40 CFR 132.6 - Application of part 132 requirements in Great Lakes States and Tribes.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the State of Indiana. (b) Effective September 5, 2000, the requirements of Procedure 3 in appendix F... in the States of Indiana, Michigan and Ohio. (d) Effective November 6, 2000, § 132.4(d)(2) shall...) Chemical mA bA Conversion factor (CF) Cadmium a,b 1.128 −3.6867 0.85 Chromium (III) a,b 0.819 +3.7256 0.316...

40 CFR 132.6 - Application of part 132 requirements in Great Lakes States and Tribes.

Code of Federal Regulations, 2013 CFR

2013-07-01

... the State of Indiana. (b) Effective September 5, 2000, the requirements of Procedure 3 in appendix F... in the States of Indiana, Michigan and Ohio. (d) Effective November 6, 2000, § 132.4(d)(2) shall...) Chemical mA bA Conversion factor (CF) Cadmium a,b 1.128 −3.6867 0.85 Chromium (III) a,b 0.819 +3.7256 0.316...

Monte Carlo calculation of dose rate conversion factors for external exposure to photon emitters in soil

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

Clovas, A.; Zanthos, S.; Antonopoulos-Domis, M.

2000-03-01

The dose rate conversion factors {dot D}{sub CF} (absorbed dose rate in air per unit activity per unit of soil mass, nGy h{sup {minus}1} per Bq kg{sup {minus}1}) are calculated 1 m above ground for photon emitters of natural radionuclides uniformly distributed in the soil. Three Monte Carlo codes are used: (1) The MCNP code of Los Alamos; (2) The GEANT code of CERN; and (3) a Monte Carlo code developed in the Nuclear Technology Laboratory of the Aristotle University of Thessaloniki. The accuracy of the Monte Carlo results is tested by the comparison of the unscattered flux obtained bymore » the three Monte Carlo codes with an independent straightforward calculation. All codes and particularly the MCNP calculate accurately the absorbed dose rate in air due to the unscattered radiation. For the total radiation (unscattered plus scattered) the {dot D}{sub CF} values calculated from the three codes are in very good agreement between them. The comparison between these results and the results deduced previously by other authors indicates a good agreement (less than 15% of difference) for photon energies above 1,500 keV. Antithetically, the agreement is not as good (difference of 20--30%) for the low energy photons.« less

Pseudomonas aeruginosa Regulated Intramembrane Proteolysis (RIP): Protease MucP can Overcome Mutations in the AlgO Periplasmic Protease to Restore Alginate Production in Nonmucoid Revertants.

PubMed

Delgado, Camila; Florez, Laura; Lollett, Ivonne; Lopez, Christine; Kangeyan, Shiva; Kumari, Hansi; Stylianou, Marios; Smiddy, Robert J; Schneper, Lisa; Sautter, Robert T; Szatmari, George; Mathee, Kalai

2018-05-21

The progression of cystic fibrosis (CF) from an acute to a chronic disease is often associated with the conversion of the opportunistic pathogen Pseudomonas aeruginosa from a nonmucoid form to a mucoid form in the lung. This conversion involves the overproduction of the exopolysaccharide alginate, whose production is under control of the AlgT/U sigma factor. This factor is regulated posttranslationally by an extremely unstable process and has been commonly attributed to mutations in the algT/U gene. By exploiting this unstable phenotype, we isolated 34 spontaneous nonmucoid variants arising from the mucoid strain PDO300, a PAO1 derivative containing the mucA22 allele commonly found in mucoid CF isolates. Complementation analysis using a minimal tiling path cosmid library revealed that most of these mutants mapped to two protease-encoding genes, algO also known as prc or PA3257 , and mucP. Interestingly, our algO mutations were complemented by both mucP and algO , leading us to delete, clone and overexpress mucP , algO , mucE and mucD in both wild-type PAO1 and in PDO300 backgrounds to better understand the regulation of this complex regulatory mechanism. Our findings suggest the regulatory proteases follow two pathways for regulated intramembrane proteolysis (RIP), where both the AlgO/MucP pathway and MucE/AlgW pathway are required in the wild type strain, but where the AlgO/MucP pathway can bypass the MucE/AlgW pathway in mucoid strains with membrane-associated forms of MucA with shortened C-termini, such as the MucA22 variant. This work gives us a better understanding of how alginate production is regulated in the clinically important mucoid variants of Pseudomonas aeruginosa. IMPORTANCE: Infection by the opportunistic pathogen Pseudomonas aeruginosa is the leading cause of morbidity and mortality seen in cystic fibrosis (CF) patients. Poor patient prognosis correlates with the genotypic and phenotypic change of the bacteria from a typical nonmucoid to a mucoid form in the CF lung, characterized by the overproduction of alginate. The expression of this exopolysaccharide is under the control an alternate sigma factor, AlgT/U, that is regulated post translationally by a series of proteases. A better understanding of this regulatory phenomenon will help in the development of therapies targeting alginate production, ultimately leading to an increase in the length and quality of life for those suffering from CF. Copyright © 2018 American Society for Microbiology.

Effect of echolocation behavior-related constant frequency-frequency modulation sound on the frequency tuning of inferior collicular neurons in Hipposideros armiger.

PubMed

Tang, Jia; Fu, Zi-Ying; Wei, Chen-Xue; Chen, Qi-Cai

2015-08-01

In constant frequency-frequency modulation (CF-FM) bats, the CF-FM echolocation signals include both CF and FM components, yet the role of such complex acoustic signals in frequency resolution by bats remains unknown. Using CF and CF-FM echolocation signals as acoustic stimuli, the responses of inferior collicular (IC) neurons of Hipposideros armiger were obtained by extracellular recordings. We tested the effect of preceding CF or CF-FM sounds on the shape of the frequency tuning curves (FTCs) of IC neurons. Results showed that both CF-FM and CF sounds reduced the number of FTCs with tailed lower-frequency-side of IC neurons. However, more IC neurons experienced such conversion after adding CF-FM sound compared with CF sound. We also found that the Q 20 value of the FTC of IC neurons experienced the largest increase with the addition of CF-FM sound. Moreover, only CF-FM sound could cause an increase in the slope of the neurons' FTCs, and such increase occurred mainly in the lower-frequency edge. These results suggested that CF-FM sound could increase the accuracy of frequency analysis of echo and cut-off low-frequency elements from the habitat of bats more than CF sound.

Empirical Leucine-to-Carbon Conversion Factors for Estimating Heterotrophic Bacterial Production: Seasonality and Predictability in a Temperate Coastal Ecosystem▿

PubMed Central

Calvo-Díaz, Alejandra; Morán, Xosé Anxelu G.

2009-01-01

Leucine-to-carbon conversion factors (CFs) are needed for converting substrate incorporation into biomass production of heterotrophic bacteria. During 2006 we performed 20 dilution experiments for determining the spatiotemporal variability of empirical CFs in temperate Atlantic coastal waters. Values (0.49 to 1.92 kg C mol Leu−1) showed maxima in autumn to early winter and minima in summer. Spatially averaged CFs were significantly negatively correlated with in situ leucine incorporation rates (r = −0.91) and positively correlated with phosphate concentrations (r = 0.76). These relationships, together with a strong positive covariation between cell-specific leucine incorporation rates and carbon contents (r = 0.85), were interpreted as a strategy to maximize survival through protein synthesis and low growth rates under nutrient limitation (low CFs) until favorable conditions stimulate cell division relative to protein synthesis (high CFs). A multiple regression with in situ leucine incorporation rates and cellular carbon contents explained 96% of CF variance in our ecosystem, suggesting their potential prediction from more easily measurable routine variables. The use of the theoretical CF of 1.55 kg C mol Leu−1 would have resulted in a serious overestimation (73%) of annual bacterial production rates. Our results emphasize the need for considering the temporal scale in CFs for bacterial production studies. PMID:19304821

Analysis of contributing factors associated to related patients safety incidents in Intensive Care Medicine.

PubMed

Martín Delgado, M C; Merino de Cos, P; Sirgo Rodríguez, G; Álvarez Rodríguez, J; Gutiérrez Cía, I; Obón Azuara, B; Alonso Ovies, Á

2015-01-01

To explore contributing factors (CF) associated to related critical patients safety incidents. SYREC study pos hoc analysis. A total of 79 Intensive Care Departments were involved. The study sample consisted of 1.017 patients; 591 were affected by one or more incidents. The CF were categorized according to a proposed model by the National Patient Safety Agency from United Kingdom that was modified. Type, class and severity of the incidents was analyzed. A total 2,965 CF were reported (1,729 were associated to near miss and 1,236 to adverse events). The CF group more frequently reported were related patients factors. Individual factors were reported more frequently in near miss and task related CF in adverse events. CF were reported in all classes of incidents. The majority of CF were reported in the incidents classified such as less serious, even thought CF patients factors were associated to serious incidents. Individual factors were considered like avoidable and patients factors as unavoidable. The CF group more frequently reported were patient factors and was associated to more severe and unavoidable incidents. By contrast, individual factors were associated to less severe and avoidable incidents. In general, CF most frequently reported were associated to near miss. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Phase II study of chemoselection with docetaxel plus cisplatin and 5-fluorouracil induction chemotherapy and subsequent conversion surgery for locally advanced unresectable oesophageal cancer.

PubMed

Yokota, Tomoya; Kato, Ken; Hamamoto, Yasuo; Tsubosa, Yasuhiro; Ogawa, Hirofumi; Ito, Yoshinori; Hara, Hiroki; Ura, Takashi; Kojima, Takashi; Chin, Keisho; Hironaka, Shuichi; Kii, Takayuki; Kojima, Yasushi; Akutsu, Yasunori; Matsushita, Hisayuki; Kawakami, Kentaro; Mori, Keita; Nagai, Yushi; Asami, Chika; Kitagawa, Yuko

2016-11-22

The standard treatment for locally advanced unresectable squamous cell carcinoma (SCC) of the oesophagus is chemoradiation with cisplatin and 5-fluorouracil (CF-RT). This multicentre phase II trial assessed the safety and efficacy of chemoselection with docetaxel plus cisplatin and 5-fluorouracil (DCF) induction chemotherapy (ICT) and subsequent conversion surgery (CS) for initially unresectable locally advanced SCC of the oesophagus. Patients with clinical T4 and/or unresectable supraclavicular lymph node metastasis were eligible. Treatment started with three cycles of DCF-ICT, followed by CS if resectable, or by CF-RT if unresectable. The resectability was re-evaluated at 30-40 Gy of CF-RT, followed by CS if resectable, or by completion of 60 Gy of CF-RT. If resectable after CF-RT, CS was performed. The primary end point was 1-year overall survival (OS). From April 2013 to July 2014, 48 patients were enrolled. CS was performed in 41.7% (n=20), including DCF-CS (n=18), DCF-CF-RT40Gy-CS (n=1), and DCF-CF-RT60Gy-CS (n=1). R0 resection was confirmed in 19 patients (39.6%). Grade ⩾3 postoperative complications included one event each of recurrent laryngeal nerve palsy, lung infection, wound infection, pulmonary fistula, and dysphagia; but no serious postoperative complications were observed in patients undergoing CS. Clinical complete response after CF-RT was confirmed in 4 patients (8.3%). The estimated 1-year OS was 67.9% and lower limit of 80% confidence interval was 59.7%. There was one treatment-related death in patient receiving DCF-CF-RT60Gy. Chemoselection with DCF-ICT followed by CS as a multidisciplinary treatment strategy showed promising signs of tolerability and efficacy in patients with locally advanced unresectable SCC of the oesophagus.

Phase II study of chemoselection with docetaxel plus cisplatin and 5-fluorouracil induction chemotherapy and subsequent conversion surgery for locally advanced unresectable oesophageal cancer

PubMed Central

Yokota, Tomoya; Kato, Ken; Hamamoto, Yasuo; Tsubosa, Yasuhiro; Ogawa, Hirofumi; Ito, Yoshinori; Hara, Hiroki; Ura, Takashi; Kojima, Takashi; Chin, Keisho; Hironaka, Shuichi; Kii, Takayuki; Kojima, Yasushi; Akutsu, Yasunori; Matsushita, Hisayuki; Kawakami, Kentaro; Mori, Keita; Nagai, Yushi; Asami, Chika; Kitagawa, Yuko

2016-01-01

Background: The standard treatment for locally advanced unresectable squamous cell carcinoma (SCC) of the oesophagus is chemoradiation with cisplatin and 5-fluorouracil (CF-RT). This multicentre phase II trial assessed the safety and efficacy of chemoselection with docetaxel plus cisplatin and 5-fluorouracil (DCF) induction chemotherapy (ICT) and subsequent conversion surgery (CS) for initially unresectable locally advanced SCC of the oesophagus. Methods: Patients with clinical T4 and/or unresectable supraclavicular lymph node metastasis were eligible. Treatment started with three cycles of DCF-ICT, followed by CS if resectable, or by CF-RT if unresectable. The resectability was re-evaluated at 30–40 Gy of CF-RT, followed by CS if resectable, or by completion of 60 Gy of CF-RT. If resectable after CF-RT, CS was performed. The primary end point was 1-year overall survival (OS). Results: From April 2013 to July 2014, 48 patients were enrolled. CS was performed in 41.7% (n=20), including DCF-CS (n=18), DCF-CF-RT40Gy-CS (n=1), and DCF-CF-RT60Gy-CS (n=1). R0 resection was confirmed in 19 patients (39.6%). Grade ⩾3 postoperative complications included one event each of recurrent laryngeal nerve palsy, lung infection, wound infection, pulmonary fistula, and dysphagia; but no serious postoperative complications were observed in patients undergoing CS. Clinical complete response after CF-RT was confirmed in 4 patients (8.3%). The estimated 1-year OS was 67.9% and lower limit of 80% confidence interval was 59.7%. There was one treatment-related death in patient receiving DCF-CF-RT60Gy. Conclusions: Chemoselection with DCF-ICT followed by CS as a multidisciplinary treatment strategy showed promising signs of tolerability and efficacy in patients with locally advanced unresectable SCC of the oesophagus. PMID:27811857

Production of fermentable sugars from corn fiber using soaking in aqueous ammonia (saa) pretreatment and fermentation to succinic acid by Escherichia coli afp184

USDA-ARS?s Scientific Manuscript database

Conversion of corn fiber (CF), a by-product from the corn-to-ethanol conversion process, into fermentable sugar and succinic acid was investigated using soaking in aqueous ammonia (SAA) pretreatment followed by biological conversions including enzymatic hydrolysis and fermentation using genetically ...

Nitric oxide deficiency contributes to impairment of airway relaxation in cystic fibrosis mice.

PubMed

Mhanna, M J; Ferkol, T; Martin, R J; Dreshaj, I A; van Heeckeren, A M; Kelley, T J; Haxhiu, M A

2001-05-01

The pulmonary disease of cystic fibrosis (CF) is characterized by persistent airway obstruction, which has been attributed to chronic endobronchial infection and inflammation. The levels of exhaled nitric oxide (NO) are reduced in CF patients, which could contribute to bronchial obstruction through dysregulated constriction of airway smooth muscle. Because airway epithelium from CF mice has been shown to have reduced expression of inducible NO synthase, we examined airway responsiveness and relaxation in isolated tracheas of CF mice. Airway relaxation as measured by percent relaxation of precontracted tracheal segments to electrical field stimulation (EFS) and substance P, a nonadrenergic, noncholinergic substance, was significantly impaired in CF mice. The airway relaxation in response to prostaglandin E2 was similar in CF and non-CF animals. Treatment with the NO synthase inhibitor NG-nitro-L-arginine methylester reduced tracheal relaxation induced by EFS in wild-type animals but had virtually no effect in the CF mice. Conversely, exogenous NO and L-arginine, a NO substrate, reversed the relaxation defect in CF airway. We conclude that the relative absence of NO compromises airways relaxation in CF, and may contribute to the bronchial obstruction seen in the disease.

Uptake of dissolved inorganic and organic nitrogen by the benthic toxic dinoflagellate Ostreopsis cf. ovata.

PubMed

Jauzein, Cécile; Couet, Douglas; Blasco, Thierry; Lemée, Rodolphe

2017-05-01

Environmental factors that shape dynamics of benthic toxic blooms are largely unknown. In particular, for the toxic dinoflagellate Ostreopsis cf. ovata, the importance of the availability of nutrients and the contribution of the inorganic and organic pools to growth need to be quantified in marine coastal environments. The present study aimed at characterizing N-uptake of dissolved inorganic and organic sources by O. cf. ovata cells, using the 15 N-labelling technique. Experiments were conducted taking into account potential interactions between nutrient uptake systems as well as variations with the diel cycle. Uptake abilities of O. cf. ovata were parameterized for ammonium (NH 4 + ), nitrate (NO 3 - ) and N-urea, from the estimation of kinetic and inhibition parameters. In the range of 0 to 10μmolNL -1 , kinetic curves showed a clear preference pattern following the ranking NH 4 + >NO 3 - >N-urea, where the preferential uptake of NH 4 + relative to NO 3 - was accentuated by an inhibitory effect of NH 4 + concentration on NO 3 - uptake capabilities. Conversely, under high nutrient concentrations, the preference for NH 4 + relative to NO 3 - was largely reduced, probably because of the existence of a low-affinity high capacity inducible NO 3 - uptake system. Ability to take up nutrients in darkness could not be defined as a competitive advantage for O. cf. ovata. Species competitiveness can also be defined from nutrient uptake kinetic parameters. A strong affinity for NH 4 + was observed for O. cf. ovata cells that may partly explain the success of this toxic species during the summer season in the Bay of Villefranche-sur-mer (France). Copyright © 2017 Elsevier B.V. All rights reserved.

Spectral correction factors for conventional neutron dosemeters used in high-energy neutron environments.

PubMed

Lee, K W; Sheu, R J

2015-04-01

High-energy neutrons (>10 MeV) contribute substantially to the dose fraction but result in only a small or negligible response in most conventional moderated-type neutron detectors. Neutron dosemeters used for radiation protection purpose are commonly calibrated with (252)Cf neutron sources and are used in various workplace. A workplace-specific correction factor is suggested. In this study, the effect of the neutron spectrum on the accuracy of dose measurements was investigated. A set of neutron spectra representing various neutron environments was selected to study the dose responses of a series of Bonner spheres, including standard and extended-range spheres. By comparing (252)Cf-calibrated dose responses with reference values based on fluence-to-dose conversion coefficients, this paper presents recommendations for neutron field characterisation and appropriate correction factors for responses of conventional neutron dosemeters used in environments with high-energy neutrons. The correction depends on the estimated percentage of high-energy neutrons in the spectrum or the ratio between the measured responses of two Bonner spheres (the 4P6_8 extended-range sphere versus the 6″ standard sphere). © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lipotoxin F of Pseudomonas aeruginosa is an AlgU-dependent and alginate-independent outer membrane protein involved in resistance to oxidative stress and adhesion to A549 human lung epithelia.

PubMed

Damron, F Heath; Napper, Jennifer; Teter, M Allison; Yu, Hongwei D

2009-04-01

Chronic lung infection with P. aeruginosa and excessive neutrophil-associated inflammation are major causes of morbidity and mortality in patients with cystic fibrosis (CF). Overproduction of an exopolysaccharide known as alginate leads to the formation of mucoid biofilms that are resistant to antibiotics and host defences. Alginate overproduction or mucoidy is controlled by a stress-related ECF sigma factor AlgU/T. Mutation in the anti-sigma factor MucA is a known mechanism for conversion to mucoidy. Recently, we showed that inactivation of a kinase (KinB) in nonmucoid strain PAO1 results in overproduction of alginate. Here, we report the initial characterization of lipotoxin F (LptF, PA3692), an OmpA-like outer membrane protein that exhibited increased expression in the mucoid PAO1kinB mutant. The lipotoxin family of proteins has been previously shown to induce inflammation in lung epithelia, which may play a role in CF disease progression. Expression of LptF was observed to be AlgU-dependent and upregulated in CF isolates. Deletion of lptF from the kinB mutant had no effect on alginate production. Deletion of lptF from PAO1 caused a differential susceptibility to oxidants that can be generated by phagocytes. The lptF and algU mutants were more sensitive to hypochlorite than PAO1. However, the lptF mutant displayed increased resistance to hydrogen peroxide. LptF also contributed to adhesion to A549 human lung epithelial cells. Our data suggest that LptF is an outer membrane protein that may be important for P. aeruginosa survival in harsh environments, including lung colonization in CF.

Lipotoxin F of Pseudomonas aeruginosa is an AlgU-dependent and alginate-independent outer membrane protein involved in resistance to oxidative stress and adhesion to A549 human lung epithelia

PubMed Central

Damron, F. Heath; Napper, Jennifer; Teter, M. Allison; Yu, Hongwei D.

2009-01-01

Chronic lung infection with P. aeruginosa and excessive neutrophil-associated inflammation are major causes of morbidity and mortality in patients with cystic fibrosis (CF). Overproduction of an exopolysaccharide known as alginate leads to the formation of mucoid biofilms that are resistant to antibiotics and host defences. Alginate overproduction or mucoidy is controlled by a stress-related ECF sigma factor AlgU/T. Mutation in the anti-sigma factor MucA is a known mechanism for conversion to mucoidy. Recently, we showed that inactivation of a kinase (KinB) in nonmucoid strain PAO1 results in overproduction of alginate. Here, we report the initial characterization of lipotoxin F (LptF, PA3692), an OmpA-like outer membrane protein that exhibited increased expression in the mucoid PAO1kinB mutant. The lipotoxin family of proteins has been previously shown to induce inflammation in lung epithelia, which may play a role in CF disease progression. Expression of LptF was observed to be AlgU-dependent and upregulated in CF isolates. Deletion of lptF from the kinB mutant had no effect on alginate production. Deletion of lptF from PAO1 caused a differential susceptibility to oxidants that can be generated by phagocytes. The lptF and algU mutants were more sensitive to hypochlorite than PAO1. However, the lptF mutant displayed increased resistance to hydrogen peroxide. LptF also contributed to adhesion to A549 human lung epithelial cells. Our data suggest that LptF is an outer membrane protein that may be important for P. aeruginosa survival in harsh environments, including lung colonization in CF. PMID:19332805

Mixed Communities of Mucoid and Nonmucoid Pseudomonas aeruginosa Exhibit Enhanced Resistance to Host Antimicrobials.

PubMed

Malhotra, Sankalp; Limoli, Dominique H; English, Anthony E; Parsek, Matthew R; Wozniak, Daniel J

2018-03-27

Pseudomonas aeruginosa causes chronic pulmonary infections in patients with cystic fibrosis (CF). P. aeruginosa mucoid conversion, defined by overproduction of the exopolysaccharide alginate, correlates with accelerated decline in CF patient lung function. Recalcitrance of the mucoid phenotype to clearance by antibiotics and the immune response is well documented. However, despite advantages conferred by mucoidy, mucoid variants often revert to a nonmucoid phenotype both in vitro and in vivo Mixed populations of mucoid isolates and nonmucoid revertants are recovered from CF lungs, suggesting a selective benefit for coexistence of these variants. In this study, cocultures of mucoid and nonmucoid variants exhibited enhanced resistance to two host antimicrobials: LL-37, a cationic antimicrobial peptide, and hydrogen peroxide (H 2 O 2 ). Alginate production by mucoid isolates protected nonmucoid variants in consortia from LL-37, as addition of alginate exogenously to nonmucoid variants abrogated LL-37 killing. Conversely, nonmucoid revertants shielded mucoid variants from H 2 O 2 stress via catalase (KatA) production, which was transcriptionally repressed by AlgT and AlgR, central regulators of alginate biosynthesis. Furthermore, extracellular release of KatA by nonmucoid revertants was dependent on lys , encoding an endolysin implicated in autolysis and extracellular DNA (eDNA) release. Overall, these data provide a rationale to study interactions of P. aeruginosa mucoid and nonmucoid variants as contributors to evasion of innate immunity and persistence within the CF lung. IMPORTANCE P. aeruginosa mucoid conversion within lungs of cystic fibrosis (CF) patients is a hallmark of chronic infection and predictive of poor prognosis. The selective benefit of mixed populations of mucoid and nonmucoid variants, often isolated from chronically infected CF patients, has not been explored. Here, we show that mixed-variant communities of P. aeruginosa demonstrate advantages in evasion of innate antimicrobials via production of shared goods: alginate and catalase. These data argue for therapeutically targeting multiple constituents (both mucoid and nonmucoid variants) within diversified P. aeruginosa communities in vivo , as these variants can differentially shield one another from components of the host response. Copyright © 2018 Malhotra et al.

Factors Accounting for a Missed Diagnosis of Cystic Fibrosis After Newborn Screening

PubMed Central

Rock, Michael J.; Levy, Hara; Zaleski, Christina; Farrell, Philip M.

2015-01-01

Summary Newborn screening is a public health policy program involving the centralized testing laboratory, infant and their family, primary care provider, and subspecialist for confirmatory testing and follow-up of abnormal results. Cystic fibrosis (CF) newborn screening has now been enacted in all 50 states and the District of Columbia and throughout many countries in the world. Although CF neonatal screening will identify the vast majority of infants with CF, there are many factors in the newborn screening system that can lead to a missed diagnosis of CF. To inform clinicians, this article summarizes the CF newborn screening system and highlights 14 factors that can account for a missed diagnosis of CF. Care providers should maintain a high suspicion for CF if there are compatible symptoms, regardless of the results of the newborn screening test. These factors in newborn screening programs leading to a missed diagnosis of CF present opportunities for quality improvement in specimen collection, laboratory analysis of immunoreactive tryspinogen (IRT) and CF mutation testing, communication, and sweat testing. PMID:22081556

Towards Computational Fronesis: Verifying Contextual Appropriateness of Emotions

ERIC Educational Resources Information Center

Ptaszynski, Michal; Dybala, Pawel; Mazur, Michal; Rzepka, Rafal; Araki, Kenji; Momouchi, Yoshio

2013-01-01

This paper presents research in Contextual Affect Analysis (CAA) for the need of future application in intelligent agents, such as conversational agents or artificial tutors. The authors propose a new term, Computational Fronesis (CF), to embrace the tasks included in CAA applied to development of conversational agents such as artificial tutors.…

Multiphoton correlations in parametric down-conversion and their measurement in the pulsed regime

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

Ivanova, O A; Iskhakov, T Sh; Penin, A N

2006-10-31

We consider normalised intensity correlation functions (CFs) of different orders for light emitted via parametric down-conversion (PDC) and their dependence on the number of photons per mode. The main problem in measuring such correlation functions is their extremely small width, which considerably reduces their contrast. It is shown that if the radiation under study is modulated by a periodic sequence of pulses that are short compared to the CF width, no decrease in the contrast occurs. A procedure is proposed for measuring normalised CFs of various orders in the pulsed regime. For nanosecond-pulsed PDC radiation, normalised second-order CF is measuredmore » experimentally as a function of the mean photon number. (nonlinear optical phenomena)« less

Long-term-average spectrum characteristics of Kunqu Opera singers' speaking, singing and stage speech.

PubMed

Dong, Li; Kong, Jiangping; Sundberg, Johan

2014-07-01

Long-term-average spectrum (LTAS) characteristics were analyzed for ten Kunqu Opera singers, two in each of five roles. Each singer performed singing, stage speech, and conversational speech. Differences between the roles and between their performances of these three conditions are examined. After compensating for Leq difference LTAS characteristics still differ between the roles but are similar for the three conditions, especially for Colorful face (CF) and Old man roles, and especially between reading and singing. The curves show no evidence of a singer's formant cluster peak, but the CF role demonstrates a speaker's formant peak near 3 kHz. The LTAS characteristics deviate markedly from non-singers' standard conversational speech as well as from those of Western opera singing.

Applicability of the quantification of genetically modified organisms to foods processed from maize and soy.

PubMed

Yoshimura, Tomoaki; Kuribara, Hideo; Matsuoka, Takeshi; Kodama, Takashi; Iida, Mayu; Watanabe, Takahiro; Akiyama, Hiroshi; Maitani, Tamio; Furui, Satoshi; Hino, Akihiro

2005-03-23

The applicability of quantifying genetically modified (GM) maize and soy to processed foods was investigated using heat treatment processing models. The detection methods were based on real-time quantitative polymerase chain reaction (PCR) analysis. Ground seeds of insect resistant GM maize (MON810) and glyphosate tolerant Roundup Ready (RR) soy were dissolved in water and were heat treated by autoclaving for various time intervals. The calculated copy numbers of the recombinant and taxon specific deoxyribonucleic acid (DNA) sequences in the extracted DNA solution were found to decrease with time. This decrease was influenced by the PCR-amplified size. The conversion factor (Cf), which is the ratio of the recombinant DNA sequence to the taxon specific DNA sequence and is used as a constant number for calculating GM% at each event, tended to be stable when the sizes of PCR products of two DNA sequences were nearly equal. The results suggested that the size of the PCR product plays a key role in the quantification of GM organisms in processed foods. It is believed that the Cf of the endosperm (3n) is influenced by whether the GM originated from a paternal or maternal source. The embryos and endosperms were separated from the F1 generation seeds of five GM maize events, and their Cf values were measured. Both paternal and maternal GM events were identified. In these, the endosperm Cf was lower than that of the embryo, and the embryo Cf was lower than that of the endosperm. These results demonstrate the difficulties encountered in the determination of GM% in maize grains (F2 generation) and in processed foods from maize and soy.

A mechanism accounting for the low cellular level of linoleic acid in cystic fibrosis and its reversal by DHA.

PubMed

Al-Turkmani, M Rabie; Andersson, Charlotte; Alturkmani, Ragheed; Katrangi, Waddah; Cluette-Brown, Joanne E; Freedman, Steven D; Laposata, Michael

2008-09-01

Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The principal alterations include decreased levels of linoleic acid (LA) and docosahexaenoic acid (DHA). We investigated the potential mechanisms of these alterations by studying the cellular uptake of LA and DHA, their distribution among lipid classes, and the metabolism of LA in a human bronchial epithelial cell model of CF. CF (antisense) cells demonstrated decreased levels of LA and DHA compared with wild type (WT, sense) cells expressing normal CFTR. Cellular uptake of LA and DHA was higher in CF cells compared with WT cells at 1 h and 4 h. Subsequent incorporation of LA and DHA into most lipid classes and individual phospholipids was also increased in CF cells. The metabolic conversion of LA to n-6 metabolites, including 18:3n-6 and arachidonic acid, was upregulated in CF cells, indicating increased flux through the n-6 pathway. Supplementing CF cells with DHA inhibited the production of LA metabolites and corrected the n-6 fatty acid defect. In conclusion, the evidence suggests that low LA level in cultured CF cells is due to its increased metabolism, and this increased LA metabolism is corrected by DHA supplementation.

Development and validation of an event-specific quantitative PCR method for genetically modified maize MIR162.

PubMed

Takabatake, Reona; Masubuchi, Tomoko; Futo, Satoshi; Minegishi, Yasutaka; Noguchi, Akio; Kondo, Kazunari; Teshima, Reiko; Kurashima, Takeyo; Mano, Junichi; Kitta, Kazumi

2014-01-01

A novel real-time PCR-based analytical method was developed for the event-specific quantification of a genetically modified (GM) maize event, MIR162. We first prepared a standard plasmid for MIR162 quantification. The conversion factor (Cf) required to calculate the genetically modified organism (GMO) amount was empirically determined for two real-time PCR instruments, the Applied Biosystems 7900HT (ABI7900) and the Applied Biosystems 7500 (ABI7500) for which the determined Cf values were 0.697 and 0.635, respectively. To validate the developed method, a blind test was carried out in an interlaboratory study. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDr). The determined biases were less than 25% and the RSDr values were less than 20% at all evaluated concentrations. These results suggested that the limit of quantitation of the method was 0.5%, and that the developed method would thus be suitable for practical analyses for the detection and quantification of MIR162.

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

Resch, M.

Enzymatic depolymerization of polysaccharides is a key step in the production of fuels and chemicals from lignocellulosic biomass, and discovery of synergistic biomass-degrading enzyme paradigms will enable improved conversion processes. Historically, revealing insights into enzymatic saccharification mechanisms on plant cell walls has been hindered by uncharacterized substrates and low resolution imaging techniques. Also, translating findings between model substrates to intact biomass is critical for evaluating enzyme performance. Here we employ a fungal free enzyme cocktail, a complexed cellulosomal system, and a combination of the two to investigate saccharification mechanisms on cellulose I, II and III along with corn stover frommore » Clean Fractionation (CF), which is an Organosolv pretreatment. The insoluble Cellulose Enriched Fraction (CEF) from CF contains mainly cellulose with minor amounts of residual hemicellulose and lignin, the amount of which depends on the CF pretreatment severity. Enzymatic digestions at both low and high-solids loadings demonstrate that CF reduces the amount of enzyme required to depolymerize polysaccharides relative to deacetylated, dilute acid pretreated corn stover. Transmission and scanning electron microscopy of the biomass provides evidence for the different mechanisms of enzymatic deconstruction between free and complexed enzyme systems, and reveals the basis for the synergistic relationship between the two enzyme paradigms on a process-relevant substrate for the first time. These results also demonstrate that the presence of lignin, rather than cellulose morphology, is more detrimental to cellulosome action than to free cellulases. As enzyme costs are a major economic driver for biorefineries, this study provides key inputs for the evaluation of CF as a pretreatment method for biomass conversion.« less

Development of a Method to Implement Whole-Genome Bisulfite Sequencing of cfDNA from Cancer Patients and a Mouse Tumor Model.

PubMed

Maggi, Elaine C; Gravina, Silvia; Cheng, Haiying; Piperdi, Bilal; Yuan, Ziqiang; Dong, Xiao; Libutti, Steven K; Vijg, Jan; Montagna, Cristina

2018-01-01

The goal of this study was to develop a method for whole genome cell-free DNA (cfDNA) methylation analysis in humans and mice with the ultimate goal to facilitate the identification of tumor derived DNA methylation changes in the blood. Plasma or serum from patients with pancreatic neuroendocrine tumors or lung cancer, and plasma from a murine model of pancreatic adenocarcinoma was used to develop a protocol for cfDNA isolation, library preparation and whole-genome bisulfite sequencing of ultra low quantities of cfDNA, including tumor-specific DNA. The protocol developed produced high quality libraries consistently generating a conversion rate >98% that will be applicable for the analysis of human and mouse plasma or serum to detect tumor-derived changes in DNA methylation.

Research on Organofluorine Chemistry for 700 Degrees F Thermooxidative Stability

DTIC Science & Technology

1994-06-29

8217) 4 NC-OC (CF’), CH, + NC- OCH2CF3 The products can be readily converted to amides , i.e., R-O CN H O,/KOH >C2H3OH 0()~ Conversion of these amides ...isopropyl)phenyl, pentamethylcyclopentadiene (Cp’), (b) highly substituted methyl systems, e.g., bis (trimethylsilyl)methyl and tris(trimethylsilyl)methyl... fluorosulfonyl derivatives, find application in the production of strong sulfonic acids, ion-exchange resins, surface active agents and perfluorinated

Related factors of dental caries and molar incisor hypomineralisation in a group of children with cystic fibrosis.

PubMed

Peker, S; Mete, S; Gokdemir, Y; Karadag, B; Kargul, B

2014-08-01

To investigate dental caries and molar incisor hypomineralisation (MIH)-related factors such as treatment, diet, brushing and salivary factors in children with cystic fibrosis (CF) compared with healthy peers. A cohort study was performed. This study was performed on 30 CF children comprising patients at the Faculty of Medicine and 30 control children recruited from the Dental School. Salivary factors, dental caries, MIH, daily diet, brushing habits were analysed. Statistical analysis was calculated by SPSS for Windows. Decay missing filled teeth (DMF-T) score was 4.6 ± 4.0 in CF and 7.7 ± 2.7 in control (p = 0.001). 43% of CF children with MIH were found to use antibiotics, but no significant difference in the caries experience was found with antibiotic usage (p > 0.05). DMF-T of CF adolescents (23%) who use Tobramycin was 7 ± 3.5. DMF-T of CF children (20%) who take other antibiotics was 2.5 ± 3.5, but no statistical difference was found (p = 0.054). Saliva pH, salivary flow rate, and buffering capacity were not found statistically significant (p > 0.05). Percentage arithmetic mean value, standard deviation, independent sample t test, Fisher's exact test, Chi-square test and Mann-Whitney U test were used, while a p value of <0.05 was considered statistically significant. Medication and diet could be considered as a risk factor for dental caries and factors such as salivary pH, good oral hygiene could play a protective role for oral health CF children. MIH frequency and lower caries experience seen in CF children could be due to salivary factors or pharmacological treatment they take. The multidisciplinary approach team would be advantageous in the management of children with CF and oral health should be under control during early years of life by paediatric dentists.

Pseudomonas Pyocyanin Increases Interleukin-8 Expression by Human Airway Epithelial Cells

PubMed Central

Denning, Gerene M.; Wollenweber, Laura A.; Railsback, Michelle A.; Cox, Charles D.; Stoll, Lynn L.; Britigan, Bradley E.

