Tedaldi, F.; Pandolfi, F.; Pata, J.; Pauss, F.; Perrin, G.; Perrozzi, L.; Quittnat, M.; Reichmann, M.; Sanz Becerra, D. A.; Schönenberger, M.; Shchutska, L.; Tavolaro, V. R.; Theofilatos, K.; Vesterbacka Olsson, M. L.; Wallny, R.; Zhu, D. H.; Aarrestad, T. K.; Amsler, C.; Canelli, M. F.; De Cosa, A.; Del Burgo, R.; Donato, S.; Galloni, C.; Hreus, T.; Kilminster, B.; Pinna, D.; Rauco, G.; Robmann, P.; Salerno, D.; Schweiger, K.; Seitz, C.; Takahashi, Y.; Zucchetta, A.; Candelise, V.; Chang, Y. H.; Cheng, K. y.; Doan, T. H.; Jain, Sh.; Khurana, R.; Kuo, C. M.; Lin, W.; Pozdnyakov, A.; Yu, S. S.; Kumar, Arun; Chang, P.; Chao, Y.; Chen, K. F.; Chen, P. H.; Fiori, F.; Hou, W.-S.; Hsiung, Y.; Liu, Y. F.; Lu, R.-S.; Paganis, E.; Psallidas, A.; Steen, A.; Tsai, J. f.; Asavapibhop, B.; Kovitanggoon, K.; Singh, G.; Srimanobhas, N.; Bat, A.; Boran, F.; Cerci, S.; Damarseckin, S.; Demiroglu, Z. S.; Dozen, C.; Dumanoglu, I.; Girgis, S.; Gokbulut, G.; Guler, Y.; Hos, I.; Kangal, E. E.; Kara, O.; Kayis Topaksu, A.; Kiminsu, U.; Oglakci, M.; Onengut, G.; Ozdemir, K.; Sunar Cerci, D.; Tali, B.; Tok, U. G.; Turkcapar, S.; Zorbakir, I. S.; Zorbilmez, C.; Karapinar, G.; Ocalan, K.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Kaya, M.; Kaya, O.; Tekten, S.; Yetkin, E. A.; Agaras, M. N.; Atay, S.; Cakir, A.; Cankocak, K.; Komurcu, Y.; Grynyov, B.; Levchuk, L.; Ball, F.; Beck, L.; Brooke, J. J.; Burns, D.; Clement, E.; Cussans, D.; Davignon, O.; Flacher, H.; Goldstein, J.; Heath, G. P.; Heath, H. F.; Kreczko, L.; Newbold, D. M.; Paramesvaran, S.; Sakuma, T.; Seif El Nasr-storey, S.; Smith, D.; Smith, V. J.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Calligaris, L.; Cieri, D.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Linacre, J.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Williams, T.; Womersley, W. J.; Auzinger, G.; Bainbridge, R.; Borg, J.; Breeze, S.; Buchmuller, O.; Bundock, A.; Casasso, S.; Citron, M.; Colling, D.; Corpe, L.; Dauncey, P.; Davies, G.; De Wit, A.; Della Negra, M.; Di Maria, R.; Elwood, A.; Haddad, Y.; Hall, G.; Iles, G.; James, T.; Lane, R.; Laner, C.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mastrolorenzo, L.; Matsushita, T.; Nash, J.; Nikitenko, A.; Palladino, V.; Pesaresi, M.; Raymond, D. M.; Richards, A.; Rose, A.; Scott, E.; Seez, C.; Shtipliyski, A.; Summers, S.; Tapper, A.; Uchida, K.; Vazquez Acosta, M.; Virdee, T.; Wardle, N.; Winterbottom, D.; Wright, J.; Zenz, S. C.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Reid, I. D.; Teodorescu, L.; Zahid, S.; Borzou, A.; Call, K.; Dittmann, J.; Hatakeyama, K.; Liu, H.; Pastika, N.; Smith, C.; Bartek, R.; Dominguez, A.; Buccilli, A.; Cooper, S. I.; Henderson, C.; Rumerio, P.; West, C.; Arcaro, D.; Avetisyan, A.; Bose, T.; Gastler, D.; Rankin, D.; Richardson, C.; Rohlf, J.; Sulak, L.; Zou, D.; Benelli, G.; Cutts, D.; Garabedian, A.; Hadley, M.; Hakala, J.; Heintz, U.; Hogan, J. M.; Kwok, K. H. M.; Laird, E.; Landsberg, G.; Lee, J.; Mao, Z.; Narain, M.; Pazzini, J.; Piperov, S.; Sagir, S.; Syarif, R.; Yu, D.; Band, R.; Brainerd, C.; Burns, D.; Calderon De La Barca Sanchez, M.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Flores, C.; Funk, G.; Ko, W.; Lander, R.; Mclean, C.; Mulhearn, M.; Pellett, D.; Pilot, J.; Shalhout, S.; Shi, M.; Smith, J.; Stolp, D.; Tos, K.; Tripathi, M.; Wang, Z.; Bachtis, M.; Bravo, C.; Cousins, R.; Dasgupta, A.; Florent, A.; Hauser, J.; Ignatenko, M.; Mccoll, N.; Regnard, S.; Saltzberg, D.; Schnaible, C.; Valuev, V.; Bouvier, E.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Ghiasi Shirazi, S. M. A.; Hanson, G.; Heilman, J.; Karapostoli, G.; Kennedy, E.; Lacroix, F.; Long, O. R.; Olmedo Negrete, M.; Paneva, M. I.; Si, W.; Wang, L.; Wei, H.; Wimpenny, S.; Yates, B. R.; Branson, J. G.; Cittolin, S.; Derdzinski, M.; Gerosa, R.; Gilbert, D.; Hashemi, B.; Holzner, A.; Klein, D.; Kole, G.; Krutelyov, V.; Letts, J.; Masciovecchio, M.; Olivito, D.; Padhi, S.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Tadel, M.; Vartak, A.; Wasserbaech, S.; Wood, J.; Würthwein, F.; Yagil, A.; Zevi Della Porta, G.; Amin, N.; Bhandari, R.; Bradmiller-Feld, J.; Campagnari, C.; Dishaw, A.; Dutta, V.; Franco Sevilla, M.; Gouskos, L.; Heller, R.; Incandela, J.; Ovcharova, A.; Qu, H.; Richman, J.; Stuart, D.; Suarez, I.; Yoo, J.; Anderson, D.; Bornheim, A.; Bunn, J.; Lawhorn, J. M.; Newman, H. B.; Nguyen, T. Q.; Pena, C.; Spiropulu, M.; Vlimant, J. R.; Wilkinson, R.; Xie, S.; Zhang, Z.; Zhu, R. Y.; Andrews, M. B.; Ferguson, T.; Mudholkar, T.; Paulini, M.; Russ, J.; Sun, M.; Vogel, H.; Vorobiev, I.; Weinberg, M.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; Mcdermott, K.; Mirman, N.; Patterson, J. R.; Quach, D.; Rinkevicius, A.; Ryd, A.; Skinnari, L.; Soffi, L.; Tan, S. M.; Tao, Z.; Thom, J.; Tucker, J.; Wittich, P.; Zientek, M.; Abdullin, S.; Albrow, M.; Alyari, M.; Apollinari, G.; Apresyan, A.; Apyan, A.; Banerjee, S.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Bolla, G.; Burkett, K.; Butler, J. N.; Canepa, A.; Cerati, G. B.; Cheung, H. W. K.; Chlebana, F.; Cremonesi, M.; Duarte, J.; Elvira, V. D.; Freeman, J.; Gecse, Z.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hanlon, J.; Harris, R. M.; Hasegawa, S.; Hirschauer, J.; Hu, Z.; Jayatilaka, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Klima, B.; Kreis, B.; Lammel, S.; Lincoln, D.; Lipton, R.; Liu, M.; Liu, T.; Lopes De Sá, R.; Lykken, J.; Maeshima, K.; Magini, N.; Marraffino, J. M.; Mason, D.; McBride, P.; Merkel, P.; Mrenna, S.; Nahn, S.; O'Dell, V.; Pedro, K.; Prokofyev, O.; Rakness, G.; Ristori, L.; Schneider, B.; Sexton-Kennedy, E.; Soha, A.; Spalding, W. J.; Spiegel, L.; Stoynev, S.; Strait, J.; Strobbe, N.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vernieri, C.; Verzocchi, M.; Vidal, R.; Wang, M.; Weber, H. A.; Whitbeck, A.; Wu, W.; Acosta, D.; Avery, P.; Bortignon, P.; Bourilkov, D.; Brinkerhoff, A.; Carnes, A.; Carver, M.; Curry, D.; Field, R. D.; Furic, I. K.; Gleyzer, S. V.; Joshi, B. M.; Konigsberg, J.; Korytov, A.; Kotov, K.; Ma, P.; Matchev, K.; Mei, H.; Mitselmakher, G.; Shi, K.; Sperka, D.; Terentyev, N.; Thomas, L.; Wang, J.; Wang, S.; Yelton, J.; Joshi, Y. R.; Linn, S.; Markowitz, P.; Rodriguez, J. L.; Ackert, A.; Adams, T.; Askew, A.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Kolberg, T.; Martinez, G.; Perry, T.; Prosper, H.; Saha, A.; Santra, A.; Sharma, V.; Yohay, R.; Baarmand, M. M.; Bhopatkar, V.; Colafranceschi, S.; Hohlmann, M.; Noonan, D.; Roy, T.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Berry, D.; Betts, R. R.; Cavanaugh, R.; Chen, X.; Evdokimov, O.; Gerber, C. E.; Hangal, D. A.; Hofman, D. J.; Jung, K.; Kamin, J.; Sandoval Gonzalez, I. D.; Tonjes, M. B.; Trauger, H.; Varelas, N.; Wang, H.; Wu, Z.; Zhang, J.; Bilki, B.; Clarida, W.; Dilsiz, K.; Durgut, S.; Gandrajula, R. P.; Haytmyradov, M.; Khristenko, V.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Snyder, C.; Tiras, E.; Wetzel, J.; Yi, K.; Blumenfeld, B.; Cocoros, A.; Eminizer, N.; Fehling, D.; Feng, L.; Gritsan, A. V.; Maksimovic, P.; Roskes, J.; Sarica, U.; Swartz, M.; Xiao, M.; You, C.; Al-bataineh, A.; Baringer, P.; Bean, A.; Boren, S.; Bowen, J.; Castle, J.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Mcbrayer, W.; Murray, M.; Rogan, C.; Royon, C.; Sanders, S.; Schmitz, E.; Tapia Takaki, J. D.; Wang, Q.; Ivanov, A.; Kaadze, K.; Maravin, Y.; Mohammadi, A.; Saini, L. K.; Skhirtladze, N.; Rebassoo, F.; Wright, D.; Baden, A.; Baron, O.; Belloni, A.; Eno, S. C.; Feng, Y.; Ferraioli, C.; Hadley, N. J.; Jabeen, S.; Jeng, G. Y.; Kellogg, R. G.; Kunkle, J.; Mignerey, A. C.; Ricci-Tam, F.; Shin, Y. H.; Skuja, A.; Tonwar, S. C.; Abercrombie, D.; Allen, B.; Azzolini, V.; Barbieri, R.; Baty, A.; Bauer, G.; Bi, R.; Brandt, S.; Busza, W.; Cali, I. A.; D'Alfonso, M.; Demiragli, Z.; Gomez Ceballos, G.; Goncharov, M.; Hsu, D.; Hu, M.; Iiyama, Y.; Innocenti, G. M.; Klute, M.; Kovalskyi, D.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Maier, B.; Marini, A. C.; Mcginn, C.; Mironov, C.; Narayanan, S.; Niu, X.; Paus, C.; Roland, C.; Roland, G.; Salfeld-Nebgen, J.; Stephans, G. S. F.; Sumorok, K.; Tatar, K.; Velicanu, D.; Wang, J.; Wang, T. W.; Wyslouch, B.; Benvenuti, A. C.; Chatterjee, R. M.; Evans, A.; Hansen, P.; Hiltbrand, J.; Kalafut, S.; Kubota, Y.; Lesko, Z.; Mans, J.; Nourbakhsh, S.; Ruckstuhl, N.; Rusack, R.; Turkewitz, J.; Wadud, M. A.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Golf, F.; Gonzalez Suarez, R.; Kamalieddin, R.; Kravchenko, I.; Monroy, J.; Siado, J. E.; Snow, G. R.; Stieger, B.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alverson, G.; Barberis, E.; Freer, C.; Hortiangtham, A.; Massironi, A.; Morse, D. M.; Orimoto, T.; Teixeira De Lima, R.; Trocino, D.; Wamorkar, T.; Wang, B.; Wisecarver, A.; Wood, D.; Bhattacharya, S.; Charaf, O.; Hahn, K. A.; Mucia, N.; Odell, N.; Schmitt, M. H.; Sung, K.; Trovato, M.; Velasco, M.; Bucci, R.; Dev, N.; Hildreth, M.; Hurtado Anampa, K.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Li, W.; Loukas, N.; Marinelli, N.; Meng, F.; Mueller, C.; Musienko, Y.; Planer, M.; Reinsvold, A.; Ruchti, R.; Siddireddy, P.; Smith, G.; Taroni, S.; Wayne, M.; Wightman, A.; Wolf, M.; Woodard, A.; Alimena, J.; Antonelli, L.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Francis, B.; Hart, A.; Hill, C.; Ji, W.; Ling, T. Y.; Liu, B.; Luo, W.; Winer, B. L.; Wulsin, H. W.; Cooperstein, S.; Driga, O.; Elmer, P.; Hardenbrook, J.; Hebda, P.; Higginbotham, S.; Kalogeropoulos, A.; Lange, D.; Luo, J.; Marlow, D.; Mei, K.; Ojalvo, I.; Olsen, J.; Palmer, C.; Piroué, P.; Stickland, D.; Tully, C.; Malik, S.; Norberg, S.; Barker, A.; Barnes, V. E.; Das, S.; Folgueras, S.; Gutay, L.; Jones, M.; Jung, A. W.; Khatiwada, A.; Miller, D. H.; Neumeister, N.; Peng, C. C.; Qiu, H.; Schulte, J. F.; Sun, J.; Wang, F.; Xiao, R.; Xie, W.; Cheng, T.; Parashar, N.; Stupak, J.; Chen, Z.; Ecklund, K. M.; Freed, S.; Geurts, F. J. M.; Guilbaud, M.; Kilpatrick, M.; Li, W.; Michlin, B.; Padley, B. P.; Roberts, J.; Rorie, J.; Shi, W.; Tu, Z.; Zabel, J.; Zhang, A.; Bodek, A.; de Barbaro, P.; Demina, R.; Duh, Y. t.; Ferbel, T.; Galanti, M.; Garcia-Bellido, A.; Han, J.; Hindrichs, O.; Khukhunaishvili, A.; Lo, K. H.; Tan, P.; Verzetti, M.; Ciesielski, R.; Goulianos, K.; Mesropian, C.; Agapitos, A.; Chou, J. P.; Gershtein, Y.; Gómez Espinosa, T. A.; Halkiadakis, E.; Heindl, M.; Hughes, E.; Kaplan, S.; Kunnawalkam Elayavalli, R.; Kyriacou, S.; Lath, A.; Montalvo, R.; Nash, K.; Osherson, M.; Saka, H.; Salur, S.; Schnetzer, S.; Sheffield, D.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Delannoy, A. G.; Heideman, J.; Riley, G.; Rose, K.; Spanier, S.; Thapa, K.; Bouhali, O.; Castaneda Hernandez, A.; Celik, A.; Dalchenko, M.; De Mattia, M.; Delgado, A.; Dildick, S.; Eusebi, R.; Gilmore, J.; Huang, T.; Kamon, T.; Mueller, R.; Pakhotin, Y.; Patel, R.; Perloff, A.; Perniè, L.; Rathjens, D.; Safonov, A.; Tatarinov, A.; Ulmer, K. A.; Akchurin, N.; Damgov, J.; De Guio, F.; Dudero, P. R.; Faulkner, J.; Gurpinar, E.; Kunori, S.; Lamichhane, K.; Lee, S. W.; Libeiro, T.; Mengke, T.; Muthumuni, S.; Peltola, T.; Undleeb, S.; Volobouev, I.; Wang, Z.; Greene, S.; Gurrola, A.; Janjam, R.; Johns, W.; Maguire, C.; Melo, A.; Ni, H.; Padeken, K.; Sheldon, P.; Tuo, S.; Velkovska, J.; Xu, Q.; Arenton, M. W.; Barria, P.; Cox, B.; Hirosky, R.; Joyce, M.; Ledovskoy, A.; Li, H.; Neu, C.; Sinthuprasith, T.; Wang, Y.; Wolfe, E.; Xia, F.; Harr, R.; Karchin, P. E.; Poudyal, N.; Sturdy, J.; Thapa, P.; Zaleski, S.; Brodski, M.; Buchanan, J.; Caillol, C.; Carlsmith, D.; Dasu, S.; Dodd, L.; Duric, S.; Gomber, B.; Grothe, M.; Herndon, M.; Hervé, A.; Hussain, U.; Klabbers, P.; Lanaro, A.; Levine, A.; Long, K.; Loveless, R.; Ruggles, T.; Savin, A.; Smith, N.; Smith, W. H.; Taylor, D.; Woods, N.