1998-01-01

Pseudomonas aeruginosa, an opportunistic human pathogen, causes acute pneumonia in patients with hospital-acquired infections and is commonly associated with chronic lung disease in individuals with cystic fibrosis (CF). Evidence suggests that the pathophysiological effects of P. aeruginosa are mediated in part by virulence factors secreted by the bacterium. Among these factors is pyocyanin, a redox active compound that increases intracellular oxidant stress. We find that pyocyanin increases release of interleukin-8 (IL-8) by both normal and CF airway epithelial cell lines and by primary airway epithelial cells. Moreover, pyocyanin synergizes with the inflammatory cytokines tumor necrosis factor alpha and IL-1α. RNase protection assays indicate that increased IL-8 release is accompanied by increased levels of IL-8 mRNA. The antioxidant n-acetyl cysteine, general inhibitors of protein tyrosine kinases, and specific inhibitors of mitogen-activated protein kinases diminish pyocyanin-dependent increases in IL-8 release. Conversely, inhibitors of protein kinases C (PKC) and PKA have no effect. In contrast to its effects on IL-8 expression, pyocyanin inhibits cytokine-dependent expression of the monocyte/macrophage/T-cell chemokine RANTES. Increased release of IL-8, a potent neutrophil chemoattractant, in response to pyocyanin could contribute to the marked infiltration of neutrophils and subsequent neutrophil-mediated tissue damage that are observed in Pseudomonas-associated lung disease. PMID:9826354

Mixed Communities of Mucoid and Nonmucoid Pseudomonas aeruginosa Exhibit Enhanced Resistance to Host Antimicrobials

PubMed Central

Malhotra, Sankalp; Limoli, Dominique H.; English, Anthony E.; Parsek, Matthew R.

2018-01-01

ABSTRACT Pseudomonas aeruginosa causes chronic pulmonary infections in patients with cystic fibrosis (CF). P. aeruginosa mucoid conversion, defined by overproduction of the exopolysaccharide alginate, correlates with accelerated decline in CF patient lung function. Recalcitrance of the mucoid phenotype to clearance by antibiotics and the immune response is well documented. However, despite advantages conferred by mucoidy, mucoid variants often revert to a nonmucoid phenotype both in vitro and in vivo. Mixed populations of mucoid isolates and nonmucoid revertants are recovered from CF lungs, suggesting a selective benefit for coexistence of these variants. In this study, cocultures of mucoid and nonmucoid variants exhibited enhanced resistance to two host antimicrobials: LL-37, a cationic antimicrobial peptide, and hydrogen peroxide (H2O2). Alginate production by mucoid isolates protected nonmucoid variants in consortia from LL-37, as addition of alginate exogenously to nonmucoid variants abrogated LL-37 killing. Conversely, nonmucoid revertants shielded mucoid variants from H2O2 stress via catalase (KatA) production, which was transcriptionally repressed by AlgT and AlgR, central regulators of alginate biosynthesis. Furthermore, extracellular release of KatA by nonmucoid revertants was dependent on lys, encoding an endolysin implicated in autolysis and extracellular DNA (eDNA) release. Overall, these data provide a rationale to study interactions of P. aeruginosa mucoid and nonmucoid variants as contributors to evasion of innate immunity and persistence within the CF lung. PMID:29588399

Accuracy of effective dose estimation in personal dosimetry: a comparison between single-badge and double-badge methods and the MOSFET method.

PubMed

Januzis, Natalie; Belley, Matthew D; Nguyen, Giao; Toncheva, Greta; Lowry, Carolyn; Miller, Michael J; Smith, Tony P; Yoshizumi, Terry T

2014-05-01

The purpose of this study was three-fold: (1) to measure the transmission properties of various lead shielding materials, (2) to benchmark the accuracy of commercial film badge readings, and (3) to compare the accuracy of effective dose (ED) conversion factors (CF) of the U.S. Nuclear Regulatory Commission methods to the MOSFET method. The transmission properties of lead aprons and the accuracy of film badges were studied using an ion chamber and monitor. ED was determined using an adult male anthropomorphic phantom that was loaded with 20 diagnostic MOSFET detectors and scanned with a whole body CT protocol at 80, 100, and 120 kVp. One commercial film badge was placed at the collar and one at the waist. Individual organ doses and waist badge readings were corrected for lead apron attenuation. ED was computed using ICRP 103 tissue weighting factors, and ED CFs were calculated by taking the ratio of ED and badge reading. The measured single badge CFs were 0.01 (±14.9%), 0.02 (±9.49%), and 0.04 (±15.7%) for 80, 100, and 120 kVp, respectively. Current regulatory ED CF for the single badge method is 0.3; for the double-badge system, they are 0.04 (collar) and 1.5 (under lead apron at the waist). The double-badge system provides a better coefficient for the collar at 0.04; however, exposure readings under the apron are usually negligible to zero. Based on these findings, the authors recommend the use of ED CF of 0.01 for the single badge system from 80 kVp (effective energy 50.4 keV) data.

Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype.

PubMed

De Lisle, Robert C; Mueller, Racquel; Roach, Eileen

2010-09-15

Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl- channel, would improve the intestinal phenotype in CF mice. Cftr(tm1UNC) (CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR. Crypt width in control CF mice was 700% that of WT mice (P < 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (P = 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P = 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P = 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (P < 0.001) and CF mice (P < 0.001). Lubiprostone enhanced small intestinal transit in WT mice (P = 0.024) but not in CF mice (P = 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels. These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion.

Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype

PubMed Central

2010-01-01

Background Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl- channel, would improve the intestinal phenotype in CF mice. Methods Cftrtm1UNC (CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR. Results Crypt width in control CF mice was 700% that of WT mice (P < 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (P = 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P = 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P = 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (P < 0.001) and CF mice (P < 0.001). Lubiprostone enhanced small intestinal transit in WT mice (P = 0.024) but not in CF mice (P = 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels. Conclusions These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion. PMID:20843337

Influence of the DSM-IV Outline for Cultural Formulation on multidisciplinary case conferences in mental health.

PubMed

Dinh, Nathalie M H; Groleau, Danielle; Kirmayer, Laurence J; Rodriguez, Charo; Bibeau, Gilles

2012-01-01

The Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (DSM-IV-TR) includes an Outline for Cultural Formulation (CF) that identifies cultural information that can be used to modify diagnosis, clinical assessment and treatment plan. This study examined the use of the CF by a Cultural Consultation Service in the psychiatric assessment of patients referred by primary care providers. The study uses conversation analysis of 12 clinical case conferences to explore the ways in which the CF influenced the interaction of a multidisciplinary group of mental health professionals in conceptualizing the implications of patients' cultural background and current context for diagnosis and treatment planning. The results suggest that the CF can be a useful tool for interdisciplinary collaboration and knowledge transfer by providing a framework to systematically introduce different disciplinary perspectives and levels of description that transcend the narrow frame of disorder-centred psychiatric diagnosis, assessment and care.

Early severe anemia as the first sign of cystic fibrosis.

PubMed

Sismanlar, Tugba; Aslan, Ayşe Tana; Köse, Mehmet; Pekcan, Sevgi; Ezgü, Fatih Süheyl; Budakoğlu, Işıl İrem; Yenicesu, İdil

2016-09-01

Severe anemia is reported to occur rarely in patients with cystic fibrosis (CF). This study aimed to determine the factors associated with early severe anemia in infants with CF. This study included 231 infants with CF from 3 pediatric CF centers ten year period that were retrospectively reviewed in terms of severe anemia as the first sign of CF. Factors that could affect anemia, such as age, pancreatic insufficiency, mutations, vitamin A and E, and albumin level were evaluated. Clinical and laboratory findings in CF patients that presented with severe anemia and no respiratory symptoms were compared to those in CF patients that did not present with severe anemia. Severe anemia as the first sign of CF was noted in 17 of 231 patients. Patient age, prolonged PT/INR and the albumin level differed significantly between the 2 groups of patients (P < 0.001). Feeding pattern, pancreatic insufficiency, vitamin E and A levels, and the types of genetic mutations did not differ between the 2 groups. The mean hemoglobin level was 5.59 ± 0.21 g/dL and respiratory symptoms began a mean 6.3 months after diagnosis of CF in the anemia group. In early infancy severe anemia in the absence of respiratory symptoms can be the first sign of CF. CF should be considered in the differential diagnosis of severe anemia in infants. Anemia can occur several months before respiratory symptoms in patients with CF and may be caused due to several reasons. • Severe anemia as a first sign is reported to occur rarely in patients with cystic fibrosis. • Although anemia is well known in cystic fibrosis, factors that cause severe anemia are not known clearly. What is New: • This study shows the importance of severe anemia as the first sign of cystic fibrosis. • Anemia can occur several months before respiratory symptoms in patients with CF.

Factor Rotation and Standard Errors in Exploratory Factor Analysis

ERIC Educational Resources Information Center

Zhang, Guangjian; Preacher, Kristopher J.

2015-01-01

In this article, we report a surprising phenomenon: Oblique CF-varimax and oblique CF-quartimax rotation produced similar point estimates for rotated factor loadings and factor correlations but different standard error estimates in an empirical example. Influences of factor rotation on asymptotic standard errors are investigated using a numerical…

Work disability in adults with cystic fibrosis.

PubMed

Gillen, M; Lallas, D; Brown, C; Yelin, E; Blanc, P

1995-07-01

Greater numbers of persons with cystic fibrosis (CF) reach adulthood and, therefore, actively participate in the labor force. In this study, we estimated labor force participation rates and determined risk factors for work disability among persons with CF. We recruited 49 (73%) of 67 adults followed at one of two hospital-based CF centers. We ascertained employment history and CF-attributed work disability by structured questionnaire. Independently, we reviewed medical records for demographics and illness severity indicators. We analyzed potential risk factors for work disability by logistic regression analysis. All of those studied reported past or present labor force participation, consistent with high work motivation. Complete cessation of work attributed to CF was reported by 17 (35%; 95% CI, 21 to 49%). Although 23 (47%; 95% CI, 32 to 60%) of those surveyed stated that CF had affected career choice, only nine respondents had ever received career counselling and 16 had ever discussed job choice with their physicians. After adjusting for standard measures of disease severity by multiple logistic regression, age, adult diagnosis of CF, female gender, and single marital status, analyzed as a group, provided significant additional explanatory power to a predictive model of disability risk (model chi square [4 d.f.] = 11.5, p < 0.05). Health care professionals who design interventions targeted at work disability among persons with CF should address demographic factors as well as illness severity and should assess the vocational needs of persons with CF and the potential benefit of career counselling.

Regions of the Cf-9B disease resistance protein able to cause spontaneous necrosis in Nicotiana benthamiana lie within the region controlling pathogen recognition in tomato.

PubMed

Chakrabarti, Apratim; Panter, Stephen N; Harrison, Kate; Jones, Jonathan D G; Jones, David A

2009-10-01

The tomato Cf-9 and Cf-9B genes both confer resistance to the leaf mold fungus Cladosporium fulvum but only Cf-9 confers seedling resistance and recognizes the avirulence (Avr) protein Avr9 produced by C. fulvum. Using domain swaps, leucine-rich repeats (LRR) 5 to 15 of Cf-9 were shown to be required for Cf-9-specific resistance to C. fulvum in tomato, and the entire N-terminus up to LRR15 of Cf-9B was shown to be required for Cf-9B-specific resistance. Finer domain swaps showed that nine amino-acid differences in LRR 13 to 15 provided sufficient Cf-9-specific residues in a Cf-9B context for recognition of Avr9 in Nicotiana tabacum or sufficient Cf-9B residues in a Cf-9 context for a novel necrotic response caused by the expression of Cf-9B in N. benthamiana. The responses conferred by LRR 13 to 15 were enhanced by addition of LRR 10 to 12, and either region of Cf-9B was found to cause necrosis in N. benthamiana when the other was replaced by Cf-9 sequence in a Cf-9B context. As a consequence, the domain swap with LRR 13 to 15 of Cf-9 in a Cf-9B context gained the dual ability to recognize Avr9 and cause necrosis in N. benthamiana. Intriguingly, two Cf-9B-specific domain swaps gave differing results for necrosis assays in N. benthamiana compared with disease resistance assays in transgenic tomato. The different domain requirements in these two cases suggest that the two assays detect unrelated ligands or detect related ligands in slightly different ways. A heat-sensitive necrosis-inducing factor present in N. benthamiana intercellular washing fluids was found to cause a necrotic response in N. tabacum plants carrying Hcr9-9A, Cf-9B, and Cf-9 but not in plants carrying only Cf-9. We postulate that this necrosis-inducing factor is recognized by Cf-9B either directly as a ligand or indirectly as a regulator of Cf-9B autoactivity.

A numerical model for explaining the role of the interface morphology in composite solar cells

NASA Astrophysics Data System (ADS)

Martin, C. M.; Burlakov, V. M.; Assender, H. E.; Barkhouse, D. A. R.

2007-11-01

We have developed a numerical model that simulates the operation of organic/inorganic photovoltaic devices. Using this model, we have investigated the effect of the interface morphology and have shown that for a given system, there is both a most efficient device thickness and the interfacial feature size for overall power conversion. The variation of current-voltage (I-V) curves with differing recombination rates, anode barrier height, and light intensity has been simulated with reducing the recombination rate and lowering the anode barrier height shown to lead to improved open circuit voltages and fill factors. Through this model, we show that the increase in fill factor observed when the lithium salt Li[CF3SO2]2N is added to devices can be explained by an increase in the polymer hole mobility.

An exploration of the experience of compassion fatigue in clinical oncology nurses.

PubMed

Perry, Beth; Toffner, Greg; Merrick, Trish; Dalton, Janice

2011-01-01

Compassion fatigue (CF) is "debilitating weariness brought about by repetitive, empathic responses to the pain and suffering of others" (LaRowe, 2005, p. 21). The work performed by oncology nurses, and the experiences of the people they care for, place oncology nurses at high risk for CF (Pierce et al., 2007; Ferrell & Coyle, 2008). Thus oncology nurses were chosen as the study focus. This paper details a descriptive exploratory qualitative research study that investigated the experience of CF in Canadian clinical oncology registered nurses (RNs). A conceptual stress process model by Aneshensel, Pearlin, Mullan, Zarit, and Whitlatch (1995) that considers caregivers' stress in four domains provided the study framework (see Figure 1). Nineteen study participants were recruited through an advertisement in the Canadian Oncology Nursing Journal (CONJ). The advertisement directed potential participants to a university-based online website developed for this study. Participants completed a questionnaire and wrote a narrative describing an experience with CF and submitted these through the secure research website. Data were analyzed thematically. Five themes include: defining CF, causes of CF, factors that worsen CF, factors that lessen CF, and outcomes of CF. Participants had limited knowledge about CF, about lack of external support, and that insufficient time to provide high quality, care may precipitate CF. The gap between quality of care nurses wanted to provide and what they were able to do, compounded by coexisting physical and emotional stress, worsened CF. CF was lessened by colleague support, work-life balance, connecting with others, acknowledgement, and maturity and experience. Outcomes of CF included profound fatigue of mind and body, negative effects on personal relationships, and considering leaving the specialty. Recommendations that may enhance oncology nurse well-being are provided.

Attitudes and Decision Making Related to Pregnancy Among Young Women with Cystic Fibrosis.

PubMed

Kazmerski, Traci M; Gmelin, Theresa; Slocum, Breonna; Borrero, Sonya; Miller, Elizabeth

2017-04-01

Introduction The number of female patients with CF able to consider pregnancy has increased with improved therapies. This study explored attitudes and decision making regarding pregnancy among young women with CF. Methods Twenty-two women with CF ages 18-30 years completed semi-structured, in-person interviews exploring experiences with preconception counseling and reproductive care in the CF setting. Interviews were audio-recorded, transcribed, and coded using a thematic analysis approach. Results Participants indicated CF is a major factor in pregnancy decision making. Although women acknowledged that CF influences attitudes toward pregnancy, many expressed confusion about how CF can affect fertility/pregnancy. Many perceived disapproval from CF providers regarding pregnancy and were dissatisfied with reproductive care in the CF setting. Discussion Young female patients with CF reported poor understanding of the effect of CF on fertility and pregnancy and limited preconception counseling in CF care. Improvements in female sexual and reproductive health care in CF are warranted.

Growth assessment and risk factors of malnutrition in children with cystic fibrosis

PubMed Central

Isa, Hasan M.; Al-Ali, Lina F.; Mohamed, Afaf M.

2016-01-01

Objectives: To evaluate the nutritional status, to screen for the presence of malnutrition, and to study the possible risk factors associated with malnutrition in patients with cystic fibrosis (CF). Methods: A retrospective cross-sectional review of medical records of all diagnosed CF patients in the Pediatric Department, Salmaniya Medical Complex, Manama, Kingdom of Bahrain, between January 1984 and May 2015 was conducted. Demographic and anthropometric data were collected from records of last visit to CF clinic. Nutritional status and risk factors of malnutrition were assessed. Results: All records of 109 CF patients were reviewed. Forty-seven pediatric patients were included in the study. All included patients were on pancreatic enzyme replacement and 42 (89%) received high-calorie supplementation. Growth failure was noted in 34 (72%) patients, 19 (56%) were wasted and stunted, 8 (23.5%) were wasted only, and 7 (20.5%) were stunted. Low birth weight (p=0.032), and the presence of gastroesophageal reflux disease (GERD) (p=0.039) were the significant risk factors for malnutrition. Conclusion: Most CF patients in Bahrain (72%) are malnourished. Low birth weight and the presence of GERD are risk factors. PMID:26905352

Motility and Adhesiveness in Human Neutrophils

PubMed Central

Smith, C. Wayne; Hollers, James C.; Patrick, Richard A.; Hassett, Clare

1979-01-01

Human peripheral blood neutrophils (PMN) obtained from healthy adults were examined in vitro with techniques adapted to assess the effects of chemotactic factors (CF) on cellular configuration and adhesiveness. The results were compared with those that use certain conventional techniques for assessing chemotaxis and chemokinesis. Exposure of PMN to N-formyl-l-methionyl-l-phenylalanine (f-Met-Phe), zymosan-activated serum, bacterial chemotactic factor, or a low molecular weight chemotactic factor from activated serum (C5a) in the absence of a gradient resulted in a change in cellular shape from a spherical to a polarized configuration in a high percentage of cells. This occurred rapidly in suspension, under conditions designed to exclude a role for cell adhesiveness, and was reversible upon removal of the CF. Restimulation of cells with the CF resulted in reappearance of the polarized configuration to the same extent as on initial stimulation with one exception: f-Met-Phe pretreated cells failed to respond to f-Met-Phe, though they responded fully to the other CF. Each CF caused a significant increase in PMN attachment to protein-coated glass. This enhanced adhesiveness was not reversible upon removal of the CF when the cells were treated under conditions shown to produce chemotactic deactivation. Cells treated under these conditions also exhibited significantly reduced motility on glass and in micropore filters in the absence of a gradient of CF. Bacterial chemotactic factor, even at high concentrations, failed to produce deactivation and did not cause a sustained enhancement of adhesiveness. Images PMID:372238

Maternal cfDNA screening for Down syndrome--a cost sensitivity analysis.

PubMed

Cuckle, Howard; Benn, Peter; Pergament, Eugene

2013-07-01

This study aimed to determine the principal factors contributing to the cost of avoiding a birth with Down syndrome by using cell-free DNA (cfDNA) to replace conventional screening. A range of unit costs were assigned to each item in the screening process. Detection rates were estimated by meta-analysis and modeling. The marginal cost associated with the detection of additional cases using cfDNA was estimated from the difference in average costs divided by the difference in detection. The main factor was the unit cost of cfDNA testing. For example, replacing a combined test costing $150 with 3% false-positive rate and invasive testing at $1000, by cfDNA tests at $2000, $1500, $1000, and $500, the marginal cost is $8.0, $5.8, $3.6, and $1.4m, respectively. Costs were lower when replacing a quadruple test and higher for a 5% false-positive rate, but the relative importance of cfDNA unit cost was unchanged. A contingent policy whereby 10% to 20% women were selected for cfDNA testing by conventional screening was considerably more cost-efficient. Costs were sensitive to cfDNA uptake. Universal cfDNA screening for Down syndrome will only become affordable by public health purchasers if costs fall substantially. Until this happens, the contingent use of cfDNA is recommended. © 2013 John Wiley & Sons, Ltd.

Spatial Resolution Effects of Digital Terrain Models on Landslide Susceptibility Analysis

NASA Astrophysics Data System (ADS)

Chang, K. T.; Dou, J.; Chang, Y.; Kuo, C. P.; Xu, K. M.; Liu, J. K.

2016-06-01

The purposes of this study are to identify the maximum number of correlated factors for landslide susceptibility mapping and to evaluate landslide susceptibility at Sihjhong river catchment in the southern Taiwan, integrating two techniques, namely certainty factor (CF) and artificial neural network (ANN). The landslide inventory data of the Central Geological Survey (CGS, MOEA) in 2004-2014 and two digital elevation model (DEM) datasets including a 5-meter LiDAR DEM and a 30-meter Aster DEM were prepared. We collected thirteen possible landslide-conditioning factors. Considering the multi-collinearity and factor redundancy, we applied the CF approach to optimize these thirteen conditioning factors. We hypothesize that if the CF values of the thematic factor layers are positive, it implies that these conditioning factors have a positive relationship with the landslide occurrence. Therefore, based on this assumption and positive CF values, seven conditioning factors including slope angle, slope aspect, elevation, terrain roughness index (TRI), terrain position index (TPI), total curvature, and lithology have been selected for further analysis. The results showed that the optimized-factors model provides a better accuracy for predicting landslide susceptibility in the study area. In conclusion, the optimized-factors model is suggested for selecting relative factors of landslide occurrence.

CFTR and/or pancreatitis susceptibility genes mutations as risk factors of pancreatitis in cystic fibrosis patients?

PubMed

Gaitch, Natacha; Hubert, Dominique; Gameiro, Christine; Burgel, Pierre-Régis; Houriez, Florence; Martinez, Brigitte; Honoré, Isabelle; Chapron, Jeanne; Kanaan, Reem; Dusser, Daniel; Girodon, Emmanuelle; Bienvenu, Thierry

2016-01-01

Currently, factors that promote the occurrence of pancreatitis episodes in patients affected with cystic fibrosis (CF) and pancreatic sufficiency (PS) are largely unknown. Six genes involved in pancreatitis or in ion transport into the pancreatic duct were investigated by next generation sequencing in 59 adult CF-PS patients with two identified CF mutations. Data on predisposing environmental factors were also recorded. 19 experienced at least one episode of acute pancreatitis (AP) (AP+) and 40 patients did not (AP-). No influence of environmental factor was evidenced. No specific CFTR genotype was found predictive of pancreatitis. Patients sharing the same CFTR genotype may or may not experience AP episodes. Frequent and rare missense variants were found in 78.9% patients in group AP+ and 67.5% in group AP- but a few of them were pathogenic. AP or recurrent AP (RAP) is a frequent complication in our series of adult CF-PS patients. The majority of mild CFTR mutations found in group AP+ were located in the first transmembrane region. No clear other genetic factor could be found predictive of AP/RAP. Further experiments in large homogenous cohorts of CF-PS patients, including whole genome sequencing, may identify genetic predisposing factors to pancreatitis. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Rate constants and temperature dependences for the reactions of hydroxyl radical with several halogenated methanes, ethanes, and propanes by relative rate measurements

NASA Technical Reports Server (NTRS)

Hsu, K.-J.; DeMore, W. B.

1995-01-01

Rate constants of 15 OH reactions with halogen-substituted alkanes, C1 to C3, were studied using a relative rate technique in the temperature range 283-403 K. Compounds studied were CHF2Cl (22), CHF2Br (22B), CH3F (41), CH2F2 (32), CHF3 (23), CHClFCCl2F (122a), CHCl2CF3 (123), CHClFCF3 (124), CH3CF3 (143a), CH3CH2F (161), CF3CHFCF3 (227ea), CF3CH2CF3 (236fa), CF3CHFCHF2 (236ea), and CHF2CF2CH2F (245ca). Using CH4, CH3CCl3, CF3CF2H, and C2H6 as primary reference standards (JPL 92-20 rate constants), absolute rate constants are derived. Results are in good agreement with previous experimental results for six of the compounds studied, including CHF2Cl, CHF2Br, CH2F2, CH3CF3, CHFClCFCl2, and CF3CHFCF3. For the remainder the relative rate constants are lower than those derived from experiments in which OH loss was used to measure the reaction rate. Comparisons of the derived Arrhenius A factors with previous literature transition-state calculations show order of magnitude agreement in most cases. However, the experimental A factors show a much closer proportionality to the number of H atoms in the molecule than is evident from the transition state calculations. For most of the compounds studied, an A factor of (8 +/- 3)E-13 cm(exp 3)/(molecule s) per C-H bond is observed. A new measurement of the ratio k(CH3CCl3)/k(CH4) is reported that is in good agreement with previous data.

Development and Interlaboratory Validation of a Simple Screening Method for Genetically Modified Maize Using a ΔΔC(q)-Based Multiplex Real-Time PCR Assay.

PubMed

Noguchi, Akio; Nakamura, Kosuke; Sakata, Kozue; Sato-Fukuda, Nozomi; Ishigaki, Takumi; Mano, Junichi; Takabatake, Reona; Kitta, Kazumi; Teshima, Reiko; Kondo, Kazunari; Nishimaki-Mogami, Tomoko

2016-04-19

A number of genetically modified (GM) maize events have been developed and approved worldwide for commercial cultivation. A screening method is needed to monitor GM maize approved for commercialization in countries that mandate the labeling of foods containing a specified threshold level of GM crops. In Japan, a screening method has been implemented to monitor approved GM maize since 2001. However, the screening method currently used in Japan is time-consuming and requires generation of a calibration curve and experimental conversion factor (C(f)) value. We developed a simple screening method that avoids the need for a calibration curve and C(f) value. In this method, ΔC(q) values between the target sequences and the endogenous gene are calculated using multiplex real-time PCR, and the ΔΔC(q) value between the analytical and control samples is used as the criterion for determining analytical samples in which the GM organism content is below the threshold level for labeling of GM crops. An interlaboratory study indicated that the method is applicable independently with at least two models of PCR instruments used in this study.

Monitoring liver damage using hepatocyte-specific methylation markers in cell-free circulating DNA.

PubMed

Lehmann-Werman, Roni; Magenheim, Judith; Moss, Joshua; Neiman, Daniel; Abraham, Ofri; Piyanzin, Sheina; Zemmour, Hai; Fox, Ilana; Dor, Talya; Grompe, Markus; Landesberg, Giora; Loza, Bao-Li; Shaked, Abraham; Olthoff, Kim; Glaser, Benjamin; Shemer, Ruth; Dor, Yuval

2018-06-21

Liver damage is typically inferred from serum measurements of cytoplasmic liver enzymes. DNA molecules released from dying hepatocytes are an alternative biomarker, unexplored so far, potentially allowing for quantitative assessment of liver cell death. Here we describe a method for detecting acute hepatocyte death, based on quantification of circulating, cell-free DNA (cfDNA) fragments carrying hepatocyte-specific methylation patterns. We identified 3 genomic loci that are unmethylated specifically in hepatocytes, and used bisulfite conversion, PCR, and massively parallel sequencing to quantify the concentration of hepatocyte-derived DNA in mixed samples. Healthy donors had, on average, 30 hepatocyte genomes/ml plasma, reflective of basal cell turnover in the liver. We identified elevations of hepatocyte cfDNA in patients shortly after liver transplantation, during acute rejection of an established liver transplant, and also in healthy individuals after partial hepatectomy. Furthermore, patients with sepsis had high levels of hepatocyte cfDNA, which correlated with levels of liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Duchenne muscular dystrophy patients, in which elevated AST and ALT derive from damaged muscle rather than liver, did not have elevated hepatocyte cfDNA. We conclude that measurements of hepatocyte-derived cfDNA can provide specific and sensitive information on hepatocyte death, for monitoring human liver dynamics, disease, and toxicity.

Optimization of Causative Factors for Landslide Susceptibility Evaluation Using Remote Sensing and GIS Data in Parts of Niigata, Japan.

PubMed

Dou, Jie; Tien Bui, Dieu; Yunus, Ali P; Jia, Kun; Song, Xuan; Revhaug, Inge; Xia, Huan; Zhu, Zhongfan

2015-01-01

This paper assesses the potentiality of certainty factor models (CF) for the best suitable causative factors extraction for landslide susceptibility mapping in the Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a landslide inventory map provided by National Research Institute for Earth Science and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the landslides in the inventory to be used for building the CF based model; (ii) 30% of the landslides to be used for the validation purpose. A spatial database with fifteen landslide causative factors was then constructed by processing ALOS satellite images, aerial photos, topographical and geological maps. CF model was then applied to select the best subset from the fifteen factors. Using all fifteen factors and the best subset factors, landslide susceptibility maps were produced using statistical index (SI) and logistic regression (LR) models. The susceptibility maps were validated and compared using landslide locations in the validation data. The prediction performance of two susceptibility maps was estimated using the Receiver Operating Characteristics (ROC). The result shows that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is slightly higher than those obtained from the SI model (AUC = 0.801). Further, it is noted that the SI and LR models using the best subset outperform the models using the fifteen original factors. Therefore, we conclude that the optimized factor model using CF is more accurate in predicting landslide susceptibility and obtaining a more homogeneous classification map. Our findings acknowledge that in the mountainous regions suffering from data scarcity, it is possible to select key factors related to landslide occurrence based on the CF models in a GIS platform. Hence, the development of a scenario for future planning of risk mitigation is achieved in an efficient manner.

Optimization of Causative Factors for Landslide Susceptibility Evaluation Using Remote Sensing and GIS Data in Parts of Niigata, Japan

PubMed Central

Dou, Jie; Tien Bui, Dieu; P. Yunus, Ali; Jia, Kun; Song, Xuan; Revhaug, Inge; Xia, Huan; Zhu, Zhongfan

2015-01-01

This paper assesses the potentiality of certainty factor models (CF) for the best suitable causative factors extraction for landslide susceptibility mapping in the Sado Island, Niigata Prefecture, Japan. To test the applicability of CF, a landslide inventory map provided by National Research Institute for Earth Science and Disaster Prevention (NIED) was split into two subsets: (i) 70% of the landslides in the inventory to be used for building the CF based model; (ii) 30% of the landslides to be used for the validation purpose. A spatial database with fifteen landslide causative factors was then constructed by processing ALOS satellite images, aerial photos, topographical and geological maps. CF model was then applied to select the best subset from the fifteen factors. Using all fifteen factors and the best subset factors, landslide susceptibility maps were produced using statistical index (SI) and logistic regression (LR) models. The susceptibility maps were validated and compared using landslide locations in the validation data. The prediction performance of two susceptibility maps was estimated using the Receiver Operating Characteristics (ROC). The result shows that the area under the ROC curve (AUC) for the LR model (AUC = 0.817) is slightly higher than those obtained from the SI model (AUC = 0.801). Further, it is noted that the SI and LR models using the best subset outperform the models using the fifteen original factors. Therefore, we conclude that the optimized factor model using CF is more accurate in predicting landslide susceptibility and obtaining a more homogeneous classification map. Our findings acknowledge that in the mountainous regions suffering from data scarcity, it is possible to select key factors related to landslide occurrence based on the CF models in a GIS platform. Hence, the development of a scenario for future planning of risk mitigation is achieved in an efficient manner. PMID:26214691

External Ballistics. Part 2

DTIC Science & Technology

1978-07-11

ucaymaetrically. Page £98. is a result cf the elastic iroperties cf rccket, of launcher and scil , the initial conditicns of moving the rocket differ from...instrument depends or. many factors: the elastic Fropesties of shaft and gur carriaSe, scil cf the firing position, tallistics of instrument, which

Genetically and Phenotypically Distinct Pseudomonas aeruginosa Cystic Fibrosis Isolates Share a Core Proteomic Signature

PubMed Central

Penesyan, Anahit; Kumar, Sheemal S.; Kamath, Karthik; Shathili, Abdulrahman M.; Venkatakrishnan, Vignesh; Krisp, Christoph; Packer, Nicolle H.; Molloy, Mark P.; Paulsen, Ian T.

2015-01-01

The opportunistic pathogen Pseudomonas aeruginosa is among the main colonizers of the lungs of cystic fibrosis (CF) patients. We have isolated and sequenced several P. aeruginosa isolates from the sputum of CF patients and compared them with each other and with the model strain PAO1. Phenotypic analysis of CF isolates showed significant variability in colonization and virulence-related traits suggesting different strategies for adaptation to the CF lung. Genomic analysis indicated these strains shared a large set of core genes with the standard laboratory strain PAO1, and identified the genetic basis for some of the observed phenotypic differences. Proteomics revealed that in a conventional laboratory medium PAO1 expressed 827 proteins that were absent in the CF isolates while the CF isolates shared a distinctive signature set of 703 proteins not detected in PAO1. PAO1 expressed many transporters for the uptake of organic nutrients and relatively few biosynthetic pathways. Conversely, the CF isolates expressed a narrower range of transporters and a broader set of metabolic pathways for the biosynthesis of amino acids, carbohydrates, nucleotides and polyamines. The proteomic data suggests that in a common laboratory medium PAO1 may transport a diverse set of “ready-made” nutrients from the rich medium, whereas the CF isolates may only utilize a limited number of nutrients from the medium relying mainly on their own metabolism for synthesis of essential nutrients. These variations indicate significant differences between the metabolism and physiology of P. aeruginosa CF isolates and PAO1 that cannot be detected at the genome level alone. The widening gap between the increasing genomic data and the lack of phenotypic data means that researchers are increasingly reliant on extrapolating from genomic comparisons using experimentally characterized model organisms such as PAO1. While comparative genomics can provide valuable information, our data suggests that such extrapolations may be fraught with peril. PMID:26431321

Multiplex real time PCR panels to identify fourteen colonization factors of enterotoxigenic Escherichia coli (ETEC).

PubMed

Liu, Jie; Silapong, Sasikorn; Jeanwattanalert, Pimmada; Lertsehtakarn, Paphavee; Bodhidatta, Ladaporn; Swierczewski, Brett; Mason, Carl; McVeigh, Annette L; Savarino, Stephen J; Nshama, Rosemary; Mduma, Esto; Maro, Athanasia; Zhang, Jixian; Gratz, Jean; Houpt, Eric R

2017-01-01

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood diarrhea in low income countries and in travelers to those areas. Inactivated enterotoxins and colonization factors (CFs) are leading vaccine candidates, therefore it is important to determine the prevailing CF types in different geographic locations and populations. Here we developed real time PCR (qPCR) assays for 14 colonization factors, including the common vaccine targets. These assays, along with three enterotoxin targets (STh, STp, and LT) were formulated into three 5-plex qPCR panels, and validated on 120 ETEC isolates and 74 E. coli colony pools. The overall sensitivity and specificity was 99% (199/202) and 99% (2497/2514), respectively, compared to the CF results obtained with conventional PCR. Amplicon sequencing of discrepant samples revealed that the qPCR was 100% accurate. qPCR panels were also performed on nucleic acid extracted from stool and compared to the results of the ETEC isolates or E. coli colony pools cultured from them. 95% (105/110) of the CF detections in the cultures were confirmed in the stool. Additionally, direct testing of stool yielded 30 more CF detections. Among 74 randomly selected E. coli colony pools with paired stool, at least one CF was detected in 63% (32/51) of the colony pools while at least one CF was detected in 78% (47/60) of the stool samples (P = NS). We conclude that these ETEC CF assays can be used on both cultures and stool samples to facilitate better understanding of CF distribution for ETEC epidemiology and vaccine development.

Continuous application of compressive force induces fusion of osteoclast-like RAW264.7 cells via upregulation of RANK and downregulation of LGR4.

PubMed

Matsuike, Rieko; Tanaka, Hideki; Nakai, Kumiko; Kanda, Mai; Nagasaki, Maki; Murakami, Fumiko; Shibata, Chika; Mayahara, Kotoe; Nakajima, Akira; Tanabe, Natsuko; Kawato, Takayuki; Maeno, Masao; Shimizu, Noriyoshi

2018-05-15

During orthodontic treatment, facilitating osteoclastic bone resorption in the alveolar bone exposed to the compressive force (CF) is an important factor for tooth movement. The present study investigated the effect of CF stimulation on the differentiation of RAW264.7 cells from precursors to mature osteoclasts. The cells were continuously stimulated with 0.3, 0.6, or 1.1 g/cm 2 CF-which was generated by increasing the volume of culture medium in the wells of a 96-well plate-in the presence or absence of receptor activator of nuclear factor κB (RANK) ligand (RANKL) for 4 days. In the presence of RANKL, the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells and the mRNA levels of dendritic cell-specific transmembrane protein (DC-STAMP) and osteoclast-stimulatory transmembrane protein (OC-STAMP) were increased by application of 0.6 and 1.1 g/cm 2 CF as compared to 0.3 g/cm 2 CF. The mRNA level of RANK was upregulated whereas that of leucine-rich repeat-containing G-protein-coupled receptor (LGR)4-another RANKL receptor was downregulated by 0.6 and 1.1 g/cm 2 CF as compared to 0.3 g/cm 2 CF in the absence of RANKL. The proportion of cells with nuclear translocation of the nuclear translocation of nuclear factor of activated T cells (NFAT)c1 was increased by 0.6 and 1.1 g/cm 2 CF in the presence of RANKL. Continuous application of CF induced the differentiation of RAW264.7 cells into TRAP-positive multinuclear cells by enhancing the expression of DC- and OC-STAMP and the nuclear translocation of NFATc1. This may result from the CF-induced increase in RANK and decrease in LGR4 expression. Copyright © 2018 Elsevier Inc. All rights reserved.