2018-04-01

This paper presents combinations of inclusive and differential measurements of the charge asymmetry ( A C) in top quark pair (t\\overline{t}) events with a lepton+jets signature by the ATLAS and CMS Collaborations, using data from LHC proton-proton collisions at centre-of-mass energies of 7 and 8 TeV. The data correspond to integrated luminosities of about 5 and 20 fb-1 for each experiment, respectively. The resulting combined LHC measurements of the inclusive charge asymmetry are A C CHC7 = 0.005 ± 0.007 (stat) ± 0.006(syst) at 7 TeV and A C CHC8 = 0.0055 ± 0.0023 (stat) ± 0.0025 (syst) at 8 TeV. These values, as well as the combination of A C measurements as a function of the invariant mass of the t\\overline{t} system at 8 TeV, are consistent with the respective standard model predictions. [Figure not available: see fulltext.

Hypoxia-mediated upregulation of MCT1 expression supports the glycolytic phenotype of glioblastomas

PubMed Central

Miranda-Gonçalves, Vera; Granja, Sara; Martinho, Olga; Honavar, Mrinalini; Pojo, Marta; Costa, Bruno M.; Pires, Manuel M.; Pinheiro, Célia; Cordeiro, Michelle; Bebiano, Gil; Costa, Paulo; Reis, Rui M.; Baltazar, Fátima

2016-01-01

Background Glioblastomas (GBM) present a high cellular heterogeneity with conspicuous necrotic regions associated with hypoxia, which is related to tumor aggressiveness. GBM tumors exhibit high glycolytic metabolism with increased lactate production that is extruded to the tumor microenvironment through monocarboxylate transporters (MCTs). While hypoxia-mediated regulation of MCT4 has been characterized, the role of MCT1 is still controversial. Thus, we aimed to understand the role of hypoxia in the regulation of MCT expression and function in GBM, MCT1 in particular. Methods Expression of hypoxia- and glycolytic-related markers, as well as MCT1 and MCT4 isoforms was assessed in in vitro and in vivo orthotopic glioma models, and also in human GBM tissues by immunofluorescence/immunohistochemistry and Western blot. Following MCT1 inhibition, either pharmacologically with CHC (α-cyano-4-hydroxynnamic acid) or genetically with siRNAs, we assessed GBM cell viability, proliferation, metabolism, migration and invasion, under normoxia and hypoxia conditions. Results Hypoxia induced an increase in MCT1 plasma membrane expression in glioma cells, both in in vitro and in vivo models. Additionally, treatment with CHC and downregulation of MCT1 in glioma cells decreased lactate production, cell proliferation and invasion under hypoxia. Moreover, in the in vivo orthotopic model and in human GBM tissues, there was extensive co-expression of MCT1, but not MCT4, with the GBM hypoxia marker CAIX. Conclusion Hypoxia-induced MCT1 supports GBM glycolytic phenotype, being responsible for lactate efflux and an important mediator of cell survival and aggressiveness. Therefore, MCT1 constitutes a promising therapeutic target in GBM. PMID:27331625

Legal Aspects of Public Lending Right.

ERIC Educational Resources Information Center

Hyatt, Dennis

1981-01-01

Discusses national differences, natural justice, and protection of tangible expressions in the copyright law and tactical and practical considerations regarding the legal aspects of author compensation for library lending. Special problems for public lending rights legislation (PLR) in the U.S. are cited. Eighteen references are provided. (CHC)

A learning collaborative of CMHCs and CHCs to support integration of behavioral health and general medical care.

PubMed

Vannoy, Steven D; Mauer, Barbara; Kern, John; Girn, Kamaljeet; Ingoglia, Charles; Campbell, Jeannie; Galbreath, Laura; Unützer, Jürgen

2011-07-01

Integration of general medical and mental health services is a growing priority for safety-net providers. The authors describe a project that established a one-year learning collaborative focused on integration of services between community health centers (CHCs) and community mental health centers (CMHCs). Specific targets were treatment for general medical and psychiatric symptoms related to depression, bipolar disorder, alcohol use disorders, and metabolic syndrome. This observational study used mixed methods. Quantitative measures included 15 patient-level health indicators, practice self-assessment of resources and support for chronic disease self-management, and participant satisfaction. Sixteen CHC-CMHC pairs were selected for the learning collaborative series. One pair dropped out because of personnel turnover. All teams increased capacity on one or more patient health indicators. CHCs scored higher than CMHCs on support for chronic disease self-management. Participation in the learning collaborative increased self-assessment scores for CHCs and CMHCs. Participant satisfaction was high. Observations by faculty indicate that quality improvement challenges included tracking patient-level outcomes, workforce issues, and cross-agency communication. Even though numerous systemic barriers were encountered, the findings support existing literature indicating that the learning collaborative is a viable quality improvement approach for enhancing integration of general medical and mental health services between CHCs and CMHCs. Real-world implementation of evidence-based guidelines presents challenges often absent in research. Technical resources and support, a stable workforce with adequate training, and adequate opportunities for collaborator communications are particular challenges for integrating behavioral and general medical services across CHCs and CMHCs.

Burden of common mental disorders in a community health centre sample.

PubMed

Ahmad, Farah; Shakya, Yogendra; Ginsburg, Liane; Lou, Wendy; Ng, Peggy T; Rashid, Meb; Ferrari, Manuela; Ledwos, Cliff; McKenzie, Kwame

2016-12-01

To examine the rates of common mental disorders (CMDs) such as depression, anxiety, posttraumatic stress disorder (PTSD), and alcohol use in an urban community health care centre (CHC) serving vulnerable immigrant and ethnoracial communities in order to improve knowledge on the rates of CMDs specific to these groups accessing primary care settings. English or Spanish, self-administered, tablet-based survey known as the Interactive Computer-Assisted Client Assessment Survey (iCCAS). Access Alliance Multicultural Health and Community Services CHC in Toronto, Ont. Adult patients waiting to see a clinician. The iCCAS screened for depression (using the PHQ-9 [Patient Health Questionnaire]), anxiety (using the GAD-7 [Generalized Anxiety Disorder 7-item scale]), PTSD (using the PC-PTSD [Primary Care PTSD Screen]), and alcohol dependency (using the CAGE questionnaire); those with an existing diagnosis and active treatment for one of these conditions were not asked to complete that condition-specific screening scale. An exit survey measured demographic characteristics and relevant indicators. A response rate of 78.6% was achieved. The iCCAS survey was completed by 75 patients (26 men and 49 women) with a mean age of 36.5 years. Almost all were first-generation immigrants: 32.0% originated from Latin America, 28.0% from South Asia, and 17.3% from Africa or the Middle East. Major depression was found among 44.0% of participants (11 with diagnosis and treatment, 22 with a score of 10 or greater on the PHQ-9). Generalized anxiety disorder was present in 26.7% of participants (7 with diagnosis and treatment, 13 with a score of 10 or greater on the GAD-7 scale). Posttraumatic stress disorder was detected in 37.3% of participants (7 with diagnosis and treatment, 21 with a score of 3 or greater on the PC-PTSD tool). Alcohol dependency was found among 10.7% of participants (1 with diagnosis and treatment, 7 with a score of 2 or greater on the CAGE questionnaire). The high rates of probable depression, generalized anxiety, and PTSD that were found in the studied population suggest a need for systematic assessment of CMDs in CHCs, as well as training and resources to increase readiness to handle identified cases. Copyright© the College of Family Physicians of Canada.

School-Based Clinics That Work.

ERIC Educational Resources Information Center

Public Health Service (DHHS), Rockville, MD.

This paper describes a small set of successful school-based clinics (SBCs) that provide primary health care services for the underserved and identifies factors contributing to their success. Six sites were selected on the basis of three general criteria: (1) direct involvement between the SBC and a federally-funded community health center (CHC);…

78 FR 36794 - Regular Board of Directors Meeting; Sunshine Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

..., Washington, DC 20002. STATUS: Open. CONTACT PERSON FOR MORE INFORMATION: Erica Hall, Assistant Corporate... Session IV. Board Elections & Appointments V. CHC/NC Grants VI. Financial Report VII. DC Office Move VIII.... Adjournment Erica Hall, Assistant Corporate Secretary. [FR Doc. 2013-14757 Filed 6-17-13; 4:15 pm] BILLING...

Academic Expectations as Sources of Stress in Asian Students

ERIC Educational Resources Information Center

Tan, Joyce Beiyu; Yates, Shirley

2011-01-01

Education is highly valued in Confucian Heritage Culture (CHC) countries such as China, Taiwan, Singapore, Hong Kong, Japan and Korea but the expectations of parents, teachers and students themselves to excel academically can also be a source of intense stress for many students. The "Academic Expectations Stress Inventory" (AESI),…

Deflating the "Confucian Heritage Culture" Thesis in Intercultural and Academic English Education

ERIC Educational Resources Information Center

O'Dwyer, Shaun

2017-01-01

This paper develops an interdisciplinary critical perspective on the concept of "Confucian Heritage Cultures" (CHC), used in intercultural and English language teaching theory to explain the supposed culturally distinct learning habits, expectations and schemas many Asian students bring to academic classrooms in English-speaking…

Globes: A Librarian's Guide to Selection and Purchase.