CFTR gene variant IVS8-5T in disseminated bronchiectasis

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

Pignatti, P.F.; Bombieri, C.; Benetazzo, M.

1996-04-01

Obstructive pulmonary disease includes asthma, chronic obstructive pulmonary disease (COPD; i.e., pulmonary emphysema and chronic bronchitis), bronchiectasis, and cystic fibrosis (CF). It represents a leading cause of death in developed countries. Both familial clustering of non-CF obstructive pulmonary disease and familial aggregation of impaired lung function have been described. This suggests that genetic factors contribute to non-CF obstructive pulmonary disease, even if it is difficult to determine the relative contribution of environmental factors. 11 refs., 1 tab.

Controlling the Morphology of BDTT-DPP-Based Small Molecules via End-Group Functionalization for Highly Efficient Single and Tandem Organic Photovoltaic Cells.

PubMed

Kim, Ji-Hoon; Park, Jong Baek; Yang, Hoichang; Jung, In Hwan; Yoon, Sung Cheol; Kim, Dongwook; Hwang, Do-Hoon

2015-11-04

A series of narrow-band gap, π-conjugated small molecules based on diketopyrrolopyrrole (DPP) electron acceptor units coupled with alkylthienyl-substituted-benzodithiophene (BDTT) electron donors were designed and synthesized for use as donor materials in solution-processed organic photovoltaic cells. In particular, by end-group functionalization of the small molecules with fluorine derivatives, the nanoscale morphologies of the photoactive layers of the photovoltaic cells were successfully controlled. The influences of different fluorine-based end-groups on the optoelectronic and morphological properties, carrier mobilities, and the photovoltaic performances of these materials were investigated. A high power conversion efficiency (PCE) of 6.00% under simulated solar light (AM 1.5G) illumination has been achieved for organic photovoltaic cells based on a small-molecule bulk heterojunction system consisting of a trifluoromethylbenzene (CF3) end-group-containing oligomer (BDTT-(DPP)2-CF3) as the donor and [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) as the acceptor. As a result, the introduction of CF3 end-groups has been found to enhance both the short circuit current density (JSC) and fill factor (FF). A tandem photovoltaic device comprising an inverted BDTT-(DPP)2-CF3:PC71BM cell and a poly(3-hexylthiophene) (P3HT):indene-C60-bisadduct (IC60BA)-based cell as the top and bottom cell components, respectively, showed a maximum PCE of 8.30%. These results provide valuable guidelines for the rational design of conjugated small molecules for applications in high-performance organic photovoltaic cells. Furthermore, to the best of our knowledge, this is the first report on the design of fluorine-functionalized BDTT-DPP-based small molecules, which have been shown to be a viable candidate for use in inverted tandem cells.

Carotid-femoral pulse wave velocity in a healthy adult sample: The ELSA-Brasil study.

PubMed

Baldo, Marcelo Perim; Cunha, Roberto S; Molina, Maria Del Carmen B; Chór, Dora; Griep, Rosane H; Duncan, Bruce B; Schmidt, Maria Inês; Ribeiro, Antonio L P; Barreto, Sandhi M; Lotufo, Paulo A; Bensenor, Isabela M; Pereira, Alexandre C; Mill, José Geraldo

2018-01-15

Aging declines essential physiological functions, and the vascular system is strongly affected by artery stiffening. We intended to define the age- and sex-specific reference values for carotid-to-femoral pulse wave velocity (cf-PWV) in a sample free of major risk factors. The ELSA-Brasil study enrolled 15,105 participants aged 35-74years. The healthy sample was achieved by excluding diabetics, those over the optimal and normal blood pressure levels, body mass index ≤18.5 or ≥25kg/m 2 , current and former smokers, and those with self-report of previous cardiovascular disease. After exclusions, the sample consisted of 2158 healthy adults (1412 women). Although cf-PWV predictors were similar between sex (age, mean arterial pressure (MAP) and heart rate), cf-PWV was higher in men (8.74±1.15 vs. 8.31±1.13m/s; adjusted for age and MAP, P<0.001) for all age intervals. When divided by MAP categories, cf-PWV was significantly higher in those which MAP ≥85mmHg, regardless of sex, and for all age intervals. Risk factors for arterial stiffening in the entire ELSA-Brasil population (n=15,105) increased by twice the age-related slope of cf-PWV growth, regardless of sex (0.0919±0.182 vs. 0.0504±0.153m/s per year for men, 0.0960±0.173 vs. 0.0606±0.139m/s per year for women). cf-PWV is different between men and women and even in an optimal and normal range of MAP and free of other classical risk factors for arterial stiffness, reference values for cf-PWV should take into account MAP levels. Also, the presence of major risk factors in the general population doubles the age-related rise in cf-PWV. Copyright © 2017 Elsevier B.V. All rights reserved.

UK NHS pilot study on cell-free DNA testing in screening for fetal trisomies: factors affecting uptake.

PubMed

Gil, M M; Giunta, G; Macalli, E A; Poon, L C; Nicolaides, K H

2015-01-01

This study reports on the clinical implementation of cell-free DNA (cfDNA) testing, contingent on the results of the combined test, in screening for fetal trisomies 21, 18 and 13 in two UK National Health Service hospitals. Women with a combined-test risk of ≥ 1:100 (high risk) were offered the options of chorionic villus sampling (CVS), cfDNA testing or no further testing and those with a risk of 1:101 to 1:2500 (intermediate risk) were offered cfDNA or no further testing. The objective of the study was to examine the factors affecting patient decisions concerning their options. Combined screening was performed in 6651 singleton pregnancies in which the risk for trisomies was high in 260 (3.9%), intermediate in 2017 (30.3%) and low in 4374 (65.8%). Logistic regression analysis was used to determine which factors among maternal characteristics, fetal nuchal translucency thickness (NT) and risk for trisomies were significant predictors of opting for CVS in the high-risk group and opting for cfDNA testing in the intermediate-risk group. In the high-risk group, 104 (40.0%) women opted for CVS; predictors for CVS were increasing fetal NT and increasing risk for trisomies, while the predictor against CVS was being of Afro-Caribbean racial origin (r = 0.366). In the intermediate-risk group, 1850 (91.7%) women opted for cfDNA testing; predictors for cfDNA testing were increasing maternal age, increasing risk for trisomies and university education, while predictors against cfDNA testing were being of Afro-Caribbean racial origin, smoking and being parous (r = 0.105). This study has identified factors that can influence the decision of women undergoing combined screening in favor of or against CVS and in favor of or against cfDNA testing. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Independent associations of physical activity and cardiovascular fitness with cardiovascular risk in adults.

PubMed

Ekblom-Bak, Elin; Hellénius, Mai-Lis; Ekblom, Orjan; Engström, Lars-Magnus; Ekblom, Björn

2010-04-01

Uncertainty still exists whether physical activity (PA) and cardiovascular fitness (CF) contribute separately to cardiovascular disease (CVD) risk. This study examined the associations of PA and CF on individual as well as clustered CVD risk factors. Cross-sectional. Seven hundred and eighty-one men and 890 women, aged 20-65 years, from two random population-based samples of Swedish women and men were included. PA was assessed by questionnaire and CF was predicted by a submaximal cycle ergometry test. Waist circumference, blood pressure, and fasting levels of blood lipids were assessed and dichotomized by conventional cut-off points. Participants reporting high PA level benefited from lower triglycerides and atherogenic cholesterol levels, regardless of CF. Higher CF level was, regardless of PA, associated with lower risk for all risk factors. With regard to clustering of risk factors, each higher CF level was associated with a gradually reduced risk by half or more, independent of PA. Furthermore, being unfit but reporting high PA was associated with a 50% lower risk compared with being unfit and inactive. Furthermore, high reported PA was associated with an additional reduced risk among fit participants. In addition, an excess risk of interaction was found for waist circumference, triglycerides, and the clustered CVD risk between neither being sufficiently active nor being fit. This study suggests that both PA and CF are independently associated with lower cardiovascular risk, and that both variables should be taken into account when CVD risk is estimated.

Regional pulse wave velocities and their cardiovascular risk factors among healthy middle-aged men: a cross-sectional population-based study.

PubMed

Choo, Jina; Shin, Chol; Barinas-Mitchell, Emma; Masaki, Kamal; Willcox, Bradley J; Seto, Todd B; Ueshima, Hirotsugu; Lee, Sunghee; Miura, Katsuyuki; Venkitachalam, Lakshmi; Mackey, Rachel H; Evans, Rhobert W; Kuller, Lewis H; Sutton-Tyrrell, Kim; Sekikawa, Akira

2014-01-13

Both carotid-femoral (cf) pulse wave velocity (PWV) and brachial-ankle (ba) PWV employ arterial sites that are not consistent with the path of blood flow. Few previous studies have reported the differential characteristics between cfPWV and baPWV by simultaneously comparing these with measures of pure central (aorta) and peripheral (leg) arterial stiffness, i.e., heart-femoral (hf) PWV and femoral-ankle (fa) PWV in healthy populations. We aimed to identify the degree to which these commonly used measures of cfPWV and baPWV correlate with hfPWV and faPWV, respectively, and to evaluate whether both cfPWV and baPWV are consistent with either hfPWV or faPWV in their associations with cardiovascular (CV) risk factors. A population-based sample of healthy 784 men aged 40-49 (202 white Americans, 68 African Americans, 202 Japanese-Americans, and 282 Koreans) was examined in this cross-sectional study. Four regional PWVs were simultaneously measured by an automated tonometry/plethysmography system. cfPWV correlated strongly with hfPWV (r = .81, P < .001), but weakly with faPWV (r = .12, P = .001). baPWV correlated moderately with both hfPWV (r = .47, P < .001) and faPWV (r = .62, P < .001). After stepwise regression analyses with adjustments for race, cfPWV shared common significant correlates with both hfPWV and faPWV: systolic blood pressure (BP) and body mass index (BMI). However, BMI was positively associated with hfPWV and cfPWV, and negatively associated with faPWV. baPWV shared common significant correlates with hfPWV: age and systolic BP. baPWV also shared the following correlates with faPWV: systolic BP, triglycerides, and current smoking. Among healthy men aged 40 - 49, cfPWV correlated strongly with central PWV, and baPWV correlated with both central and peripheral PWVs. Of the CV risk factors, systolic BP was uniformly associated with all the regional PWVs. In the associations with factors other than systolic BP, cfPWV was consistent with central PWV, while baPWV was consistent with both central and peripheral PWVs.

Blocking effect of rheumatoid factor and cold agglutinins on complement fixation tests for histoplasmosis.

PubMed Central

Johnson, J E; Roberts, G D

1976-01-01

The blocking effect of rheumatoid factor (RF) and cold agglutinins (CA) on the detection of complement-fixing (CF) antibodies for Histoplasma capsulatum using a mycelial (histoplasmin) and a yeast antigen was studied. Sera from 213 patients serologically positive for histoplasmosis were screened for the presence of RF or CA. CF antibodies to H. capsulatum in sera containing RF or CA were studied before and after removal of these factors (RF and CA) by treatment with dithiothreitol. Results suggest that RF or CA may interfere with the CF reaction to the yeast antigen of H. capsulatum but not to the mycelial antigen (histoplasmin). PMID:1254713

Chinese Secondary EFL Learners' and Teachers' Preferences for Types of Written Corrective Feedback

ERIC Educational Resources Information Center

Li, Haishan; He, Qingshun

2017-01-01

How learners perceive written corrective feedback (CF) associates with its effectiveness in language learning. This research investigates students' preferences for three types of written CF, i.e., direct, indirect and metalinguistic written CF, and explores the factors that encourage the teachers to employ these CFs in teaching practice. The…

Dye-sensitized solar cells with vertically aligned TiO2 nanowire arrays grown on carbon fibers.

PubMed

Cai, Xin; Wu, Hongwei; Hou, Shaocong; Peng, Ming; Yu, Xiao; Zou, Dechun

2014-02-01

One-dimensional semiconductor TiO2 nanowires (TNWs) have received widespread attention from solar cell and related optoelectronics scientists. The controllable synthesis of ordered TNW arrays on arbitrary substrates would benefit both fundamental research and practical applications. Herein, vertically aligned TNW arrays in situ grown on carbon fiber (CF) substrates through a facile, controllable, and seed-assisted thermal process is presented. Also, hierarchical TiO2 -nanoparticle/TNW arrays were prepared that favor both the dye loading and depressed charge recombination of the CF/TNW photoanode. An impressive conversion efficiency of 2.48 % (under air mass 1.5 global illumination) and an apparent efficiency of 4.18 % (with a diffuse board) due to the 3D light harvesting of the wire solar cell were achieved. Moreover, efficient and inexpensive wire solar cells made from all-CF electrodes and completely flexible CF-based wire solar cells were demonstrated, taking into account actual application requirements. This work may provide an intriguing avenue for the pursuit of lightweight, cost-effective, and high-performance flexible/wearable solar cells. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation of ortho-para ratio controlled D2 gas for muon-catalyzed fusion.

PubMed

Imao, H; Ishida, K; Kawamura, N; Matsuzaki, T; Matsuda, Y; Toyoda, A; Strasser, P; Iwasaki, M; Nagamine, K

2008-05-01

A negative muon in hydrogen targets, e.g., D2 or D-T mixture, can catalyze nuclear fusions following a series of atomic processes involving muonic hydrogen molecular formation (muon-catalyzed fusion, muCF). The ortho-para state of D2 is a crucial parameter not only for enhancing the fusion rate but also to precisely investigate various muonic atom processes. We have developed a system for controlling and measuring the ortho-para ratio of D2 gas for muCF experiments. We successfully collected para-enriched D2 without using liquid-hydrogen coolant. Ortho-enriched D2 was also obtained by using a catalytic conversion method with a mixture of chromium oxide and alumina. The ortho-para ratio of D2 gas was measured with a compact Raman spectroscopy system. We produced large volume (5-30 l at STP), high-purity (less than ppm high-Z contaminant) D2 targets with a wide range of ortho-para ratios (ortho 20%-99%). By using the ortho-para controlled D2 in muCF experiments, we observed the dependence of muCF phenomena on the ortho-para ratio.

Preparation of ortho-para ratio controlled D{sub 2} gas for muon-catalyzed fusion

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

Imao, H.; Ishida, K.; Matsuzaki, T.

2008-05-15

A negative muon in hydrogen targets, e.g., D{sub 2} or D-T mixture, can catalyze nuclear fusions following a series of atomic processes involving muonic hydrogen molecular formation (muon-catalyzed fusion, {mu}CF). The ortho-para state of D{sub 2} is a crucial parameter not only for enhancing the fusion rate but also to precisely investigate various muonic atom processes. We have developed a system for controlling and measuring the ortho-para ratio of D{sub 2} gas for {mu}CF experiments. We successfully collected para-enriched D{sub 2} without using liquid-hydrogen coolant. Ortho-enriched D{sub 2} was also obtained by using a catalytic conversion method with a mixturemore » of chromium oxide and alumina. The ortho-para ratio of D{sub 2} gas was measured with a compact Raman spectroscopy system. We produced large volume (5-30 l at STP), high-purity (less than ppm high-Z contaminant) D{sub 2} targets with a wide range of ortho-para ratios (ortho 20%-99%). By using the ortho-para controlled D{sub 2} in {mu}CF experiments, we observed the dependence of {mu}CF phenomena on the ortho-para ratio.« less

Development and evaluation of a palliative care curriculum for cystic fibrosis healthcare providers.

PubMed

Linnemann, Rachel W; O'Malley, Patricia J; Friedman, Deborah; Georgiopoulos, Anna M; Buxton, David; Altstein, Lily L; Sicilian, Leonard; Lapey, Allen; Sawicki, Gregory S; Moskowitz, Samuel M

2016-01-01

Primary palliative care refers to basic skills that all healthcare providers can employ to improve quality of life for patients at any stage of disease. Training in these core skills is not commonly provided to clinicians caring for cystic fibrosis (CF) patients. The objective of this study was to assess change in comfort with core skills among care team members after participation in CF-specific palliative care training focused on management of burdensome symptoms and difficult conversations. A qualitative needs assessment was performed to inform the development of an 18-hour curriculum tailored to the chronicity and complexity of CF care. A 32-question pre- and post-course survey assessed CF provider comfort with the targeted palliative care skills in 5 domains using a 5-point Likert scale (1=very uncomfortable, 3=neutral, 5=very comfortable). Among course participants (n=16), mean overall comfort score increased by 0.9, from 3 (neutral) to 3.9 (comfortable) (p<0.001). Mean comfort level increased significantly (range 0.8 to 1.4) in each skill domain: use of supportive care resources, pain management, non-pain symptom management, communication, and psychosocial skills. CF-specific palliative care training was well received by participants and significantly improved self-assessed comfort with core skills. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Gastrointestinal Pathology in Juvenile and Adult CFTR-Knockout Ferrets

PubMed Central

Sun, Xingshen; Olivier, Alicia K.; Yi, Yaling; Pope, Christopher E.; Hayden, Hillary S.; Liang, Bo; Sui, Hongshu; Zhou, Weihong; Hager, Kyle R.; Zhang, Yulong; Liu, Xiaoming; Yan, Ziying; Fisher, John T.; Keiser, Nicholas W.; Song, Yi; Tyler, Scott R.; Goeken, J. Adam; Kinyon, Joann M.; Radey, Matthew C.; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J.; Kaminsky, Paul M.; Brittnacher, Mitchell J.; Miller, Samuel I.; Parekh, Kalpaj; Meyerholz, David K.; Hoffman, Lucas R.; Frana, Timothy; Stewart, Zoe A.; Engelhardt, John F.

2015-01-01

Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients. PMID:24637292

Aspergillus infection in lung transplant recipients with cystic fibrosis: risk factors and outcomes comparison to other types of transplant recipients.

PubMed

Helmi, Mohamed; Love, Robert B; Welter, Debbie; Cornwell, Richard D; Meyer, Keith C

2003-03-01

To characterize Aspergillus infections in lung transplant recipients with cystic fibrosis (CF). A retrospective analysis of 32 consecutive lung transplant recipients with CF who underwent bilateral lung transplant at the University of Wisconsin from 1994 to 2000 to determine the incidence, risk factors, and consequences of Aspergillus infection. The findings were compared to 101 non-CF recipients of lung transplants (93) and heart-lung transplants (8) for other transplant indications. A university hospital. Lung transplant recipients with CF or other indications for transplantation. None. Seventeen of 32 CF recipients (53%) had Aspergillus fumigatus isolated from their respiratory secretions prior to undergoing transplantation. Ten of these 17 (59%) recipients had A fumigatus persistently found in their respiratory secretions posttransplant vs 6 of 15 CF patients (40%) who had not been colonized pretransplant and 28 of 101 of the non-CF recipients (28%). Four of the preoperatively colonized CF recipients developed tracheobronchial aspergillosis (TBA) just distal to the bronchial anastomoses, and one recipient had dehiscence of the involved anastomosis. None of the CF recipients developed disseminated aspergillosis or pneumonia. Prophylactic antifungal therapy did not prevent TBA, and IV amphotericin B therapy was required to clear the infection in all four patients, with endobronchial debridement of necrotic tissue required in two of them. In contrast, 10 of the non-CF (10%) recipients developed Aspergillus infections posttransplant (TBA, 4 recipients; pneumonitis, 6 recipients), and only 3 patients had successful treatment and long-term survival (TBA, 2 patients; pneumonia, 1 patient). Donor lung ischemia time, cytomegalovirus infection or pneumonia, or pretransplant mechanical ventilation did not increase the risk of developing TBA in CF recipients. The risk of TBA for patients receiving lung transplants for CF warrants early surveillance bronchoscopy to detect TBA, particularly in recipients with pretransplant colonization.

New Horizons in C-F Activation by Main Group Electrophiles

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

Ozerov, Oleg V.

2016-02-13

This technical report describes progress on the DOE sponsored project "New Horizons in C-F Activation by Main Group Electrophiles" during the period of 09/15/2010 – 08/31/2015. The main goal of this project was to develop improved catalysts for conversion of carbon-fluorine bonds in potentially harmful compounds. The approach involved combining of a highly reactive positively charged main-group compound with a highly unreactive negatively charged species (anions) as a way to access potent catalysts for carbon-fluorine bond activation. This report details progress made in improving synthetic pathways to a variety of new anions with improved properties and analysis of their potentialmore » in catalysis.« less

Isolation of bioactive and other oxoaporphine alkaloids from two annonaceous plants, Xylopia aethiopica and Miliusa cf. banacea.

PubMed

Harrigan, G G; Gunatilaka, A A; Kingston, D G; Chan, G W; Johnson, R K

1994-01-01

The oxoaporphine alkaloids oxophoebine [1] and liriodenine [2] have been isolated from Xylopia aethiopica (Annonaceae). Both showed selective toxicity against DNA repair and recombination deficient mutants of the yeast Saccharomyces cerevisae. Three related but inactive compounds, oxoglaucine [3], O-methylmoschatoline [4], and lysicamine [5], were also isolated from this plant. Selective toxicity was also observed for 10-methoxyliriodenine (lauterine) [6] and 10-hydroxyliriodenine [7], two oxoaporphine alkaloids isolated from Miliusa cf. banacea (Annonaceae). The structure of 10-hydroxyliriodenine [7], a novel oxoaporphine, was determined by spectroscopic methods and chemical conversion to compound 6. The role of the bioactive oxoaporphine alkaloids as DNA topoisomerase inhibitors is discussed.

Crystal Structure of the 25 kDa Subunit of Human Cleavage Factor I{m}

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

Coseno,M.; Martin, G.; Berger, C.

Cleavage factor Im is an essential component of the pre-messenger RNA 3'-end processing machinery in higher eukaryotes, participating in both the polyadenylation and cleavage steps. Cleavage factor Im is an oligomer composed of a small 25 kDa subunit (CF Im25) and a variable larger subunit of either 59, 68 or 72 kDa. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein. These protein-protein interactions are thought to be facilitated by the Nudix domain of CF Im25, a hydrolase motif with a characteristic {alpha}/{beta}/{alpha} fold and a conserved catalytic sequence or Nudix box. We present heremore » the crystal structures of human CF Im25 in its free and diadenosine tetraphosphate (Ap4A) bound forms at 1.85 and 1.80 Angstroms, respectively. CF Im25 crystallizes as a dimer and presents the classical Nudix fold. Results from crystallographic and biochemical experiments suggest that CF Im25 makes use of its Nudix fold to bind but not hydrolyze ATP and Ap4A. The complex and apo protein structures provide insight into the active oligomeric state of CF Im and suggest a possible role of nucleotide binding in either the polyadenylation and/or cleavage steps of pre-messenger RNA 3'-end processing.« less

Crystal structure of the 25 kDa subunit of human cleavage factor Im

PubMed Central

Coseno, Molly; Martin, Georges; Berger, Christopher; Gilmartin, Gregory; Keller, Walter; Doublié, Sylvie

2008-01-01

Cleavage factor Im is an essential component of the pre-messenger RNA 3′-end processing machinery in higher eukaryotes, participating in both the polyadenylation and cleavage steps. Cleavage factor Im is an oligomer composed of a small 25 kDa subunit (CF Im25) and a variable larger subunit of either 59, 68 or 72 kDa. The small subunit also interacts with RNA, poly(A) polymerase, and the nuclear poly(A)-binding protein. These protein–protein interactions are thought to be facilitated by the Nudix domain of CF Im25, a hydrolase motif with a characteristic α/β/α fold and a conserved catalytic sequence or Nudix box. We present here the crystal structures of human CF Im25 in its free and diadenosine tetraphosphate (Ap4A) bound forms at 1.85 and 1.80 Å, respectively. CF Im25 crystallizes as a dimer and presents the classical Nudix fold. Results from crystallographic and biochemical experiments suggest that CF Im25 makes use of its Nudix fold to bind but not hydrolyze ATP and Ap4A. The complex and apo protein structures provide insight into the active oligomeric state of CF Im and suggest a possible role of nucleotide binding in either the polyadenylation and/or cleavage steps of pre-messenger RNA 3′-end processing. PMID:18445629

Validation of a nutrition risk screening tool for children and adolescents with cystic fibrosis ages 2-20 years.

PubMed

McDonald, Catherine M

2008-04-01

According to the 2002 Cystic Fibrosis (CF) Foundation nutrition consensus report, children with CF should grow normally. Cross-sectional data from the foundation's patient registry concluded that a body mass index at or greater than the 50th percentile is associated with better lung function. A consistent, evidence-based screening process can identify those individuals with CF having nutrition risk factors associated with a decrease in pulmonary function, target early intervention, and prevent further decline. A tool for screening nutrition risk is described to identify those children with CF who would benefit from more extensive nutrition intervention. The proposed screening tool is a risk-based classification system with 3 categories: weight gain, height velocity, and body mass index. The CF Foundation recommendations regarding these parameters are incorporated, with risk points assigned when minimum body mass index, weight gain, and/or height gain standards are unmet. An interrater measure of agreement determined a satisfactory level of reliability (kappa = 0.85). Patient records (n = 85) were reviewed to determine nutrition status category (no risk or at risk) of this tool compared with the CF Foundation 2002 Nutrition Consensus, yielding sensitivity and specificity at 84% and 75%, respectively. A second comparison was made with combined, independent nutrition risk factors not included in the screening tool. The sensitivity and specificity of the screening tool compared with the combined risk factors were 86% and 78%, respectively. This tool for screening nutrition risk for CF is reliable and valid, with consistent, reproducible results, free from subject or observer bias.

Wind and boundary layers in Rayleigh-Bénard convection. II. Boundary layer character and scaling.

PubMed

van Reeuwijk, Maarten; Jonker, Harm J J; Hanjalić, Kemo

2008-03-01

The scaling of the kinematic boundary layer thickness lambda(u) and the friction factor C(f) at the top and bottom walls of Rayleigh-Bénard convection is studied by direct numerical simulation (DNS). By a detailed analysis of the friction factor, a new parameterisation for C(f) and lambda(u) is proposed. The simulations were made of an L/H=4 aspect-ratio domain with periodic lateral boundary conditions at Ra=(10(5), 10(6), 10(7), 10(8)) and Pr=1. The continuous spectrum, as well as significant forcing due to Reynolds stresses, clearly indicates a turbulent character of the boundary layer, while viscous effects cannot be neglected, judging from the scaling of classical integral boundary layer parameters with Reynolds number. Using a conceptual wind model, we find that the friction factor C(f) should scale proportionally to the thermal boundary layer thickness as C(f) proportional variant lambda(Theta)/H, while the kinetic boundary layer thickness lambda(u) scales inversely proportionally to the thermal boundary layer thickness and wind Reynolds number lambda(u)/H proportional variant (lambda(Theta)/H)(-1)Re(-1). The predicted trends for C(f) and lambda(u) are in agreement with DNS results.

Brittleness index of machinable dental materials and its relation to the marginal chipping factor.

PubMed

Tsitrou, Effrosyni A; Northeast, Simon E; van Noort, Richard

2007-12-01

The machinability of a material can be measured with the calculation of its brittleness index (BI). It is possible that different materials with different BI could produce restorations with varied marginal integrity. The degree of marginal chipping of a milled restoration can be estimated by the calculation of the marginal chipping factor (CF). The aim of this study is to investigate any possible correlation between the BI of machinable dental materials and the CF of the final restorations. The CEREC system was used to mill a wide range of materials used with that system; namely the Paradigm MZ100 (3M/ESPE), Vita Mark II (VITA), ProCAD (Ivoclar-Vivadent) and IPS e.max CAD (Ivoclar-Vivadent). A Vickers Hardness Tester was used for the calculation of BI, while for the calculation of CF the percentage of marginal chipping of crowns prepared with bevelled marginal angulations was estimated. The results of this study showed that Paradigm MZ100 had the lowest BI and CF, while IPS e.max CAD demonstrated the highest BI and CF. Vita Mark II and ProCAD had similar BI and CF and were lying between the above materials. Statistical analysis of the results showed that there is a perfect positive correlation between BI and CF for all the materials. The BI and CF could be both regarded as indicators of a material's machinability. Within the limitations of this study it was shown that as the BI increases so does the potential for marginal chipping, indicating that the BI of a material can be used as a predictor of the CF.

Gastrointestinal pathology in juvenile and adult CFTR-knockout ferrets.

PubMed

Sun, Xingshen; Olivier, Alicia K; Yi, Yaling; Pope, Christopher E; Hayden, Hillary S; Liang, Bo; Sui, Hongshu; Zhou, Weihong; Hager, Kyle R; Zhang, Yulong; Liu, Xiaoming; Yan, Ziying; Fisher, John T; Keiser, Nicholas W; Song, Yi; Tyler, Scott R; Goeken, J Adam; Kinyon, Joann M; Radey, Matthew C; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J; Kaminsky, Paul M; Brittnacher, Mitchell J; Miller, Samuel I; Parekh, Kalpaj; Meyerholz, David K; Hoffman, Lucas R; Frana, Timothy; Stewart, Zoe A; Engelhardt, John F

2014-05-01

Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chitinase activation in patients with fungus-associated cystic fibrosis lung disease.

PubMed

Hector, Andreas; Chotirmall, Sanjay H; Lavelle, Gillian M; Mirković, Bojana; Horan, Deirdre; Eichler, Laura; Mezger, Markus; Singh, Anurag; Ralhan, Anjai; Berenbrinker, Sina; Mack, Ines; Ensenauer, Regina; Riethmüller, Joachim; Graepler-Mainka, Ute; Murray, Michelle A; Griese, Matthias; McElvaney, N Gerry; Hartl, Dominik

2016-10-01

Chitinases have recently gained attention in the field of pulmonary diseases, particularly in asthma and chronic obstructive pulmonary disease, but their potential role in patients with cystic fibrosis (CF)-associated lung disease remains unclear. The aim of this study was to assess chitinase activity systemically and in the airways of patients with CF and asthma compared with healthy subjects. Additionally, we assessed factors that regulate chitinase activity within the lungs of patients with CF. Chitinase activities were quantified in serum and bronchoalveolar lavage fluid from patients with CF, asthmatic patients, and healthy control subjects. Mechanistically, the role of CF airway proteases and genetic chitinase deficiency was assessed. Chitinase activity was systemically increased in patients with CF compared with that in healthy control subjects and asthmatic patients. Further stratification showed that chitinase activity was enhanced in patients with CF colonized with Candida albicans compared with that in noncolonized patients. CF proteases degraded chitinases in the airway microenvironment of patients with CF. Genetic chitinase deficiency was associated with C albicans colonization in patients with CF. Patients with CF have enhanced chitinase activation associated with C albicans colonization. Therefore chitinases might represent a novel biomarker and therapeutic target for CF-associated fungal disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Inferring genetic parameters on latent variables underlying milk yield and quality, protein composition, curd firmness and cheese-making traits in dairy cattle.

PubMed

Dadousis, C; Cipolat-Gotet, C; Bittante, G; Cecchinato, A

2018-02-01

We studied the genetics of cheese-related latent variables (factors; Fs) for application in dairy cattle breeding. In total, 26 traits, recorded in 1264 Brown Swiss cows, were analyzed through multivariate factor analysis (MFA). Traits analyzed were descriptors of milk quality and yield (including protein fractions) and measures of coagulation, curd firmness (CF), cheese yields (%CY) and nutrient recoveries in the curd (REC). A total of 10 Fs (mutual orthogonal with a varimax rotation) were obtained. To assess the practical use of the Fs into breeding, we inferred their genetic parameters using single and bivariate animal models under a Bayesian framework. Heritability estimates (intra-herd) varied between 0.11 and 0.72 (F3: Yield and F7: κ-β-CN, respectively). The Fs underlined basic characteristics of the cheese-making process, milk components and udder health, while retaining 74% of the original variability. The first two Fs were indicators of the CY percentage (F1: %CY) and the CF process (F2: CF t ), and presented similar heritability estimates: 0.268 and 0.295, respectively. The third factor was associated with the yield of milk and solids (F3: Yield) characterized by a low heritability (0.108) and the fourth with the cheese nitrogen (N) (F4: Cheese N) that conversely appeared to be characterized by a high heritability (0.618). Three Fs were associated with the proportion of the basic milk caseins on total milk protein (F5: as1-β-CN, F7: κ-β-CN, F8: as2-CN), also highly heritable (0.565, 0.723 and 0.397, respectively) and 1 factor with the phosphorylated form of the as1-CN (F9: as1-CN-Ph; 0.318). Moreover, 1 factor was linked to the whey protein α-LA (F10: α-LA; 0.147). An indicator factor of a cow's udder health (F6: Udder health) was also obtained and showed a moderate heritability (0.204). Although the Fs were phenotypically uncorrelated, considerable additive genetic correlations existed among them, with highest values observed between F10: α-LA and F6: Udder health (-0.67) as well as between F9: as1-CN-Ph and F3: Yield (-0.60). Our results show the usefulness of MFA in dairy cattle breeding. The ability to replace a large number of variables with a few latent indicators of the same biological meaning marks MFA as a valuable tool for developing breeding strategies to improve cow's cheese-related traits.

Cell-free DNA testing after combined test: factors affecting the uptake.

PubMed

Maiz, Nerea; Alzola, Irune; Murua, Emerson J; Rodríguez Santos, Javier

2016-11-01

First, to assess what was the uptake of cell free DNA (cfDNA) testing after a combined test and the maternal and fetal factors that influenced this decision, and second, to assess the uptake and factors that influence the choice of invasive testing. This observational retrospective study included 1083 singleton pregnancies who had a combined test for screening for Down syndrome between 11 (+) (0) and 13 (+) (6) weeks. Multivariate logistic regression analysis was used to determine which factors affected the uptake of cfDNA test and invasive testing among risk for trisomies 21, 18, and 13, maternal characteristics and fetal nuchal translucency (NT) thickness. Two-hundred fifty-seven (23.7%) women had a cfDNA test, 89 (8.2%) had an invasive test, and 737 (68.1%) had no further test. The uptake of cfDNA increased with the risk for trisomies (p < 0.001), maternal age (p = 0.013), and was higher in nulliparous women (p = 0.004). The uptake of invasive test increased with the risk for trisomies (p < 0.001) and NT thickness (p < 0.001). This study shows that the uptake of cfDNA testing increases with the risk for trisomies, maternal age, and is higher in nulliparous, whereas the uptake of invasive testing increases with the risk for trisomies and NT thickness.

Synergistic effect of co-digestion to enhance anaerobic degradation of catering waste and orange peel for biogas production.

PubMed

Anjum, Muzammil; Khalid, Azeem; Qadeer, Samia; Miandad, Rashid

2017-09-01

Catering waste and orange peel were co-digested using an anaerobic digestion process. Orange peel is difficult to degrade anaerobically due to the presence of antimicrobial agents such as limonene. The present study aimed to examine the feasibility of anaerobic co-digestion of catering waste with orange peel to provide the optimum nutrient balance with reduced inhibitory effects of orange peel. Batch experiments were conducted using catering waste as a potential substrate mixed in varying ratios (20-50%) with orange peel. Similar ratios were followed using green vegetable waste as co-substrate. The results showed that the highest organic matter degradation (49%) was achieved with co-digestion of catering waste and orange peel at a 50% mixing ratio (CF4). Similarly, the soluble chemical oxygen demand (sCOD) was increased by 51% and reached its maximum value (9040 mg l -1 ) due to conversion of organic matter from insoluble to soluble form. Biogas production was increased by 1.5 times in CF4 where accumulative biogas was 89.61 m 3 t -1 substrate compared with 57.35 m 3 t -1 substrate in the control after 80 days. The main reason behind the improved biogas production and degradation is the dilution of inhibitory factors (limonene), with subsequent provision of balanced nutrients in the co-digestion system. The tCOD of the final digestate was decreased by 79.9% in CF4, which was quite high as compared with 68.3% for the control. Overall, this study revealed that orange peel waste is a highly feasible co-substrate for anaerobic digestion with catering waste for enhanced biogas production.

Compassion fatigue, burnout and compassion satisfaction among family physicians in the Negev area - a cross-sectional study.

PubMed

El-Bar, Nurit; Levy, Amalia; Wald, Hedy S; Biderman, Aya

2013-08-15

Compassion fatigue among health care professionals has gained interest over the past decade. Compassion fatigue, as well as burnout, has been associated with depersonalization and suboptimal patient care. Professional caregivers in general are exposed to the risk of compassion fatigue (CF), burnout (BO) and low levels of compassion satisfaction (CS). While CF has been studied in health care professionals, few publications address its incidence among family physicians, specifically. The objectives of this study were to assess the prevalence and severity of CF among family practitioners (FPs) in the Negev (Israel's southern region), evaluating the correlations between CF, BO and CS and their relations with socio-demographic variables and work related characteristics. Self-report anonymous Compassion Satisfaction and Fatigue Test questionnaires (CSFT) measuring CF, BO, and CS were distributed among 194 family physicians at Clalit Health Services clinics in the Negev between July 2007 and April 2008. Correlations between CF, BO and CS were assessed. Multivariable logistic regression models with backward elimination were constructed. 128 (66%) physicians responded. 46.1% of respondents scored extremely high and high for CF, 21.1% scored low for CS and 9.4% scored high for BO. Strong correlations were found between BO and CF (r = 0.769, p < 0.001), and between BO and CS (r = -0.241, p = 0.006), but no correlation was found between CS and CF. The logistic regression model showed that the only factor associated with a significantly increased risk for CF was former immigration to Israel. Increased risk for BO was associated with female gender, history of personal trauma and lack of academic affiliation. Higher CS was associated with holding management positions and teaching residents. Family physicians in the Negev are at high risk for CF, with the potential for CF- associated patient dissatisfaction, compromised patient safety and increased medical error. We propose creation of a CF educational and early intervention treatment program for family physicians and other health care professionals. Such programs would train facilitators of physician well-being and resiliency building. We also recommend analyzing contributing variables and organizational factors related to higher CF. Policy recommendations include integrating such programs within required risk management continuing medical education.