ERIC Educational Resources Information Center

Coombs, James

1981-01-01

Provides a guide for librarians to use in selecting globes by discussing how globes are made, types of globes, special and extraterrestrial globes, selecting criteria, and comparing such features as aesthetic appeal, readability, and currency of political information. A list of globe manufacturers and a selected bibliography are provided. (CHC)

Cardiovascular care guideline implementation in community health centers in Oregon: a mixed-methods analysis of real-world barriers and challenges.

PubMed

Gold, Rachel; Bunce, Arwen; Cowburn, Stuart; Davis, James V; Hollombe, Celine; Nelson, Christine A; Puro, Jon; Muench, John; Hill, Christian; Jaworski, Victoria; Mercer, MaryBeth; Howard, Colleen; Perrin, Nancy; DeVoe, Jennifer

2017-04-05

Spreading effective, guideline-based cardioprotective care quality improvement strategies between healthcare settings could yield great benefits, particularly in under-resourced contexts. Understanding the diverse factors facilitating or impeding such guideline implementation could improve cardiovascular care quality and outcomes for vulnerable patients. We sought to identify multi-level factors affecting uptake of cardioprotective care guidelines in community health centers (CHCs), within a successful trial of cross-setting implementation of an effective intervention. Quantitative analyses used multivariable logistic regression to examine in-person patient encounters at 10 CHCs from June 2011-May 2014. At these encounters, a point-of-care alert flagged adults with diabetes who were clinically indicated for, but not currently prescribed, cardioprotective medications. The main outcome measure was the rate of relevant prescriptions issued within two days of encounters. Qualitative analyses focused on CHC providers and staff, and, guided by the constant comparative method, were used to enhance understanding of the factors that influenced this prescribing. Recommended prescribing occurred at 13-16% of encounters with patients who were indicated for such prescribing. The odds of this prescribing were higher when the patient was male, had HbA1c ≥7, was previously prescribed a similar medication, gave diabetes as the chief complaint, saw a mid-level practitioner, or saw their primary care provider. The odds were lower when the patient was insured, had ≥1 clinic visits in the past year, had kidney disease, or was prescribed certain other medications. Additional factors were associated with prescribing of each medication class. Qualitative results both supported and challenged the quantitative findings, illustrating important tensions involved in guideline-based prescribing. Clinic staff stressed the importance of the provider-patient relationship in guiding prescribing decisions in the face of competing priorities and care needs, and the impact of rapidly changing guidelines. Diverse factors associated with guideline-concordant prescribing illuminate the complexity of delivering evidence-based care in CHCs. We present possible strategies for addressing barriers to guideline-based prescribing. This trial was registered retrospectively. Currently Controlled Trials NCT02299791 . Retrospectively registered 10 November 2014.

Efficacy of HCV treatment in Poland at the turn of the interferon era – the EpiTer study

PubMed Central

Pogorzelska, Joanna; Berak, Hanna; Horban, Andrzej; Orłowska, Iwona; Simon, Krzysztof; Tuchendler, Ewelina; Madej, Grzegorz; Piekarska, Anna; Jabłkowski, Maciej; Deroń, Zbigniew; Mazur, Włodzimierz; Kaczmarczyk, Marcin; Janczewska, Ewa; Pisula, Arkadiusz; Smykał, Jacek; Nowak, Krzysztof; Matukiewicz, Marek; Halota, Waldemar; Wernik, Joanna; Sikorska, Katarzyna; Mozer-Lisewska, Iwona; Rozpłochowski, Błażej; Garlicki, Aleksander; Tomasiewicz, Krzysztof; Krzowska-Firych, Joanna; Baka-Ćwierz, Barbara; Kryczka, Wiesław; Zarębska-Michaluk, Dorota; Olszok, Iwona; Boroń-Kaczmarska, Anna; Sobala-Szczygieł, Barbara; Szlauer, Bronisława; Korcz-Ondrzejek, Bogumiła; Sieklucki, Jerzy; Pleśniak, Robert; Ruszała, Agata; Postawa-Kłosińska, Barbara; Citko, Jolanta; Lachowicz-Wawrzyniak, Anna; Musialik, Joanna; Jezierska, Edyta; Dobracki, Witold; Dobracka, Beata; Hałubiec, Jan; Krygier, Rafał; Strokowska, Anna; Chomczyk, Wojciech; Witczak-Malinowska, Krystyna

2016-01-01

The aim of the study Was to analyze the efficacy achieved with regimens available for chronic hepatitis C (CHC) in Poland between 2013 and 2016. Material and methods Data were collected from 29 centers and included 6786 patients with available sustained virologic response (SVR) data between 1 January 2013 and 31 March 2016. Results The sustained virologic response rate for genotypes (G) 1a, 1b, 2, 3 and 4 was 62%, 56%, 92%, 67% and 56% respectively; 71% patients (n = 4832) were treated with pegylated interferon α (Peg-IFNα) and ribavirin (RBV), with SVR rates of 58%, 49%, 92%, 67% and 55% respectively. The sustained virologic response among 5646 G1 infected patients was the lowest with natural interferon α (7%, n = 70) or PegIFN (50%, n = 3779) with RBV, and improved in those receiving triple regimens of Peg-IFN + RBV combined with boceprevir (47%, n = 485), telaprevir (64%, n = 805), simeprevir (73%, n = 132) or sofosbuvir (70%, n = 23). The sustained virologic response with interferon-free regimens of sofosbuvir and RBV (n = 7), sofosbuvir and simeprevir (n = 53), and ledipasvir and sofosbuvir (n = 64) achieved 86%, 89% and 94% respectively. The highest SVR of 98% was observed with ombitasvir/paritaprevir combined with dasabuvir (n = 227). Patients infected with G3 (n = 896) and G4 (n = 220) received mostly Peg-IFN + RBV with SVR of 67% and 56% respectively. Interferon-free regimens were administered in 18 G3/G4 patients and all achieved an SVR. Sofosbuvir combined with Peg-IFN and RBV was administered to 33 patients with an SVR rate of 94%, and a similar rate was achieved among 13 G2 patients treated with interferon and RBV. Conclusions We observed significant differences in efficacy of HCV regimens available in Poland at the turn of the interferon era. The data will be useful as a comparison for therapeutic options expected in the next few years. PMID:28856278

An inductance Fourier decomposition-based current-hysteresis control strategy for switched reluctance motors

NASA Astrophysics Data System (ADS)

Hua, Wei; Qi, Ji; Jia, Meng

2017-05-01

Switched reluctance machines (SRMs) have attracted extensive attentions due to the inherent advantages, including simple and robust structure, low cost, excellent fault-tolerance and wide speed range, etc. However, one of the bottlenecks limiting the SRMs for further applications is its unfavorable torque ripple, and consequently noise and vibration due to the unique doubly-salient structure and pulse-current-based power supply method. In this paper, an inductance Fourier decomposition-based current-hysteresis-control (IFD-CHC) strategy is proposed to reduce torque ripple of SRMs. After obtaining a nonlinear inductance-current-position model based Fourier decomposition, reference currents can be calculated by reference torque and the derived inductance model. Both the simulations and experimental results confirm the effectiveness of the proposed strategy.

Auto-antibodies and Autoimmune Disease during Treatment of Children with Chronic Hepatitis C

PubMed Central

Molleston, Jean P.; Mellman, William; Narkewicz, Michael R.; Balistreri, William F.; Gonzalez-Peralta, Regino P.; Jonas, Maureen M.; Lobritto, Steven J.; Mohan, Parvathi; Murray, Karen F.; Njoku, Dolores; Rosenthal, Philip; Barton, Bruce A.; Talor, Monica V.; Cheng, Irene; Schwarz, Kathleen B.; Haber, Barbara A.

2012-01-01

Objectives Auto-antibodies were studied in a well-characterized cohort of children with chronic hepatitis C (CHC) during treatment with PEG-IFN and ribavirin to assess the relationship to treatment and development of autoimmune disease. Methods 114 children (5–17 years), previously screened for the presence of high titer autoantibodies, were randomized to Peg-IFN with or without ribavirin. Anti-nuclear (ANA), anti-liver-kidney-microsomal (LKM), anti-thyroglobulin (TG), anti-thyroid peroxidase (TPO), insulin (IA2), anti-glutamic acid decarboxylase (GAD) antibodies were measured after trial completion using frozen sera. Results At baseline,19% had auto-antibodies: ANA (8%), LKM (4%), and GAD (4%). At 24 and 72 weeks (24 weeks after treatment completion), 23% and 26% had auto-antibodies (p=0.50, 0.48 compared to baseline). One child developed diabetes and two hypothyroidism during treatment; none developed autoimmune hepatitis. At 24 weeks, the incidence of flu-like symptoms, gastrointestinal symptoms, and headaches were 42%, 8% and 19% in those with auto-antibodies vs. 52%, 17%, and 26% in those without (p=0.18, 0.36, and 0.20, respectively). In children with negative HCV PCR at 24 weeks, there was no difference in the rate of early virologic response /sustained virologic response respectively in those with auto-antibodies 76%/69%, vs 58%/65% in those without (p=0.48). Conclusions Despite screening, we found autoantibodies commonly at baseline, during treatment for CHC and after. The presence of antibodies did not correlate with viral response, side effects, or autoimmune hepatitis. Neither screening nor archived samples assayed for thyroid and diabetes-related antibodies identified the 3 subjects who developed overt autoimmune disease, diabetes (1) and hypothyroidism (2). PMID:23439301

Examining the integrity of measurement of cognitive abilities in the prediction of achievement: Comparisons and contrasts across variables from higher-order and bifactor models.

PubMed

Benson, Nicholas F; Kranzler, John H; Floyd, Randy G

2016-10-01

Prior research examining cognitive ability and academic achievement relations have been based on different theoretical models, have employed both latent variables as well as observed variables, and have used a variety of analytic methods. Not surprisingly, results have been inconsistent across studies. The aims of this study were to (a) examine how relations between psychometric g, Cattell-Horn-Carroll (CHC) broad abilities, and academic achievement differ across higher-order and bifactor models; (b) examine how well various types of observed scores corresponded with latent variables; and (c) compare two types of observed scores (i.e., refined and non-refined factor scores) as predictors of academic achievement. Results suggest that cognitive-achievement relations vary across theoretical models and that both types of factor scores tend to correspond well with the models on which they are based. However, orthogonal refined factor scores (derived from a bifactor model) have the advantage of controlling for multicollinearity arising from the measurement of psychometric g across all measures of cognitive abilities. Results indicate that the refined factor scores provide more precise representations of their targeted constructs than non-refined factor scores and maintain close correspondence with the cognitive-achievement relations observed for latent variables. Thus, we argue that orthogonal refined factor scores provide more accurate representations of the relations between CHC broad abilities and achievement outcomes than non-refined scores do. Further, the use of refined factor scores addresses calls for the application of scores based on latent variable models. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

The occupational safety of health professionals working at community and family health centers.

PubMed

Ozturk, Havva; Babacan, Elif

2014-10-01

Healthcare professionals encounter many medical risks while providing healthcare services to individuals and the community. Thus, occupational safety studies are very important in health care organizations. They involve studies performed to establish legal, technical, and medical measures that must be taken to prevent employees from sustaining physical or mental damage because of work hazards. This study was conducted to determine if the occupational safety of health personnel at community and family health centers (CHC and FHC) has been achieved. The population of this cross-sectional study comprised 507 nurses, 199 physicians, and 237 other medical personnel working at a total of 18 family health centers (FHC) and community health centers (CHC) in Trabzon, Turkey. The sample consisted of a total of 418 nurses, 156 physicians, and 123 other medical personnel. Sampling method was not used, and the researchers tried to reach the whole population. Data were gathered with the Occupational Safety Scale (OSS) and a questionnaire regarding demographic characteristics and occupational safety. According to the evaluations of all the medical personnel, the mean ± SD of total score of the OSS was 3.57 ± 0.98; of the OSS's subscales, the mean ± SD of the health screening and registry systems was 2.76 ± 1.44, of occupational diseases and problems was 3.04 ± 1.3 and critical fields control was 3.12 ± 1.62. In addition, occupational safety was found more insufficient by nurses (F = 14.18; P < 0.001). All healthcare personnel, particularly nurses working in CHCs and FHCs found occupational safety to be insufficient as related to protective and supportive activities.

THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM

EPA Science Inventory

THE INFLUENCE OF ADVANCED AGE ON THE HEPATIC AND RENAL TOXICITY OF CHLOROFORM (CHC13). A McDonald, Y M Sey and J E Simmons. NHEERL, ORD, U.S. EPA, RTP, NC.
Disinfection, by chlorination or by ozonation followed by treatment with either chlorine or chloramine, of water containi...