Compassion fatigue, burnout and compassion satisfaction among family physicians in the Negev area - a cross-sectional study

PubMed Central

2013-01-01

Background Compassion fatigue among health care professionals has gained interest over the past decade. Compassion fatigue, as well as burnout, has been associated with depersonalization and suboptimal patient care. Professional caregivers in general are exposed to the risk of compassion fatigue (CF), burnout (BO) and low levels of compassion satisfaction (CS). While CF has been studied in health care professionals, few publications address its incidence among family physicians, specifically. The objectives of this study were to assess the prevalence and severity of CF among family practitioners (FPs) in the Negev (Israel’s southern region), evaluating the correlations between CF, BO and CS and their relations with socio-demographic variables and work related characteristics. Methods Self-report anonymous Compassion Satisfaction and Fatigue Test questionnaires (CSFT) measuring CF, BO, and CS were distributed among 194 family physicians at Clalit Health Services clinics in the Negev between July 2007 and April 2008. Correlations between CF, BO and CS were assessed. Multivariable logistic regression models with backward elimination were constructed. Results 128 (66%) physicians responded. 46.1% of respondents scored extremely high and high for CF, 21.1% scored low for CS and 9.4% scored high for BO. Strong correlations were found between BO and CF (r = 0.769, p < 0.001), and between BO and CS (r = −0.241, p = 0.006), but no correlation was found between CS and CF. The logistic regression model showed that the only factor associated with a significantly increased risk for CF was former immigration to Israel. Increased risk for BO was associated with female gender, history of personal trauma and lack of academic affiliation. Higher CS was associated with holding management positions and teaching residents. Conclusions and policy recommendations Family physicians in the Negev are at high risk for CF, with the potential for CF- associated patient dissatisfaction, compromised patient safety and increased medical error. We propose creation of a CF educational and early intervention treatment program for family physicians and other health care professionals. Such programs would train facilitators of physician well-being and resiliency building. We also recommend analyzing contributing variables and organizational factors related to higher CF. Policy recommendations include integrating such programs within required risk management continuing medical education. PMID:23947591

Complement Factor B is the Downstream Effector of Toll-Like Receptors and Plays an Important Role in a Mouse Model of Severe Sepsis¶

PubMed Central

Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei

2013-01-01

Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

[A comparative and technical assessment of the HELP system (heparin extracorporeal LDL precipitation) and cascade filtration (CF) for the treatment of high plasma lipids].

PubMed

Loschiavo, Carmelo

2013-01-01

Extracorporeal techniques for the removal of plasma lipids, known as LDL-apheresis, have improved treatment of atherosclerotic lesions in patients with familial hyperlipidemia (FH). In the homozygous form, such treatment is to be considered a life-saving therapy, and in heterozygous forms, which are widely distributed in the population, it is also used when there is a high risk of coronary atherogenic lesions and where a dietary and pharmacological approach has failed to satisfy the objective of a LDL-C 2.6 mmol/L. Of the various techniques available, we believe that cascade filtration (CF) and extracorporeal LDL precipitation with heparin (HELP) are the methods of choice for technical reasons, clinical efficacy and safety. HELP provides, at long-term follow-up, a 5% greater decrease in LDL-C and Lp (a) compared to CF, and about 10% increase in fibrinogen removal resulting in decreased blood viscosity. Conversely, CF produces a concomitant elimination of up to 20% of HDL-C, whereas HELP results in around 5% elimination. CF determines a loss of protein which over time can impact negatively on the protein profile, while HELP results in negligible protein loss. Finally, a significant dampening effect on the intermediate products of inflammation, which initiate the process of vessel atheroma development, has been documented only with HELP. Therefore, the HELP procedure appears to inhibit the development of atheromatous plaques via several different routes.

Evaluation of internal refraction with the optical path difference scan.

PubMed

Muftuoglu, Orkun; Erdem, Uzeyir

2008-01-01

To evaluate internal refraction and its relation to other optical properties of the eye across a large range of refractive errors, which can provide useful information for the assessment and design of intraocular lenses and corneal ablation patterns. Cohort study. Three hundred ninety-four eyes of 197 healthy subjects with a mean age of 27+/-7 years (range, 18-42). All eyes underwent optical path difference scans to evaluate corneal topography, whole and internal ocular refraction (determined by the subtraction of corneal refraction from whole ocular refraction), and total and higher-order aberrations (HOAs) were assessed. After the conversion of any spherocylindrical refractive errors to vectorial data (sphere equivalent, blurring strength; cylinder, J(0) [power of Jackson cross cylinder at 90 degrees and 180 degrees] and J45 [power of Jackson cross cylinder at 45 degrees and 135 degrees]), the distribution of internal refraction among refraction groups (high myopes, low to moderate myopes, hyperopes, mixed astigmats, and emmetropes) and relationships between internal refraction, corneal refraction, and wavefront aberrations were analyzed. The compensation relation and its rate between corneal and internal astigmatism was assessed by the compensation factor (CF). Whole ocular power and astigmatism, corneal power and astigmatism, internal power and astigmatism, CF for astigmatic data, location of the highest internal refraction zone, and wavefront aberrations. The highest refraction zone was mostly (90%) located in the center in myopes, whereas it was located at the nasal side (71%) in hyperopes. There was a significant correlation between whole ocular and internal powers (P<0.01), but no correlation was observed between corneal and internal powers (P>0.05). Internal astigmatism was mostly against the rule. The mean CF J(0) was 0.63+/-3.78 and CF J(45) was 0.57+/-2.47. The magnitude of the internal astigmatism under the 3-mm zone was correlated with the magnitude of corneal astigmatism (P<0.05). The distribution of astigmatic CF differed among refraction groups. There were significant correlations between internal power and spherical aberration (P<0.05) and internal cylinder under the 5-mm zone and HOAs (P<0.001). There is a remarkable tilt in internal refraction in hyperopes. Although there is a tendency of undercompensation of the corneal astigmatism by internal astigmatism in the entire group of eyes, the compensation differs among refraction groups.

Age at first introduction to complementary foods is associated with sociodemographic factors in children with increased genetic risk of developing type 1 diabetes.

PubMed

Andrén Aronsson, Carin; Uusitalo, Ulla; Vehik, Kendra; Yang, Jimin; Silvis, Katherine; Hummel, Sandra; Virtanen, Suvi M; Norris, Jill M

2015-10-01

Infant's age at introduction to certain complementary foods (CF) has in previous studies been associated with islet autoimmunity, which is an early marker for type 1 diabetes (T1D). Various maternal sociodemographic factors have been found to be associated with early introduction to CF. The aims of this study were to describe early infant feeding and identify sociodemographic factors associated with early introduction to CF in a multinational cohort of infants with an increased genetic risk for T1D. The Environmental Determinants of Diabetes in the Young study is a prospective longitudinal birth cohort study. Infants (N = 6404) screened for T1D high risk human leucocyte antigen-DQ genotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4, DR4/1, DR4/13, DR4/9 and DR3/9) were followed for 2 years at six clinical research centres: three in the United States (Colorado, Georgia/Florida, Washington) and three in Europe (Sweden, Finland, Germany). Age at first introduction to any food was reported at clinical visits every third month from the age of 3 months. Maternal sociodemographic data were self-reported through questionnaires. Age at first introduction to CF was primarily associated with country of residence. Root vegetables and fruits were usually the first CF introduced in Finland and Sweden and cereals were usually the first CF introduced in the United States. Between 15% and 20% of the infants were introduced to solid foods before the age of 4 months. Young maternal age (<25 years), low educational level (<12 years) and smoking during pregnancy were significant predictors of early introduction to CF in this cohort. Infants with a relative with T1D were more likely to be introduced to CF later. © 2013 John Wiley & Sons Ltd.

Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation.

PubMed

Maitra, Rangan; Porter, Melissa A; Huang, Shan; Gilmour, Brian P

2009-05-13

Cystic Fibrosis (CF) is one of the most common autosomal genetic disorders in humans. This disease is caused by mutations within a single gene, coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The phenotypic hallmark of CF is chronic lung infection and associated inflammation from opportunistic microbes such as Pseudomonas aeruginosa (PA), Haemophilus influenzae, and Staphylococcus aureus. This eventually leads to deterioration of lung function and death in most CF patients. Unfortunately, there is no approved therapy for correcting the genetic defect causal to the disease. Hence, controlling inflammation and infection in CF patients are critical to disease management. Accordingly, anti-inflammatory agents and antibiotics are used to manage chronic inflammation and infection in CF patients. However, most of the anti-inflammatory agents in CF have severe limitations due to adverse side effects, and resistance to antibiotics is becoming an even more prominent problem. Thus, new agents that can be used to control chronic inflammation in CF are needed in the absence of a cure for the disease. Activation of the transcription factor NFkappaB through Toll-like receptors (TLR) following bacterial infection is principally involved in regulating lung inflammation in CF. NFkappaB regulates the transcription of several genes that are involved in inflammation, anti-apoptosis and anti-microbial activity, and hyper-activation of this transcription factor leads to a potent inflammatory response. Thus, NFkappaB is a potential anti-inflammatory drug target in CF. Screening of several compounds from natural sources in an in vitro model of CF-related inflammation wherein NFkappaB is activated by filtrates of a clinically isolated strain of PA (PAF) led us to Withaferin A (WFA), a steroidal lactone from the plant Withania Somnifera L. Dunal. Our data demonstrate that WFA blocks PAF-induced activation of NFkappaB as determined using reporter assays, IL-8 measurements and high-content fluorescent imaging of NFkappaB subunit p65 translocation. Since the airways of CF patients can be specifically targeted for delivery of therapeutics, we propose that WFA should be further studied as an anti-inflammatory agent in models of CF related inflammation mediated by NFkappaB.

Demonstration of Robustness and Integrated Operation of a Series-Bosch System

NASA Technical Reports Server (NTRS)

Abney, Morgan B.; Mansell, Matthew J.; Stanley, Christine; Barnett, Bill; Junaedi, Christian; Vilekar, Saurabh A.; Ryan, Kent

2016-01-01

Manned missions beyond low Earth orbit will require highly robust, reliable, and maintainable life support systems that maximize recycling of water and oxygen. Bosch technology is one option to maximize oxygen recovery, in the form of water, from metabolically-produced carbon dioxide (CO2). A two stage approach to Bosch, called Series-Bosch, reduces metabolic CO2 with hydrogen (H2) to produce water and solid carbon using two reactors: a Reverse Water-Gas Shift (RWGS) reactor and a carbon formation (CF) reactor. Previous development efforts demonstrated the stand-alone performance of a NASA-designed RWGS reactor designed for robustness against carbon formation, two membrane separators intended to maximize single pass conversion of reactants, and a batch CF reactor with both transit and surface catalysts. In the past year, Precision Combustion, Inc. (PCI) developed and delivered a RWGS reactor for testing at NASA. The reactor design was based on their patented Microlith® technology and was first evaluated under a Phase I Small Business Innovative Research (SBIR) effort in 2010. The RWGS reactor was recently evaluated at NASA to compare its performance and operating conditions with NASA's RWGS reactor. The test results will be provided in this paper. Separately, in 2015, a semi-continuous CF reactor was designed and fabricated at NASA based on the results from batch CF reactor testing. The batch CF reactor and the semi-continuous CF reactor were individually integrated with an upstream RWGS reactor to demonstrate the system operation and to evaluate performance. Here, we compare the performance and robustness to carbon formation of both RWGS reactors. We report the results of the integrated operation of a Series-Bosch system and we discuss the technology readiness level.

Carotid femoral pulse wave velocity in type 2 diabetes and hypertension: capturing arterial health effects of step counts

PubMed Central

Dasgupta, Kaberi; Rosenberg, Ellen; Joseph, Lawrence; Trudeau, Luc; Garfield, Natasha; Chan, Deborah; Sherman, Mark; Rabasa-Lhoret, Rémi; Daskalopoulou, Stella S.

2017-01-01

Objective: Optimal medication use obscures the impact of physical activity on traditional cardiometabolic risk factors. We evaluated the relationship between step counts and carotid-femoral pulse wave velocity (cfPWV), a summative risk indicator, in patients with type 2 diabetes and/or hypertension. Research design and methods: Three hundred and sixty-nine participants were recruited (outpatient clinics; Montreal, Quebec; 2011–2015). Physical activity (pedometer/accelerometer), cfPWV (applanation tonometry), and risk factors (A1C, Homeostatic Model Assessment–Insulin Resistance, blood pressure, lipid profiles) were evaluated. Linear regression models were constructed to quantify the relationship of steps/day with cfPWV. Results: The study population comprised 191 patients with type 2 diabetes and hypertension, 39 with type 2 diabetes, and 139 with hypertension (mean ± SD: age 59.6 ± 11.2 years; BMI 31.3 ± 4.8 kg/m2; 54.2% women). Blood pressure (125/77 ± 15/9 mmHg), A1C (diabetes: 7.7 ± 1.3%; 61 mmol/mol), and low-density lipoprotein cholesterol (diabetes: 2.19 ± 0.8 mmol/l; without diabetes: 3.13 ± 1.1mmol/l) were close to target. Participants averaged 5125 ± 2722 steps/day. Mean cfPWV was 9.8 ± 2.2 m/s. Steps correlated with cfPWV, but not with other risk factors. A 1000 steps/day increment was associated with a 0.1 m/s cfPWV decrement across adjusted models and in subgroup analysis by diabetes status. In a model adjusted for age, sex, BMI, ethnicity, immigrant status, employment, education, diabetes, hypertension, medication classes, the mean cfPWV decrement was 0.11 m/s (95% confidence interval −0.2, −0.02). Conclusions: cfPWV is responsive to step counts in patients who are well controlled on cardioprotective medications. This ability to capture the ‘added value’ of physical activity supports the emerging role of cfPWV in arterial health monitoring. PMID:28129250

Unstimulated Saliva-Related Caries Risk Factors in Individuals with Cystic Fibrosis: A Cross-Sectional Analysis of Unstimulated Salivary Flow, pH, and Buffering Capacity.

PubMed

Alkhateeb, Alaa A; Mancl, Lloyd A; Presland, Richard B; Rothen, Marilynn L; Chi, Donald L

2017-01-01

Salivary flow rate, pH, and buffering capacity are associated with dental caries, but studies from the cystic fibrosis (CF) literature are inconclusive regarding these salivary factors and caries. The aim of this study was to evaluate these factors and their associations with dental caries in individuals with CF. Unstimulated whole saliva was collected from individuals aged 6-20 years at Seattle Children's Hospital CF Clinic, USA (n = 83). Salivary flow rate was measured in milliliters per minute. Salivary pH was assessed using a laboratory pH meter. Buffering capacity was assessed by titration with HCl. The outcome measure was caries prevalence, defined as the number of decayed, missing, or filled primary and permanent tooth surfaces. Spearman's rank correlation coefficient and the t test were used to test for bivariate associations. Multiple variable linear regression models were used to (1) run confounder-adjusted analyses and (2) assess for potential interactions. There was no significant association between salivary flow rate or buffering capacity and caries prevalence. There was a significant negative association between salivary pH and caries prevalence, but this association was no longer significant after adjusting for age. There was no significant interaction between salivary flow rate and buffering capacity or between antibiotic use and the 3 salivary factors. Our results indicate that unstimulated salivary factors are not associated with dental caries prevalence in individuals with CF. Future studies should investigate other potential saliva-related caries risk factors in individuals with CF such as cariogenic bacteria levels, salivary host defense peptide levels, and medication use. © 2016 S. Karger AG, Basel.

Risk factors for persistent Aspergillus respiratory isolation in cystic fibrosis.

PubMed

Hong, Gina; Psoter, Kevin J; Jennings, Mark T; Merlo, Christian A; Boyle, Michael P; Hadjiliadis, Denis; Kawut, Steven M; Lechtzin, Noah

2018-02-12

Aspergillus species are increasingly detected in the respiratory tracts of individuals with cystic fibrosis (CF), and chronic Aspergillus fumigatus is associated with more frequent hospitalizations for pulmonary exacerbations. However, patient and clinical factors that may contribute to the acquisition of persistent Aspergillus infection have yet to be identified. The objective of this study was to identify risk factors for development of Aspergillus respiratory isolation in CF. A retrospective cohort study of participants in the CF Foundation Patient Registry between 2006 and 2012 was conducted. Generalized estimating equation models were used to evaluate the association between the development of persistent Aspergillus respiratory isolation and individual level demographic and clinical characteristics. Among 16,095 individuals with CF followed from 2006 to 2012, 1541 (9.6%) subjects developed persistent Aspergillus isolation. White race (Odds Ratio [OR] 1.74, 95% confidence interval 1.23, 2.48, p<0.001) and pancreatic insufficiency (OR 1.50, 95% CI 1.09, 2.06, p<0.001) were found to be risk factors for persistent Aspergillus isolation. Chronic therapies, including inhaled antibiotics (OR 1.33; 95% CI 1.21, 1.46), macrolides (OR 1.23, 95% CI 1.14, 1.32, p<0.001), and inhaled corticosteroids (OR 1.13, 95% CI 1.04, 1.20, p<0.001) were also independently associated with an increased risk for persistent Aspergillus isolation. We identified macrolides and inhaled antibiotics, which individually have been shown to improve CF outcomes, and inhaled corticosteroids as risk factors for developing persistent Aspergillus isolation. Further work is needed to determine whether these associations are causal or due to confounding by other factors. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Factors affecting nebulised medicine adherence in adult patients with cystic fibrosis: a qualitative study.

PubMed

Hogan, Alice; Bonney, Mary-Ann; Brien, Jo-Anne; Karamy, Rita; Aslani, Parisa

2015-02-01

Nebulised medicines contribute to the high treatment burden experienced by patients with cystic fibrosis (CF). This study explored experiences of adult patients with CF when using nebulised medicines, factors impacting on their adherence to nebulised therapy and strategies they used to facilitate adherence. Community setting, in Sydney, Australia. Ten patients with CF were recruited through a CF patient organisation. Semi-structured face-to-face interviews were conducted, addressing the study objectives. Interviews were audio-recorded, transcribed verbatim and content analysed for anticipated and emergent themes. Experiences with using nebulised medicines; and barriers and facilitators of adherence to nebulised medicines. Participants' age ranged from 22 to 45 years, with half being male. Four broad themes (with more specific sub-themes) were identified from the interviews: experiences with using nebulised medicines (cleaning nebuliser, time taken to use nebuliser medicine, flexibility in use of nebuliser); feelings about using nebulised medicines (necessary/important, dislike, part of life); factors impacting non-adherence (time consuming therapy, side effects/effects of medicine, work/social demands, lack of perceived importance); factors and strategies facilitating adherence (perceived medicine importance, habit/routine, support, health benefits, technology/medicine dose form, timetabling). Nebulised therapy for cystic fibrosis patients takes a substantial amount of time, with patients trying to alter their routine to incorporate nebulising into their daily lives. However there are still many factors that lead to low adherence, including work/social demands and travelling. Patients balance the necessity for nebulised therapy against the barriers, and engage in intentional non-adherence at times. Future strategies and resources should target and address specific factors identified by patients with CF as being important and impacting their adherence to nebulised medicines.

Disease-modifying genetic factors in cystic fibrosis.

PubMed

Marson, Fernando A L

2018-05-01

To compile data from the past 10 years regarding the role of modifying genes in cystic fibrosis (CF). CF is a model disease for understanding of the action of modifying genes. Although it is a monogenic (CFTR) autosomal recessive disease, CF presents with wide phenotypic variability. In CF, variability occurs with different intensity among patients by each organ, being organ-specific, resulting from the mutual interaction of environmental and genetic factors, including CFTR mutations and various other genes, most of which are associated with inflammatory processes. In individuals, using precision medicine, gene modification studies have revealed individualized responses to drugs depending on particular CFTR mutations and modifying genes, most of which are alternative ion channels. Studies of modifying genes in CF allow: understanding of clinical variability among patients with the same CFTR genotype; evaluation of precision medicine; understanding of environmental and genetic effects at the organ level; understanding the involvement of genetic variants in inflammatory responses; improvements in genetic counseling; understanding the involvement of genetic variants in inflammatory responses in lung diseases, such as asthma; and understanding the individuality of the person with the disease.

Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin.

PubMed

Keitsch, Simone; Riethmüller, Joachim; Soddemann, Matthias; Sehl, Carolin; Wilker, Barbara; Edwards, Michael J; Caldwell, Charles C; Fraunholz, Martin; Gulbins, Erich; Becker, Katrin Anne

2018-05-01

Pulmonary infections of cystic fibrosis (CF) patients with Staphylococcus aureus (S. aureus) occur very early in the disease. The molecular details that cause infection-susceptibility of CF patients to and mediate infection with S. aureus are poorly characterized. Therefore, we aimed to identify the role of α-toxin, a major S. aureus toxin, for pulmonary infection of CF mice. Infection with S. aureus JE2 resulted in severe pneumonia in CF mice, while wildtype mice were almost unaffected. Deficiency of α-toxin in JE2-Δhla reduced the pathogenicity of S. aureus in CF mice. However, CF mice were still more susceptible to the mutant S. aureus strain than wildtype mice. The S. aureus JE2 induced a marked increase of ceramide and a downregulation of sphingosine and acid ceramidase expression in bronchi of CF mice. Deletion of α-toxin reduced these changes after infection of CF mice. Similar changes were observed in wildtype mice, but at much lower levels. Our data indicate that expression of α-toxin is a major factor causing S. aureus infections in CF mice. Wildtype S. aureus induces a marked increase of ceramide and a reduction of sphingosine and acid ceramidase expression in bronchial epithelial cells of wildtype and CF mice, changes that determine infection susceptibility.

Epigenetic dysregulation of interleukin 8 (CXCL8) hypersecretion in cystic fibrosis airway epithelial cells

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

Poghosyan, Anna, E-mail: pannagos@yahoo.com; Patel, Jamie K.; Clifford, Rachel L.

Airway epithelial cells in cystic fibrosis (CF) overexpress Interleukin 8 (CXCL8) through poorly defined mechanisms. CXCL8 transcription is dependent on coordinated binding of CCAAT/enhancer binding protein (C/EBP)β, nuclear factor (NF)-κB, and activator protein (AP)-1 to the promoter. Here we show abnormal epigenetic regulation is responsible for CXCL8 overexpression in CF cells. Under basal conditions CF cells had increased bromodomain (Brd)3 and Brd4 recruitment and enhanced NF-κB and C/EBPβ binding to the CXCL8 promoter compared to non-CF cells due to trimethylation of histone H3 at lysine 4 (H3K4me3) and DNA hypomethylation at CpG6. IL-1β increased NF-κB, C/EBPβ and Brd4 binding. Furthermore, inhibitors ofmore » bromodomain and extra-terminal domain family (BET) proteins reduced CXCL8 production in CF cells suggesting a therapeutic target for the BET pathway. -- Highlights: •A regulatory mechanism of CXCL8 transcriptional control in CF airways is proposed. •There was an increased binding of NF-κB and C/EBPβ transcription factors. •There was enhanced recruitment of BET proteins to the CXCL8 promoter. •Epigenetic modifications are responsible for the aberrant CXCL8 transcription.« less

Coping styles in adults with cystic fibrosis: implications for emotional and social quality of life.

PubMed

Mc Hugh, Rachel; Mc Feeters, Danielle; Boyda, David; O'Neill, Siobhan

2016-01-01

As life expectancy increases, interest has grown surrounding the factors that may influence quality of life (QOL) for people with cystic fibrosis (CF). The aim of the current study was to examine which specific coping styles were positively or negatively associated with social and emotional QOL in a CF sample. One hundred and twenty-two respondents aged 18 and over were recruited through an online support group. Respondents completed the 'CF Questionnaire-Revised (CFQ-R)' and the 'Brief COPE'. The CFQ-R is a disease-specific instrument designed to measure the impact of CF on nine QOL domains and the Brief COPE is a 28 item questionnaire which assesses 14 coping scales. A multivariate regression model revealed that higher substance abuse and disengagement was associated with lower emotional QOL whereas greater use of religion, instrumental coping and acceptance was positively associated with emotional QOL. Active coping was linked to better social QOL and a negative association was reported between distraction coping with both emotional and social domains. Given the burden of CF, ascertaining which factors enhance or diminish emotion and social well-being is now an integral component of QOL research. The current findings may therefore have value in informing clinical interventions which aim to cater for the psychological needs of individuals with CF.

Fabrication of hierarchical ZnO nanostructures on cotton fabric for wearable device applications

NASA Astrophysics Data System (ADS)

Pandiyarasan, V.; Suhasini, S.; Archana, J.; Navaneethan, M.; Majumdar, Abhijit; Hayakawa, Y.; Ikeda, H.

2017-10-01

We have investigated ZnO nanostructures on cotton fabric (CF) s a flexible material for an application of wearable thermoelectric (TE) power generator which requires super-hydrophobicity, UV protection, and high TE efficiency. Field emission scanning electron microscopy images revealed that the formed ZnO nanostructures have a mixture of nanorods and nanosheets and are uniformly coated on the CF. XRD pattern and Raman spectra revealed that the ZnO nanostructure has a wurtzite structure. Contact angle measurements showed that the ZnO-nanostructures-coated CF possessed a high super hydrophobic nature with an angle of 132.5°. ZnO nanocomposite/CF sample exhibited an excellent UV protection factor 183.84. Seebeck coefficient, electrical resistivity and thermoelectric power factor of the ZnO nanostructures on cotton fabric were evaluated to be 28 μV/K, 0.04 Ω-cm, and 22 μW/m K2, respectively.

Compassion Fatigue and Psychological Distress Among Social Workers: A Validation Study

PubMed Central

Adams, Richard E.; Boscarino, Joseph A.; Figley, Charles R.

2009-01-01

Few studies have focused on caring professionals and their emotional exhaustion from working with traumatized clients, referred to as compassion fatigue (CF). The present study had 2 goals: (a) to assess the psychometric properties of a CF scale, and (b) to examine the scale's predictive validity in a multivariate model. The data came from a survey of social workers living in New York City following the September 11, 2001, terrorist attacks on the World Trade Center. Factor analyses indicated that the CF scale measured multiple dimensions. After overlapping items were eliminated, the scale measured 2 key underlying dimensions—secondary trauma and job burnout. In a multivariate model, these dimensions were related to psychological distress, even after other risk factors were controlled. The authors discuss the results in light of increasing the ability of professional caregivers to meet the emotional needs of their clients within a stressful environment without experiencing CF. PMID:16569133

Cost(s) of caring for patients with cystic fibrosis.

PubMed

Orenstein, David M; Abood, Robert N

2018-06-01

Cystic fibrosis (CF) has received a lot of attention in the past few years because of increased longevity and the emergence of ground-breaking new drugs targeting the molecular and cellular defects, making a huge clinical difference, and - not incidentally - carrying massive price tags. The prices of these new drugs make the question of overall costs of CF care highly relevant. This article reviews recent developments in CF science and treatment, and highlights areas that contribute to costs of CF care, emphasizing how these costs have increased. This article should help the pediatrician stay abreast of high points of CF care, with an awareness of the factors that wield the biggest influence on overall costs, to patients, families and the US healthcare system.

Real-Time PCR-Based Quantitation Method for the Genetically Modified Soybean Line GTS 40-3-2.

PubMed

Kitta, Kazumi; Takabatake, Reona; Mano, Junichi

2016-01-01

This chapter describes a real-time PCR-based method for quantitation of the relative amount of genetically modified (GM) soybean line GTS 40-3-2 [Roundup Ready(®) soybean (RRS)] contained in a batch. The method targets a taxon-specific soybean gene (lectin gene, Le1) and the specific DNA construct junction region between the Petunia hybrida chloroplast transit peptide sequence and the Agrobacterium 5-enolpyruvylshikimate-3-phosphate synthase gene (epsps) sequence present in GTS 40-3-2. The method employs plasmid pMulSL2 as a reference material in order to quantify the relative amount of GTS 40-3-2 in soybean samples using a conversion factor (Cf) equal to the ratio of the RRS-specific DNA to the taxon-specific DNA in representative genuine GTS 40-3-2 seeds.

Ostreopsis cf. ovata dynamics in the NW Mediterranean Sea in relation to biotic and abiotic factors

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

Carnicer, Olga; Guallar, Carles; IFREMER, DYNECO-PELAGOS Centre de Brest, Pointe du Diable BP70, 29280 Plouzane

2015-11-15

An expansion of the distribution of Ostreopsis cf. ovata, a dinoflagellate which produces palytoxin-like compounds, has been reported in recent years. Economical and social interests are affected by blooms, as they are responsible for respiratory and skin problems in humans and may cause damage to marine organisms. In order to identify the most influential environmental factors that trigger proliferations of O. cf. ovata in the area of the adjacent shallow rocky coast of the Ebro Delta (NW Mediterranean Sea) a three-year survey was performed on the metaphytic microalgae community growing on the macrophytes Jania rubens and Corallina elongata. Small-size diatomsmore » were more abundant than dinoflagellates; O. cf. ovata was identified as the only species present from the genus. Seawater temperature was the primary driver defining the ecological niche of O. cf. ovata. Freshwater and groundwater fluxes were more pronounced in southern than in northern sites, which may have resulted in a distinct O. cf. ovata spatial distribution, with the highest records of abundance and more frequent blooms in the north. In consequence, negative correlations between the abundance of O. cf. ovata and nitrate concentrations and significant positive correlation with salinity were observed. The temporal pattern of O. cf. ovata dynamics from mid-July to early-November is probably due to the fact that this species is observed only above a certain threshold temperature of seawater. Metaphytic cells of O. cf. ovata were smaller in the northern site than in the south, possibly as a result of an increase in cell division, coinciding with higher abundance, and this could be an indicator of favorable conditions. Toxicity in planktonic cells was negatively correlated with cell abundance in the water column, achieving maximum concentrations of 25 pg. PLTX eq cell{sup −1}. - Highlights: • Presence of a single Ostreopsis genotype in confirmed through qPCR. • Temperature confirmed as the most important parameter affecting its distribution. • Salinity positively correlated with Ostreopsis cf. ovata abundance. • Ostreopsis cf. ovata has a restricted ecological niche. • Toxicity in Ostreopsis planktonic cells negatively correlated with cell abundance.« less

The Tumor Necrosis Factor α (-308 A/G) Polymorphism Is Associated with Cystic Fibrosis in Mexican Patients

PubMed Central

Sanchez-Dominguez, Celia N.; Reyes-Lopez, Miguel A.; Bustamante, Adriana; Cerda-Flores, Ricardo M.; Villalobos-Torres, Maria del C.; Gallardo-Blanco, Hugo L.; Rojas-Martinez, Augusto; Martinez-Rodriguez, Herminia G.; Barrera-Saldaña, Hugo A.; Ortiz-Lopez, Rocio

2014-01-01

Environmental and genetic factors may modify or contribute to the phenotypic differences observed in multigenic and monogenic diseases, such as cystic fibrosis (CF). An analysis of modifier genes can be helpful for estimating patient prognosis and directing preventive care. The aim of this study is to determine the association between seven genetic variants of four modifier genes and CF by comparing their corresponding allelic and genotypic frequencies in CF patients (n = 81) and control subjects (n = 104). Genetic variants of MBL2 exon 1 (A, B, C and D), the IL-8 promoter (−251 A/T), the TNFα promoter (TNF1/TNF2), and SERPINA1 (PI*Z and PI*S) were tested in CF patients and control subjects from northeastern Mexico by PCR-RFLP. Results The TNF2 allele (P = 0.012, OR 3.43, 95% CI 1.25–9.38) was significantly associated with CF under the dominant and additive models but was not associated with CF under the recessive model. This association remained statistically significant after adjusting for multiple tests using the Bonferroni correction (P = 0.0482). The other tested variants and genotypes did not show any association with the disease. Conclusion An analysis of seven genetic variants of four modifier genes showed that one variant, the TNF2 allele, appears to be significantly associated with CF in Mexican patients. PMID:24603877

Cat and Dog Exposure and Respiratory Morbidities in Cystic Fibrosis

PubMed Central

Morrow, Christopher B.; Raraigh, Karen S.; Green, Deanna M.; Blackman, Scott M.; Cutting, Garry R.; Collaco, Joseph M.

2014-01-01

Objective To understand the triggers that may impact respiratory health in cystic fibrosis (CF), including the effects of pets, because environmental factors contribute to one-half of the variation in lung function in patients with CF. Study design A total of 703 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of cats and dogs in households with a child with CF. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track respiratory and infection outcomes. Results Within the sample 47% of subjects reported owning a dog, and 28% reported owning a cat. After adjustment for demographic factors, dog ownership was not associated with any adverse clinical outcomes, and cat ownership was associated an increased risk in developing nasal polyps (adjusted OR 1.66; p=0.024) compared with non-cat owners. Subjects who owned both cats and dogs were twice as likely to report wheezing compared with other subjects (adjusted OR: 2.01; p=0.009). There were no differences in prevalence and age of acquisition for the common CF respiratory pathogens Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus between cat/dog owners and non-cat/dog owners. Conclusions Cat ownership was associated with a higher frequency of developing nasal polyps and combined cat-dog ownership was associated with a higher rate of wheezing. Prospective studies are needed to confirm these associations and the potential psychosocial benefits of cat and/or dog ownership. PMID:25027361

Cat and dog exposure and respiratory morbidities in cystic fibrosis.

PubMed

Morrow, Christopher B; Raraigh, Karen S; Green, Deanna M; Blackman, Scott M; Cutting, Garry R; Collaco, Joseph M

2014-10-01

To understand the triggers that may impact respiratory health in cystic fibrosis (CF), including the effects of pets, because environmental factors contribute to one-half of the variation in lung function in patients with CF. A total of 703 subjects with CF were recruited through the US CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of cats and dogs in households with a child with CF. Questionnaires, chart review, and US CF Foundation Patient Registry data were used to track respiratory and infection outcomes. Within the sample, 47% of subjects reported owning a dog, and 28% reported owning a cat. After adjustment for demographic factors, dog ownership was not associated with any adverse clinical outcomes, and cat ownership was associated an increased risk in developing nasal polyps (aOR 1.66; P = .024) compared with noncat owners. Subjects who owned both cats and dogs were twice as likely to report wheezing compared with other subjects (aOR: 2.01; P = .009). There were no differences in prevalence and age of acquisition for the common CF respiratory pathogens Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus between cat/dog owners and noncat/dog owners. Cat ownership was associated with a greater frequency of developing nasal polyps and combined cat-dog ownership was associated with a greater rate of wheezing. Prospective studies are needed to confirm these associations and the potential psychosocial benefits of cat and/or dog ownership. Copyright © 2014 Elsevier Inc. All rights reserved.

Two novel LRR-only proteins in Chlamys farreri: Similar in structure, yet different in expression profile and pattern recognition.

PubMed

Wang, Mengqiang; Wang, Lingling; Xin, Lusheng; Wang, Xiudan; Wang, Lin; Xu, Jianchao; Jia, Zhihao; Yue, Feng; Wang, Hao; Song, Linsheng

2016-06-01

Leucine-rich repeat (LRR)-only proteins could mediate protein-ligand and protein-protein interactions and be involved in the immune response. In the present study, two novel LRR-only proteins, CfLRRop-2 and CfLRRop-3, were identified and characterized from scallop Chlamys farreri. They both contained nine LRR motifs with the consensus signature sequence LxxLxLxxNxL and formed typical horseshoe structure. The CfLRRop-2 and CfLRRop-3 mRNA transcripts were constitutively expressed in haemocytes, muscle, mantle, gill, haepatopancreas and gonad, with the highest expression level in haepatopancreas and gill, respectively. During the ontogenesis of scallop, the mRNA transcripts of CfLRRop-2 were kept at a high level in oocytes and embryos, while those of CfLRRop-3 were expressed at a rather low level from oocytes to blastula. Their mRNA transcripts were significantly increased after the stimulation of lipopolysaccharide (LPS), peptidoglycan (PGN), glucan (GLU) and polyinosinic-polycytidylic acid (poly I:C), and the mRNA expression of CfLRRop-2 rose more intensely than that of CfLRRop-3. After the suppression of CfTLR (previously identified Toll-like receptor in C. farreri) via RNA interference (RNAi), CfLRRop-3 mRNA transcripts increased more intensely and lastingly than those of CfLRRop-2. The rCfLRRop-3 protein could bind LPS, PGN, GLU and poly I:C, while rCfLRRop-2 exhibited no significant binding activity to them. Additionally, rCfLRRop-2 could significantly induce the release of TNF-α from the mixed primary cultured scallop haemocytes, but rCfLRRop-3 failed. These results collectively indicated that CfLRRop-2 might act as an immune effector or pro-inflammatory factor, while CfLRRop-3 would function as a pattern recognition receptor (PRR), suggesting the function of LRR-only protein family has differentiated in scallop. Copyright © 2016 Elsevier Ltd. All rights reserved.

EG-VEGF, BV8, and their receptor expression in human bronchi and their modification in cystic fibrosis: Impact of CFTR mutation (delF508).

PubMed

Chauvet, Sylvain; Traboulsi, Wael; Thevenon, Laura; Kouadri, Amal; Feige, Jean-Jacques; Camara, Boubou; Alfaidy, Nadia; Benharouga, Mohamed

2015-08-01

Enhanced lung angiogenesis has been reported in cystic fibrosis (CF). Recently, two highly homologous ligands, endocrine gland vascular endothelial growth factor (EG-VEGF) and mammalian Bv8, have been described as new angiogenic factors. Both ligands bind and activate two closely related G protein-coupled receptors, the prokineticin receptor (PROKR) 1 and 2. Yet, the expression, regulation, and potential role of EG-VEGF, BV8, and their receptors in normal and CF lung are still unknown. The expression of the receptors and their ligands was examined using molecular, biochemical, and immunocytochemistry analyses in lungs obtained from CF patients vs. control and in normal and CF bronchial epithelial cells. Cystic fibrosis transmembrane conductance regulator (CFTR) activity was evaluated in relation to both ligands, and concentrations of EG-VEGF were measured by ELISA. At the mRNA level, EG-VEGF, BV8, and PROKR2 gene expression was, respectively, approximately five, four, and two times higher in CF lungs compared with the controls. At the cellular level, both the ligands and their receptors showed elevated expressions in the CF condition. Similar results were observed at the protein level. The EG-VEGF secretion was apical and was approximately two times higher in CF compared with the normal epithelial cells. This secretion was increased following the inhibition of CFTR chloride channel activity. More importantly, EG-VEGF and BV8 increased the intracellular concentration of Ca(2+) and cAMP and stimulated CFTR-chloride channel activity. Altogether, these data suggest local roles for epithelial BV8 and EG-VEGF in the CF airway peribronchial vascular remodeling and highlighted the role of CFTR activity in both ligand biosynthesis and secretion. Copyright © 2015 the American Physiological Society.

Chronic fatigue in 812 testicular cancer survivors during long-term follow-up: increasing prevalence and risk factors.

PubMed

Sprauten, M; Haugnes, H S; Brydøy, M; Kiserud, C; Tandstad, T; Bjøro, T; Bjerner, J; Cvancarova, M; Fosså, S D; Oldenburg, J

2015-10-01

Chronic fatigue (CF) has been reported to be slightly more prevalent in testicular cancer survivors (TCSs) than in the general population. In this study, we wished to explore possible determinants of CF in TCSs median 12 (survey I) and 19 years (survey II) after treatment, in particular the relation to late effects after treatment. Overall, 812 TCSs treated between 1980 and 1994 provided blood samples (testosterone and luteinizing hormone) and completed questionnaires at survey I (1998-2002) and survey II (2007-2008). Hormone levels were categorized according to quartile thresholds for decadal age groups of controls. Associations between CF and possible risk factors, including the Hospital Anxiety and Depression Scale (HADS), treatment, physical activity, hormone levels, neurotoxicity, and comorbidity, were analyzed by logistic regression. Prevalence of CF increased from 15% at survey I to 27% at survey II (P < 0.001). At survey II, risk for CF was increased three- to four-fold for high levels of neuropathy compared with no neuropathy, and two- to three-fold for high levels of Raynaud-like phenomena, and having testosterone levels in the lowest quartile, while being moderately and highly physically active, had a protective effect. Risk for CF in TCSs with higher levels of HADS-Anxiety and HADS-Depression was increased two- to five-fold, respectively. The increasing prevalence of CF in TCSs is a novel finding. Lifestyle interventions, early detection and treatment of depression and anxiety, and possibly testosterone substitution might reduce the risk of CF. Extended long-term follow-up seems to be important. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Relative Contribution of Genetic and Non-genetic Modifiers to Intestinal Obstruction in Cystic Fibrosis

PubMed Central

Blackman, Scott M.; Deering-Brose, Rebecca; McWilliams, Rita; Naughton, Kathleen; Coleman, Barbara; Lai, Teresa; Algire, Marilyn; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Fallin, M. Daniele; West, Kristen; Arking, Dan E.; Chakravarti, Aravinda; Cutler, David J.; Cutting, Garry R

2006-01-01

Background & Aims Neonatal intestinal obstruction (meconium ileus or MI) occurs in 15% of patients with cystic fibrosis (CF). Our aim was to determine the relative contribution of genetic and non-genetic modifiers to the development of this major complication of CF. Methods Using clinical data and DNA collected by the CF Twin and Sibling Study, 65 monozygous twin pairs, 23 dizygous twin/triplet sets, and 349 sets of siblings with CF were analyzed for MI status, significant covariates, and genome-wide linkage. Results Specific mutations in CFTR, the gene responsible for CF, correlated with MI indicating a role for CFTR genotype. Monozygous twins showed substantially greater concordance for MI than dizygous twins and siblings (p=1×10−5) demonstrating that modifier genes independent of CFTR contribute substantially to this trait. Regression analysis revealed that MI was correlated with distal intestinal obstruction syndrome (DIOS; p=8×10−4). Unlike MI, concordance analysis indicated that the risk for development of DIOS in CF patients is primarily due to non-genetic factors. Regions of suggestive linkage (logarithm of the odds of linkage >2.0) for modifier genes that cause MI (chromosomes 4q35.1, 8p23.1, and 11q25) or protect from MI (chromosomes 20p11.22 and 21q22.3) were identified by genome-wide analyses. These analyses did not support the existence of a major modifier gene within the CFM1 region on chromosome 19 that had previously been linked to MI. Conclusions The CFTR gene along with two or more modifier genes are the major determinants of intestinal obstruction in newborn CF patients, while intestinal obstruction in older CF patients is primarily due to non-genetic factors. PMID:17030173

Serum insulin-like growth factor-1 (IGF-1) during CF pulmonary exacerbation: trends and biomarker correlations.

PubMed

Gifford, A H; Nymon, A B; Ashare, A

2014-04-01

Cystic fibrosis (CF) is characterized by low circulating levels of insulin-like growth factor-1 (IGF-1), a hormone produced by the liver that governs anabolism and influences immune cell function. Because treatment of CF pulmonary exacerbation (CFPE) often improves body weight and lung function, we questioned whether serum IGF-1 trends were emblematic of these responses. Initially, we compared serum levels between healthy adults with CF and controls of similar age. We then measured serum IGF-1 throughout the CFPE cycle. We also investigated correlations among IGF-1 and other serum biomarkers during CFPE. Anthopometric, spirometric, and demographic data were collected. Serum IGF-1 concentrations were measured by ELISA. CF subjects in their usual state of health had lower serum IGF-1 levels than controls. Serum IGF-1 concentrations fell significantly from baseline at the beginning of CFPE. Treatment with intravenous antibiotics was associated with significant improvement in serum IGF-1 levels, body mass index (BMI), and percent-predicted forced expiratory volume in 1 sec (FEV1 %). At early and late CFPE, serum IGF-1 was directly correlated with FEV1 %, serum iron, hemoglobin concentration, and transferrin saturation (TSAT) and indirectly correlated with alpha-1-antitrypsin. This study not only supports the paradigm that CF is characterized by IGF-1 deficiency but also that trends in lung function, nutritional status, and serum IGF-1 are related. Improvements in all three parameters after antibiotics for CFPE likely highlight the connection between lung function and nutritional status in CF. Close correlations among IGF-1 and iron-related hematologic parameters suggest that IGF-1 may participate in CF iron homeostasis, another process that is known to be influenced by CFPE. © 2013 Wiley Periodicals, Inc.

Development of two measures of client engagement for use in home aged care.

PubMed

Baker, Jess Rose; Harrison, Fleur; Low, Lee-Fay

2016-05-01

The aim of the study was to develop and validate measures of client engagement in aged homecare. The Homecare Measure of Engagement-Staff questionnaire (HoME-S) is a self-complete measure of six dimensions of client engagement: client acceptance, attention, attitude, appropriateness, engagement duration and passivity. The Homecare Measure of Engagement-Client/Family report (HoME-CF) is a researcher-rated interview which obtains client and/or family perspectives regarding frequency and valence of conversational and recreational engagement during care worker visits. Care workers (n = 84) completed the HoME-S and a measure of relationship bond with client. Researchers interviewed clients (n = 164) and/or their family (n = 117) and completed the HoME-CF, and measures of agitation, dysphoria, apathy and cognitive functioning. The HoME-S and HoME-CF demonstrated good test-retest and inter-rater reliability, and showed significant negative correlations with apathy, agitation and non-English-speaking background. Controlling for client and care service characteristics, a stronger care worker-client relationship bond and English-speaking background were independently associated with higher HoME-S scores, and apathy was independently associated with higher HoME-CF scores. In conclusion, the HoME-S and HoME-CF are psychometrically sound engagement measures for use in homecare. Clients who are apathetic or from non-English-speaking backgrounds may be less responsive to traditional care worker engagement strategies. Engagement may be augmented in clients who have stronger relationships with their care workers. © 2015 John Wiley & Sons Ltd.

Mechanisms and seasonal drivers of calcification in the temperate coral Turbinaria reniformis at its latitudinal limits.

PubMed

Ross, Claire L; Schoepf, Verena; DeCarlo, Thomas M; McCulloch, Malcolm T

2018-05-30

High-latitude coral reefs provide natural laboratories for investigating the mechanisms and limits of coral calcification. While the calcification processes of tropical corals have been studied intensively, little is known about how their temperate counterparts grow under much lower temperature and light conditions. Here, we report the results of a long-term (2-year) study of seasonal changes in calcification rates, photo-physiology and calcifying fluid (cf) chemistry (using boron isotope systematics and Raman spectroscopy) for the coral Turbinaria reniformis growing near its latitudinal limits (34.5° S) along the southern coast of Western Australia. In contrast with tropical corals, calcification rates were found to be threefold higher during winter (16 to 17° C) compared with summer (approx. 21° C), and negatively correlated with light, but lacking any correlation with temperature. These unexpected findings are attributed to a combination of higher chlorophyll a, and hence increased heterotrophy during winter compared with summer, together with the corals' ability to seasonally modulate pH cf , with carbonate ion concentration [Formula: see text] being the main controller of calcification rates. Conversely, calcium ion concentration [Ca 2+ ] cf declined with increasing calcification rates, resulting in aragonite saturation states Ω cf that were stable yet elevated fourfold above seawater values. Our results show that corals growing near their latitudinal limits exert strong physiological control over their cf in order to maintain year-round calcification rates that are insensitive to the unfavourable temperature regimes typical of high-latitude reefs. © 2018 The Author(s).

PAH emissions from coal combustion and waste incineration.

PubMed

Hsu, Wei Ting; Liu, Mei Chen; Hung, Pao Chen; Chang, Shu Hao; Chang, Moo Been

2016-11-15

The characteristics of PAHs that are emitted by a municipal waste incinerator (MWI) and coal-fired power plant are examined via intensive sampling. Results of flue gas sampling reveal the potential for PAH formation within the selective catalytic reduction (SCR) system of a coal-fired power plant. In the large-scale MWI, the removal efficiency of PAHs achieved with the pilot-scaled catalytic filter (CF) exceeds that achieved by activated carbon injection with a bag filter (ACI+BF) owing to the effective destruction of gas-phase contaminants by a catalyst. A significantly lower PAH concentration (1640ng/g) was measured in fly ash from a CF module than from an ACI+BF system (5650ng/g). Replacing the ACI+BF system with CF technology would significantly reduce the discharge factor (including emission and fly ash) of PAHs from 251.6 to 77.8mg/ton-waste. The emission factors of PAHs that are obtained using ACI+BF and the CF system in the MWI are 8.05 and 7.13mg/ton, respectively. However, the emission factor of MWI is significantly higher than that of coal-fired power plant (1.56mg/ton). From the perspective of total environmental management to reduce PAH emissions, replacing the original ACI+BF process with a CF system is expected to reduce environmental impact thereof. Copyright © 2016 Elsevier B.V. All rights reserved.

Sources of Variation in Sweat Chloride Measurements in Cystic Fibrosis.

PubMed

Collaco, Joseph M; Blackman, Scott M; Raraigh, Karen S; Corvol, Harriet; Rommens, Johanna M; Pace, Rhonda G; Boelle, Pierre-Yves; McGready, John; Sosnay, Patrick R; Strug, Lisa J; Knowles, Michael R; Cutting, Garry R

2016-12-01

Expanding the use of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators and correctors for the treatment of cystic fibrosis (CF) requires precise and accurate biomarkers. Sweat chloride concentration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFTR mutations account for sweat chloride variation. To estimate potential sources of variation for sweat chloride measurements, including demographic factors, testing variability, recording biases, and CFTR genotype itself. A total of 2,639 sweat chloride measurements were obtained in 1,761 twins/siblings from the CF Twin-Sibling Study, French CF Modifier Gene Study, and Canadian Consortium for Genetic Studies. Variance component estimation was performed by nested mixed modeling. Across the tested CF population as a whole, CFTR gene mutations were found to be the primary determinant of sweat chloride variability (56.1% of variation) with contributions from variation over time (e.g., factors related to testing on different days; 13.8%), environmental factors (e.g., climate, family diet; 13.5%), other residual factors (e.g., test variability; 9.9%), and unique individual factors (e.g., modifier genes, unique exposures; 6.8%) (likelihood ratio test, P < 0.001). Twin analysis suggested that modifier genes did not play a significant role because the heritability estimate was negligible (H 2  = 0; 95% confidence interval, 0.0-0.35). For an individual with CF, variation in sweat chloride was primarily caused by variation over time (58.1%) with the remainder attributable to residual/random factors (41.9%). Variation in the CFTR gene is the predominant cause of sweat chloride variation; most of the non-CFTR variation is caused by testing variability and unique environmental factors. If test precision and accuracy can be improved, sweat chloride measurement could be a valuable biomarker for assessing response to therapies directed at mutant CFTR.

Sources of Variation in Sweat Chloride Measurements in Cystic Fibrosis

PubMed Central

Blackman, Scott M.; Raraigh, Karen S.; Corvol, Harriet; Rommens, Johanna M.; Pace, Rhonda G.; Boelle, Pierre-Yves; McGready, John; Sosnay, Patrick R.; Strug, Lisa J.; Knowles, Michael R.; Cutting, Garry R.

2016-01-01

Rationale: Expanding the use of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators and correctors for the treatment of cystic fibrosis (CF) requires precise and accurate biomarkers. Sweat chloride concentration provides an in vivo assessment of CFTR function, but it is unknown the degree to which CFTR mutations account for sweat chloride variation. Objectives: To estimate potential sources of variation for sweat chloride measurements, including demographic factors, testing variability, recording biases, and CFTR genotype itself. Methods: A total of 2,639 sweat chloride measurements were obtained in 1,761 twins/siblings from the CF Twin-Sibling Study, French CF Modifier Gene Study, and Canadian Consortium for Genetic Studies. Variance component estimation was performed by nested mixed modeling. Measurements and Main Results: Across the tested CF population as a whole, CFTR gene mutations were found to be the primary determinant of sweat chloride variability (56.1% of variation) with contributions from variation over time (e.g., factors related to testing on different days; 13.8%), environmental factors (e.g., climate, family diet; 13.5%), other residual factors (e.g., test variability; 9.9%), and unique individual factors (e.g., modifier genes, unique exposures; 6.8%) (likelihood ratio test, P < 0.001). Twin analysis suggested that modifier genes did not play a significant role because the heritability estimate was negligible (H2 = 0; 95% confidence interval, 0.0–0.35). For an individual with CF, variation in sweat chloride was primarily caused by variation over time (58.1%) with the remainder attributable to residual/random factors (41.9%). Conclusions: Variation in the CFTR gene is the predominant cause of sweat chloride variation; most of the non-CFTR variation is caused by testing variability and unique environmental factors. If test precision and accuracy can be improved, sweat chloride measurement could be a valuable biomarker for assessing response to therapies directed at mutant CFTR. PMID:27258095

VizieR Online Data Catalog: Ba V, Ba VI, and Ba VII oscillator strengths (Rauch+, 2014)

NASA Astrophysics Data System (ADS)

Rauch, T.; Werner, K.; Quinet, P.; Kruk, J. W.

2014-04-01

table1.dat contains calculated HFR oscillator strengths (loggf) and transition probabilities (gA, in 1/s) in Ba V. CF is the cancellation factor as defined by Cowan (1981). In columns 3 and 6, e is written for even and o for odd. table2.dat contains calculated HFR oscillator strengths (loggf) and transition probabilities (gA, in 1/s) in Ba VI. CF is the cancellation factor as defined by Cowan (1981). In columns 3 and 6, e is written for even and o for odd. table3.dat contains calculated HFR oscillator strengths (loggf) and transition probabilities (gA, in 1/s) in Ba VII. CF is the cancellation factor as defined by Cowan (1981). In columns 3 and 6, e is written for even and o for odd. (3 data files).

Genetic Expression in Cystic Fibrosis Related Bone Disease. An Observational, Transversal, Cross-Sectional Study.

PubMed

Ciuca, Ioana M; Pop, Liviu L; Rogobete, Alexandru F; Onet, Dan I; Guta-Almajan, Bogdan; Popa, Zoran; Horhat, Florin G

2016-09-01

Cystic fibrosis (CF) is the most frequent monogenic genetic disease with autosomal recessive transmission and characterized by important clinical polymorphism and significant lethal prospective. CF related bone disease occurs frequently in adults with CF. Childhood is the period of bone formation, and therefore, children are more susceptible to low bone density. Several factors like pancreatic insufficiency, hormone imbalance, and physical inactivity contribute to CF bone disease development. Revealing this would be important for prophylactic treatment against bone disease occurrence. The study was observational, transversal, with a cross-sectional design. The study included 68 children with cystic fibrosis, genotyped and monitored in the National CF Centre. At the annual assessment, besides clinical examination, biochemical evaluation for pancreatic insufficiency, and diabetes, they were evaluated for bone mineral density using dual energy X-ray absorptiometry (DXA). Twenty-six patients, aged over 10 years were diagnosed with CF bone disease, without significant gender gap. Bone disease was frequent in patients aged over 10 years with exocrine pancreatic insufficiency, carriers of severe mutations, and CF liver disease. CF carriers of a severe genotype which associates pancreatic insufficiency and CF liver disease, are more likely predisposed to low bone mineral density. Further studies should discover other significant influences in order to prevent the development of CF bone disease and an improved quality of life in cystic fibrosis children.

Ostreopsis cf. ovata dynamics in the NW Mediterranean Sea in relation to biotic and abiotic factors.

PubMed

Carnicer, Olga; Guallar, Carles; Andree, Karl B; Diogène, Jorge; Fernández-Tejedor, Margarita

2015-11-01

An expansion of the distribution of Ostreopsis cf. ovata, a dinoflagellate which produces palytoxin-like compounds, has been reported in recent years. Economical and social interests are affected by blooms, as they are responsible for respiratory and skin problems in humans and may cause damage to marine organisms. In order to identify the most influential environmental factors that trigger proliferations of O. cf. ovata in the area of the adjacent shallow rocky coast of the Ebro Delta (NW Mediterranean Sea) a three-year survey was performed on the metaphytic microalgae community growing on the macrophytes Jania rubens and Corallina elongata. Small-size diatoms were more abundant than dinoflagellates; O. cf. ovata was identified as the only species present from the genus. Seawater temperature was the primary driver defining the ecological niche of O. cf. ovata. Freshwater and groundwater fluxes were more pronounced in southern than in northern sites, which may have resulted in a distinct O. cf. ovata spatial distribution, with the highest records of abundance and more frequent blooms in the north. In consequence, negative correlations between the abundance of O. cf. ovata and nitrate concentrations and significant positive correlation with salinity were observed. The temporal pattern of O. cf. ovata dynamics from mid-July to early-November is probably due to the fact that this species is observed only above a certain threshold temperature of seawater. Metaphytic cells of O. cf. ovata were smaller in the northern site than in the south, possibly as a result of an increase in cell division, coinciding with higher abundance, and this could be an indicator of favorable conditions. Toxicity in planktonic cells was negatively correlated with cell abundance in the water column, achieving maximum concentrations of 25pg. PLTX eqcell(-1). Copyright © 2015 Elsevier Inc. All rights reserved.

A cross-sectional pilot study of compassion fatigue, burnout, and compassion satisfaction in pediatric palliative care providers in the United States.

PubMed

Kase, Samuel M; Waldman, Elisha D; Weintraub, Andrea S

2018-02-05

Compassion fatigue (CF) is secondary traumatic distress experienced by providers from contact with patients' suffering. Burnout (BO) is job-related distress resulting from uncontrollable workplace factors that manifest in career dissatisfaction. Compassion satisfaction (CS) is emotional fulfillment derived from caring for others. The literature on BO in healthcare providers is extensive, whereas CF and CS have not been comprehensively studied. Because of ongoing exposure to patient and family distress, pediatric palliative care (PPC) providers may be at particular risk for CF. We conducted a cross-sectional pilot study of CF, BO, and CS among PPC providers across the United States. The Compassion Fatigue and Satisfaction Self-Test for Helpers and a questionnaire of professional and personal characteristics were distributed electronically and anonymously to PPC physicians and nurses. Logistic and linear regression models for CF, BO, and CS as a function of potential risk factors were constructed. The survey response rate was 39%, primarily consisting of female, Caucasian providers. The prevalence of CF, BO, and CS was 18%, 12%, and 25%, respectively. Distress about a "clinical situation," physical exhaustion, and personal loss were identified as significant determinants of CF. Distress about "coworkers," emotional depletion, social isolation, and "recent involvement in a clinical situation in which life-prolonging activities were not introduced" were significant determinants of BO. Physical exhaustion, personal history of trauma, "recent involvement in a clinical situation in which life-prolonging activities were not introduced," and not discussing distressing issues were significant predictors of lower CS scores. Significance of results CF and BO directly influence the well-being and professional performance of PPC providers. To provide effective compassionate care to patients, PPC providers must be attentive to predictors of these phenomena. Further work is needed to explore additional causes of CF, BO, and CS in PPC providers as well as potential interventions.

Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a cross-sectional study in patients without known cardiovascular comorbidities

PubMed Central

Vázquez-Del Mercado, Mónica; Gomez-Bañuelos, Eduardo; Chavarria-Avila, Efrain; Cardona-Muñoz, Ernesto; Ramos-Becerra, Carlos; Alanis-Sanchez, Adrián; Cardona-Muller, David; Grover-Paez, Fernando; Perez-Vazquez, Felipe de J.; Navarro-Hernandez, Rosa-Elena; Valadez-Soto, Jorge M.; Saldaña-Millan, Adan A.; Gonzalez-Rosas, Lorena; Ramos-Lopez, Gabriel; Petri, Marcelo H.; Bäck, Magnus

2017-01-01

Abstract The aim of this study was to analyze the impact of disease duration on carotid to femoral pulse wave velocity (cfPWV) in rheumatoid arthritis (RA) patients without either known traditional cardiovascular risk factors or previous comorbidities. Patients with RA diagnosis attending the rheumatology outpatient clinic of Hospital Civil Juan I. Menchaca, Guadalajara, Mexico, were analyzed. A total of 106 RA patients without known traditional cardiovascular risk factors were selected. All subjects were evaluated for RA disease duration, RA disease activity score on 28 joints (DAS28), serum lipids, rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Arterial stiffness was measured as cfPWV by noninvasive tonometry. A multivariate regression model was used to analyze the contribution of RA disease duration and age on cfPWV. cfPWV was positively correlated with age (r = 0.450, P < .001), RA disease duration (r = 0.340, P < .001), total cholesterol (r = 0.312, P = .002), and low density lipoprotein (LDL-c) cholesterol (r = 0.268, P = .012). Patients with a RA disease duration ≥10 years exhibited significantly increased cfPWV compared with patients with disease duration <2 years (8.4 ± 1.8 vs 7.0 ± 0.8) and ≥2 to <10 years (8.4 ± 1.8 vs 7.8 ± 1.3), respectively. Age, RA disease duration, and triglycerides were predictors of cfPWV in multivariate analyses. According to the β-coefficients, each year of disease duration (β = 0.072) had a greater impact on cfPWV than age (β = 0.054). Each year of life with RA contributes to a higher rate of vascular aging or stiffening than a year of life without RA. The cumulative damage provided by RA was most pronounced in patients with disease duration ≥10 years. PMID:28816989

Long-term combined chemical and manure fertilizations increase soil organic carbon and total nitrogen in aggregate fractions at three typical cropland soils in China.

PubMed

He, Y T; Zhang, W J; Xu, M G; Tong, X G; Sun, F X; Wang, J Z; Huang, S M; Zhu, P; He, X H

2015-11-01

Soil organic carbon (SOC), total nitrogen (TN), microbial biomass carbon (MBC) and nitrogen (MBN) are important factors of soil fertility. However, effects of the combined chemical fertilizer and organic manure or straw on these factors and their relationships are less addressed under long-term fertilizations. This study addressed changes in SOC, TN, MBC and MBN at 0-20 cm soil depth under three 17 years (September 1990-September 2007) long-term fertilization croplands along a heat and water gradient in China. Four soil physical fractions (coarse free and fine free particulate organic C, cfPOC and ffPOC; intra-microaggregate POC, iPOC; and mineral associated organic C, MOC) were examined under five fertilizations: unfertilized control, chemical nitrogen (N), phosphorus (P) and potassium (K) (NPK), NPK plus straw (NPKS, hereafter straw return), and NPK plus manure (NPKM and 1.5NPKM, hereafter manure). Compared with Control, manure significantly increased all tested parameters. SOC and TN in fractions distributed as MOC > iPOC > cfPOC > ffPOC with the highest increase in cfPOC (329.3%) and cfPTN (431.1%), and the lowest in MOC (40.8%) and MTN (45.4%) under manure. SOC significantly positively correlated with MBC, cfPOC, ffPOC, iPOC and MOC (R(2) = 0.51-0.84, P < 0.01), while TN with cfPTN, ffPTN, iPTN and MTN (R(2) = 0.45-0.79, P < 0.01), but not with MBN, respectively. Principal component analyses explained 86.9-91.2% variance of SOC, TN, MBC, MBN, SOC and TN in each fraction. Our results demonstrated that cfPOC was a sensitive SOC indicator and manure addition was the best fertilization for improving soil fertility while straw return should take into account climate factors in Chinese croplands. Copyright © 2015 Elsevier B.V. All rights reserved.

A statistical model to predict one-year risk of death in patients with cystic fibrosis.

PubMed

Aaron, Shawn D; Stephenson, Anne L; Cameron, Donald W; Whitmore, George A

2015-11-01

We constructed a statistical model to assess the risk of death for cystic fibrosis (CF) patients between scheduled annual clinical visits. Our model includes a CF health index that shows the influence of risk factors on CF chronic health and on the severity and frequency of CF exacerbations. Our study used Canadian CF registry data for 3,794 CF patients born after 1970. Data up to 2010 were analyzed, yielding 44,390 annual visit records. Our stochastic process model postulates that CF health between annual clinical visits is a superposition of chronic disease progression and an exacerbation shock stream. Death occurs when an exacerbation carries CF health across a critical threshold. The data constitute censored survival data, and hence, threshold regression was used to connect CF death to study covariates. Maximum likelihood estimates were used to determine which clinical covariates were included within the regression functions for both CF chronic health and CF exacerbations. Lung function, Pseudomonas aeruginosa infection, CF-related diabetes, weight deficiency, pancreatic insufficiency, and the deltaF508 homozygous mutation were significantly associated with CF chronic health status. Lung function, age, gender, age at CF diagnosis, P aeruginosa infection, body mass index <18.5, number of previous hospitalizations for CF exacerbations in the preceding year, and decline in forced expiratory volume in 1 second in the preceding year were significantly associated with CF exacerbations. When combined in one summative model, the regression functions for CF chronic health and CF exacerbation risk provided a simple clinical scoring tool for assessing 1-year risk of death for an individual CF patient. Goodness-of-fit tests of the model showed very encouraging results. We confirmed predictive validity of the model by comparing actual and estimated deaths in repeated hold-out samples from the data set and showed excellent agreement between estimated and actual mortality. Our threshold regression model incorporates a composite CF chronic health status index and an exacerbation risk index to produce an accurate clinical scoring tool for prediction of 1-year survival of CF patients. Our tool can be used by clinicians to decide on optimal timing for lung transplant referral. Copyright © 2015 Elsevier Inc. All rights reserved.

Chronobiological factors for compassion satisfaction and fatigue among ambulatory oncology caregivers.

PubMed

Bellicoso, Daniela; Trudeau, Maureen; Fitch, Margaret I; Ralph, Martin R

2017-01-01

Primary caregivers for victims of chronic illness and or trauma experience both positive and negative emotional consequences. These are broadly classified as compassion satisfaction (CS) and compassion fatigue (CF). Because one of the components of CF, burnout, varies with chronotype and sleep quality, we assessed the influence of chronobiological features on the broader constructs of CS and CF. Responses from primary ambulatory care oncology staff working dayshifts were assessed for potential relationships of chronotype and sleep quality with CS and CF using the professional quality of life scale. These were analyzed further in a multivariate model that included personality and job satisfaction as cofactors. We found that sleep quality was a key contributor to CS development and CF reduction. Morningness was positively linked to CS, but the univariate association was masked in the multivariate model. Job satisfaction (contingent rewards, nature of work and operating procedures) heavily influenced CS and CF development. Agreeableness and openness showed positive correlations with CS and negative with burnout, while emotional stability was linked to reduced CF. While job satisfaction and personality predictably played roles in the development of CS and CF, sleep quality and chronotype contributed significantly to benefits and negative consequences of providing care.

Risk factors for onset of persistent respiratory symptoms in children with cystic fibrosis.

PubMed

McColley, Susanna A; Ren, Clement L; Schechter, Michael S; Regelmann, Warren E; Pasta, David J; Konstan, Michael W

2012-10-01

To characterize the onset of persistent signs and symptoms of cystic fibrosis (CF) lung disease and identify characteristics that predict onset. Patients in the Epidemiologic Study of CF who were <4 years of age at enrollment and had ≥2 years of follow-up were included. We defined persistence as a sign or symptom that was present during two consecutive encounters separated by 60-365 days, and persistent clubbing as ≥50% of encounters with clubbing within 365 days. Predictors were assessed in a Cox proportional hazards model for age at first occurrence of each symptom. Each sign or symptom met the criterion of persistence in a substantial proportion of patients during a follow-up period of 7 ± 3 years (mean ± SD; range 2-12). Risk factors that predicted earlier onset of signs and symptoms included pancreatic enzyme use, Pseudomonas aeruginosa infection, and prior diagnosis of asthma. Other risk factors had variable effects on signs and symptoms. Signs and symptoms of lung disease begin early in CF. Risk factors previously reported for lower forced expiratory volume in 1 sec are also associated with earlier onset of persistent signs and symptoms of CF lung disease, but their impact varies. Copyright © 2012 Wiley Periodicals, Inc.

Nutritive value of full-fat sunflower seeds in broiler diets.

PubMed

Selvaraj, R K; Purushothaman, M R

2004-03-01

A study was conducted to evaluate the nutritive value and inclusion level of sunflower seed (SFS) in broiler diets. SFS contained 38.7% ether extract (EE), 16.9% CP, 14.9% crude fiber (CF), 3.5% ash, 0.57% lysine, and 0.46% methionine (89.2% DM basis). The AME (kcal/ kg) content of SFS in roosters was 5,225 and in broilers at 4, 18, and 35 d of age was 3,493, 5,132, and 5,162, respectively. The CP, EE, and CF digestibilities were 80.4, 71.2, and 11.4%, respectively. In an isocaloric and isonitrogenous diet containing SFS at 0, 5, 10, 15, and 20%, SFS up to 20% did not affect weight gain and feed consumption, but the feed conversion ratio was improved (P < 0.05) when broilers were fed 15 or 20% SFS in the starter and finisher diets. CF digestibility of starter diet was significantly lower when 15 or 20% SFS was included. CF digestibility of the finisher diet and digestibility of other nutrients in starter and finisher diets were comparable in all treatment groups. Liver and muscle lipid content, plasma total and high-density lipoprotein cholesterol content, muscle cholesterol content, dressing percentage, liver weight, and giblet weight (as % live weight) were comparable among all treatment groups. Abdominal fat was increased in birds fed 20% SFS. Percentage skin was decreased in broilers fed > or = 10% SFS.

Correlation of Streptococcus mutans and Streptococcus sanguinis colonization and ex vivo hydrogen peroxide production in carious lesion-free and high caries adults.

PubMed

Giacaman, Rodrigo A; Torres, Sebastián; Gómez, Yenifer; Muñoz-Sandoval, Cecilia; Kreth, Jens

2015-01-01

This study was conducted to estimate oral colonization by Streptococcus mutans and Streptococcus sanguinis in adults with high and without any caries experience. Furthermore, differences in the amount of hydrogen peroxide (H2O2) produced by S. sanguinis isolated from both groups were assessed. Forty adults were divided into: (i) carious lesion-free, without any carious lesion, assessed by the International Caries Detection and Assessment System (ICDAS), or restoration, (CF) and (ii) high caries experience (HC). Saliva samples were collected and seeded on respective agar-plates for enumeration of total streptococci, S. mutans and S. sanguinis (CFU/mL) and compared between groups. Additionally, S. sanguinis colonies obtained from both groups were inoculated on Prussian blue agar for H2O2 detection. Production of H2O2 was quantified and compared between the two groups. S. sanguinis counts were significantly higher in CF than HC individuals (p<0.05). Conversely, S. mutans showed significantly higher levels in HC than CF subjects (p<0.001). S. sanguinis colonies from CF individuals produced significantly larger H2O2 halos compared with HC subjects. S. sanguinis predominates over S. mutans in saliva of adults without caries experience. In those people, S. sanguinis produces more H2O2ex vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

South African adolescents with cystic fibrosis: a qualitative exploration of their bio-psychosocial fields.

PubMed

Hugo, Carina Jacobie; van der Merwe, Mariette

2014-01-01

This qualitative case study explored risk factors and protective factors in the bio-psychosocial fields of adolescents living with cystic fibrosis (CF). Semi-structured interviews were conducted with adolescents in the middle and late adolescent years (15-22 years) who had the defining characteristics of CF and were living in Gauteng province. Themes emerged from individual interviews. The fundamental human need to be understood and to understand was negatively affected as the illness affected socialisation and learning. Participants experienced an array of emotions including loss and bereavement linked to their illness and when friends with CF died. Constructive internal dialogue and positive thinking emerged as protective variables. Participants generally showed awareness of how they regulated their contact with the illness and how they self-regulate. Despite the severity of their symptoms and the taxing demands of managing CF, participants expressed hope for the future and could find some meaning in the illness. Adolescents with CF who participated in this study indicated that they felt different from their peers. Apart from the general developmental tasks typical to adolescence they faced the challenge of managing a severe chronic and potentially terminal illness.

A Preliminary Analysis of Compassion Satisfaction and Compassion Fatigue With Considerations for Nursing Unit Specialization and Demographic Factors.

PubMed

Mooney, Claire; Fetter, Katrina; Gross, Brian W; Rinehart, Cole; Lynch, Caitlin; Rogers, Frederick B

Compassion fatigue (CF), or vicarious traumatization, is a state of physical/emotional distress that results from caring for those experiencing pain. We sought to characterize levels of CF in intensive care unit (ICU) and oncology nursing populations with subanalyses comparing specific personal/professional demographic factors. The Professional Quality of Life (ProQOL) scale, a validated tool for assessing CF, burnout (BO), and compassion satisfaction (CS), was distributed to the ICU and oncology divisions of a community hospital. Demographic data and ProQOL scale scores were collected and compared within specialty and gender subgroups. Two-sample t tests and regression analyses were used to compare groups. Statistical significance was defined as p < .05. A total of 86 nurses submitted completed surveys able to be analyzed. Levels of CS were significantly lower (p = .023) and levels of BO were significantly higher (p = .029) in ICU nurses than in oncology nurses. Male nurses exhibited significantly higher CS (p = .001) and significantly lower BO (p = .021) and CF (p = .014) than female nurses. Intensive care unit nurses and female nurses from both ICU and oncology specialties may be at increased risk for developing a poorer overall ProQOL and CF.

Airway inflammation in cystic fibrosis: molecular mechanisms and clinical implications.

PubMed

Cohen-Cymberknoh, Malena; Kerem, Eitan; Ferkol, Thomas; Elizur, Arnon

2013-12-01

Airway epithelial cells and immune cells participate in the inflammatory process responsible for much of the pathology found in the lung of patients with cystic fibrosis (CF). Intense bronchial neutrophilic inflammation and release of proteases and oxygen radicals perpetuate the vicious cycle and progressively damage the airways. In vitro studies suggest that CF transmembrane conductance regulator (CFTR)-deficient airway epithelial cells display signalling abnormalities and aberrant intracellular processes which lead to transcription of inflammatory mediators. Several transcription factors, especially nuclear factor-κB, are activated. In addition, the accumulation of abnormally processed CFTR in the endoplasmic reticulum results in unfolded protein responses that trigger 'cell stress' and apoptosis leading to dysregulation of the epithelial cells and innate immune function in the lung, resulting in exaggerated and ineffective airway inflammation. Measuring airway inflammation is crucial for initiating treatment and monitoring its effect. No inflammatory biomarker predictive for the clinical course of CF lung disease is currently known, although neutrophil elastase seems to correlate with lung function decline. CF animal models mimicking human lung disease may provide an important insight into the pathogenesis of lung inflammation in CF and identify new therapeutic targets.