The Impact of Microtechnology. A Case for Reassessing the Role of Computers in Learning.

ERIC Educational Resources Information Center

Alty, J. L.

1982-01-01

Reviews recent advances in microtechnology and describes the impact they will have on computer aided instruction and learning. It is suggested that distributed systems based on network technology will become widespread, and computer assisted guidance systems will be developed to assist new unskilled users. Eight references are given. (CHC)

The Encyclopedia of Library and Information Science: A Review of Reviews, a Summary Evaluation and a Suggested Salvage Operation.

ERIC Educational Resources Information Center

Meredith, Joseph C.

1980-01-01

Provides a critical evaluation of the not yet completed "Encyclopedia of Library and Information Science" with quotations from numerous reviews and presents a plan for the selection of articles and revision of this work in order to salvage the project. (CHC)

Test Review: Beal, A. L. (2011). "Insight Test of Cognitive Abilities." Markham, Ontario, Canadian Test Centre

ERIC Educational Resources Information Center

Colp, S. Mitchell; Nordstokke, David W.

2014-01-01

Published by the Canadian Test Centre (CTC), "Insight" represents a group-administered test of cognitive functioning that has been built entirely upon the Cattell-Horn-Carroll (CHC) theoretical framework. "Insight" is intended to be administered by educators and screen entire classrooms for students who present learning…

Differential Ability Scales-II Prediction of Reading Performance: Global Scores Are Not Enough

ERIC Educational Resources Information Center

Elliott, Colin D.; Hale, James B.; Fiorello, Catherine A.; Dorvil, Cledicianne; Moldovan, Jaime

2010-01-01

This study investigated the effects of broad cognitive abilities derived from the Cattell-Horn-Carroll (CHC) taxonomy, together with the effect of the general factor ("g"), on Wechsler Individual Achievement Test, Second Edition (WIAT-II) reading achievement. Structural equation modeling (SEM) and commonality analyses were applied to the…

Clinical Reasoning in the Assessment and Intervention Planning for a Reading Disability

ERIC Educational Resources Information Center

Sotelo-Dynega, Marlene

2017-01-01

The purpose of this article is to provide the reader with insight into the clinical reasoning process involved in the assessment and intervention planning for a child with a reading disability. A Cattell-Horn-Carroll (CHC) theoretical/neuropsychological approach shall serve as the foundational theoretical framework for this case study, and…

Identifying the Effects of Specific CHC Factors on College Students' Reading Comprehension

ERIC Educational Resources Information Center

Taub, Gordon E.; Benson, Nicholas

2013-01-01

Reading comprehension is an important skill for college academic success. Much of the research pertaining to reading in general, and reading comprehension specifically, focuses on the success of primary and secondary school-age students. The present study goes beyond previous research by extending such investigation to the reading comprehension of…

HEPATOTOXIC EVALUATION OF THE BINARY INTERACTIONS OF BROMODICHLOROMETHANE WITH CHLOROFORM, CHLORODIBROMOMETHANE AND BROMOFORM

EPA Science Inventory

HEPATOTOXIC EVALUATION OF THE BINARY INTERACTIONS OF BROMODICHLOROMETHANE (BDCM) WITH CHLOROFORM (CHC13), CHLORODIBROMOMETHANE (CDBM) AND BROMOFORM (CHBr3). Y M Se'', C Gennings2, A McDonald', L K Teuschler3, A Hamm2and J E Simmons .'NHEERL, ORD, U.S. EPA, RTP, NC; 2MCV, VCU, Ric...

How to Measure Critical Health Competences: Development and Validation of the Critical Health Competence Test (CHC Test)

ERIC Educational Resources Information Center

Steckelberg, Anke; Hulfenhaus, Christian; Kasper, Jurgen; Rost, Jurgen; Muhlhauser, Ingrid

2009-01-01

Consumers' autonomy regarding health increasingly requires competences to critically appraise health information. Critical health literacy refers to the concept of evidence-based medicine. Instruments to measure these competences in curriculum evaluation and surveys are lacking. We aimed to develop and validate an instrument to measure critical…

Confirmatory Factor Analysis of the KABC-II in Preschool Children

ERIC Educational Resources Information Center

Morgan, Kimberly E.; Rothlisberg, Barbara A.; McIntosh, David E.; Hunt, Madeline S.

2009-01-01

The present study assessed the Kaufman Assessment Battery for Children, Second Edition (KABC-II) in relation to the synthesized Cattell-Horn-Carroll (CHC) theory of intelligence with a preschool sample. Participants were 200 preschool children between four and five years of age. A confirmatory factor analysis (CFA) was conducted, and different…

International Student Participation in Higher Education: Changing the Focus From "International Students" to "Participation"

ERIC Educational Resources Information Center

Straker, John

2016-01-01

This is a conceptually oriented article which questions established notions concerning the framing of international students in Anglo-Western universities through a literature review. Focusing largely on students from Confucian Heritage Cultures (CHC), and resulting from concerns regarding their level of participation, the literature is considered…

Community Health Center Utilization Following the 2008 Medicaid Expansion in Oregon: Implications for the Affordable Care Act.

PubMed

Hatch, Brigit; Bailey, Steffani R; Cowburn, Stuart; Marino, Miguel; Angier, Heather; DeVoe, Jennifer E

2016-04-01

To assess longitudinal patterns of community health center (CHC) utilization and the effect of insurance discontinuity after Oregon's 2008 Medicaid expansion (the Oregon Experiment). We conducted a retrospective cohort study with electronic health records and Medicaid data. We divided individuals who gained Medicaid in the Oregon Experiment into those who maintained (n = 788) or lost (n = 944) insurance coverage. We compared these groups with continuously insured (n = 921) and continuously uninsured (n = 5416) reference groups for community health center utilization rates over a 36-month period. Both newly insured groups increased utilization in the first 6 months. After 6 months, use among those who maintained coverage stabilized at a level consistent with the continuously insured, whereas it returned to baseline for those who lost coverage. Individuals who maintained coverage through Oregon's Medicaid expansion increased long-term utilization of CHCs, whereas those with unstable coverage did not. This study predicts long-term increase in CHC utilization following Affordable Care Act Medicaid expansion and emphasizes the need for policies that support insurance retention.

Ebola Virus Enters Host Cells by Macropinocytosis and Clathrin-Mediated Endocytosis

PubMed Central

Aleksandrowicz, Paulina; Marzi, Andrea; Biedenkopf, Nadine; Beimforde, Nadine; Becker, Stephan; Hoenen, Thomas; Feldmann, Heinz

2011-01-01

Virus entry into host cells is the first step of infection and a crucial determinant of pathogenicity. Here we show that Ebola virus-like particles (EBOV-VLPs) composed of the glycoprotein GP1,2 and the matrix protein VP40 use macropinocytosis and clathrin-mediated endocytosis to enter cells. EBOV-VLPs applied to host cells induced actin-driven ruffling and enhanced FITC-dextran uptake, which indicated macropinocytosis as the main entry mechanism. This was further supported by inhibition of entry through inhibitors of actin polymerization (latrunculin A), Na+/H+-exchanger (EIPA), and PI3-kinase (wortmannin). A fraction of EBOV-VLPs, however, colocalized with clathrin heavy chain (CHC), and VLP uptake was reduced by CHC small interfering RNA transfection and expression of the dominant negative dynamin II–K44A mutant. In contrast, we found no evidence that EBOV-VLPs enter cells via caveolae. This work identifies macropinocytosis as the major, and clathrin-dependent endocytosis as an alternative, entry route for EBOV particles. Therefore, EBOV seems to utilize different entry pathways depending on both cell type and virus particle size. PMID:21987776

Does the KABC-II Display Ethnic Bias in the Prediction of Reading, Math, and Writing in Elementary School Through High School?

PubMed

Scheiber, Caroline

2017-09-01

This study explored whether the Kaufman Assessment Battery for Children-Second Edition (KABC-II) predicted academic achievement outcomes of the Kaufman Test of Educational Achievement-Second Edition (KTEA-II) equally well across a representative sample of African American, Hispanic, and Caucasian school-aged children ( N = 2,001) in three grade groups (1-4, 5-8, 9-12). It was of interest to study possible prediction bias in the slope and intercept of the five underlying Cattell-Horn-Carroll (CHC) cognitive factors of the KABC-II-Sequential/Gsm (Short-Term Memory), Learning/Glr (Long-Term Storage and Retrieval), Simultaneous/Gv (Visual Processing), Planning/Gf (Fluid Reasoning), and Knowledge/Gc (Crystallized Ability)-in estimating reading, writing, and math. Structural equation modeling techniques demonstrated a lack of bias in the slopes; however, four of the five CHC indexes showed a persistent overprediction of the minority groups' achievement in the intercept. The overprediction is likely attributable to institutional or societal contributions, which limit the students' ability to achieve to their fullest potential.

Male mate recognition via cuticular hydrocarbons facilitates sexual isolation between sympatric leaf beetle sister species.

PubMed

Zhang, Bin; Xue, Huai-Jun; Song, Ke-Qing; Liu, Jie; Li, Wen-Zhu; Nie, Rui-E; Yang, Xing-Ke

2014-11-01

Chemical signals in insects have been documented to play an important role in mate recognition, and divergence in chemical signals can often cause sexual isolation between closely related species or populations within species. We investigated the role of cuticular hydrocarbons (CHCs), short distance chemical signals, in male mate recognition between the two sympatric elm leaf beetles, Pyrrhalta maculicollis and Pyrrhaltaaenescens. Mating experiments demonstrated that strong sexual isolation between the two species was driven by CHCs divergence. Males preferred to mate with conspecific females with intact conspecific CHCs or conspecific CHCs reapplied after removal. Males also preferred heterospecific females that were treated with conspecific CHCs. Chemical analysis showed that the CHC profiles differ significantly between species. In P. maculicollis dimethyl-branched alkanes between C29 and C35 account for the majority of the saturated alkanes while the CHC profile of P. aenescens mostly consisted of monomethyl-branched alkanes between C22 and C29. Additionally, some compounds, such as 12,18-diMeC32, 12,18-diMeC34, are unique to P. maculicollis. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Role of Community Health Centers in Reducing Racial Disparities in Spatial Access to Primary Care.

PubMed

Seymour, Jane W; Polsky, Daniel E; Brown, Elizabeth J; Barbu, Corentin M; Grande, David

2017-07-01

Racial minorities are more likely to live in primary care shortage areas. We sought to understand community health centers' (CHCs) role in reducing disparities. We surveyed all primary care practices in an urban area, identified low access areas, and examined how CHCs influence spatial accessibility. Census tracts with higher rates of public insurance (≥40% vs <10%, odds ratio [OR] = 31.06, P < .001; 30-39% vs 10%, OR = 7.84, P = 0.001) were more likely to be near a CHC and those with moderate rates of uninsurance (10%-19% vs <10%, OR = 0.42, P = .045) were less likely. Racial composition was not associated with proximity. Tracts close to a CHC were less likely (OR = 0.11, P < .0001) to be in a low access area. This association did not differ based on racial composition. Although CHCs were more likely to be in areas with a greater fraction of racial minorities, location was more strongly influenced by public insurance rates. CHCs reduced the likelihood of being in low access areas but the effect did not vary by tract racial composition.

Cytochrome P450 associated with insecticide resistance catalyzes cuticular hydrocarbon production in Anopheles gambiae.

PubMed

Balabanidou, Vasileia; Kampouraki, Anastasia; MacLean, Marina; Blomquist, Gary J; Tittiger, Claus; Juárez, M Patricia; Mijailovsky, Sergio J; Chalepakis, George; Anthousi, Amalia; Lynd, Amy; Antoine, Sanou; Hemingway, Janet; Ranson, Hilary; Lycett, Gareth J; Vontas, John

2016-08-16

The role of cuticle changes in insecticide resistance in the major malaria vector Anopheles gambiae was assessed. The rate of internalization of (14)C deltamethrin was significantly slower in a resistant strain than in a susceptible strain. Topical application of an acetone insecticide formulation to circumvent lipid-based uptake barriers decreased the resistance ratio by ∼50%. Cuticle analysis by electron microscopy and characterization of lipid extracts indicated that resistant mosquitoes had a thicker epicuticular layer and a significant increase in cuticular hydrocarbon (CHC) content (∼29%). However, the CHC profile and relative distribution were similar in resistant and susceptible insects. The cellular localization and in vitro activity of two P450 enzymes, CYP4G16 and CYP4G17, whose genes are frequently overexpressed in resistant Anopheles mosquitoes, were analyzed. These enzymes are potential orthologs of the CYP4G1/2 enzymes that catalyze the final step of CHC biosynthesis in Drosophila and Musca domestica, respectively. Immunostaining indicated that both CYP4G16 and CYP4G17 are highly abundant in oenocytes, the insect cell type thought to secrete hydrocarbons. However, an intriguing difference was indicated; CYP4G17 occurs throughout the cell, as expected for a microsomal P450, but CYP4G16 localizes to the periphery of the cell and lies on the cytoplasmic side of the cell membrane, a unique position for a P450 enzyme. CYP4G16 and CYP4G17 were functionally expressed in insect cells. CYP4G16 produced hydrocarbons from a C18 aldehyde substrate and thus has bona fide decarbonylase activity similar to that of dmCYP4G1/2. The data support the hypothesis that the coevolution of multiple mechanisms, including cuticular barriers, has occurred in highly pyrethroid-resistant An gambiae.

Cytochrome P450 associated with insecticide resistance catalyzes cuticular hydrocarbon production in Anopheles gambiae

PubMed Central

Balabanidou, Vasileia; Kampouraki, Anastasia; MacLean, Marina; Blomquist, Gary J.; Tittiger, Claus; Juárez, M. Patricia; Mijailovsky, Sergio J.; Chalepakis, George; Anthousi, Amalia; Lynd, Amy; Antoine, Sanou; Hemingway, Janet; Ranson, Hilary; Lycett, Gareth J.; Vontas, John

2016-01-01

The role of cuticle changes in insecticide resistance in the major malaria vector Anopheles gambiae was assessed. The rate of internalization of 14C deltamethrin was significantly slower in a resistant strain than in a susceptible strain. Topical application of an acetone insecticide formulation to circumvent lipid-based uptake barriers decreased the resistance ratio by ∼50%. Cuticle analysis by electron microscopy and characterization of lipid extracts indicated that resistant mosquitoes had a thicker epicuticular layer and a significant increase in cuticular hydrocarbon (CHC) content (∼29%). However, the CHC profile and relative distribution were similar in resistant and susceptible insects. The cellular localization and in vitro activity of two P450 enzymes, CYP4G16 and CYP4G17, whose genes are frequently overexpressed in resistant Anopheles mosquitoes, were analyzed. These enzymes are potential orthologs of the CYP4G1/2 enzymes that catalyze the final step of CHC biosynthesis in Drosophila and Musca domestica, respectively. Immunostaining indicated that both CYP4G16 and CYP4G17 are highly abundant in oenocytes, the insect cell type thought to secrete hydrocarbons. However, an intriguing difference was indicated; CYP4G17 occurs throughout the cell, as expected for a microsomal P450, but CYP4G16 localizes to the periphery of the cell and lies on the cytoplasmic side of the cell membrane, a unique position for a P450 enzyme. CYP4G16 and CYP4G17 were functionally expressed in insect cells. CYP4G16 produced hydrocarbons from a C18 aldehyde substrate and thus has bona fide decarbonylase activity similar to that of dmCYP4G1/2. The data support the hypothesis that the coevolution of multiple mechanisms, including cuticular barriers, has occurred in highly pyrethroid-resistant An. gambiae. PMID:27439866

Estimating the Cost-Effectiveness of One-Time Screening and Treatment for Hepatitis C in Korea

PubMed Central

Kim, Do Young; Han, Kwang-Hyub; Jun, Byungyool; Kim, Tae Hyun; Park, Sohee; Ward, Thomas; Webster, Samantha; McEwan, Phil

2017-01-01

Background and Aims This study aims to investigate the cost-effectiveness of a one-time hepatitis C virus (HCV) screening and treatment program in South Korea where hepatitis B virus (HBV) prevails, in people aged 40–70, compared to current practice (no screening). Methods A published Markov model was used in conjunction with a screening and treatment decision tree to model patient cohorts, aged 40–49, 50–59 and 60–69 years, distributed across chronic hepatitis C (CHC) and compensated cirrhosis (CC) health states (82.5% and 17.5%, respectively). Based on a published seroepidemiology study, HCV prevalence was estimated at 0.60%, 0.80% and 1.53%, respectively. An estimated 71.7% of the population was screened. Post-diagnosis, 39.4% of patients were treated with a newly available all-oral direct-acting antiviral (DAA) regimen over 5 years. Published rates of sustained virologic response, disease management costs, transition rates and utilities were utilised. Results Screening resulted in the identification of 43,635 previously undiagnosed patients across all cohorts. One-time HCV screening and treatment was estimated to be cost-effective across all cohorts; predicted incremental cost-effectiveness ratios ranged from $5,714 to $8,889 per quality-adjusted life year gained. Incremental costs associated with screening, treatment and disease management ranged from $156.47 to $181.85 million USD; lifetime costs-offsets associated with the avoidance of end stage liver disease complications ranged from $51.47 to $57.48 million USD. Conclusions One-time HCV screening and treatment in South Korean people aged 40–70 is likely to be highly cost-effective compared to the current practice of no screening. PMID:28060834

Use of a pLDH-based dipstick in the diagnostic and therapeutic follow-up of malaria patients in Mali

PubMed Central

2011-01-01

Background Malaria is a major public health problem in Mali and diagnosis is typically based on microscopy. Microscopy requires a well trained technician, a reliable power source, a functioning microscope and adequate supplies. The scarcity of resources of community health centres (CHC) does not allow for such a significant investment in only one aspect of malaria control. In this context, Rapid Diagnostic Tests (RDTs) may improve case management particularly in remote areas. Methods This multicentre study included 725 patients simultaneously screened with OptiMal-IT test and thick smears for malaria parasite detection. While evaluating the therapeutic efficacy of choroquine in 2 study sites, we compared the diagnostic values of thick smear microscopy to OptiMal-IT test applying the WHO 14 days follow-up scheme using samples collected from 344 patients. Results The sensitivity and the specificity of OptiMal-IT compared to thick smear was 97.2% and 95.4%, whereas the positive and negative predictive values were 96.7 and 96.1%, respectively. The percent agreement between the two diagnostic tests was 0.93. The two tests were comparable in detecting malaria at day 0, day 3 and day 14. The only difference was observed at day 7 due to high gametocytemia. Subjectively, health care providers found OptiMal-IT easier to use and store under field conditions. Conclusion OptiMal-IT test revealed similar results when compared to microscopy which is considered the gold standard for malaria diagnostics. The test was found to have a short processing time and was easier to use. These advantages may improve malaria case management by providing a diagnostic and drug efficacy follow-up tool to peripheral health centres with limited resources. PMID:22114867

Discriminative Ability of CHC Factor Scores from the WJ III Tests of Cognitive Abilities in Children with ADHD

ERIC Educational Resources Information Center

Rowland, Julie Elizabeth

2013-01-01

Students with attention-deficit/hyperactivity disorder (ADHD) make up approximately 5% of the school-aged population and they often experience significant difficulties in school, particularly in the areas of academics, disruptive behavior, and social relationships. A diagnosis of ADHD does not provide guidance for creating interventions to address…

Is the Learning Approach of Students from the Confucian Heritage Culture Problematic?

ERIC Educational Resources Information Center

Tran, Thi Tuyet

2013-01-01

This article is concerned with the learning style adopted by Asian students who come from a Confucian heritage culture (CHC) such countries as China, Vietnam, Singapore, Korea and Japan are considered countries with Confucian heritage culture (Phuong-Mai et al. 2005). These students are generally viewed as typically passive, unwilling to ask…

An Exploration of the Relationships among Cattell-Horn-Carroll (CHC) Theory-Aligned Cognitive Abilities and Math Fluency

ERIC Educational Resources Information Center

Piselli, Katherine D.

2017-01-01

Math fluency, which refers to the ability to solve single digit arithmetic problems quickly and accurately, is a foundational mathematical skill. Recent research has examined the role of phonological processing, executive control, and number sense in explaining differences in math fluency performance in school-aged children. Identifying the links…

32 CFR 161.14 - Benefits for MOH recipients.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the case of a divorce, children residing in the household of a former spouse ARE NOT considered to be... Recipients and Dependents CHC DC C MWR E Self 1 2 Yes Yes Yes. Lawful Spouse 1 2 Yes Yes Yes. Children, Unmarried, Under 21 Years: Legitimate, adopted, stepchild, illegitimate child of record of female member, or...

32 CFR 161.13 - Benefits for retired members of the uniformed services.

Code of Federal Regulations, 2014 CFR

2014-07-01

... for commissary privileges until there is a final divorce decree. In the case of a divorce, children... Uniformed Services Members CHC DC C MWR E Lawful Spouse 1 2 Yes Yes Yes. Children, Unmarried, Under 21 Years: Legitimate, adopted, stepchild, illegitimate child of record of female member, or illegitimate child of male...

32 CFR 161.21 - Benefits for retired civilian personnel.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Benefits for retired civilian personnel. 161.21 Section 161.21 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE SECURITY... to part 161. Table 44 to Part 161—Benefits for Retired DoD Civilian Employees CHC DC C MWR E Self No...

Assessment of Cognitive Abilities and Reading Comprehension across School-Age Development: A Meta-Analysis

ERIC Educational Resources Information Center

Finn, Diana Baker

2014-01-01

The purpose of this study was to examine the relationship of specific cognitive abilities and reading comprehension across a variety of norm referenced tests that align with Cattell-Horn-Carroll (CHC) theory of cognitive abilities and integrative models of reading. Data from existing studies was analyzed by comparing the relationships of four…

Metamorphosis of Confucian Heritage Culture and the Possibility of an Asian Education Research Methodology

ERIC Educational Resources Information Center

Park, Jae

2011-01-01

This paper opens with a critical analysis of a paradox in contemporary educational research in and about Confucian Heritage Culture (CHC): the assumption that national boundaries coincide with those of a distinct and homogeneous culture, which consistently renders a rather homogenous set of educational phenomena, and collides against a more widely…

Technical and Practical Issues in the Structure and Clinical Invariance of the Wechsler Scales: A Rejoinder to Commentaries

ERIC Educational Resources Information Center

Weiss, Lawrence G.; Keith, Timothy Z.; Zhu, Jianjun; Chen, Hsinyi

2013-01-01

This discussion article addresses issues related to expansion of the Wechsler model from four to five factors; multiple broad CHC abilities measured by the Arithmetic subtest; advantages and disadvantages of including complex tasks requiring integration of multiple broad abilities when measuring intelligence; limitations of factor analysis, which…

A Bilingual (English and Spanish) Psychoeducational Assessment MODEL Grounded in Cattell-Horn Carroll (CHC) Theory: A Cross Battery Approach

ERIC Educational Resources Information Center

Olvera, Pedro; Gomez-Cerrillo, Lino

2011-01-01

The Individual with Disabilities Education Act mandates nondiscriminatory assessment for children who are culturally and linguistically diverse. Because of the overrepresentation of English Language Learners (ELL) in special education programs in the United States, the focus of this article is the psychoeducational assessment of Spanish- and…

The Effects of Wechsler Intelligence Scale for Children-Fourth Edition Cognitive Abilities on Math Achievement

ERIC Educational Resources Information Center

Parkin, Jason R.; Beaujean, A. Alexander

2012-01-01

This study used structural equation modeling to examine the effect of Stratum III (i.e., general intelligence) and Stratum II (i.e., Comprehension-Knowledge, Fluid Reasoning, Short-Term Memory, Processing Speed, and Visual Processing) factors of the Cattell-Horn-Carroll (CHC) cognitive abilities, as operationalized by the Wechsler Intelligence…

Broad and Narrow CHC Abilities Measured and Not Measured by the Wechsler Scales: Moving beyond Within-Battery Factor Analysis

ERIC Educational Resources Information Center

Flanagan, Dawn P.; Alfonso, Vincent C.; Reynolds, Matthew R.

2013-01-01

In this commentary, we reviewed two clinical validation studies on the Wechsler Scales conducted by Weiss and colleagues. These researchers used a rigorous within-battery model-fitting approach that demonstrated the factorial invariance of the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and Wechsler Adult Intelligence…

Relations between Measures of Cattell-Horn-Carroll (CHC) Cognitive Abilities and Mathematics Achievement across the School-Age Years

ERIC Educational Resources Information Center

Floyd, Randy G.; Evans, Jeffrey J.; McGrew, Kevin S.

2003-01-01

Cognitive clusters from the Woodcock-Johnson III (WJ III) Tests of Cognitive Abilities that measure select Cattell-Horn-Carroll broad and narrow cognitive abilities were shown to be significantly related to mathematics achievement in a large, nationally representative sample of children and adolescents. Multiple regression analyses were used to…

Higher-Order Factor Structure of the Differential Ability Scales-II: Consistency across Ages 4 to 17

ERIC Educational Resources Information Center

Keith, Timothy Z.; Low, Justin A.; Reynolds, Matthew R.; Patel, Puja G.; Ridley, Kristen P.

2010-01-01

The recently published second edition of the Differential Abilities Scale (DAS-II) is designed to measure multiple broad and general abilities from Cattell-Horn-Carroll (CHC) theory. Although the technical manual presents information supporting the test's structure, additional research is needed to determine the constructs measured by the test and…

Moderation of Cognitive-Achievement Relations for Children with Specific Learning Disabilities: A Multi-Group Latent Variable Analysis Using CHC Theory

ERIC Educational Resources Information Center

Niileksela, Christopher R.