HIV Infection Is Not Associated With Aortic Stiffness. Traditional Cardiovascular Risk Factors Are the Main Determinants-Cross-sectional Results of INI-ELSA-BRASIL.

PubMed

Moreira, Rodrigo C; Mill, José G; Grinsztejn, Beatriz; Veloso, Valdilea; Fonseca, Maria de Jesus; Griep, Rosane H; Bensenor, Isabela; Cardoso, Sandra W; Lotufo, Paulo; Chor, Dora; Pacheco, Antonio G

2018-05-01

Aortic stiffness measured by carotid-femoral pulse wave velocity (cf-PWV) is a marker of subclinical atherosclerosis. We propose to assess whether HIV infection is associated with arterial stiffness and their determinants in HIV-infected subjects. We compared data from an HIV cohort (644 patients, HIV+) in Rio de Janeiro with 2 groups: 105 HIV-negative (HIV-) individuals and 14,873 participants of the ELSA-Brasil study. We used multivariable linear regression to investigate factors associated with cf-PWV and whether HIV was independently associated with aortic stiffness and propensity score weighting to control for imbalances between groups. From 15,860 participants, cf-PWV was obtained in 15,622 (98.5%). Median age was 51 (interquartile range 45-58), 44.41 (35.73, 54.72), and 43.60 (36.01, 50.79) years (P < 0.001), and median cf-PWV (m/s; interquartile range) was 9.0 (8.10, 10.20), 8.70 (7.90, 10.20), and 8.48 (7.66, 9.40) for ELSA-Brasil, HIV- and HIV+, respectively (P < 0.001). In the final weighted multivariable models, HIV group was not associated with cf-PWV when compared either with ELSA-Brasil [β = -0.05; 95% confidence interval (CI) = -0.23; P = 0.12; P = 0.52] or with the HIV- groups (β = 0.10; 95% CI = -0.10; 0, 31; P = 0.32). Traditional risk factors were associated with higher cf-PWV levels in the HIV+ group, particularly waist-to-hip ratio (β = 0.20; 95% CI = 0.10; 0.30; P < 0.001, result per one SD change). HIV infection was not associated with higher aortic stiffness according to our study. In HIV-infected subjects, the stiffness of large arteries is mainly associated with traditional risk factors and not to the HIV infection per se.

Respiratory physicians and clinic coordinators' attitudes to population-based cystic fibrosis carrier screening.

PubMed

Cunningham, Fiona; Lewis, Sharon; Curnow, Lisette; Glazner, Judith; Massie, John

2014-01-01

Attitudes of Australian CF healthcare professionals toward population-based cystic fibrosis (CF) carrier screening were examined. A purpose-designed questionnaire was distributed to 111 respiratory physicians and 30 CF clinic coordinators throughout Australia. Seventy-one questionnaires (52 physicians and 19 coordinators (46.8%, 63.3% respectively)) were returned. Forty respondents (56.3%) supported population-based carrier screening for CF. Support for screening was associated with rating the factors: carrier risk being 1 in 25 (OR 1.72 (1.12, 2.65)), reassurance when both partners test negative (OR 1.67 (1.12, 2.46)) and the daily treatment regimen for CF patients (OR 1.59 (1.05, 2.42)) as important. Opposition to screening was associated with identifying potential discrimination against carriers as a disadvantage (OR 0.3 (0.12, 0.88)), and limitations of predicting clinical outcomes as a barrier (OR 0.46 (0.25, 0.83)). There is moderate support for population-based carrier screening for CF by Australian CF healthcare professionals. Perceived barriers to implementation are surmountable. © 2013.

Correlates of Segmental Pulse Wave Velocity in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study.

PubMed

Meyer, Michelle L; Tanaka, Hirofumi; Palta, Priya; Cheng, Susan; Gouskova, Natalia; Aguilar, David; Heiss, Gerardo

2016-01-01

Carotid-femoral PWV (cfPWV) is a well-established measure of central arterial stiffness, while brachial-ankle PWV (baPWV) is being used more frequently in East Asian countries. Few studies have simultaneously characterized the distributions and correlates of segment-specific PWV measures and their associations with cardiovascular risk factors. We evaluated segment-specific PWV (cfPWV, baPWV, and femoral-ankle (faPWV)) in 4,974 older-aged African American and Caucasian adults in the community-based Atherosclerosis Risk in Communities (ARIC) Study using a standardized protocol and the OMRON VP-1000 Plus system. We examined the distribution and multivariable-adjusted correlates of PWV measures by race and sex. Mean age ranged from 74 ± 5 to 76 ± 5 years across race-sex groups. In all race-sex groups, cfPWV correlated with baPWV but not with faPWV, and cfPWV and baPWV were higher with age, whereas faPWV was not. Heart rate and systolic blood pressure (SBP) were positively associated and weight was negatively associated with all PWV measures; however, the associations with age, glycated hemoglobin, triglycerides, and high-density lipoprotein (HDL) cholesterol varied by segment and race-sex group. Our findings indicate that cfPWV and faPWV reflect distinct aspects of segment-specific vascular stiffness and their associated profile of cardiovascular risk factors. Even among older adults, age is associated with higher cfPWV and baPWV, but not with faPWV. Understanding factors that ostensibly play a role in increasing arterial stiffness in different arterial territories can inform opportunities for cardiovascular disease (CVD) prevention and risk management. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Endoplasmic Reticulum Protein TXNDC5 Augments Myocardial Fibrosis by Facilitating Extracellular Matrix Protein Folding and Redox-Sensitive Cardiac Fibroblast Activation.

PubMed

Shih, Ying-Chun; Chen, Chao-Ling; Zhang, Yan; Mellor, Rebecca L; Kanter, Evelyn M; Fang, Yun; Wang, Hua-Chi; Hung, Chen-Ting; Nong, Jing-Yi; Chen, Hui-Ju; Lee, Tzu-Han; Tseng, Yi-Shuan; Chen, Chiung-Nien; Wu, Chau-Chung; Lin, Shuei-Liong; Yamada, Kathryn A; Nerbonne, Jeanne M; Yang, Kai-Chien

2018-04-13

Cardiac fibrosis plays a critical role in the pathogenesis of heart failure. Excessive accumulation of extracellular matrix (ECM) resulting from cardiac fibrosis impairs cardiac contractile function and increases arrhythmogenicity. Current treatment options for cardiac fibrosis, however, are limited, and there is a clear need to identify novel mediators of cardiac fibrosis to facilitate the development of better therapeutics. Exploiting coexpression gene network analysis on RNA sequencing data from failing human heart, we identified TXNDC5 (thioredoxin domain containing 5), a cardiac fibroblast (CF)-enriched endoplasmic reticulum protein, as a potential novel mediator of cardiac fibrosis, and we completed experiments to test this hypothesis directly. The objective of this study was to determine the functional role of TXNDC5 in the pathogenesis of cardiac fibrosis. RNA sequencing and Western blot analyses revealed that TXNDC5 mRNA and protein were highly upregulated in failing human left ventricles and in hypertrophied/failing mouse left ventricle. In addition, cardiac TXNDC5 mRNA expression levels were positively correlated with those of transcripts encoding transforming growth factor β1 and ECM proteins in vivo. TXNDC5 mRNA and protein were increased in human CF (hCF) under transforming growth factor β1 stimulation in vitro. Knockdown of TXNDC5 attenuated transforming growth factor β1-induced hCF activation and ECM protein upregulation independent of SMAD3 (SMAD family member 3), whereas increasing expression of TXNDC5 triggered hCF activation and proliferation and increased ECM protein production. Further experiments showed that TXNDC5, a protein disulfide isomerase, facilitated ECM protein folding and that depletion of TXNDC5 led to ECM protein misfolding and degradation in CF. In addition, TXNDC5 promotes hCF activation and proliferation by enhancing c-Jun N-terminal kinase activity via increased reactive oxygen species, derived from NAD(P)H oxidase 4. Transforming growth factor β1-induced TXNDC5 upregulation in hCF was dependent on endoplasmic reticulum stress and activating transcription factor 6-mediated transcriptional control. Targeted disruption of Txndc5 in mice ( Txndc5 -/- ) revealed protective effects against isoproterenol-induced cardiac hypertrophy, reduced fibrosis (by ≈70%), and markedly improved left ventricle function; post-isoproterenol left ventricular ejection fraction was 59.1±1.5 versus 40.1±2.5 ( P <0.001) in Txndc5 -/- versus wild-type mice, respectively. The endoplasmic reticulum protein TXNDC5 promotes cardiac fibrosis by facilitating ECM protein folding and CF activation via redox-sensitive c-Jun N-terminal kinase signaling. Loss of TXNDC5 protects against β agonist-induced cardiac fibrosis and contractile dysfunction. Targeting TXNDC5, therefore, could be a powerful new therapeutic approach to mitigate excessive cardiac fibrosis, thereby improving cardiac function and outcomes in patients with heart failure. © 2018 American Heart Association, Inc.

Carbon footprint and land requirement for dairy herd rations: impacts of feed production practices and regional climate variations.

PubMed

Henriksson, M; Cederberg, C; Swensson, C

2014-08-01

Feed production is a significant source of greenhouse gas (GHG) emissions from dairy production and demands large arable and pasture acreage. This study analysed how regional conditions influence GHG emissions of dairy feed rations in a life cycle perspective, that is the carbon footprint (CF) and the land area required. Factors assessed included regional climate variations, grass/clover silage nutrient quality, feedstuff availability, crop yield and feed losses. Using the Nordic feed evaluation model NorFor, rations were optimised for different phases of lactation, dry and growing periods for older cows, first calvers and heifers by regional feed advisors and combined to annual herd rations. Feed production data at farm level were based on national statistics and studies. CF estimates followed standards for life cycle assessment and used emissions factors provided by IPCC. The functional unit was 'feed consumption to produce 1 kg energy corrected milk (ECM) from a cow with annual milk yield of 9 900 kg ECM including replacement animals and feed losses'. Feed ration CF varied from 417 to 531 g CO2 e/kg ECM. Grass/clover silage contributed more than 50% of total GHG emissions. Use of higher quality silage increased ration CF by up to 5% as a result of an additional cut and increased rates of synthetic N-fertiliser. Domestically produced horse bean (Vicia faba), by-products from the sugar industry and maize silage were included in the rations with the lowest CF, but horse bean significantly increased ration land requirement. Rations required between 1.4 to 2 m2 cropland and 0.1 to 0.2 m2/kg semi-natural grassland per kg ECM and year. Higher yield levels reduced ration total CF. Inclusion of GHG emissions from land use change associated with Brazilian soya feed significantly increased ration CF. Ration CF and land use depended on ration composition, which was highly influenced by the regional availability and production of feedstuffs. The impact of individual feedstuffs on ration CF varies due to, for example, cultivation practices and climate conditions and feedstuffs should therefore be assessed in a ration and regional perspective before being used to decrease milk CF. Land use efficiency should be considered together with ration CF, as these can generate goal conflicts.

Cystic Fibrosis and Its Management Through Established and Emerging Therapies.

PubMed

Spielberg, David R; Clancy, John P

2016-08-31

Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disorder in the Caucasian population and occurs in many other ethnicities worldwide. The daily treatment burden is substantial for CF patients even when they are well, with numerous pharmacologic and physical therapies targeting lung disease requiring the greatest time commitment. CF treatments continue to advance with greater understanding of factors influencing long-term morbidity and mortality. In recent years, in-depth understanding of genetic and protein structure-function relationships has led to the introduction of targeted therapies for patients with specific CF genotypes. With these advances, CF has become a model of personalized or precision medicine. The near future will see greater access to targeted therapies for most patients carrying common mutations, which will mandate individualized bench-to-bedside methodologies for those with rare genotypes.

High incidence of non-tuberculous mycobacteria-positive cultures among adolescent with cystic fibrosis.

PubMed

Cavalli, Zoé; Reynaud, Quitterie; Bricca, Romain; Nove-Josserand, Raphaële; Durupt, Stéphane; Reix, Philippe; Perceval, Marie; de Montclos, Michèle Pérouse; Lina, Gérard; Durieu, Isabelle

2017-09-01

We evaluated the prevalence of non-tuberculous mycobacteria (NTM)-positive cultures among our cystic fibrosis (CF) center patients, reviewed risk factors for NTM positivity, and determined its impact on lung function evolution. From 2009 to 2014, CF adults and children attending the CF center of Lyon (France) and having at least one positive NTM isolate were included. Each case was matched by age and gender with two CF patients with no NTM isolate (controls). 48 CF patients with NTM-positive isolates were matched to 96 controls. The age group for whom incident NTM was higher was young adolescents aged 13 to 17. A significant association for NTM positivity was found with Staphylococcusaureus in multivariate analysis and with allergic bronchopulmonary aspergillosis, corticosteroid and itraconazole in univariate analysis. Mean annual FEV1 decline was faster for NTM-positive patients compared to controls. These data highlight the high incidence of NTM-positive cultures among young adolescents with CF. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Defective innate immunity and hyperinflammation in newborn cystic fibrosis transmembrane conductance regulator-knockout ferret lungs.

PubMed

Keiser, Nicholas W; Birket, Susan E; Evans, Idil A; Tyler, Scott R; Crooke, Adrianne K; Sun, Xingshen; Zhou, Weihong; Nellis, Joseph R; Stroebele, Elizabeth K; Chu, Kengyeh K; Tearney, Guillermo J; Stevens, Mark J; Harris, J Kirk; Rowe, Steven M; Engelhardt, John F

2015-06-01

Mucociliary clearance (MCC) and submucosal glands are major components of airway innate immunity that have impaired function in cystic fibrosis (CF). Although both of these defense systems develop postnatally in the ferret, the lungs of newborn ferrets remain sterile in the presence of a functioning cystic fibrosis transmembrane conductance regulator gene. We evaluated several components of airway innate immunity and inflammation in the early CF ferret lung. At birth, the rates of MCC did not differ between CF and non-CF animals, but the height of the airway surface liquid was significantly reduced in CF newborn ferrets. CF ferrets had impaired MCC after 7 days of age, despite normal rates of ciliogenesis. Only non-CF ferrets eradicated Pseudomonas directly introduced into the lung after birth, whereas both genotypes could eradicate Staphylococcus. CF bronchoalveolar lavage fluid (BALF) had significantly lower antimicrobial activity selectively against Pseudomonas than non-CF BALF, which was insensitive to changes in pH and bicarbonate. Liquid chromatography-tandem mass spectrometry and cytokine analysis of BALF from sterile Caesarean-sectioned and nonsterile naturally born animals demonstrated CF-associated disturbances in IL-8, TNF-α, and IL-β, and pathways that control immunity and inflammation, including the complement system, macrophage functions, mammalian target of rapamycin signaling, and eukaryotic initiation factor 2 signaling. Interestingly, during the birth transition, IL-8 was selectively induced in CF BALF, despite no genotypic difference in bacterial load shortly after birth. These results suggest that newborn CF ferrets have defects in both innate immunity and inflammatory signaling that may be important in the early onset and progression of lung disease in these animals.

Defective Innate Immunity and Hyperinflammation in Newborn Cystic Fibrosis Transmembrane Conductance Regulator–Knockout Ferret Lungs

PubMed Central

Keiser, Nicholas W.; Birket, Susan E.; Evans, Idil A.; Tyler, Scott R.; Crooke, Adrianne K.; Sun, Xingshen; Zhou, Weihong; Nellis, Joseph R.; Stroebele, Elizabeth K.; Chu, Kengyeh K.; Tearney, Guillermo J.; Stevens, Mark J.; Harris, J. Kirk; Rowe, Steven M.

2015-01-01

Mucociliary clearance (MCC) and submucosal glands are major components of airway innate immunity that have impaired function in cystic fibrosis (CF). Although both of these defense systems develop postnatally in the ferret, the lungs of newborn ferrets remain sterile in the presence of a functioning cystic fibrosis transmembrane conductance regulator gene. We evaluated several components of airway innate immunity and inflammation in the early CF ferret lung. At birth, the rates of MCC did not differ between CF and non-CF animals, but the height of the airway surface liquid was significantly reduced in CF newborn ferrets. CF ferrets had impaired MCC after 7 days of age, despite normal rates of ciliogenesis. Only non-CF ferrets eradicated Pseudomonas directly introduced into the lung after birth, whereas both genotypes could eradicate Staphylococcus. CF bronchoalveolar lavage fluid (BALF) had significantly lower antimicrobial activity selectively against Pseudomonas than non-CF BALF, which was insensitive to changes in pH and bicarbonate. Liquid chromatography–tandem mass spectrometry and cytokine analysis of BALF from sterile Caesarean-sectioned and nonsterile naturally born animals demonstrated CF-associated disturbances in IL-8, TNF-α, and IL-β, and pathways that control immunity and inflammation, including the complement system, macrophage functions, mammalian target of rapamycin signaling, and eukaryotic initiation factor 2 signaling. Interestingly, during the birth transition, IL-8 was selectively induced in CF BALF, despite no genotypic difference in bacterial load shortly after birth. These results suggest that newborn CF ferrets have defects in both innate immunity and inflammatory signaling that may be important in the early onset and progression of lung disease in these animals. PMID:25317669

Atrial rhythm influences catheter tissue contact during radiofrequency catheter ablation of atrial fibrillation: comparison of contact force between sinus rhythm and atrial fibrillation.

PubMed

Matsuda, Hisao; Parwani, Abdul Shokor; Attanasio, Philipp; Huemer, Martin; Wutzler, Alexander; Blaschke, Florian; Haverkamp, Wilhelm; Boldt, Leif-Hendrik

2016-09-01

Catheter tissue contact force (CF) is an important factor for durable lesion formation during radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Since CF varies in the beating heart, atrial rhythm during RFCA may influence CF. A high-density map and RFCA points were obtained in 25 patients undergoing RFCA of AF using a CF-sensing catheter (Tacticath, St. Jude Medical). The operators were blinded to the CF information. Contact type was classified into three categories: constant, variable, and intermittent contact. Average CF and contact type were analyzed according to atrial rhythm (SR vs. AF) and anatomical location. A total of 1364 points (891 points during SR and 473 points during AF) were analyzed. Average CFs showed no significant difference between SR (17.2 ± 11.3 g) and AF (17.2 ± 13.3 g; p = 0.99). The distribution of points with an average CF of ≥20 and <10 g also showed no significant difference. However, the distribution of excessive CF (CF ≥40 g) was significantly higher during AF (7.4 %) in comparison with SR (4.2 %; p < 0.05). At the anterior area of the right inferior pulmonary vein (RIPV), the average CF during AF was significantly higher than during SR (p < 0.05). Constant contact was significantly higher during AF (32.2 %) when compared to SR (9.9 %; p < 0.01). Although the average CF was not different between atrial rhythms, constant contact was more often achievable during AF than it was during SR. However, excessive CF also seems to occur more frequently during AF especially at the anterior part of RIPV.

Relationship between catheter contact force and radiofrequency lesion size and incidence of steam pop in the beating canine heart: electrogram amplitude, impedance, and electrode temperature are poor predictors of electrode-tissue contact force and lesion size.

PubMed

Ikeda, Atsushi; Nakagawa, Hiroshi; Lambert, Hendrik; Shah, Dipen C; Fonck, Edouard; Yulzari, Aude; Sharma, Tushar; Pitha, Jan V; Lazzara, Ralph; Jackman, Warren M

2014-12-01

Electrode-tissue contact force (CF) is believed to be a major factor in radiofrequency lesion size. The purpose of this study was to determine, in the beating canine heart, the relationship between CF and radiofrequency lesion size and the accuracy of predicting CF and lesion size by measuring electrogram amplitude, impedance, and electrode temperature. Eight dogs were studied closed chest. Using a 7F catheter with a 3.5 mm irrigated electrode and CF sensor (TactiCath, St. Jude Medical), radiofrequency applications were delivered to 3 separate sites in the right ventricle (30 W, 60 seconds, 17 mL/min irrigation) and 3 sites in the left ventricle (40 W, 60 seconds, 30 mL/min irrigation) at (1) low CF (median 8 g); (2) moderate CF (median 21 g); and (3) high CF (median 60 g). Dogs were euthanized and lesion size was measured. At constant radiofrequency and time, lesion size increased significantly with increasing CF (P<0.01). The incidence of a steam pop increased with both increasing CF and higher power. Peak electrode temperature correlated poorly with lesion size. The decrease in impedance during the radiofrequency application correlated well with lesion size for lesions in the left ventricle but less well for lesions in the right ventricle. There was a poor relationship between CF and the amplitude of the bipolar or unipolar ventricular electrogram, unipolar injury current, and impedance. Radiofrequencylesion size and the incidence of steam pop increase strikingly with increasing CF. Electrogram parameters and initial impedance are poor predictors of CF for radiofrequency ablation. © 2014 American Heart Association, Inc.

Self-efficacy: empowering parents of children with cystic fibrosis.

PubMed

McDonald, Catherine M; Haberman, Diane; Brown, Natalie

2013-09-01

Can parent engagement in the development and delivery of educational materials for cystic fibrosis (CF) promote increased self-efficacy and confidence in self-management skills? Standard therapies for a child with CF frequently involve pulmonary treatment, medications, and behavioral and nutritional interventions. Parents report that the prescribed CF care can be overwhelming. Previous research at this pediatric CF Center indicated the parental perception of the difficulty in managing CF-related nutrition therapy. Parents' nutrition knowledge was an initial target of this continuous quality improvement (CQI) project with a long-range aim of increasing children's median body mass index (BMI) percentiles for patients at this pediatric CF center. The local CF Parent Advisory Council, CF parents and staff collaborated on this family-centered CQI project. A CF parent website with weekly email newsletters and a facebook page were developed and evolved with input from parents. Parental feedback was gathered through electronic surveys, written questionnaires, focus groups and informal interviews. A convenience sample of parents participated in pre- and post-intervention surveys to determine change in self-confidence in effectively managing their children's CF treatment regimens. Results were also compared with responses from a larger previous survey. Parental knowledge of nutrition facts and medical nutrition therapy for CF did not increase significantly over the course of the CQI project. Surveyed parents reported increased confidence in their self-management skills. Although mean BMI percentiles have increased at this center, they remain below the national average. Parent-driven educational strategies provide an opportunity to promote reliable CF-related information in parent-preferred formats that enhance self-management skills in caring for children with CF. Parental confidence to follow CF center recommendations increased between 2004 and 2011. Although many factors may impact confidence, parent satisfaction with the creation of electronic resources and engagement in the CQI process were intangible, but important outcomes. Copyright © 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Baseline predictors of aortic stiffness progression among multi-ethnic Asians with type 2 diabetes.

PubMed

Moh, Mei Chung; Sum, Chee Fang; Tavintharan, Subramaniam; Ang, Keven; Lee, Simon Biing Ming; Tang, Wern Ee; Lim, Su Chi

2017-05-01

This 3-year prospective study aimed to identify baseline parameters that predicted the progression of carotid-femoral pulse wave velocity (cf-PWV), which was used to evaluate aortic stiffness, among Singapore's multi-ethnic Asians with type 2 diabetes (T2DM). The cf-PWV was measured by the gold-standard tonometry method in 994 T2DM subjects at baseline and follow-up. The annual rate of cf-PWV change was calculated, and individuals above the 90 th percentile with rate≥1.42 m/s per year were regarded as rapid progressors (n = 104). In a subgroup analysis of subjects with normal cf-PWV at 1 st visit (n = 611), incident aortic stiffness was defined as follow-up cf-PWV≥10 m/s (n = 188). The total cohort (mean age:57 ± 10 years; 53.4% Chinese, 20.4% Malay, 22.9% Indian, 3.2% 'Others') displayed a median annual cf-PWV progression rate of 0.2 m/s. Adjusted multivariate regression analyses showed that baseline age, cf-PWV and body mass index (BMI) constantly predicted follow-up cf-PWV, annual cf-PWV progression rate, rapid cf-PWV progression, and incident aortic stiffness. Paradoxically, lower baseline cf-PWV was associated with elevated annual cf-PWV progression rate and rapid progressors. This inverse relationship remained significant across ethnicities after ethnic stratification. Higher BMI independently predicted cf-PWV progression in Chinese and Indians, but not in Malay and 'Others' ethnic groups. Increased age was a significant predictor in Chinese and 'Others' ethnicities. We demonstrated that baseline BMI is a modifiable independent risk factor of cf-PWV progression and incident aortic stiffness. Therefore, better obesity management may impede aortic stiffness in Singapore's T2DM patients, especially in the Chinese and Indians. Copyright © 2017. Published by Elsevier B.V.

Genetic and Environmental Influences on Disability Pension Due To Mental Diagnoses: Limited Importance of Major Depression, Generalized Anxiety, and Chronic Fatigue.

PubMed

Narusyte, Jurgita; Ropponen, Annina; Alexanderson, Kristina; Svedberg, Pia

2016-02-01

Previous research indicates that liability to disability pension (DP) due to mental diagnoses is moderately influenced by genetic factors. This study investigates whether genetic contributions to the liability to DP due to mood and neurotic diagnoses overlap with the genetic influences on major depression (MD), generalized anxiety disorder (GAD), or chronic fatigue (CF). A prospective cohort study including 9,985 female twins born in Sweden 1933-1958. The presence of MD, GAD, and CF was assessed by computer-assisted telephone interviews conducted in 1998-2002. Data on DP due to mood and neurotic diagnoses were obtained from nationwide registers for the years 1998-2010. Common genetic and environmental influences on the phenotypes were estimated by applying structural equation modeling. The prevalence of MD/GAD was 30%, CF 8%, and DP due to mood and neurotic diagnoses 3% in 2010. Genetic effects on MD/GAD explained 31% of the total genetic variation in DP, whereas genetic contributions in common with CF were small and not significant. The majority of the total non-shared environmental variance in DP (85%) was explained by the factors that were unique to DP. Large proportions of genetic and non-shared environmental influences in DP due to mood and neurotic diagnoses were not explained by the contributions from MD/GAD or CF. The results suggest that the process leading to DP is complex and influenced by factors other than those related to the disorder underlying DP.

Long-term mortality from cardiac causes after adjuvant hypofractionated vs. conventional radiotherapy for localized left-sided breast cancer.

PubMed

Chan, Elisa K; Woods, Ryan; Virani, Sean; Speers, Caroline; Wai, Elaine S; Nichol, Alan; McBride, Mary L; Tyldesley, Scott

2015-01-01

Ongoing concern remains regarding cardiac injury with hypofractionated whole breast/chest-wall radiotherapy (HF-WBI) compared to conventional radiotherapy (CF-WBI) in left-sided breast cancer patients. The purpose was to determine if cardiac mortality increases with HF-WBI relative to CF-WBI. Between 1990 and 1998, 5334 women with early-stage breast cancer received post-operative radiotherapy to the breast/chest wall alone. A population-based database recorded baseline patient, tumor and treatment factors. Baseline cardiovascular risk factors were identified from hospital administrative records. A propensity-score model balanced risk factors between radiotherapy groups. Cause of death was coded as breast cancer, cardiac or other cause. Cumulative mortality from each cause after radiotherapy was estimated using a competing risk approach. For left-sided cases, median follow-up was 14.2 years. 485 women received CF-WBI, 2221 women received HF-WBI. There was no difference in 15-year mortality from cardiac causes: 4.8% with HF-WBI and 4.2% with CF-WBI (p=0.74), even after propensity-score adjustment (p=0.45). There was no difference in breast cancer mortality or other cause mortality. For right-sided cases, there was no difference in mortality for the three causes of death. At 15-years follow-up, cardiac mortality is not statistically different among left-sided breast cancer patients treated with HF-WBI or CF-WBI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Double-letter processing in surface dyslexia and dysgraphia following a left temporal lesion: A multimodal neuroimaging study.

PubMed

Tomasino, Barbara; Marin, Dario; Maieron, Marta; D'Agostini, Serena; Fabbro, Franco; Skrap, Miran; Luzzatti, Claudio

2015-12-01

Neuropsychological data about acquired impairments in reading and writing provide a strong basis for the theoretical framework of the dual-route models. The present study explored the functional neuroanatomy of the reading and spelling processing system. We describe the reading and writing performance of patient CF, an Italian native speaker who developed an extremely selective reading and spelling deficit (his spontaneous speech, oral comprehension, repetition and oral picture naming were almost unimpaired) in processing double letters associated with surface dyslexia and dysgraphia, following a tumor in the left temporal lobe. In particular, the majority of CF's errors in spelling were phonologically plausible substitutions, errors concerning letter numerosity of consonants, and syllabic phoneme-to-grapheme conversion (PGC) errors. A similar pattern of impairment also emerged in his reading behavior, with a majority of lexical stress errors (the only possible type of surface reading errors in the Italian language, due the extreme regularity of print-to-sound correspondence). CF's neuropsychological profile was combined with structural neuroimaging data, fiber tracking, and functional maps and compared to that of healthy control participants. We related CF's deficit to a dissociation between impaired ventral/lexical route (as evidenced by a fractional anisotropy - FA decrease along the inferior fronto-occipital fasciculus - IFOF) and relatively preserved dorsal/phonological route (as evidenced by a rather full integrity of the superior longitudinal fasciculus - SLF). In terms of functional processing, the lexical-semantic ventral route network was more activated in controls than in CF, while the network supporting the dorsal route was shared by CF and the control participants. Our results are discussed within the theoretical framework of dual-route models of reading and spelling, emphasize the importance of the IFOF both in lexical reading and spelling, and offer a better comprehension of the neurological and functional substrates involved in written language and, in particular, in surface dyslexia and dysgraphia and in doubling/de-doubling consonant sounds and letters. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development and interlaboratory validation of quantitative polymerase chain reaction method for screening analysis of genetically modified soybeans.

PubMed

Takabatake, Reona; Onishi, Mari; Koiwa, Tomohiro; Futo, Satoshi; Minegishi, Yasutaka; Akiyama, Hiroshi; Teshima, Reiko; Kurashima, Takeyo; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi

2013-01-01

A novel real-time polymerase chain reaction (PCR)-based quantitative screening method was developed for three genetically modified soybeans: RRS, A2704-12, and MON89788. The 35S promoter (P35S) of cauliflower mosaic virus is introduced into RRS and A2704-12 but not MON89788. We then designed a screening method comprised of the combination of the quantification of P35S and the event-specific quantification of MON89788. The conversion factor (Cf) required to convert the amount of a genetically modified organism (GMO) from a copy number ratio to a weight ratio was determined experimentally. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDR), respectively. The determined RSDR values for the method were less than 25% for both targets. We consider that the developed method would be suitable for the simple detection and approximate quantification of GMO.

Validation of the Compassion Fatigue Short Scale among Chinese medical workers and firefighters: a cross-sectional study

PubMed Central

Sun, Binghai; Hu, Mengna; Yu, Shitian; Jiang, Yiru; Lou, Baona

2016-01-01

Objectives To examine the psychometric properties of the Chinese version of the C-Compassion Fatigue (CF)-Short Scale among 4 independent samples of Chinese emergency workers (medical workers and firefighters). Design Cross-sectional. Setting 6 hospitals in Zhejiang Province and 12 fire stations in Shanghai. Participants Emergency workers (medical and firefighters) were consecutively recruited and divided into 4 groups: the MW1 group (medical workers, n=167), the FF1 group (firefighters, n=157), the MW2 group (medical workers, n=265) and the FF2 group (firefighters, n=231). Interventions All patients completed the C-CF-Short Scale to identify factors associated with compassion fatigue. The MW1 and FF1 groups were used for the exploratory analyses. The MW2 and FF2 groups were used for the confirmatory factor analyses. Primary and secondary outcome measures Factor loading, correlations with previously validated questionnaires (the Ego-Resiliency Scale, the Social Support Questionnaire and the Job Pressure Scale) and Cronbach's α coefficient were tested for each factor. Results The C-CF-Short Scale demonstrated excellent construct validity and good internal consistency. Specifically, the results of exploratory factor analyses in the MW1 and FF1 groups showed that secondary trauma and job burnout were associated with compassion fatigue in these emergency workers. The confirmatory factor analyses in the MW2 and FF2 groups indicated that all the fit indices of the 2-factor model were satisfactory. Finally, the Cronbach's α coefficient of each factor was excellent. Conclusions The findings suggest that the C-CF-Short Scale has good psychometric properties and can be applied to study Chinese emergency workers. PMID:27363817

Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosis-like phenotypes.

PubMed

Ramos, M D; Trujillano, D; Olivar, R; Sotillo, F; Ossowski, S; Manzanares, J; Costa, J; Gartner, S; Oliva, C; Quintana, E; Gonzalez, M I; Vazquez, C; Estivill, X; Casals, T

2014-07-01

The term cystic fibrosis (CF)-like disease is used to describe patients with a borderline sweat test and suggestive CF clinical features but without two CFTR(cystic fibrosis transmembrane conductance regulator) mutations. We have performed the extensive molecular analysis of four candidate genes (SCNN1A, SCNN1B, SCNN1G and SERPINA1) in a cohort of 10 uncharacterized patients with CF and CF-like disease. We have used whole-exome sequencing to characterize mutations in the CFTR gene and these four candidate genes. CFTR molecular analysis allowed a complete characterization of three of four CF patients. Candidate variants in SCNN1A, SCNN1B, SCNN1G and SERPINA1 in six patients with CF-like phenotypes were confirmed by Sanger sequencing and were further supported by in silico predictive analysis, pedigree studies, sweat test in other family members, and analysis in CF patients and healthy subjects. Our results suggest that CF-like disease probably results from complex genotypes in several genes in an oligogenic form, with rare variants interacting with environmental factors. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: results of supervised learning techniques applied on clinical and inflammatory data.

PubMed

Maes, Michael; Twisk, Frank N M; Johnson, Cort

2012-12-30

There is much debate on the diagnostic classification of Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS) and chronic fatigue (CF). Post-exertional malaise (PEM) is stressed as a key feature. This study examines whether CF and CFS, with and without PEM, are distinct diagnostic categories. Fukuda's criteria were used to diagnose 144 patients with chronic fatigue and identify patients with CFS and CF, i.e. those not fulfilling the Fukuda's criteria. PEM was rated by means of a scale with defined scale steps between 0 and 6. CFS patients were divided into those with PEM lasting more than 24h (labeled: ME) and without PEM (labeled: CFS). The 12-item Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to measure severity of illness. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, and lysozyme, and serum neopterin were employed as external validating criteria. Using fatigue, a subjective feeling of infection and PEM we found that ME, CFS, and CF were distinct categories. Patients with ME had significantly higher scores on concentration difficulties and a subjective experience of infection, and higher levels of IL-1, TNFα, and neopterin than patients with CFS. These biomarkers were significantly higher in ME and CFS than in CF patients. PEM loaded highly on the first two factors subtracted from the data set, i.e. "malaise-sickness" and "malaise-hyperalgesia". Fukuda's criteria are adequate to make a distinction between ME/CFS and CF, but ME/CFS patients should be subdivided into ME (with PEM) and CFS (without PEM). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The A3 adenosine receptor agonist CF502 inhibits the PI3K, PKB/Akt and NF-kappaB signaling pathway in synoviocytes from rheumatoid arthritis patients and in adjuvant-induced arthritis rats.

PubMed

Ochaion, A; Bar-Yehuda, S; Cohen, S; Amital, H; Jacobson, K A; Joshi, B V; Gao, Z G; Barer, F; Patoka, R; Del Valle, L; Perez-Liz, G; Fishman, P

2008-08-15

The A(3) adenosine receptor (A(3)AR) is over-expressed in inflammatory cells and was defined as a target to combat inflammation. Synthetic agonists to this receptor, such as IB-MECA and Cl-IB-MECA, exert an anti-inflammatory effect in experimental animal models of adjuvant- and collagen-induced arthritis. In this study we present a novel A(3)AR agonist, CF502, with high affinity and selectivity at the human A(3)AR. CF502 induced a dose dependent inhibitory effect on the proliferation of fibroblast-like synoviocytes (FLS) via de-regulation of the nuclear factor-kappa B (NF-kappaB) signaling pathway. Furthermore, CF502 markedly suppressed the clinical and pathological manifestations of adjuvant-induced arthritis (AIA) in a rat experimental model when given orally at a low dose (100 microg/kg). As is typical of other G-protein coupled receptors, the A(3)AR expression level was down-regulated shortly after treatment with agonist CF502 in paw and in peripheral blood mononuclear cells (PBMCs) derived from treated AIA animals. Subsequently, a decrease in the expression levels of protein kinase B/Akt (PKB/Akt), IkappaB kinase (IKK), I kappa B (IkappaB), NF-kappaB and tumor necrosis factor-alpha (TNF-alpha) took place. In addition, the expression levels of glycogen synthase kinase-3 beta (GSK-3beta), beta-catenin, and poly(ADP-ribose)polymerase (PARP), known to control the level and activity of NF-kappaB, were down-regulated upon treatment with CF502. Taken together, CF502 inhibits FLS growth and the inflammatory manifestations of arthritis, supporting the development of A(3)AR agonists for the treatment of rheumatoid arthritis.