2012-01-01

Recent advances in the understanding of the relations between cognitive abilities and academic skills have helped shape a better understanding of which cognitive processes may underlie different types of SLD (Flanagan, Fiorello, & Ortiz, 2010). Similarities and differences in cognitive-achievement relations for children with and without SLDs…

The New York City eClinician Project: using Personal Digital Assistants and wireless internet access to support emergency preparedness and enhance clinical care in community health centers.

PubMed

Adusumilli, Sri Raj; Tobin, Jonathan N; Younge, Richard G; Kendall, Mat; Kukafka, Rita; Khan, Sharib; Chang, Otto; Mahabir, Kasandra

2006-01-01

The New York City Department of Health and Mental Hygiene, The Community Health Care Association of New York State and Clinical Directors Network are collaborating on the "eClinician Project," which has distributed seven hundred public health-friendly, wireless (WiFi) enabled Personal Digital Assistants (PDAs) to primary care clinicians working in New York City, federally funded, Community Health Centers (CHC) which serve minority underserved communities that suffer a disproportionate burden of chronic disease and lack access to health promotion disease prevention services. Each participating health center also received a wireless router to create an onsite internet hot spot to enable clinicians to have internet access. The goals of the eClinician Project are to: 1) To encourage adoption of information technology among providers in Community Health Centers in New York City by providing PDAs as a first line strategy towards achieving this goal, 2) enhance access to information on emergency preparedness, 3) improve patient outcomes by providing PDA-based clinical decision-support tools that support evidence-based care, 4) encourage chronic care management and health promotion/disease prevention activities, and 5) increase productivity and efficiency. CHC clinicians have received a hands-on, on-site orientation to PDAs. Ongoing training has continued via online CME-accredited webcasts (see www.CDNetwork.org). Clinical decision-support tools are available for download via the eClinician project web portal (see www.eClinician.org ). Public health alerts can be delivered to the PDAs or to the clinicians' desktop computers. Pre and post training surveys, in addition to a case study, have been used to evaluate the population demographics, PDA adoption by the clinicians, clinician attitudes towards using PDAs, PDA influence on clinical-decision making and barriers to adoption of PDAs and information technology in general.

Detection methods for atoms and radicals in the gas phase

NASA Astrophysics Data System (ADS)

Hack, W.

This report lists atoms and free radicals in the gas phase which are of interest for environmental and flame chemistry and have been detected directly. The detection methods which have been used are discussed with respect to their range of application, specificity and sensitivity. In table 1, detection methods for the five atoms of group IV (C, Si, Ge, Sn, Pb) and about 60 radicals containing at least one atom of group IV are summarized (CH, Cd, Cf, CC1, CBr, Cn, Cs, CSe, CH2, CD2, Chf, Cdf, CHC1, CHBr, CF2, CC12, CBr2, CFC1, CFBr, CH3, CD3, CF3, CH2F, CH2C1, CH2Br, CHF2, CHC12, CHBr2, Hco, Fco, CH30, CD30, CH2OH, CH3S, Nco, CH4N, CH302, CF302; C2, C2N, C2H, C20, C2HO, C2H3, C2F3, C2H5, C2HsO, C2H4OH, CH3CO, CD3CO, C2H3O, C2H502, CH3COO2, C2H4N, C2H6N, C3; Si, SiF, SiF2, SiO, SiC, Si2; Ge, GeC, GeO, GeF, GeF2, GeCl2, Sn, SnF, SnO, SnF2, Pb, PbF, PbF2, PbO, PbS). In table 2 detection methods for about 25 other atoms and 60 radicals are listed: (H, D, O, O2, Oh, Od, HO2, DO2, F, Ci, Br, I, Fo, Cio, BrO, Io, FO2, C1O2, Li, Na, K, Rb, Cs, N, N3, Nh, Nd, Nf, Nci, NBr, NH2, ND2, Nhd, Nhf, NF2, NC12, N2H3, No, NO2, NO3, Hno, Dno, P, Ph, Pd, Pf, Pci, PH2, PD2, PF2, Po, As, AsO, AsS, Sb, Bi, S, S2, Sh, Sd, Sf, SF2, So, Hso, Dso, Sn, Se, Te, Se2, SeH, SeD, SeF, SeO, SeS, SeN, TeH, TeO, Bh, BH2, Bo, Bn, B02, Cd, Hg, UF5). The tables also cite some recent kinetic applications of the various methods.

An Investigation of CHC Cognitive Patterns among School Students in Grades Five through Nine with Learning Disabilities

ERIC Educational Resources Information Center

McClain-Pace, Erin Marie

2012-01-01

Interest in students who exhibit characteristics with difficulties in learning can be traced as far back as 1800. In order to better understand the complexities and causes of learning disabilities, many researchers (Bannatyne, 1968, 1974; Rugal, 1974) have investigated ways to better identify learners who struggle with academics. A strong argument…

Physiologically-based pharmacokinetic (PBPK) modeling of two binary mixtures: metabolic activation of carbon tetrachloride by trichloroethylene and metabolic inhibition of chloroform by trichloroethylene.

EPA Science Inventory

The interaction between trichloroethylene (TCE) and chloroform (CHCI3) has been described as less than additive, with co-exposure to TCE and CHC13 resulting in less hepatic and renal toxicity than observed with CHCl3 alone. In contrast, the nonadditive interaction between TCE and...

The Relative Contributions of the Cattell-Horn-Carroll Cognitive Abilities in Explaining Writing Achievement during Childhood and Adolescence

ERIC Educational Resources Information Center

Floyd, Randy G.; McGrew, Kevin S.; Evans, Jeffrey J.

2008-01-01

This study examined the relative contributions of measures of Cattell-Horn-Carroll (CHC) cognitive abilities in explaining writing achievement. Drawing from samples that covered the age range of 7 to 18 years, simultaneous multiple regression was used to regress scores from the Woodcock-Johnson III (WJ III; Woodcock, McGrew, & Mather, 2001) that…

Revisiting the Relations between the WJ-IV Measures of Cattell-Horn-Carroll (CHC) Cognitive Abilities and Reading Achievement during the School-Age Years

ERIC Educational Resources Information Center

Cormier, Damien C.; McGrew, Kevin S.; Bulut, Okan; Funamoto, Allyson

2017-01-01

This study examined associations between broad cognitive abilities (Fluid Reasoning [Gf], Short-Term Working Memory [Gwm], Long-Term Storage and Retrieval [Glr], Processing Speed [Gs], Comprehension-Knowledge [Gc], Visual Processing [Gv], and Auditory Processing [Ga]) and reading achievement (Basic Reading Skills, Reading Rate, Reading Fluency,…

Profile Analysis of the Kaufman Assessment Battery for Children, Second Edition, with African American and Caucasian Preschool Children

ERIC Educational Resources Information Center

Dale, Brittany A.; McIntosh, David E.; Rothlisberg, Barbara A.; Ward, Kimberly E.; Bradley, Madeline Hunt

2011-01-01

This study used profile analysis to investigate the interpretability of the Kaufman Assessment Battery for Children, Second Edition (KABC-II), in terms of the Cattell-Horn-Carroll (CHC) theory among ethnically diverse preschool children. Forty-nine African American and 49 Caucasian preschool children from a Midwestern city were included in the…

Sexual selection on cuticular hydrocarbons of male sagebrush crickets in the wild

PubMed Central

Steiger, Sandra; Ower, Geoffrey D.; Stökl, Johannes; Mitchell, Christopher; Hunt, John; Sakaluk, Scott K.

2013-01-01

Cuticular hydrocarbons (CHCs) play an essential role in mate recognition in insects but the form and intensity of sexual selection on CHCs has only been evaluated in a handful of studies, and never in a natural population. We quantified sexual selection operating on CHCs in a wild population of sagebrush crickets, a species in which nuptial feeding by females imposes an unambiguous phenotypic marker on males. Multivariate selection analysis revealed a saddle-shaped fitness surface, suggesting a complex interplay between the total abundance of CHCs and specific CHC combinations in their influence on female choice. The fitness surface resulting from two axes of disruptive selection reflected a trade-off between short- and long-chained CHCs, suggesting that males may be sacrificing some level of desiccation resistance in favour of increased attractiveness. There was a significant correlation between male body size and total CHC abundance, suggesting that male CHCs provide females with a reliable cue for maximizing benefits obtained from males. Notwithstanding the conspicuousness of males’ acoustic signals, our results suggest that selection imposed on males via female mating preferences may be far more complex than previously appreciated and operating in multiple sensory modalities. PMID:24197415

ENHANCED DISEASE RESISTANCE4 Associates with CLATHRIN HEAVY CHAIN2 and Modulates Plant Immunity by Regulating Relocation of EDR1 in Arabidopsis

PubMed Central

Wu, Guangheng; Liu, Simu; Zhao, Yaofei; Wang, Wei; Kong, Zhaosheng; Tang, Dingzhong

2015-01-01

Obligate biotrophs, such as the powdery mildew pathogens, deliver effectors to the host cell and obtain nutrients from the infection site. The interface between the plant host and the biotrophic pathogen thus represents a major battleground for plant-pathogen interactions. Increasing evidence shows that cellular trafficking plays an important role in plant immunity. Here, we report that Arabidopsis thaliana ENHANCED DISEASE RESISTANCE4 (EDR4) plays a negative role in resistance to powdery mildew and that the enhanced disease resistance in edr4 mutants requires salicylic acid signaling. EDR4 mainly localizes to the plasma membrane and endosomal compartments. Genetic analyses show that EDR4 and EDR1 function in the same genetic pathway. EDR1 and EDR4 accumulate at the penetration site of powdery mildew infection, and EDR4 physically interacts with EDR1, recruiting EDR1 to the fungal penetration site. In addition, EDR4 interacts with CLATHRIN HEAVY CHAIN2 (CHC2), and edr4 mutants show reduced endocytosis rates. Taken together, our data indicate that EDR4 associates with CHC2 and modulates plant immunity by regulating the relocation of EDR1 in Arabidopsis. PMID:25747881

Sexual selection on cuticular hydrocarbons of male sagebrush crickets in the wild.

PubMed

Steiger, Sandra; Ower, Geoffrey D; Stökl, Johannes; Mitchell, Christopher; Hunt, John; Sakaluk, Scott K

2013-12-22

Cuticular hydrocarbons (CHCs) play an essential role in mate recognition in insects but the form and intensity of sexual selection on CHCs has only been evaluated in a handful of studies, and never in a natural population. We quantified sexual selection operating on CHCs in a wild population of sagebrush crickets, a species in which nuptial feeding by females imposes an unambiguous phenotypic marker on males. Multivariate selection analysis revealed a saddle-shaped fitness surface, suggesting a complex interplay between the total abundance of CHCs and specific CHC combinations in their influence on female choice. The fitness surface resulting from two axes of disruptive selection reflected a trade-off between short- and long-chained CHCs, suggesting that males may be sacrificing some level of desiccation resistance in favour of increased attractiveness. There was a significant correlation between male body size and total CHC abundance, suggesting that male CHCs provide females with a reliable cue for maximizing benefits obtained from males. Notwithstanding the conspicuousness of males' acoustic signals, our results suggest that selection imposed on males via female mating preferences may be far more complex than previously appreciated and operating in multiple sensory modalities.

Sexual selection and population divergence II. Divergence in different sexual traits and signal modalities in field crickets (Teleogryllus oceanicus).

PubMed

Pascoal, Sonia; Mendrok, Magdalena; Wilson, Alastair J; Hunt, John; Bailey, Nathan W

2017-06-01

Sexual selection can target many different types of traits. However, the relative influence of different sexually selected traits during evolutionary divergence is poorly understood. We used the field cricket Teleogryllus oceanicus to quantify and compare how five traits from each of three sexual signal modalities and components diverge among allopatric populations: male advertisement song, cuticular hydrocarbon (CHC) profiles and forewing morphology. Population divergence was unexpectedly consistent: we estimated the among-population (genetic) variance-covariance matrix, D, for all 15 traits, and D max explained nearly two-thirds of its variation. CHC and wing traits were most tightly integrated, whereas song varied more independently. We modeled the dependence of among-population trait divergence on genetic distance estimated from neutral markers to test for signatures of selection versus neutral divergence. For all three sexual trait types, phenotypic variation among populations was largely explained by a neutral model of divergence. Our findings illustrate how phenotypic integration across different types of sexual traits might impose constraints on the evolution of mating isolation and divergence via sexual selection. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Structural modeling of djenkolic acid with sulfur replaced by selenium and tellurium.

PubMed

Melnikov, Petr; Nascimento, Valter A; Silva, Anderson F; Consolo, Lourdes Z Z

2014-04-17

The comparative structural modeling of djenkolic acid and its derivatives containing selenium and tellurium in chalcogen sites (Ch=Se, Te) has provided detailed information about the bond lengths and bond angles, filling the gap in what we know about the structural characteristics of these aminoacids. The investigation using the molecular mechanics technique with good approximation confirmed the available information on X-ray refinements for the related compounds methionine and selenomethionine, as well as for an estimate made earlier for telluromethionine. It was shown that the Ch-C(3) and Ch-C(4) bond lengths grow in parallel with the increasing anionic radii. Although the distances C-C, C-O, and C-N are very similar, the geometry of conformers is quite different owing to the possibility of rotation about four carbon atoms, hence the remarkable variability observed in dihedral angles. It was shown that the compounds contain a rigid block with two Ch atoms connected through a methylene group. The standard program Gaussian 03 with graphical interface Gaussview 4.1.2 has proved to be satisfactory tool for the structural description of less-common bioactive compositions when direct X-ray results are absent.

Reconciliation of Cahn-Hilliard predictions for spinodal decomposition lengthscales in polymer blends

NASA Astrophysics Data System (ADS)

Cabral, Joao

Spinodal decomposition (SD) of partially miscible polymer blends can yield well-defined nanostructures with prescribed lengthscales and connectivity, and applications ranging from membranes and scaffolds to photovoltaics. Cahn-Hilliard-Cook (CHC) theory estimates the initial, dominant SD wavenumber to be qm =√{G''/4 k } , where G'' is the second derivative of the free energy of mixing with respect to concentration and k is a structural parameter which can be computed from the segment lengths and volumes of monomer units. Tuning G'', with quench depth into the two phase region, for instance, should thus provide a facile and precise means for designing polymeric bicontinuous structures. The fulfillment of this potential rests on the thermodynamics of available polymer systems, coarsening kinetics, as well as engineering constraints. We extensively review experimental measurements of G'' in both one- and two-phase blend systems, and critically examine the accuracy of this fundamental prediction against achievements over the past 4 decades of polymer blend demixing. Despite widespread misconceptions in detecting and describing SD, we find the CHC relation to be remarkably accurate and conclude with design considerations and limitations for polymer nanostructures via SD, reflecting on John Cahn's contributions to the field.

Global, broad, or specific cognitive differences? Using a MIMIC model to examine differences in CHC abilities in children with learning disabilities.

PubMed

Niileksela, Christopher R; Reynolds, Matthew R

2014-01-01

This study was designed to better understand the relations between learning disabilities and different levels of latent cognitive abilities, including general intelligence (g), broad cognitive abilities, and specific abilities based on the Cattell-Horn-Carroll theory of intelligence (CHC theory). Data from the Differential Ability Scales-Second Edition (DAS-II) were used to create a multiple-indicator multiple cause model to examine the latent mean differences in cognitive abilities between children with and without learning disabilities in reading (LD reading), math (LD math), and reading and writing(LD reading and writing). Statistically significant differences were found in the g factor between the norm group and the LD groups. After controlling for differences in g, the LD reading and LD reading and writing groups showed relatively lower latent processing speed, and the LD math group showed relatively higher latent comprehension-knowledge. There were also some differences in some specific cognitive abilities, including lower scores in spatial relations and numerical facility for the LD math group, and lower scores in visual memory for the LD reading and writing group. These specific mean differences were above and beyond any differences in the latent cognitive factor means.

The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design.

PubMed

Jiménez-Sousa, María Ángeles; Gómez-Moreno, Ana Zaida; Pineda-Tenor, Daniel; Medrano, Luz Maria; Sánchez-Ruano, Juan José; Fernández-Rodríguez, Amanda; Artaza-Varasa, Tomas; Saura-Montalbán, José; Vázquez-Morón, Sonia; Ryan, Pablo; Resino, Salvador

2018-01-01

The polymorphisms at the α-chain of the IL-7 receptor (IL7RA) have been related to T-cell homeostasis and development and may contribute to immune system deregulation. In the present study, we analyzed the association between IL7RA polymorphisms and the progression of liver fibrosis in patients infected with HCV. We carried out a retrospective study with a design consisting of repeated measurements in 187 HCV-infected patients, to study the risk prediction of liver fibrosis progression using genetic factors. We genotyped the rs6897932, rs987106 and rs3194051 IL7RA polymorphisms using the Agena Bioscience's MassARRAY. Transient elastography was used to measure liver stiffness. The used cut-offs were: <7.1 kPa (F0-F1), 7.1-9.4 kPa (F2; significant fibrosis), 9.5-12.4 kPa (F3; advanced fibrosis), and ≥12.5 kPa (F4; cirrhosis). All HCV genotypes were analyzed. The median of follow-up time was 47.9 months. Baseline liver stiffness measurement (LSM) values did not show significant statistical differences for IL7RA genotypes (p>0.05). In univariate analysis, the rs6897932 T allele had a positive relationship with an increase in LSM (arithmetic mean ratio (AMR) = 1.21 (95%CI = 1.08; 1.36); p = 0.001), progression to advanced fibrosis (F≥3) (odds ratio (OR) = 2.51 (95%CI = 1.29; 4.88); p = 0.006) and progression to cirrhosis (F4) (OR = 2.71 (95%CI = 0.94; 5.03); p = 0.069). In multivariable analysis, the rs6897932 T allele was related to a higher increase of LSM values during follow-up (adjusted AMR = 1.27 (95%CI = 1.13; 1.42); p<0.001) and higher odds of progression to advanced fibrosis [adjusted OR = 4.46 (95%CI = 1.87; 10.62); p = 0.001], and progression to cirrhosis [adjusted OR = 3.92 (95%CI = 1.30; 11.77); p = 0.015]. Regarding IL7RA rs987106 and rs3194051 polymorphisms, we did not find significant results except for the relationship between IL7RA rs987106 and the increase in LSM values [adjusted OR = 1.12 (95%CI = 1.02; 1.23); p = 0.015]. The IL7RA rs6897932 polymorphism seems to be related to increased risk of liver fibrosis progression in HCV-infected patients. Thus, the rs6897932 polymorphism could be related to the physiopathology of CHC and might be used to successfully stratify the risk of CHC progression.

Early Treatment in HCV: Is it a Cost-Utility Option from the Italian Perspective?

PubMed

Marcellusi, Andrea; Viti, Raffaella; Damele, Francesco; Cammà, Calogero; Taliani, Gloria; Mennini, Francesco Saverio

2016-08-01

In Italy, the Italian Pharmaceutical Agency (AIFA) criteria used F3-F4 fibrosis stages as the threshold to prioritise the treatment with interferon (IFN)-free regimens, while in genotype 1 chronic hepatitis C (G1 CHC) patients with fibrosis of liver stage 2, an approach with pegylated interferon (PEG-IFN)-based triple therapy with simeprevir was suggested. The key clinical question is whether, in an era of financial constraints, the application of a universal IFN-free strategy in naïve G1 CHC patients is feasible within a short time horizon. The aim of this study is to perform an economic analysis to estimate the cost-utility of the early innovative therapy in Italy for managing hepatitis C virus (HCV)-infected patients. The incremental cost-utility analysis was carried out to quantify the benefits of the early treatment approach in HCV subjects. A Markov simulation model including direct and indirect costs and health outcomes was developed from an Italian National Healthcare Service and societal perspective. A total of 5000 Monte Carlo simulations were performed on two distinct scenarios: standard of care (SoC) which includes 14,000 genotype 1 patients in Italy treated with innovative interferon-free regimens in the fibrosis of liver stages 3 and 4 (F3-F4) versus early-treatment scenario (ETS) where 2000 patients were additionally treated with simeprevir plus PEG-IFN and ribavirin in the fibrosis stage 2 (F2) (based on Italian Medicines Agency AIFA reimbursement criteria). A systematic literature review was carried out to identify epidemiological and economic data, which were subsequently used to inform the model. Furthermore, a one-way probabilistic sensitivity was performed to measure the relationship between the main parameters of the model and the cost-utility results. The model shows that, in terms of incremental cost-effectiveness ratio (ICER) per quality adjusted life year (QALY) gained, ETS appeared to be the most cost-utility option compared with both perspective societal (ICER = EUR11,396) and NHS (ICER = EUR14,733) over a time period of 10 years. The cost-utility of ETS is more sustainable as it extends the time period analysis [ICER = EUR 6778 per QALY to 20 years and EUR4474 per QALY to 30 years]. From the societal perspective, the ETS represents the dominant option at a time horizon of 30 years. If we consider the sub-group population of treated patients [16,000 patients of which 2000 not treated in the SoC, the ETS scenario was dominant after only 5 years and the cost-utility at 2 years of simulation. The one-way sensitivity analysis on the main variables confirmed the robustness of the model for the early-treatment approach. Our model represents a tool for policy makers and health-care professionals, and provided information on the cost-utility of the early-treatment approach in HCV-infected patients in Italy. Starting innovative treatment regimens earlier keeps HCV-infected patients in better health and reduces the incidence of HCV-related events; generating a gain both in terms of health of the patients and correct resource allocation.

Incremental Validity of the WJ III COG: Limited Predictive Effects beyond the GIA-E

ERIC Educational Resources Information Center

McGill, Ryan J.; Busse, R. T.

2015-01-01

This study is an examination of the incremental validity of Cattell-Horn-Carroll (CHC) broad clusters from the Woodcock-Johnson III Tests of Cognitive Abilities (WJ III COG) for predicting scores on the Woodcock-Johnson III Tests of Achievement (WJ III ACH). The participants were children and adolescents, ages 6-18 (n = 4,722), drawn from the WJ…

Cuticular hydrocarbons and soldier defense secretions of Reticulitermes in southern California: a critical analysis of the taxonomy of the genus in North America

Treesearch

Lori J. Nelson; Laurence G. Cool; Christopher W. Solek; Michael I. Haverty

2008-01-01

Cuticular hydrocarbons (CHC) and soldier defense secretions (SDS) were characterized for collections of Reticulitermes from six counties (Los Angeles, Orange, Riverside, San Bernardino, San Diego, and Santa Barbara) in southern California. Collection sites included the type locality for R. hesperus, Lake Arrowhead (formerly known as Little Bear Lake) in the San...

Waterborne Polymeric Films.

DTIC Science & Technology

1981-02-01

polymer of neopentyl glycol (NPC) and isophoronediisocyanate (IPDI) as an example: CH 3 0 CH3 0 CH- HO !Ch,,C h OCNH CH.NHCO, HCCH.OH CIF CH- Groun...copolymer of isophoronediisocyanate with neopentyl glycol and dimethylolpropionic acid. And the solibilitv parameter calculations must include this...copolymer of isophoronediiisocyanate with a diol mixture of 85 inol percent neopentyl glycol and 15 inol percent dimethyl- olpropionic acid. 0 0 0 it 0

Cattell-Horn-Carroll Cognitive Abilities and Their Effects on Reading Decoding Skills: g Has Indirect Effects, More Specific Abilities Have Direct Effects

ERIC Educational Resources Information Center

Floyd, Randy G.; Keith, Timothy Z.; Taub, Gordon E.; McGrew, Kevin S.

2007-01-01

This study employed structural equation modeling to examine the effects of Cattell-Horn-Carroll (CHC) abilities on reading decoding skills using five age-differentiated subsamples from the standardization sample of the Woodcock-Johnson III (Woodcock, McGrew, & Mather, 2001). Using the Spearman Model including only g, strong direct effects of g on…

Caring for individual patients and beyond: enhancing care through secondary use of data in a general practice setting.

PubMed

Tolar, Marianne; Balka, Ellen

2012-07-01

It is argued that with the introduction of electronic medical record (EMR) systems into the primary care sector, data collected can be used for secondary purposes which extend beyond individual patient care (e.g., for chronic disease management, prevention and clinical performance evaluation). However, EMR systems are primarily designed to support clinical tasks, and data entry practices of clinicians focus on the treatment of individual patients. Hence data collected through EMRs is not always useful in meeting these ends. In this paper we follow a community health centre (CHC), and document the changes in work practices of the personnel that were necessary in order to make EMR data useful for secondary purposes. This project followed an action research approach, in which ethnographic data were collected mainly by participant observations, by a researcher who also acted as an IT support person for the clinic's secondary usage of EMR data. Additionally, interviews were carried out with the clinical and administrative personnel of the CHC. The case study demonstrates that meaningful use of secondary data occurs only after a long process, aimed at creating the pre-conditions for meaningful use of secondary data, has taken place. PRECONDITIONS: Specific areas of focus have to be chosen for secondary data use, and initiatives have to be continuously evaluated and adapted to the workflow through a team approach. Collaboration between IT support and physicians is necessary to tailor the software to allow for the collection of clinically relevant data. Data entry procedures may have to be changed to encourage the usage of an agreed-upon coding scheme, required for meaningful use of secondary data. And finally resources in terms of additional personnel or dedicated time are necessary to keep up with data collection and other tasks required as a pre-condition to secondary use of data, communication of the results to the clinic, and eventual re-evaluation. Changes in the work practices observed in this case which were required to support secondary data use from the EMR included completion of additional tasks by clinical and administrative personnel related to the organization of follow-up tasks. Among physicians increased awareness of specific initiatives and guideline compliance in terms of chronic disease management and prevention was noticed. Finally, the clinic was able to evaluate their own practice and present the results to varied stakeholders. The case describes the secondary usage of data by a clinic aimed at improving management of the clinic's patients. It illustrates that creating the pre-conditions for secondary use of data from EMRs is a complex process which can be seen as a shift in paradigms from a focus on individual patient care to chronic disease management and performance measurement. More research is needed about how to best support clinics in the process of change management necessitated by emerging clinical management goals. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Structure of salts of lithium chloride and lithium hexafluorophosphate as solvates with pyridine and vinylpyridine and structural comparisons: (C5H5N)LiPF6, [p-(CH2=CH)C5H4N]LiPF6, [(C5H5N)LiCl]n, and [p-(CH2=CH)C5H4N]2Li(μ-Cl)2Li[p-(CH2=CH)C5H4N]2.