Influence of SNPs in Genes that Modulate Lung Disease Severity in a Group of Mexican Patients with Cystic Fibrosis.

PubMed

Yokoyama, Emiy; Chávez-Saldaña, Margarita; Orozco, Lorena; Cuevas, Francisco; Lezana, José Luis; Vigueras-Villaseñor, Rosa María; Rojas-Castañeda, Julio Cesar; Landero, Daniel Adrian

2018-04-24

The variation in cystic fibrosis (CF) lung disease not always is explained by the CFTR genotype, so it has become apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of CF, so we investigated the association of allelic variants in modifier genes that modulate the severity of lung function in a group of Mexican patients diagnosed with CF. We included 140 CF patients classified according to lung phenotype and analyzed 17 single nucleotide polymorphisms (SNPs) by TaqMan ® allelic discrimination. We demonstrated that patients with GG or GC genotype of the allelic variant rs11003125 (MBL2-550) of the MBL2 gene exhibit most of the lung manifestations at an earlier age; and the rs1042713 allelic variant of ADRB2 gene, showed statistical difference only with the age of first spirometry. When we used the dominant model, the MBL2 allele rs11003125 (MBL2-550; p = 0.022, Odds Ratio (OR) 2.87, 95% CI 1.14-7.27) was significantly associated with CF patients as risk factor, and the ADRB2 allele rs1042713 (p.Arg16Gly; p = 0.005, Odds Ratio (OR) 0.37, 95% CI 0.19-0.75) was significantly associated with CF patients as protect factor. Our findings suggest that the MBL2 and ADRB2 genes exerts an important genetic influence on the lung disease in our patients. Taking into account our results, we insist on not leaving aside this type of studies, since having techniques such as GWAS or WES will be able to advance in achieving a better quality of life for CF patients with severe lung disease. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

Identification of Novel Components Influencing Colonization Factor Antigen I Expression in Enterotoxigenic Escherichia coli

PubMed Central

Haines, Sara; Gautheron, Sylviane; Nasser, William; Renauld-Mongénie, Geneviève

2015-01-01

Colonization factors (CFs) mediate early adhesion of Enterotoxigenic Escherichia coli (ETEC) in the small intestine. Environmental signals including bile, glucose, and contact with epithelial cells have previously been shown to modulate CF expression in a strain dependent manner. To identify novel components modulating CF surface expression, 20 components relevant to the intestinal environment were selected for evaluation. These included mucin, bicarbonate, norepinephrine, lincomycin, carbon sources, and cations. Effects of individual components on surface expression of the archetype CF, CFA/I, were screened using a fractional factorial Hadamard matrix incorporating 24 growth conditions. As most CFs agglutinate erythrocytes, surface expression was evaluated by mannose resistant hemagglutination. Seven components, including porcine gastric mucin, lincomycin, glutamine, and glucose were found to induce CFA/I surface expression in vitro in a minimal media while five others were inhibitory, including leucine and 1,10-phenanthroline. To further explore the effect of components positively influencing CFA/I surface expression, a response surface methodology (RSM) was designed incorporating 36 growth conditions. The optimum concentration for each component was identified, thereby generating a novel culture media, SP1, for CFA/I expression. CFs closely related to CFA/I, including CS4 and CS14 were similarly induced in SP1 media. Other epidemiologically relevant CFs were also induced when compared to the level obtained in minimal media. These results indicate that although CF surface expression is complex and highly variable among strains, the CF response can be predicted for closely related strains. A novel culture media inducing CFs in the CF5a group was successfully identified. In addition, mucin was found to positively influence CF expression in strains expressing either CFA/I or CS1 and CS3, and may function as a common environmental cue. PMID:26517723

Identification of Novel Components Influencing Colonization Factor Antigen I Expression in Enterotoxigenic Escherichia coli.

PubMed

Haines, Sara; Gautheron, Sylviane; Nasser, William; Renauld-Mongénie, Geneviève

2015-01-01

Colonization factors (CFs) mediate early adhesion of Enterotoxigenic Escherichia coli (ETEC) in the small intestine. Environmental signals including bile, glucose, and contact with epithelial cells have previously been shown to modulate CF expression in a strain dependent manner. To identify novel components modulating CF surface expression, 20 components relevant to the intestinal environment were selected for evaluation. These included mucin, bicarbonate, norepinephrine, lincomycin, carbon sources, and cations. Effects of individual components on surface expression of the archetype CF, CFA/I, were screened using a fractional factorial Hadamard matrix incorporating 24 growth conditions. As most CFs agglutinate erythrocytes, surface expression was evaluated by mannose resistant hemagglutination. Seven components, including porcine gastric mucin, lincomycin, glutamine, and glucose were found to induce CFA/I surface expression in vitro in a minimal media while five others were inhibitory, including leucine and 1,10-phenanthroline. To further explore the effect of components positively influencing CFA/I surface expression, a response surface methodology (RSM) was designed incorporating 36 growth conditions. The optimum concentration for each component was identified, thereby generating a novel culture media, SP1, for CFA/I expression. CFs closely related to CFA/I, including CS4 and CS14 were similarly induced in SP1 media. Other epidemiologically relevant CFs were also induced when compared to the level obtained in minimal media. These results indicate that although CF surface expression is complex and highly variable among strains, the CF response can be predicted for closely related strains. A novel culture media inducing CFs in the CF5a group was successfully identified. In addition, mucin was found to positively influence CF expression in strains expressing either CFA/I or CS1 and CS3, and may function as a common environmental cue.

Comparison of Carotid-Femoral and Brachial-Ankle Pulse-Wave Velocity in Association With Target Organ Damage in the Community-Dwelling Elderly Chinese: The Northern Shanghai Study.

PubMed

Lu, Yuyan; Zhu, Mengyun; Bai, Bin; Chi, Chen; Yu, Shikai; Teliewubai, Jiadela; Xu, Henry; Wang, Kai; Xiong, Jing; Zhou, Yiwu; Ji, Hongwei; Fan, Ximin; Yu, Xuejing; Li, Jue; Blacher, Jacques; Zhang, Yi; Xu, Yawei

2017-02-20

Carotid-femoral pulse-wave velocity (cf-PWV) and brachial-ankle PWV (ba-PWV) are the 2 most frequently applied PWV measurements. However, little is known about the comparison of hypertensive target organ damage (TOD) with cf-PWV and ba-PWV. A total of 1599 community-dwelling elderly subjects (age >65 years) in northern Shanghai were recruited from June 2014 to August 2015. Both cf-PWV and ba-PWV were measured using SphygmoCor and VP1000 systems, respectively. Within the framework of comprehensive cardiovascular examinations, risk factors were assessed, and asymptomatic TOD, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity (E/Ea), carotid intima-media thickness, arterial plaque, creatinine clearance rate, and urinary albumin-creatinine ratio were all evaluated. Both PWVs were significantly associated with male sex, age, waist/hip circumference, fasting plasma glucose, and systolic blood pressure, and ba-PWV was also significantly related to body mass index. Both PWVs were significantly correlated with most TOD. When cf-PWV and ba-PWV were both or separately put into the stepwise linear regression model together with cardiovascular risk factors and treatment, only cf-PWV, but not ba-PWV, was significantly associated with carotid intima-media thickness and creatinine clearance rate ( P <0.05). When cf-PWV and ba-PWV were both or separately put into the same full-mode model after adjustment for confounders, only cf-PWV, but not ba-PWV, showed significant association with carotid intima-media thickness and creatinine clearance rate ( P <0.05). Similar results were observed in logistic regression analysis. Taken together, in the community-dwelling elderly Chinese, cf-PWV seems to be more closely associated with hypertensive TOD, especially vascular and renal TOD, as compared with ba-PWV. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02368938. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Increased capillary permeability mediated by a dengue virus-induced lymphokine.

PubMed Central

Khanna, M; Chaturvedi, U C; Sharma, M C; Pandey, V C; Mathur, A

1990-01-01

The mechanism of increased capillary permeability, seen in cases of dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), is not known. Dengue type 2 virus (DV) is known to induce production of a lymphokine, the cytotoxic factor (CF), by the T lymphocytes of mouse spleen. The data presented here show that intraperitoneal inoculation of CF in mice results in increased capillary permeability in a dose-dependent manner, as shown by leakage of intravenously injected radiolabelled iodine (125I) or Evans blue dye. Peak leakage occurred 30 min after inoculation of CF and the vascular integrity was restored by 2 hr. The increase in capillary permeability was abrogated by pretreatment of mice with anti-CF antibodies, avil (H1 receptor blocker) or ranitidine (H2 receptor blocker). The findings thus show that a DV-induced lymphokine, the CF, increases the capillary permeability via release of histamine. PMID:2312168

Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening.

PubMed

Stick, Stephen M; Brennan, Siobhain; Murray, Conor; Douglas, Tonia; von Ungern-Sternberg, Britta S; Garratt, Luke W; Gangell, Catherine L; De Klerk, Nicholas; Linnane, Barry; Ranganathan, Sarath; Robinson, Phillip; Robertson, Colin; Sly, Peter D

2009-11-01

To determine the prevalence of bronchiectasis in young children with cystic fibrosis (CF) diagnosed after newborn screening (NBS) and the relationship of bronchiectasis to pulmonary inflammation and infection. Children were diagnosed with CF after NBS. Computed tomography and bronchoalveolar lavage were performed with anesthesia (n = 96). Scans were analyzed for the presence and extent of abnormalities. The prevalence of bronchiectasis was 22% and increased with age (P = .001). Factors associated with bronchiectasis included absolute neutrophil count (P = .03), neutrophil elastase concentration (P = .001), and Pseudomonas aeruginosa infection (P = .03). Pulmonary abnormalities are common in infants and young children with CF and relate to neutrophilic inflammation and infection with P. aeruginosa. Current models of care for infants with CF fail to prevent respiratory sequelae. Bronchiectasis is a clinically relevant endpoint that could be used for intervention trials that commence soon after CF is diagnosed after NBS.

Cystic Fibrosis: A Review of Associated Phenotypes, Use of Molecular Diagnostic Approaches, Genetic Characteristics, Progress, and Dilemmas.

PubMed

Brennan, Marie-Luise; Schrijver, Iris

2016-01-01

Cystic fibrosis (CF) is an autosomal recessive disease with significant associated morbidity and mortality. It is now appreciated that the broad phenotypic CF spectrum is not explained by obvious genotype-phenotype correlations, suggesting that CF transmembrane conductance regulator (CFTR)-related disease may occur because of multiple additive effects. These contributing effects include complex CFTR alleles, modifier genes, mutations in alternative genes that produce CF-like phenotypes, epigenetic factors, and environmental influences. Most patients in the United States are now diagnosed through newborn screening and use of molecular testing methods. We review the molecular testing approaches and laboratory guidelines for carrier screening, prenatal testing, newborn screening, and clinical diagnostic testing, as well as recent developments in CF treatment, and reasons for the lack of a molecular diagnosis in some patients. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

The fate of inhaled antibiotics after deposition in cystic fibrosis: How to get drug to the bug?

PubMed

Bos, Aukje C; Passé, Kimberly M; Mouton, Johan W; Janssens, Hettie M; Tiddens, Harm A W M

2017-01-01

Chronic airway infections in patients with cystic fibrosis (CF) are most often treated with inhaled antibiotics of which deposition patterns have been extensively studied. However, the journey of aerosol particles does not end after deposition within the bronchial tree. To review how local conditions affect the clinical efficacy of antibiotic aerosol particles after deposition in the airways of patients with CF. Electronic databases were searched from inception to September 2015. Original studies describing the effect of CF sputum or bacterial factors on antibiotic efficacy and formulations to increase efficacy were included. 35 articles were included which mostly described in vitro studies and mainly investigated aminoglycosides. After deposition, diffusion through the mucus layer was reduced for aminoglycosides, β-lactam antibiotics and fluoroquinolones. Within CF mucus, low oxygen tension adversely affected aminoglycosides, β-lactam antibiotics, and chloramphenicol; and molecules inactivated aminoglycosides but not β-lactam antibiotics. Finally, the alginate layer surrounding Pseudomonas aeruginosa was an important factor in the resistance against all antibiotics. After deposition in the airways, the local efficacy of inhaled antibiotics can be reduced by molecules within CF mucus and the alginate layer surrounding P. aeruginosa. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Neck circumference and early stage atherosclerosis: the cardiometabolic risk in Chinese (CRC) study.

PubMed

Liang, Jun; Wang, Yu; Li, Hongyan; Liu, Xuekui; Qiu, Qinqin; Qi, Lu

2014-07-08

Neck circumference (NC) has been previously related to cardiometabolic risk factors. In this study we examined the association between NC and early stage atherosclerosis in Chinese adults. The study samples were from a community-based health examination survey in central China. In total 2,318 men and women (18-64 y) were included in the final analyses. Carotid radial pulse wave velocity (crPWV), carotid femoral PWV (cfPWV), carotid artery dorsalis pedis PWV (cdPWV) and NC were measured. After adjustment for age, sex, lipids, glucose, blood pressure, heart rate, body mass index (BMI), high NC was significantly associated with an increasing trend of cfPWV, cdPWV and crPWV (P = 0.001, 0.049, and 0.038; respectively). In addition, we found significant interaction between hypertension status and NC level in relation to cfPWV, adjusted for age, sex, BMI, fasting glucose, lipids and heart rate(P for interaction = 0.034). The associations between NC and cfPWV were significant (P = 0.02) among those with hypertension, but not significant among those without hypertension. Our data showed that high NC was associated with an increased risk of early stage atherosclerosis in Chinese adults, independent of other metabolic risk factors. Hypertension might modify the association between NC and cfPWV.

Enhanced linear-array photoacoustic beamforming using modified coherence factor.

PubMed

Mozaffarzadeh, Moein; Yan, Yan; Mehrmohammadi, Mohammad; Makkiabadi, Bahador

2018-02-01

Photoacoustic imaging (PAI) is a promising medical imaging modality providing the spatial resolution of ultrasound imaging and the contrast of optical imaging. For linear-array PAI, a beamformer can be used as the reconstruction algorithm. Delay-and-sum (DAS) is the most prevalent beamforming algorithm in PAI. However, using DAS beamformer leads to low-resolution images as well as high sidelobes due to nondesired contribution of off-axis signals. Coherence factor (CF) is a weighting method in which each pixel of the reconstructed image is weighted, based on the spatial spectrum of the aperture, to mainly improve the contrast. We demonstrate that the numerator of the formula of CF contains a DAS algebra and propose the use of a delay-multiply-and-sum beamformer instead of the available DAS on the numerator. The proposed weighting technique, modified CF (MCF), has been evaluated numerically and experimentally compared to CF. It was shown that MCF leads to lower sidelobes and better detectable targets. The quantitative results of the experiment (using wire targets) show that MCF leads to for about 45% and 40% improvement, in comparison with CF, in the terms of signal-to-noise ratio and full-width-half-maximum, respectively. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment.

PubMed

Bar-Yehuda, S; Rath-Wolfson, L; Del Valle, L; Ochaion, A; Cohen, S; Patoka, R; Zozulya, G; Barer, F; Atar, E; Piña-Oviedo, S; Perez-Liz, G; Castel, D; Fishman, P

2009-10-01

Studies have suggested that rheumatoid arthritis (RA) and osteoarthritis (OA) share common characteristics. The highly selective A(3) adenosine receptor agonist CF101 was recently defined as a potent antiinflammatory agent for the treatment of RA. The purpose of this study was to examine the effects of CF101 on the clinical and pathologic manifestations of OA in an experimental animal model. OA was induced in rats by monosodium iodoacetate, and upon disease onset, oral treatment with CF101 (100 microg/kg given twice daily) was initiated. The A(3) adenosine receptor antagonist MRS1220 (100 microg/kg given twice daily) was administered orally, 30 minutes before CF101 treatment. The OA clinical score was monitored by knee diameter measurements and by radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin, Safranin O-fast green, or toluidine blue, and histologic changes were scored according to a modified Mankin system. Signaling proteins were assayed by Western blotting; apoptosis was detected via immunohistochemistry and TUNEL analyses. CF101 induced a marked decrease in knee diameter and improved the changes noted on radiographs. Administration of MRS1220 counteracted the effects of CF101. CF101 prevented cartilage damage, osteoclast/osteophyte formation, and bone destruction. In addition, CF101 markedly reduced pannus formation and lymphocyte infiltration. Mechanistically, CF101 induced deregulation of the NF-kappaB signaling pathway, resulting in down-regulation of tumor necrosis factor alpha. Consequently, CF101 induced apoptosis of inflammatory cells that had infiltrated the knee joints; however, it prevented apoptosis of chondrocytes. CF101 deregulated the NF-kappaB signaling pathway involved in the pathogenesis of OA. CF101 induced apoptosis of inflammatory cells and acted as a cartilage protective agent, which suggests that it would be a suitable candidate drug for the treatment of OA.

Acute cocoa flavanol improves cerebral oxygenation without enhancing executive function at rest or after exercise.

PubMed

Decroix, Lieselot; Tonoli, Cajsa; Soares, Danusa D; Tagougui, Semah; Heyman, Elsa; Meeusen, Romain

2016-12-01

Acute exercise-induced improvements in cognitive function are accompanied by increased (cerebral) blood flow and increased brain-derived neurotrophic factor (BDNF) levels. Acute cocoa flavanol (CF) intake may improve cognitive function, cerebral blood flow (in humans), and BNDF levels (in animals). This study investigated (i) the effect of CF intake in combination with exercise on cognitive function and (ii) cerebral hemodynamics and BDNF in response to CF intake and exercise. Twelve healthy men participated in this randomized, double-blind, crossover study. Participants performed a cognitive task (CT) at 100 min after acute 903-mg CF or placebo (PL) intake, followed by a 30-min time-trial. Immediately after this exercise, the same CT was performed. Prefrontal near-infrared spectroscopy was applied during CT and exercise to measure changes in oxygenated (ΔHbO 2 ), deoxygenated (ΔHHb), and total haemoglobin (ΔHb tot ) and blood samples were drawn and analyzed for BDNF. Reaction time was faster postexercise, but was not influenced by CF. ΔHbO 2 during the resting CT was increased by CF, compared with PL. ΔHbO 2 , ΔHHb, and ΔHb tot increased in response to exercise without any effect of CF. During the postexercise cognitive task, there were no hemodynamic differences between CF or PL. Serum BDNF was increased by exercise, but was not influenced by CF. In conclusion, at rest, CF intake increased cerebral oxygenation, but not BDNF concentrations, and no impact on executive function was detected. This beneficial effect of CF on cerebral oxygenation at rest was overruled by the strong exercise-induced increases in cerebral perfusion and oxygenation.

Cladosporium fulvum CfHNNI1 induces hypersensitive necrosis, defence gene expression and disease resistance in both host and nonhost plants.

PubMed

Cai, Xin-Zhong; Zhou, Xin; Xu, You-Ping; Joosten, Matthieu H A J; de Wit, Pierre J G M

2007-05-01

Nonhost resistance as a durable and broad-spectrum defence strategy is of great potential for agricultural applications. We have previously isolated a cDNA showing homology with genes encoding bZIP transcription factors from tomato leaf mould pathogen Cladosporium fulvum. Upon expression, the cDNA results in necrosis in C. fulvum host tomato and nonhost tobacco plants and is thus named CfHNNI1 (for C . f ulvum host and nonhost plant necrosis inducer 1). In the present study we report the induction of necrosis in a variety of nonhost plant species belonging to three families by the transient in planta expression of CfHNNI1 using virus-based vectors. Additionally, transient expression of CfHNNI1 also induced expression of the HR marker gene LeHSR203 and greatly reduced the accumulation of recombinant Potato virus X. Stable CfHNNI1 transgenic tobacco plants were generated in which the expression of CfHNNI1 is under the control of the pathogen-inducible hsr203J promoter. When infected with the oomycetes pathogen Phytophthora parasitica var. nicotianae, these transgenic plants manifested enhanced expression of CfHNNI1 and subsequent accumulation of CfHNNI1 protein, resulting in high expression of the HSR203J and PR genes, and strong resistance to the pathogen. The CfHNNI1 transgenic plants also exhibited induced resistance to Pseudomonas syringae pv. tabaci and Tobacco mosaic virus. Furthermore, CfHNNI1 was highly expressed and the protein was translocated into plant cells during the incompatible interactions between C. fulvum and host and nonhost plants. Our results demonstrate that CfHNNI1 is a potential general elicitor of hypersensitive response and nonhost resistance.

Liposome-chaperoned cell-free synthesis for the design of proteoliposomes: Implications for therapeutic delivery.

PubMed

Lu, Mei; Zhao, Xiaoyun; Xing, Haonan; Xun, Zhe; Yang, Tianzhi; Cai, Cuifang; Wang, Dongkai; Ding, Pingtian

2018-04-03

Cell-free (CF) protein synthesis has emerged as a powerful technique platform for efficient protein production in vitro. Liposomes have been widely studied as therapeutic carriers due to their biocompatibility, biodegradability, low toxicity, flexible surface manipulation, easy preparation, and higher cargo encapsulation capability. However, rapid immune clearance, insufficient targeting capacity, and poor cytoplasmic delivery efficiency substantially restrict their clinical application. The incorporation of functional membrane proteins (MPs) or peptides allows the transfer of biological properties to liposomes and imparts them with improved circulation, increased targeting, and efficient intracellular delivery. Liposome-chaperoned CF synthesis enables production of proteoliposomes in one-step reaction, which not only substantially simplifies the production procedure but also keeps protein functionality intact. Building off these observations, proteoliposomes with integrated MPs represent an excellent candidate for therapeutic delivery. In this review, we describe recent advances in CF synthesis with emphasis on detailing key factors for improving CF expression efficiency. Furthermore, we provide insights into strategies for rational design of proteoliposomal nanodelivery systems via CF synthesis. Liposome-chaperoned CF synthesis has emerged as a powerful approach for the design of recombinant proteoliposomes in one-step reaction. The incorporation of bioactive MPs or peptides into liposomes via CF synthesis can facilitate the development of proteoliposomal nanodelivery systems with improved circulation, increased targeting, and enhanced cellular delivery capacity. Moreover, by adapting lessons learned from natural delivery vehicles, novel bio-inspired proteoliposomes with enhanced delivery properties could be produced in CF systems. In this review, we first give an overview of CF synthesis with focus on enhancing protein expression in liposome-chaperoned CF systems. Furthermore, we intend to provide insight into harnessing CF-synthesized proteoliposomes for efficient therapeutic delivery. Copyright © 2018. Published by Elsevier Ltd.

Test-Retest Variability in Lesion SUV and Lesion SUR in 18F-FDG PET: An Analysis of Data from Two Prospective Multicenter Trials.

PubMed

Hofheinz, Frank; Apostolova, Ivayla; Oehme, Liane; Kotzerke, Jörg; van den Hoff, Jörg

2017-11-01

Quantitative assessment of radio- and chemotherapy response with 18 F-FDG whole-body PET has attracted increasing interest in recent years. In most published work, SUV has been used for this purpose. In the context of therapy response assessment, the reliability of lesion SUVs, notably their test-retest stability, thus becomes crucial. However, a recent study demonstrated substantial test-retest variability (TRV) in SUVs. The purpose of the present study was to investigate whether the tumor-to-blood SUV ratio (SUR) can improve TRV in tracer uptake. Methods: 73 patients with advanced non-small cell lung cancer from the prospective multicenter trials ACRIN 6678 ( n = 34) and MK-0646-008 ( n = 39) were included in this study. All patients underwent two 18 F-FDG PET/CT investigations on two different days (time difference, 3.6 ± 2.1 d; range, 1-7 d) before therapy. For each patient, up to 7 tumor lesions were evaluated. For each lesion, SUV max and SUV peak were determined. Blood SUV was determined as the mean value of a 3-dimensional aortic region of interest that was delineated on the attenuation CT image and transferred to the PET image. SURs were computed as the ratio of tumor SUV to blood SUV and were uptake time-corrected to 75 min after injection. TRV was quantified as 1.96 multiplied by the root-mean-square deviation of the fractional paired differences in SUV and SUR. The combined effect of blood normalization and uptake time correction was inspected by considering R TRV (TRV SUR /TRV SUV ), a ratio reflecting the reduction in the TRV in SUR relative to SUV. R TRV was correlated with the group-averaged-value difference (δ) in CF mean (δCF mean ) of the quantity δCF = |CF - 1|, where CF is the numeric factor that converts individual ratios of paired SUVs into corresponding SURs. This correlation analysis was performed by successively increasing a threshold value δCF min and computing δCF mean and R TRV for the remaining subgroup of patients/lesions with δCF ≥ δCF min Results: The group-averaged TRV SUV and TRV SUR were 32.1 and 29.0, respectively, which correspond to a reduction of variability in SUR by an R TRV factor of 0.9 in comparison to SUV. This rather marginal improvement can be understood to be a consequence of the atypically low intrasubject variability in blood SUV and uptake time and the accordingly small δCF values in the investigated prospective study groups. In fact, subgroup analysis with increasing δCF min thresholds revealed a pronounced negative correlation (Spearman ρ = -0.99, P < 0.001) between R TRV and δCF mean , where R TRV ≈ 0.4 in the δCF min = 20% subgroup, corresponding to a more than 2-fold reduction of TRV SUR compared with TRV SUV Conclusion: Variability in blood SUV and uptake time has been identified as a causal factor in the TRV in lesion SUV. Therefore, TRV in lesion uptake measurements can be reduced by replacing SUV with SUR as the uptake measure. The improvement becomes substantial for the level of variability in blood SUV and uptake time typically observed in the clinical context. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Low Levels of IGF-1 Contribute to Alveolar Macrophage Dysfunction in Cystic Fibrosis1

PubMed Central

Bessich, Jamie L.; Nymon, Amanda B.; Moulton, Lisa A; Dorman, Dana; Ashare, Alix

2013-01-01

Alveolar macrophages are major contributors to lung innate immunity. Although alveolar macrophages from CFTR−/− mice have impaired function, no study has investigated primary alveolar macrophages in adults with cystic fibrosis (CF). CF patients have low levels of insulin-like growth factor 1 (IGF-1), and our prior studies demonstrate a relationship between IGF-1 and macrophage function. We hypothesize that reduced IGF-1 in CF leads to impaired alveolar macrophage function and chronic infections. Serum and bronchoalveolar lavage (BAL) samples were obtained from 8 CF subjects and 8 healthy subjects. Macrophages were isolated from BAL fluid. We measured the ability of alveolar macrophages to kill Pseudomonas aeruginosa. Subsequently, macrophages were incubated with IGF-1 prior to inoculation with bacteria to determine the effect of IGF-1 on bacterial killing. We found a significant decrease in bacterial killing by CF alveolar macrophages compared to controls. CF subjects had lower serum and BAL IGF-1 levels compared to healthy controls. Exposure to IGF-1 enhanced alveolar macrophage macrophages in both groups. Finally, exposing healthy alveolar macrophages to CF BAL fluid decreased bacterial killing, and this was reversed by the addition of IGF-1, while IGF-1 blockade worsened bacterial killing. Our studies demonstrate that alveolar macrophage function is impaired in patients with CF. Reductions in IGF-1 levels in CF contribute to the impaired alveolar macrophage function. Exposure to IGF-1 ex vivo, results in improved function of CF alveolar macrophages. Further studies are needed to determine whether alveolar macrophage function can be enhanced in vivo with IGF-1 treatment. PMID:23698746

Enhanced IL-1{beta}-induced IL-8 production in cystic fibrosis lung epithelial cells is dependent of both mitogen-activated protein kinases and NF-{kappa}B signaling

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

Muselet-Charlier, Celine; Universite Pierre et Marie Curie-Paris 6, Paris, UMR-S719, F-75012; Roque, Telma

2007-06-01

Transcription nuclear factor-{kappa}B (NF-{kappa}B) is hyperactivated in cystic fibrosis (CF) lung epithelial cells, and participates in exaggerated IL-8 production in the CF lung. We recently found that rapid activation of NF-{kappa}B occurred in a CF lung epithelial IB3-1 cell line (CF cells) upon IL-1{beta} stimulation, which was not observed in its CFTR-corrected lung epithelial S9 cell line (corrected cells). To test whether other signaling pathways such as that of mitogen-activated protein kinases (MAPKs) could be involved in IL-1{beta}-induced IL-8 production of CF cells, we investigated ERK1/2, JNK, and p38MAP signaling compared to NF-{kappa}B. Within 30 min, exposure to IL-1{beta} causedmore » high activation of NF-{kappa}B, ERK1/2, p38MAP but not JNK in CF cells compared to corrected cells. Treatment of IL-1{beta}-stimulated CF cells with a series of chemical inhibitors of NF-{kappa}B, ERK1/2, and p38MAP, when used separately, reduced slightly IL-8 production. However, when used together, these inhibitors caused a blockade in IL-1{beta}-induced IL-8 production in CF cells. Understanding of the cross-talk between NF-{kappa}B and MAPKs signaling in CF lung epithelial cells may help in developing new therapeutics to reduce lung inflammation in patients with CF.« less

Prospective multicenter German study on pulmonary colonization with Scedosporium /Lomentospora species in cystic fibrosis: Epidemiology and new association factors.

PubMed

Schwarz, Carsten; Brandt, Claudia; Antweiler, Elisabeth; Krannich, Alexander; Staab, Doris; Schmitt-Grohé, Sabina; Fischer, Rainald; Hartl, Dominik; Thronicke, Anja; Tintelnot, Kathrin

2017-01-01

An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Clinical, microbiological and laboratory data of 161 patients aged 6-59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13-32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955-0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009-0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873-98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518-93.0705, p<0.05). Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp.

Prospective multicenter German study on pulmonary colonization with Scedosporium /Lomentospora species in cystic fibrosis: Epidemiology and new association factors

PubMed Central

Schwarz, Carsten; Brandt, Claudia; Antweiler, Elisabeth; Krannich, Alexander; Staab, Doris; Schmitt-Grohé, Sabina; Fischer, Rainald; Hartl, Dominik

2017-01-01

Background An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF. Material and methods Clinical, microbiological and laboratory data of 161 patients aged 6–59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors. Results Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13–32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955–0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009–0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873–98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518–93.0705, p<0.05). Conclusion Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp. PMID:28178337

Effects of Frequency Spreads on Beam Breakup Instabilities in Linear Accelerators

DTIC Science & Technology

1989-05-11

i - 1)A/(N - 1), i = 1, ....N. In keeping with the above model [ cf . Eq. (4)], we assume that there is an equal probability (1/N) for each of these...solution (5), which contains two approximations to (10) and (11) [ cf ., N 4 - limit, and then asymptotic analysis], could accurately model the numerical...that the transition time Tl = 0(1) is the time when the phase mixing factor A0 t is roughly balanced by the BBU exponentiation factoro 1.64W I / 3 [ cf

Adjuvant Hypofractionated Versus Conventional Whole Breast Radiation Therapy for Early-Stage Breast Cancer: Long-Term Hospital-Related Morbidity From Cardiac Causes

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

Chan, Elisa K.; Woods, Ryan; McBride, Mary L.

Purpose: The risk of cardiac injury with hypofractionated whole-breast/chest wall radiation therapy (HF-WBI) compared with conventional whole-breast/chest wall radiation therapy (CF-WBI) in women with left-sided breast cancer remains a concern. The purpose of this study was to determine if there is an increase in hospital-related morbidity from cardiac causes with HF-WBI relative to CF-WBI. Methods and Materials: Between 1990 and 1998, 5334 women ≤80 years of age with early-stage breast cancer were treated with postoperative radiation therapy to the breast or chest wall alone. A population-based database recorded baseline patient, tumor, and treatment factors. Hospital administrative records identified baseline cardiacmore » risk factors and other comorbidities. Factors between radiation therapy groups were balanced using a propensity-score model. The first event of a hospital admission for cardiac causes after radiation therapy was determined from hospitalization records. Ten- and 15-year cumulative hospital-related cardiac morbidity after radiation therapy was estimated for left- and right-sided cases using a competing risk approach. Results: The median follow-up was 13.2 years. For left-sided cases, 485 women were treated with CF-WBI, and 2221 women were treated with HF-WBI. Mastectomy was more common in the HF-WBI group, whereas boost was more common in the CF-WBI group. The CF-WBI group had a higher prevalence of diabetes. The 15-year cumulative hospital-related morbidity from cardiac causes (95% confidence interval) was not different between the 2 radiation therapy regimens after propensity-score adjustment: 21% (19-22) with HF-WBI and 21% (17-25) with CF-WBI (P=.93). For right-sided cases, the 15-year cumulative hospital-related morbidity from cardiac causes was also similar between the radiation therapy groups (P=.76). Conclusions: There is no difference in morbidity leading to hospitalization from cardiac causes among women with left-sided early-stage breast cancer treated with HF-WBI or CF-WBI at 15-year follow-up.« less

Electrocatalytic process for carbon dioxide conversion

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

Masel, Richard I.; Salehi-Khojin, Amin

2017-01-31

An electrocatalytic process for carbon dioxide conversion includes combining a Catalytically Active Element and Helper Catalyst in the presence of carbon dioxide, allowing a reaction to proceed to produce a reaction product, and applying electrical energy to said reaction to achieve electrochemical conversion of said reactant to said reaction product. The Catalytically Active Element can be a metal in the form of supported or unsupported particles or flakes with an average size between 0.6 nm and 100 nm. the reaction products comprise at least one of CO, HCO.sup.-, H.sub.2CO, (HCO.sub.2).sup.-, H.sub.2CO.sub.2, CH.sub.3OH, CH.sub.4, C.sub.2H.sub.4, CH.sub.3CH.sub.2OH, CH.sub.3COO.sup.-, CH.sub.3COOH, C.sub.2H.sub.6, (COOH).sub.2, (COO.sup.-).sub.2,more » and CF.sub.3COOH.« less

Electrocatalytic process for carbon dioxide conversion

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

Masel, Richard I.; Salehi-Khojin, Amin; Kutz, Robert

An electrocatalytic process for carbon dioxide conversion includes combining a Catalytically Active Element and a Helper Polymer in the presence of carbon dioxide, allowing a reaction to proceed to produce a reaction product, and applying electrical energy to said reaction to achieve electrochemical conversion of said carbon dioxide reactant to said reaction product. The Catalytically Active Element can be a metal in the form of supported or unsupported particles or flakes with an average size between 0.6 nm and 100 nm. The reaction products comprise at least one of CO, HCO.sup.-, H.sub.2CO, (HCO.sub.2).sup.-, H.sub.2CO.sub.2, CH.sub.3OH, CH.sub.4, C.sub.2H.sub.4, CH.sub.3CH.sub.2OH, CH.sub.3COO.sup.-, CH.sub.3COOH,more » C.sub.2H.sub.6, (COOH).sub.2, (COO.sup.-).sub.2, and CF.sub.3COOH.« less

EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6

PubMed Central

Wu, Yi-Long; Sequist, Lecia V; Hu, Cheng-Ping; Feng, Jifeng; Lu, Shun; Huang, Yunchao; Li, Wei; Hou, Mei; Schuler, Martin; Mok, Tony; Yamamoto, Nobuyuki; O'Byrne, Kenneth; Hirsh, Vera; Gibson, Neil; Massey, Dan; Kim, Miyoung; Yang, James Chih-Hsin

2017-01-01

Background: In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+). Methods: Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit. Results: EGFR mutation detection rates in cfDNA were 28.6% (serum) and 60.5% (plasma). Mutation detection in blood was associated with advanced disease characteristics, including higher performance score, number of metastatic sites and bone/liver metastases, and poorer prognosis. In patients with common EGFR mutations, afatinib improved progression-free survival vs chemotherapy in cfDNA+ (LL3: HR, 0.35; P=0.0009; LL6: HR, 0.25; P<0.0001) and cfDNA− (LL3: HR, 0.46; P<0.0001; LL6: HR, 0.12; P<0.0001) cohorts. A trend towards overall survival benefit with afatinib was observed in cfDNA+ patients. Conclusions: Plasma cfDNA is a promising alternative to biopsy for EGFR testing. Detectable mutation in blood was associated with more advanced disease and poorer prognosis. Afatinib improved outcomes in EGFR mutation-positive patients regardless of blood mutation status. PMID:28006816

Neonatal injury at cephalic vaginal delivery: a retrospective analysis of extent of association with shoulder dystocia.

PubMed

Iskender, Cantekin; Kaymak, Oktay; Erkenekli, Kudret; Ustunyurt, Emin; Uygur, Dilek; Yakut, Halil Ibrahim; Danisman, Nuri

2014-01-01

To describe the risk factors and labor characteristics of Clavicular fracture (CF) and brachial plexus injury (BPI); and compare antenatal and labor characteristics and prognosis of obstetrical BPI associated with shoulder dystocia with obstetrical BPI not associated with shoulder dystocia. This retrospective study consisted of women who gave birth to an infant with a fractured clavicle or BPI between January 2009 and June 2013. Antenatal and neonatal data were compared between groups. The control group (1300) was composed of the four singleton vaginal deliveries that immediately followed each birth injury. A multivariable logistic regression model, with backward elimination, was constructed in order to find independent risk factors associated with BPI and CF. A subgroup analysis involved comparison of features of BPI cases with or without associated shoulder dystocia. During the study period, the total number of vaginal deliveries was 44092. The rates of CF, BPI and shoulder dystocia during the study period were 0,6%, 0,16% and 0,29%, respectively. In the logistic regression model, shoulder dystocia, GDM, multiparity, gestational age >42 weeks, protracted labor, short second stage of labor and fetal birth weight greater than 4250 grams increased the risk of CF independently. Shoulder dystocia and protracted labor were independently associated with BPI when controlled for other factors. Among neonates with BPI whose injury was not associated with shoulder dystocia, five (12.2%) sustained permanent injury, whereas one neonate (4.5%) with BPI following shoulder dystocia sustained permanent injury (p = 0.34). BPI not associated with shoulder dystocia might have a higher rate of concomitant CF and permanent sequelae.