PubMed

Jalil, AbdelAziz; Clymer, Rebecca N; Hamilton, Clifton R; Vaddypally, Shivaiah; Gau, Michael R; Zdilla, Michael J

2017-03-01

Due to the flammability of liquid electrolytes used in lithium ion batteries, solid lithium ion conductors are of interest to reduce danger and increase safety. The two dominating general classes of electrolytes under exploration as alternatives are ceramic and polymer electrolytes. Our group has been exploring the preparation of molecular solvates of lithium salts as alternatives. Dissolution of LiCl or LiPF 6 in pyridine (py) or vinylpyridine (VnPy) and slow vapor diffusion with diethyl ether gives solvates of the lithium salts coordinated by pyridine ligands. For LiPF 6 , the solvates formed in pyridine and vinylpyridine, namely tetrakis(pyridine-κN)lithium(I) hexafluorophosphate, [Li(C 5 H 5 N) 4 ]PF 6 , and tetrakis(4-ethenylpyridine-κN)lithium(I) hexafluorophosphate, [Li(C 7 H 7 N) 4 ]PF 6 , exhibit analogous structures involving tetracoordinated lithium ions with neighboring PF 6 - anions in the I-4 and Aea2 space groups, respectively. For LiCl solvates, two very different structures form. catena-Poly[[(pyridine-κN)lithium]-μ 3 -chlorido], [LiCl(C 5 H 5 N)] n , crystalizes in the P2 1 2 1 2 1 space group and contains channels of edge-fused LiCl rhombs templated by rows of π-stacked pyridine ligands, while the structure of the LiCl-VnPy solvate, namely di-μ-chlorido-bis[bis(4-ethenylpyridine-κN)lithium], [Li 2 Cl 2 (C 7 H 7 N) 4 ], is described in the P2 1 /n space group as dinuclear (VnPy) 2 Li(μ-Cl) 2 Li(VnPy) 2 units packed with neighbors via a dense array of π-π interactions.

Breastfeeding and Complementary Feeding Practices among HIV-Exposed Infants in Coastal Tanzania.

PubMed

Williams, Anne M; Chantry, Caroline; Geubbels, Eveline L; Ramaiya, Astha K; Shemdoe, Aloisia I; Tancredi, Daniel J; Young, Sera L

2016-02-01

Appropriate infant feeding is a persistent challenge for human immunodeficiency virus (HIV)-infected mothers in sub-Saharan Africa. This study aimed to describe correlates of infant feeding among HIV-infected mothers in coastal Tanzania. HIV-infected women (n = 400) with infants younger than 18 months were enrolled from June to November 2011 from 3 public health facilities in Pwani, Tanzania: Tumbi Regional Hospital (TRH), Chalinze Health Center (CHC), and Bagamoyo District Hospital (BDH). Participants were surveyed about sociodemographics and infant feeding behavior at enrollment; infant feeding data were collected prospectively and retrospectively in the month of study follow-up. Statistically significant correlates of exclusive breastfeeding (EBF) were infant age (months) (adjusted odds ratio [AOR] = 0.6; 95% confidence interval [CI], 0.5-0.9), enrollment facility (TRH: reference; CHC: AOR = 5.0, 95% CI, 1.2-20.8; BDH: AOR = 11.6, 95% CI, 2.3-59.9), and HIV disclosure to one's mother (AOR = 0.2; 95% CI, 0.1-0.6). Exclusive breastfeeding prevalence among infants younger than 6 months was 77%, but 50% of infants older than 6 months no longer receiving breast milk did not receive animal source foods (ASF) daily. Enrollment facility (TRH: reference; CHC: AOR = 0.2, 95% CI, 0.1-1.0; BDH: AOR = 0.1, 95% CI, 0.01-0.4) and HIV disclosure (to mother-in-law: AOR = 0.2, 95% CI, 0.1-0.8; to brother: AOR = 0.3, 95% CI, 0.1-0.8) were negatively associated with ASF provision. High prevalence of EBF suggests that it is an attainable behavior, whereas low prevalence of daily ASF provision suggests that adequate diets are difficult to achieve after breastfeeding cessation. These findings support current recommendations for HIV-infected mothers in resource-poor regions to continue breastfeeding for at least 1 year and suggest the need for greater support with complementary feeding. Associations between HIV disclosure and infant feeding merit further exploration, and correlations between enrollment facility and infant feeding highlight the potential influence of clinics on achieving infant feeding recommendations. © The Author(s) 2015.

Designing Health Information Technology Tools to Prevent Gaps in Public Health Insurance.

PubMed

Hall, Jennifer D; Harding, Rose L; DeVoe, Jennifer E; Gold, Rachel; Angier, Heather; Sumic, Aleksandra; Nelson, Christine A; Likumahuwa-Ackman, Sonja; Cohen, Deborah J

2017-06-23

Changes in health insurance policies have increased coverage opportunities, but enrollees are required to annually reapply for benefits which, if not managed appropriately, can lead to insurance gaps. Electronic health records (EHRs) can automate processes for assisting patients with health insurance enrollment and re-enrollment. We describe community health centers' (CHC) workflow, documentation, and tracking needs for assisting families with insurance application processes, and the health information technology (IT) tool components that were developed to meet those needs. We conducted a qualitative study using semi-structured interviews and observation of clinic operations and insurance application assistance processes. Data were analyzed using a grounded theory approach. We diagramed workflows and shared information with a team of developers who built the EHR-based tools. Four steps to the insurance assistance workflow were common among CHCs: 1) Identifying patients for public health insurance application assistance; 2) Completing and submitting the public health insurance application when clinic staff met with patients to collect requisite information and helped them apply for benefits; 3) Tracking public health insurance approval to monitor for decisions; and 4) assisting with annual health insurance reapplication. We developed EHR-based tools to support clinical staff with each of these steps. CHCs are uniquely positioned to help patients and families with public health insurance applications. CHCs have invested in staff to assist patients with insurance applications and help prevent coverage gaps. To best assist patients and to foster efficiency, EHR based insurance tools need comprehensive, timely, and accurate health insurance information.

Electron collisions with methyl-substituted ethylenes: Cross section measurements and calculations for 2-methyl–2-butene and 2,3-dimethyl–2-butene

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

Szmytkowski, Czesław, E-mail: czsz@mif.pg.gda.pl; Stefanowska, Sylwia; Zawadzki, Mateusz

We report electron-scattering cross sections determined for 2-methyl–2-butene [(H{sub 3}C)HC = C(CH{sub 3}){sub 2}] and 2,3-dimethyl–2-butene [(H{sub 3}C){sub 2}C = C(CH{sub 3}){sub 2}] molecules. Absolute grand-total cross sections (TCSs) were measured for incident electron energies in the 0.5–300 eV range, using a linear electron-transmission technique. The experimental TCS energy dependences for the both targets appear to be very similar with respect to the shape. In each TCS curve, three features are discernible: the resonant-like structure located around 2.6–2.7 eV, the broad distinct enhancement peaking near 8.5 eV, and a weak hump in the vicinity of 24 eV. Theoretical integral elasticmore » (ECS) and ionization (ICS) cross sections were computed up to 3 keV by means of the additivity rule (AR) approximation and the binary-encounter-Bethe method, respectively. Their sums, (ECS+ICS), are in a reasonable agreement with the respective measured TCSs. To examine the effect of methylation of hydrogen sides in the ethylene [H{sub 2}C = CH{sub 2}] molecule on the TCS, we compared the TCS energy curves for the sequence of methylated ethylenes: propene [H{sub 2}C = CH(CH{sub 3})], 2-methylpropene [H{sub 2}C = C(CH{sub 3}){sub 2}], 2-methyl–2-butene [(H{sub 3}C)HC = C(CH{sub 3}){sub 2}], and 2,3-dimethyl–2-butene [(H{sub 3}C){sub 2}C = C(CH{sub 3}){sub 2}], measured in the same laboratory. Moreover, the isomeric effect is also discussed for the C{sub 5}H{sub 10} and C{sub 6}H{sub 12} compounds.« less

[Concordance between a head circumference growth function and intellectual disability in relation with the cause of microcephaly].

PubMed

Coronado, R; Macaya Ruíz, A; Giraldo Arjonilla, J; Roig-Quilis, M

2015-08-01

Our aim was to investigate the correlations between patterns of head growth and intellectual disability among distinct aetiological presentations of microcephaly. 3,269 head circumference (HC) charts of patients from a tertiary neuropediatric unit were reviewed and 136 microcephalic participants selected. Using the Z-scores of registered HC measurements we defined the variables: HC Minimum, HC Drop and HC Catch-up. We classified patients according to the presence or absence of intellectual disability (IQ below 71) and according to the cause of microcephaly (idiopathic, familial, syndromic, symptomatic and mixed). Using Discriminant Analysis a C-function was defined as C=HC Minimum + HC Drop with a cut-off level of C=-4.32 Z-score. In our sample 95% of patients scoring below this level, severe microcephaly, were classified in the disabled group while the overall concordance was 66%. In the symptomatic-mixed group the concordance between HC function and outcome reached 82% in contrast to only 54% in the idiopathic-syndromic group (P-value=0.0002). We defined a HC growth function which discriminates intellectual disability of microcephalic patients better than isolated HC measurements, especially for those with secondary and mixed aetiologies. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Diagnostic value of fibronectin discriminant score for predicting liver fibrosis stages in chronic hepatitis C virus patients.

PubMed

Attallah, Abdelfattah M; Abdallah, Sanaa O; Attallah, Ahmed A; Omran, Mohamed M; Farid, Khaled; Nasif, Wesam A; Shiha, Gamal E; Abdel-Aziz, Abdel-Aziz F; Rasafy, Nancy; Shaker, Yehia M

2013-01-01

Several noninvasive predictive models were developed to substitute liver biopsy for fibrosis assessment. To evaluate the diagnostic value of fibronectin which reflect extracellular matrix metabolism and standard liver functions tests which reflect alterations in hepatic functions. Chronic hepatitis C (CHC) patients (n = 145) were evaluated using ROC curves and stepwise multivariate discriminant analysis (MDA) and was validated in 180 additional patients. Liver biochemical profile including transaminases, bilirubin, alkaline phosphatase, albumin, complete blood count were estimated. Fibronectin concentration was determined using monoclonal antibody and ELISA. A novel index named fibronectin discriminant score (FDS) based on fibronectin, APRI and albumin was developed. FDS produced areas under ROC curves (AUC) of 0.91 for significant fibrosis and 0.81 for advanced fibrosis. The FDS correctly classified 79% of the significant liver fibrosis patients (F2-F4) with 87% sensitivity and 75% specificity. The relative risk [odds ratio (OR)] of having significant liver fibrosis using the cut-off values determined by ROC curve analyses were 6.1 for fibronectin, 4.9 for APRI, and 4.2 for albumin. FDS predicted liver fibrosis with an OR of 16.8 for significant fibrosis and 8.6 for advanced fibrosis. The FDS had similar AUC and OR in the validation group to the estimation group without statistically significant difference. FDS predicted liver fibrosis with high degree of accuracy, potentially decreasing the number of liver biopsy required.

Strategies to improve chronic disease management in seven metro Boston community health centers.

PubMed

Ndumele, Chima D; Russell, Beverley E; Ayanian, John Z; Landon, Bruce E; Keegan, Thomas; O'Malley, A James; Hicks, Leroi S

2009-01-01

The Community, Health Center, and Academic Medicine Partnership Project (CHAMPP) is a partnership between medical researchers, community health centers (CHCs), and a community advisory committee focused on reducing cardiovascular morbidity related to hypertension and diabetes for non-Hispanic Black and Hispanic populations in Boston, Massachusetts. We conducted site visits at seven participating CHCs, located in Boston. The visits were to solicit health center staff opinions about site-specific barriers and enabling factors for optimum preventative cardiovascular care for racial/ethnic minority patients receiving hypertension and diabetes care at their centers. Site visits included a tour of each health center and a series of directed interviews with center personnel. Site visit notes were reviewed to identify themes that emerged during the course of each site visit. A summary matrix was developed for each health center, which included information regarding the most salient and persistent themes of the visit. Site visits uncovered several patient-, provider-, CHC-, and community-based factors that either facilitate or hinder optimal care of chronic disease patients. Commonly referenced barriers included the need for improved patient adherence to provider recommendations; insufficient time for providers to address complex health issues presented by patients and the need for a broader range of healthier food options in surrounding communities. Interactive patient groups and community health workers (CHWs) have been well received when implemented. Recommendations included adopting case management as a part of usual care for chronic disease patients; additionally, widespread implementation of CHWs may to provide a platform for more comprehensive care for patients.