Crickets Are Not a Free Lunch: Protein Capture from Scalable Organic Side-Streams via High-Density Populations of Acheta domesticus

PubMed Central

Lundy, Mark E.; Parrella, Michael P.

2015-01-01

It has been suggested that the ecological impact of crickets as a source of dietary protein is less than conventional forms of livestock due to their comparatively efficient feed conversion and ability to consume organic side-streams. This study measured the biomass output and feed conversion ratios of house crickets (Acheta domesticus) reared on diets that varied in quality, ranging from grain-based to highly cellulosic diets. The measurements were made at a much greater population scale and density than any previously reported in the scientific literature. The biomass accumulation was strongly influenced by the quality of the diet (p<0.001), with the nitrogen (N) content, the ratio of N to acid detergent fiber (ADF) content, and the crude fat (CF) content (y=N/ADF+CF) explaining most of the variability between feed treatments (p = 0.02; R2 = 0.96). In addition, for populations of crickets that were able to survive to a harvestable size, the feed conversion ratios measured were higher (less efficient) than those reported from studies conducted at smaller scales and lower population densities. Compared to the industrial-scale production of chickens, crickets fed a poultry feed diet showed little improvement in protein conversion efficiency, a key metric in determining the ecological footprint of grain-based livestock protein. Crickets fed the solid filtrate from food waste processed at an industrial scale via enzymatic digestion were able to reach a harvestable size and achieve feed and protein efficiencies similar to that of chickens. However, crickets fed minimally-processed, municipal-scale food waste and diets composed largely of straw experienced >99% mortality without reaching a harvestable size. Therefore, the potential for A. domesticus to sustainably supplement the global protein supply, beyond what is currently produced via grain-fed chickens, will depend on capturing regionally scalable organic side-streams of relatively high-quality that are not currently being used for livestock production. PMID:25875026

Crickets are not a free lunch: protein capture from scalable organic side-streams via high-density populations of Acheta domesticus.

PubMed

Lundy, Mark E; Parrella, Michael P

2015-01-01

It has been suggested that the ecological impact of crickets as a source of dietary protein is less than conventional forms of livestock due to their comparatively efficient feed conversion and ability to consume organic side-streams. This study measured the biomass output and feed conversion ratios of house crickets (Acheta domesticus) reared on diets that varied in quality, ranging from grain-based to highly cellulosic diets. The measurements were made at a much greater population scale and density than any previously reported in the scientific literature. The biomass accumulation was strongly influenced by the quality of the diet (p<0.001), with the nitrogen (N) content, the ratio of N to acid detergent fiber (ADF) content, and the crude fat (CF) content (y=N/ADF+CF) explaining most of the variability between feed treatments (p = 0.02; R2 = 0.96). In addition, for populations of crickets that were able to survive to a harvestable size, the feed conversion ratios measured were higher (less efficient) than those reported from studies conducted at smaller scales and lower population densities. Compared to the industrial-scale production of chickens, crickets fed a poultry feed diet showed little improvement in protein conversion efficiency, a key metric in determining the ecological footprint of grain-based livestock protein. Crickets fed the solid filtrate from food waste processed at an industrial scale via enzymatic digestion were able to reach a harvestable size and achieve feed and protein efficiencies similar to that of chickens. However, crickets fed minimally-processed, municipal-scale food waste and diets composed largely of straw experienced >99% mortality without reaching a harvestable size. Therefore, the potential for A. domesticus to sustainably supplement the global protein supply, beyond what is currently produced via grain-fed chickens, will depend on capturing regionally scalable organic side-streams of relatively high-quality that are not currently being used for livestock production.

Learners' Perception of Corrective Feedback in Pair Work

ERIC Educational Resources Information Center

Yoshida, Reiko

2008-01-01

The present study examines Japanese language learners' perception of corrective feedback (CF) in pair work in relation to their noticing and understanding of their partners' CF and the factors that influence it. This study focuses on three learners, who worked together in pair work. The data collection methods consist of classroom observation,…

Decoupling between the response of coral calcifying fluid pH and calcification to ocean acidification.

PubMed

Comeau, S; Cornwall, C E; McCulloch, M T

2017-08-08

Evaluating the factors responsible for differing species-specific sensitivities to declining seawater pH is central to understanding the mechanisms via which ocean acidification (OA) affects coral calcification. We report here the results of an experiment comparing the responses of the coral Acropora yongei and Pocillopora damicornis to differing pH levels (8.09, 7.81, and 7.63) over an 8-week period. Calcification of A. youngei was reduced by 35% at pH 7.63, while calcification of P. damicornis was unaffected. The pH in the calcifying fluid (pH cf ) was determined using δ 11 B systematics, and for both species pH cf declined slightly with seawater pH, with the decrease being more pronounced in P. damicornis. The dissolved inorganic carbon concentration at the site of calcification (DIC cf ) was estimated using geochemical proxies (B/Ca and δ 11 B) and found to be double that of seawater DIC, and increased in both species as seawater pH decreased. As a consequence, the decline of the saturation state at the site of calcification (Ω cf ) with OA was partially moderated by the DIC cf increase. These results highlight that while pH cf , DIC cf and Ω cf are important in the mineralization process, some corals are able to maintain their calcification rates despite shifts in their calcifying fluid carbonate chemistry.

Conflict or congruence? Maternal and infant-centric factors associated with shorter exclusive breastfeeding durations among the Tsimane

PubMed Central

Martin, Melanie A.; Garcia, Geni; Kaplan, Hillard S.; Gurven, Michael D.

2016-01-01

Six months of exclusive breastfeeding (EBF) is considered optimal for infant health, though globally most infants begin complementary feeding (CF) earlier—including among populations that practice prolonged breastfeeding. Two frameworks for understanding patterns of early CF emerge in the literature. In the first, maternal and infant needs trade-off, as “maternal-centric” factors—related to time and energy demands, reproductive investment, cultural influences, and structural barriers— favor supplanting breastfeeding with earlier and increased CF. A second framework considers that “infant-centric” factors—related to infant energetic needs—favor CF before six months to supplement breastfeeding. We apply these two frameworks in examining early CF among the Tsimane—a high-fertility, high-mortality, forager-horticulturalist population residing in the Bolivian Amazon. Data were collected from a mixed-longitudinal sample of 161 Tsimane mother-infant pairs from August 2012 – April 2013. Tsimane mothers generally reported introducing CF because of perceived infant needs. However, CF is introduced with continued intensive breastfeeding, and generally coupled with premastication. Risks of earlier CF relative to the minimum hazard (estimated at 5 births) were elevated for lower and higher parity mothers, but were significantly greater only after 9 births. Seventeen percent of mothers reported introducing CF because of low milk supply. Introducing CF because of low milk was most common from 0-3 months of age and among higher parity mothers, which may reflect physiological constraints. Maternal reproductive trade-offs and perceived infant needs may help explain the low prevalence of EBF to six months among other populations in which breastfeeding is not structurally or culturally constrained. PMID:27732906

Behavioral alterations in cystic fibrosis mice are prevented by cannabinoid treatment in infancy.

PubMed

Bregman, Tatiana; Fride, Ester

2011-06-17

Substantial data have been accumulated regarding the molecular basis of cystic fibrosis (CF) pathogenesis, whereas the influence of biochemical impairments on brain processes has been the focus of much less attention. We have studied some behavioral parameters, such as motor activity and anxiety level, in a mice model of CF. We have assumed that functioning of the endocannabinoid system could be impaired in CF (endocannabinoids are fatty acid derivatives, and fatty acid deficiency is considered a major factor in CF etiology). We have suggested that chronic treatment with cannabinoid receptors agonist during infancy would balance cannabinoid levels and prevent CF-related behavioral alterations. Motor activity and anxiety level were studied in naïve adult CF mice (cftr-deficient mice) and compared with wild-type mice and to CF mice treated chronically with Δ9-tetrahydrocannabinol (Δ9-THC; endocannabinoid receptor agonist) during infancy (from days 7 to 28). Motor activity was tested in the tetrad, and level of anxiety in the plus maze, a month after cessation of treatment. Motor activity decrease and elevated anxiety level were found in adult naïve CF mice compared with wild-type mice. CF mice treated with THC in infancy showed normal motor activity and anxiety levels in adulthood. Motor function alteration and elevated anxiety levels in CF can result from lack of CFTR-channel in neurons and disturbed activity of various brain areas, as well as being secondary and mediated by fatty acids deficiency, altered levels of endocannabinoids and their receptors. It can be suggested that chronic treatment during infancy restores endocannabinoid function and thus prevents behavioral alterations.

Product toxicity and cometabolic competitive inhibition modeling of chloroform and trichloroethylene transformation by methanotrophic resting cells.

PubMed Central

Alvarez-Cohen, L; McCarty, P L

1991-01-01

The rate and capacity for chloroform (CF) and trichloroethylene (TCE) transformation by a mixed methanotrophic culture of resting cells (no exogenous energy source) and formate-fed cells were measured. As reported previously for TCE, formate addition resulted in an increased CF transformation rate (0.35 day-1 for resting cells and 1.5 day-1 for formate-fed cells) and transformation capacity (0.0065 mg of CF per mg of cells for resting cells and 0.015 mg of CF per mg of cells for formate-fed cells), suggesting that depletion of energy stores affects transformation behavior. The observed finite transformation capacity, even with an exogenous energy source, suggests that toxicity was also a factor. CF transformation capacity was significantly lower than that for TCE, suggesting a greater toxicity from CF transformation. The toxicity of CF, TCE, and their transformation products to whole cells was evaluated by comparing the formate oxidation activity of acetylene-treated cells to that of non-acetylene-treated cells with and without prior exposure to CF or TCE. Acetylene arrests the activity of methane monooxygenase in CF and TCE oxidation without halting cell activity toward formate. Significantly diminished formate oxidation by cells exposed to either CR or TCE without acetylene compared with that with acetylene suggests that the solvents themselves were not toxic under the experimental conditions but their transformation products were. The concurrent transformation of CF and TCE by resting cells was measured, and results were compared with predictions from a competitive-inhibition cometabolic transformation model. The reasonable fit between model predictions and experimental observations was supportive of model assumptions. PMID:1905516

Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process

PubMed Central

Choi, Jae Young; Khansaheb, Monal; Joo, Nam Soo; Krouse, Mauri E.; Robbins, Robert C.; Weill, David; Wine, Jeffrey J.

2009-01-01

Chronic bacterial airway infections are the major cause of mortality in cystic fibrosis (CF). Normal airway defenses include reflex stimulation of submucosal gland mucus secretion by sensory neurons that release substance P (SubP). CFTR is an anion channel involved in fluid secretion and mutated in CF; the role of CFTR in secretions stimulated by SubP is unknown. We used optical methods to measure SubP-mediated secretion from human submucosal glands in lung transplant tissue. Glands from control but not CF subjects responded to mucosal chili oil. Similarly, serosal SubP stimulated secretion in more than 60% of control glands but only 4% of CF glands. Secretion triggered by SubP was synergistic with vasoactive intestinal peptide and/or forskolin but not with carbachol; synergy was absent in CF glands. Pig glands demonstrated a nearly 10-fold greater response to SubP. In 10 of 11 control glands isolated by fine dissection, SubP caused cell volume loss, lumen expansion, and mucus flow, but in 3 of 4 CF glands, it induced lumen narrowing. Thus, in CF, the reduced ability of mucosal irritants to stimulate airway gland secretion via SubP may be another factor that predisposes the airways to infections. PMID:19381016

Along the way to developing a theory of the program: a re-examination of the conceptual framework as an organizing strategy.

PubMed

Helitzer, Deborah L; Sussman, Andrew L; Hoffman, Richard M; Getrich, Christina M; Warner, Teddy D; Rhyne, Robert L

2014-08-01

Conceptual frameworks (CF) have historically been used to develop program theory. We re-examine the literature about the role of CF in this context, specifically how they can be used to create descriptive and prescriptive theories, as building blocks for a program theory. Using a case example of colorectal cancer screening intervention development, we describe the process of developing our initial CF, the methods used to explore the constructs in the framework and revise the framework for intervention development. We present seven steps that guided the development of our CF: (1) assemble the "right" research team, (2) incorporate existing literature into the emerging CF, (3) construct the conceptual framework, (4) diagram the framework, (5) operationalize the framework: develop the research design and measures, (6) conduct the research, and (7) revise the framework. A revised conceptual framework depicted more complicated inter-relationships of the different predisposing, enabling, reinforcing, and system-based factors. The updated framework led us to generate program theory and serves as the basis for designing future intervention studies and outcome evaluations. A CF can build a foundation for program theory. We provide a set of concrete steps and lessons learned to assist practitioners in developing a CF. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical accuracy of abnormal cell-free fetal DNA results for the sex chromosomes.

PubMed

Scibetta, Emily W; Gaw, Stephanie L; Rao, Rashmi R; Silverman, Neil S; Han, Christina S; Platt, Lawrence D

2017-12-01

To investigate factors associated with abnormal cell-free DNA (cfDNA) results for sex chromosomes (SCs). This is a retrospective cohort study of abnormal cfDNA results for SC at a referral practice from March 2013 to July 2015. Cell-free DNA results were abnormal if they were positive for SC aneuploidy (SCA), inconclusive, or discordant with ultrasound (US) findings. Primary outcome was concordance with karyotype or postnatal evaluation. Of 50 abnormal cfDNA results for SC, 31 patients (62%) were positive for SCA, 13 (26%) were inconclusive, and 6 (12%) were sex discordant on US. Of SCA results, 19 (61%) were reported as 45,X and 12 (39%) were SC trisomy. Abnormal karyotypes were confirmed in 8/23 (35%) of SC aneuploidy and 1/5 (20%) of inconclusive results. Abnormal SC cfDNA results were associated with in vitro fertilization (P = .001) and twins (P < .001). Sex discordance between cfDNA and US was associated with twin gestation (P < .001). In our cohort, abnormal SC cfDNA results were associated with in vitro fertilization and twins. Our results indicate cfDNA for sex prediction in twins of limited utility. Positive predictive value and sensitivity for SC determination were lower than previously reported. © 2017 John Wiley & Sons, Ltd.

Repurposing tromethamine as inhaled therapy to treat CF airway disease

PubMed Central

Alaiwa, Mahmoud H. Abou; Launspach, Janice L.; Sheets, Kelsey A.; Rivera, Jade A.; Gansemer, Nicholas D.; Taft, Peter J.; Thorne, Peter S.; Welsh, Michael J.; Stoltz, David A.

2016-01-01

In cystic fibrosis (CF), loss of CF transmembrane conductance regulator (CFTR) anion channel activity causes airway surface liquid (ASL) pH to become acidic, which impairs airway host defenses. One potential therapeutic approach is to correct the acidic pH in CF airways by aerosolizing HCO3– and/or nonbicarbonate pH buffers. Here, we show that raising ASL pH with inhaled HCO3– increased pH. However, the effect was transient, and pH returned to baseline values within 30 minutes. Tromethamine (Tham) is a buffer with a long serum half-life used as an i.v. formulation to treat metabolic acidosis. We found that Tham aerosols increased ASL pH in vivo for at least 2 hours and enhanced bacterial killing. Inhaled hypertonic saline (7% NaCl) is delivered to people with CF in an attempt to promote mucus clearance. Because an increased ionic strength inhibits ASL antimicrobial factors, we added Tham to hypertonic saline and applied it to CF sputum. We found that Tham alone and in combination with hypertonic saline increased pH and enhanced bacterial killing. These findings suggest that aerosolizing the HCO3–-independent buffer Tham, either alone or in combination with hypertonic saline, might be of therapeutic benefit in CF airway disease. PMID:27390778

Several siblings with Cystic Fibrosis as a risk factor for poor outcome.

PubMed

Lavie, Moran; Shemer, Ofer; Sarouk, Ifat; Bar Aluma, Bat el; Dagan, Adi; Efrati, Ori; Vilozni, Daphna

2015-01-01

Occurrence of Cystic Fibrosis (CF) in more than one member in a family is not uncommon. The aim of our study was to assess the influence of multiple siblings with CF on disease expression and outcome. Study group consisted of 2-siblings (2-sibs, n = 42) or 3/4 siblings (3/4-sibs, n = 22) with CF in one family. Each sibling was matched by age, mutation, and gender to a single CF patient. 3/4-sibs subgroup compared to singles showed a lower mean FEV1 with a faster decline rate (58.4 ± 27.5 vs. 72.7 ± 25.4 and -5 ± 6.4 vs. -1.7 ± 2.8 %predicted decline/year respectively, p < .05), more airway colonization by Pseudomonas aeruginosa and Mycobacterium abscessus (15 (68%) vs. 8 (36%) and 7 (32%) vs. 4 (18%), respectively, p < .05) and more lung transplants (5 (23%) vs. 2 (9%), respectively, p < .02). Last mean FEV1 within 3/4-sibs was significantly lower for the youngest sib (p < .05). Three or more CF patients in one family may be a risk factor for more severe disease and poor prognosis. In our view this reflects the burden of disease on the patients and families. Copyright © 2014 Elsevier Ltd. All rights reserved.

Risk factors for totally implantable venous access device-associated complications in cystic fibrosis.

PubMed

McCarthy, C; O'Carroll, O; O'Brien, M E; McEnery, T; Franciosi, A; Gunaratnam, C; McElvaney, N G

2018-05-01

Candidaemia is an important nosocomial infection, seen frequently in immunocompromised and critically ill patients and increasingly recognised in cystic fibrosis (CF) patients with totally implantable venous access devices (TIVADs). This study aims to investigate the incidence and risk factors for the development of TIVAD-associated candidaemia and to assess the rate of TIVAD-related complications in CF patients. A 10-year retrospective study was carried out on adult CF patients attending a single centre. Complications were recorded including the incidence of candidaemia and correlated to clinical parameters. Complication rates were calculated based on incidence per 1000 catheter days. Statistical analysis was performed using Mann-Whitney U test and Fisher's exact test. Fourteen cases of candidaemia were observed in the CF cohort, primarily caused by Candida parapsilosis and Candida albicans. Candidaemia was associated with lower FEV1 (p = 0.0117) and higher frequency of pulmonary exacerbation (p < 0.0001). A TIVAD complication rate of 0.337/1000 catheter days was observed in the CF cohort. Complications included venous thrombosis, stenosis, and port extrusion; complications were independently associated with more frequent pulmonary exacerbations (p = 0.04). TIVAD complications are observed more commonly in those with lower FEV1 and frequent pulmonary exacerbations, suggesting that candidaemia may be related to antibiotic use and furthermore can occur following invasive procedures causing translocation of fungal species allowing transformation from colonisation to pathogenic infection.

Analyzing Fish Condition Factor Index Through Skew-Gaussian Information Theory Quantifiers

NASA Astrophysics Data System (ADS)

Contreras-Reyes, Javier E.

2016-06-01

Biological-fishery indicators have been widely studied. As such the condition factor (CF) index, which interprets the fatness level of a certain species based on length and weight, has been investigated, too. However, CF has been studied without considering its temporal features and distribution. In this paper, we analyze the CF time series via skew-gaussian distributions that consider the asymmetry produced by extreme events. This index is characterized by a threshold autoregressive model and corresponds to a stationary process depending on the shape parameter of the skew-gaussian distribution. Then we use the Jensen-Shannon (JS) distance to compare CF by length classes. This distance has mathematical advantages over other divergences such as Kullback-Leibler and Jeffrey’s, and the triangular inequality property. Our results are applied to a biological catalogue of anchovy (Engraulis ringens) from the northern coast of Chile, for the period 1990-2010 that consider monthly CF time series by length classes and sex. We find that for high values of shape parameter, JS distance tends to be more sensible to detect discrepancies than Jeffrey’s divergence. In addition, the body condition of male anchovies with higher lengths coincides with the ending of the moderate-strong El Niño event 91-92 and for both males and females, the smaller lengths coincide with the beginning of the strong El Niño event 97-98.

Serum Phospholipid Fatty Acid Composition in Cystic Fibrosis Patients with and without Liver Cirrhosis.

PubMed

Drzymała-Czyż, Sławomira; Szczepanik, Mariusz; Krzyżanowska, Patrycja; Duś-Żuchowska, Monika; Pogorzelski, Andrzej; Sapiejka, Ewa; Juszczak, Paweł; Lisowska, Aleksandra; Koletzko, Berthold; Walkowiak, Jarosław

2017-01-01

Cystic fibrosis (CF) liver disease is the third most frequent cause of death in CF patients. Although it alters fatty acid (FA) metabolism, data concerning the profile of FA in CF patients with liver cirrhosis is lacking. This study aimed to assess the FA composition of serum phospholipids in CF patients with and without liver cirrhosis. The study comprised 25 CF patients with liver cirrhosis and 25 without it. We assessed Z-scores for body height and weight, lung function, exocrine pancreatic sufficiency and colonization with Pseudomonas aeruginosa. FAs' profile of serum glycerophospholipids was quantified by gas chromatography mass spectrometry. In CF patients with liver cirrhosis, the levels of C16:0 were higher and the amounts of C20:2n-6, C20:3n-6, C20:4n-6, and all the n-3 polyunsaturated FAs (PUFAs) (C18:3n-3, C20:5n-3, C22:5n-3, C22:6n-3) were lower than those in CF subjects without liver cirrhosis. The n-6/n-3, C20:4n-6/C18:2n-6, total n-6/C18:2n-6, C20:5n-3/C18:3n-3 and total n-3/C18:3n-3 ratios did not differ between the 2 groups. Liver cirrhosis may associate with profound abnormalities in the composition of serum glycerophospholipids FAs in CF patients. None of the analyzed clinical factors could explain the greater prevalence of low levels of PUFAs in this CF subgroup. © 2017 S. Karger AG, Basel.

Developing new products in cystic fibrosis: needs and obstacles for activities of small and middle-sized companies.

PubMed

Schlangen, Miriam; Reimann, Andreas L G

2011-06-01

Small and middle-sized enterprises (SMEs) can make important contributions to medical progress through the development of new safe and effective drugs that address the greatest unmet needs of patients. Regulatory inconsistencies across agencies in various countries, however, remain major challenges in cystic fibrosis (CF) drug development. Clear and consistent treatment guidelines, well educated clinical trial sites, a patient registry and grant funding for early development programs are important success-factors for an efficient development process. SMEs developing products for CF need partners in the CF community to assist with disease education and awareness for ongoing clinical trials. SMEs should collaborate and communicate with the CF community in a legally compliant way to take a patient-centric approach to drug design, development and administration. Furthermore, they can help to develop educational tools and fund medical education activities to increase the understanding of the underlying defects and mechanisms of CF disease. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Piezonuclear battery

DOEpatents

Bongianni, Wayne L.

1992-01-01

A piezonuclear battery generates output power arising from the piezoelectric voltage produced from radioactive decay particles interacting with a piezoelectric medium. Radioactive particle energy may directly create an acoustic wave in the piezoelectric medium or a moderator may be used to generate collision particles for interacting with the medium. In one embodiment a radioactive material (.sup.252 Cf) with an output of about 1 microwatt produced a 12 nanowatt output (1.2% conversion efficiency) from a piezoelectric copolymer of vinylidene fluoride/trifluorethylene.

Neonatal Injury at Cephalic Vaginal Delivery: A Retrospective Analysis of Extent of Association with Shoulder Dystocia

PubMed Central

Iskender, Cantekin; Kaymak, Oktay; Erkenekli, Kudret; Ustunyurt, Emin; Uygur, Dilek; Yakut, Halil Ibrahim; Danisman, Nuri

2014-01-01

Purpose To describe the risk factors and labor characteristics of Clavicular fracture (CF) and brachial plexus injury (BPI); and compare antenatal and labor characteristics and prognosis of obstetrical BPI associated with shoulder dystocia with obstetrical BPI not associated with shoulder dystocia. Methods This retrospective study consisted of women who gave birth to an infant with a fractured clavicle or BPI between January 2009 and June 2013. Antenatal and neonatal data were compared between groups. The control group (1300) was composed of the four singleton vaginal deliveries that immediately followed each birth injury. A multivariable logistic regression model, with backward elimination, was constructed in order to find independent risk factors associated with BPI and CF. A subgroup analysis involved comparison of features of BPI cases with or without associated shoulder dystocia. Results During the study period, the total number of vaginal deliveries was 44092. The rates of CF, BPI and shoulder dystocia during the study period were 0,6%, 0,16% and 0,29%, respectively. In the logistic regression model, shoulder dystocia, GDM, multiparity, gestational age >42 weeks, protracted labor, short second stage of labor and fetal birth weight greater than 4250 grams increased the risk of CF independently. Shoulder dystocia and protracted labor were independently associated with BPI when controlled for other factors. Among neonates with BPI whose injury was not associated with shoulder dystocia, five (12.2%) sustained permanent injury, whereas one neonate (4.5%) with BPI following shoulder dystocia sustained permanent injury (p = 0.34). Conclusion BPI not associated with shoulder dystocia might have a higher rate of concomitant CF and permanent sequelae. PMID:25144234

Macrophage Migration Inhibitory Factor Enzymatic Activity, Lung Inflammation, and Cystic Fibrosis

PubMed Central

Adamali, Huzaifa; Armstrong, Michelle E.; McLaughlin, Anne Marie; Cooke, Gordon; McKone, Edward; Costello, Christine M.; Gallagher, Charles G.; Leng, Lin; Baugh, John A.; Fingerle-Rowson, Günter; Bucala, Richard J.; McLoughlin, Paul

2012-01-01

Rationale: Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator with unique tautomerase enzymatic activity; the precise function has not been clearly defined. We previously demonstrated that individual patients with cystic fibrosis (CF) who are genetically predisposed to be high MIF producers develop accelerated end-organ injury. Objectives: To characterize the effects of the MIF-CATT polymorphism in patients with CF ex vivo. To investigate the role of MIF’s tautomerase activity in a murine model of Pseudomonas aeruginosa infection. Methods: MIF and tumor necrosis factor (TNF)-α protein levels were assessed in plasma or peripheral blood mononuclear cell (PBMC) supernatants by ELISA. A murine pulmonary model of chronic Pseudomonas infection was used in MIF wild-type mice (mif+/+) and in tautomerase-null, MIF gene knockin mice (mif P1G/P1G). Measurements and Main Results: MIF protein was measured in plasma and PBMCs from 5- and 6-CATT patients with CF; LPS-induced TNF-α production from PBMCs was also assessed. The effect of a specific inhibitor of MIF-tautomerase activity, ISO-1, was investigated in PBMCs. In the murine infection model, total weight loss, differential cell counts, bacterial load, and intraacinar airspace/tissue volume were measured. MIF and TNF-α levels were increased in 6-CATT compared with 5-CATT patients with CF. LPS-induced TNF-α production from PBMCs was attenuated in the presence of ISO-1. In a murine model of Pseudomonas infection, significantly less pulmonary inflammation and bacterial load was observed in mifP1G/P1G compared with mif+/+ mice. Conclusions: MIF-tautomerase activity may provide a novel therapeutic target in patients with chronic inflammatory diseases such as CF, particularly those patients who are genetically predisposed to produce increased levels of this cytokine. PMID:22592805

GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS

PubMed Central

Bartlett, Jaclyn R.; Friedman, Kenneth J.; Ling, Simon C.; Pace, Rhonda G.; Bell, Scott C.; Bourke, Billy; Castaldo, Giuseppe; Castellani, Carlo; Cipolli, Marco; Colombo, Carla; Colombo, John L.; Debray, Dominique; Fernandez, Adriana; Lacaille, Florence; Macek, Milan; Rowland, Marion; Salvatore, Francesco; Taylor, Christopher J.; Wainwright, Claire; Wilschanski, Michael; Zemková, Dana; Hannah, William B.; Phillips, M. James; Corey, Mary; Zielenski, Julian; Dorfman, Ruslan; Wang, Yunfei; Zou, Fei; Silverman, Lawrence M.; Drumm, Mitchell L.; Wright, Fred A.; Lange, Ethan M.; Durie, Peter R.; Knowles, Michael R.

2013-01-01

Context A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension. Objective To assess whether any of 9 polymorphisms in 5 candidate genes (SERPINA1, ACE, GSTP1, MBL2, and TGFB1) are associated with severe liver disease in CF patients. Design, Setting, and Participants A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls. Main Outcome Measures We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD. Results The initial study showed CFLD to be associated with the SERPINA1 (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10−6; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (TGFB1) codon 10 CC genotype (P=2.8×10−3; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the SERPINA1 Z allele (P=1.4×10−3; OR 3.42, CI 1.54–7.59), but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (P=1.5×10−8; OR 5.04, CI 2.88–8.83). Conclusion The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension. PMID:19738092

Comparative Profiling and Discovery of Novel Glycosylated Mycosporine-Like Amino Acids in Two Strains of the Cyanobacterium Scytonema cf. crispum

PubMed Central

Mazmouz, Rabia; Pickford, Russell; Puranik, Pravin R.

2016-01-01

ABSTRACT The mycosporine-like amino acids (MAAs) are a group of small molecules with a diverse ecological distribution among microorganisms. MAAs have a range of physiological functions, including protection against UV radiation, making them important from a biotechnological perspective. In the present study, we identified a putative MAA (mys) gene cluster in two New Zealand isolates of Scytonema cf. crispum (UCFS10 and UCFS15). Homology to “Anabaena-type” mys clusters suggested that this cluster was likely to be involved in shinorine biosynthesis. Surprisingly, high-performance liquid chromatography analysis of S. cf. crispum cell extracts revealed a complex MAA profile, including shinorine, palythine-serine, and their hexose-bound variants. It was hypothesized that a short-chain dehydrogenase (UCFS15_00405) encoded by a gene adjacent to the S. cf. crispum mys cluster was responsible for the conversion of shinorine to palythine-serine. Heterologous expression of MysABCE and UCFS15_00405 in Escherichia coli resulted in the exclusive production of the parent compound shinorine. Taken together, these results suggest that shinorine biosynthesis in S. cf. crispum proceeds via an Anabaena-type mechanism and that the genes responsible for the production of other MAA analogues, including palythine-serine and glycosylated analogues, may be located elsewhere in the genome. IMPORTANCE Recently, New Zealand isolates of S. cf. crispum were linked to the production of paralytic shellfish toxins for the first time, but no other natural products from this species have been reported. Thus, the species was screened for important natural product biosynthesis. The mycosporine-like amino acids (MAAs) are among the strongest absorbers of UV radiation produced in nature. The identification of novel MAAs is important from a biotechnology perspective, as these molecules are able to be utilized as sunscreens. This study has identified two novel MAAs that have provided several new avenues of future research related to MAA genetics and biosynthesis. Further, we have revealed that the genetic basis of MAA biosynthesis may not be clustered on the genome. The identification of the genes responsible for MAA biosynthesis is vital for future genetic engineering. PMID:27474710

Direct measurements of rate coefficients for thermal decomposition of CF3I using shock—tube ARAS technique

NASA Astrophysics Data System (ADS)

Bystrov, N. S.; Emelianov, A. V.; Eremin, A. V.; Yatsenko, P. I.

2018-05-01

The kinetics of the dissociation of CF3I behind shock waves was experimentally investigated. The reaction CF3I  +  Ar  →  CF3  +  I  +  Ar was studied at temperatures between 900 and 1250 K and pressures of 2–3 bar. For this purpose, the time profiles of the concentration of atomic iodine were measured using a highly sensitive atomic resonance absorption spectroscopy method at a wavelength of 183.04 nm. From these data, the experimental value of the dissociation rate constant of CF3I was obtained: . We found that the investigated range of pressures and temperatures for the CF3I dissociation lies in the pressure transition region. Based on the Rice-Ramsperger–Kassel–Marcus theory, the threshold high and low-pressure rate constants ( and k 0) and falloff curves are calculated for the temperatures of 950–1200 K. As a result of this calculation, the threshold rate constants could be evaluated in the forms: and , and the center broadening factor, which takes into account the contribution of strong and weak collisions in the transition region, is .

Exposure to traumatic events at work, posttraumatic symptoms and professional quality of life among midwives.

PubMed

Cohen, Ran; Leykin, Dmitry; Golan-Hadari, Dita; Lahad, Mooli

2017-07-01

in their line of duty, midwives are often exposed to traumatic births that may lead to symptoms of compassion fatigue (CF), which includes burnout (BO) and secondary traumatic stress (STS).Conversely, midwives derive pleasure and great satisfaction in seeing the positive effect they have on their clients. This experience is known as compassion satisfaction (CS). Together, CS and CF comprise the professional quality of life (ProQOL). The aim of this paper was to study midwives' professional quality of life and traumatic experiences. The highly stressful environment of midwives may also include primary exposure to traumatic experiences and therefore PTSD levels were also assessed. the participants (N=93) were professional midwives from four medical centers in Israel. The participants answered selfreport questionnaires that assessed their ProQOL and PTSD symptoms. results indicated relatively high levels of CS which may mitigate, at least to some degree, the negative aspects of CF. PTSD levels significantly and positively correlated with STS and BO. Sixteen per cent presented with PTSD symptoms of clinical significance. Also, seniority was significantly and positively correlated with BO and PTSD symptoms. high ProQOL was found amongst the participants, with more than 74% scoring on the high range of CS. Nevertheless, we recommend further research and implementing strategies to maintain or further enhance CS and decrease CF levels. Finally, a more comprehensive understanding of the development of PTSD amongst midwives is vital in order to minimize its occurrence in the future. Copyright © 2017 Elsevier Ltd. All rights reserved.

Confronting Compassion Fatigue: Assessment and Intervention in Inpatient Oncology
.

PubMed

Zajac, Lisa M; Moran, Katherine J; Groh, Carla J

2017-08-01

A notable variation among patient satisfaction scores with nursing care was identified. Contributing factors were examined and revealed significant negative correlations between the unit death rate and surviving patients' satisfaction scores. Compassion fatigue (CF) was hypothesized to be a major contributing factor.
. The objective was to address CF in RNs and oncology care associates (assistive personnel) by developing an intervention to provide bereavement support to staff after patient deaths.
. A mixed-methods sequential design was used. Instruments included the Professional Quality of Life scale and Press Ganey survey results. Univariate descriptive statistics, frequencies, an independent t test, and an analysis of covariance were used for data analysis.
. The preintervention results revealed average compassion satisfaction and secondary traumatic stress scores and low burnout scores. No significant difference was noted between pre- and postintervention CF scores. Patients' perception of nurses' skills improved significantly in the second quarter of 2015.

Impact of low concentration factor microfiltration on milk component recovery and Cheddar cheese yield.

PubMed

Neocleous, M; Barbano, D M; Rudan, M A

2002-10-01

The effect of microfiltration (MF) on the composition of Cheddar cheese, fat, crude protein (CP), calcium, total solids recovery, and Cheddar cheese yield efficiency (i.e., composition adjusted yield divided by theoretical yield) was determined. Raw skim milk was microfiltered twofold using a 0.1-microm ceramic membrane at 50 degrees C. Four vats of cheese were made in one day using milk at lx, 1.26x, 1.51x, and 1.82x concentration factor (CF). An appropriate amount of cream was added to achieve a constant casein (CN)-to-fat ratio across treatments. Cheese manufacture was repeated on four different days using a randomized complete block design. The composition of the cheese was affected by MF. Moisture content of the cheese decreased with increasing MF CF. Standardization of milk to a constant CN-to-fat ratio did not eliminate the effect of MF on cheese moisture content. Fat recovery in cheese was not changed by MF. Separation of cream prior to MF, followed by the recombination of skim or MF retentate with cream resulted in lower fat recovery in cheese for control and all treatments and higher fat loss in whey when compared to previous yield experiments, when control Cheddar cheese was made from unseparated milk. Crude protein, calcium, and total solids recovery in cheese increased with increasing MF CF, due to partial removal of these components prior to cheese making. Calcium and calcium as a percentage of protein increased in the cheese, suggesting an increase in calcium retention in the cheese with increasing CF. While the actual and composition adjusted cheese yields increased with increasing MF CF, as expected, there was no effect of MF CF on cheese yield efficiency.

A Cell Number Counting Factor Regulates Akt/Protein Kinase B To Regulate Dictyostelium discoideum Group Size

PubMed Central

Gao, Tong; Knecht, David; Tang, Lei; Hatton, R. Diane; Gomer, Richard H.

2004-01-01

Little is known about how individual cells can organize themselves to form structures of a given size. During development, Dictyostelium discoideum aggregates in dendritic streams and forms groups of ∼20,000 cells. D. discoideum regulates group size by secreting and simultaneously sensing a multiprotein complex called counting factor (CF). If there are too many cells in a stream, the associated high concentration of CF will decrease cell-cell adhesion and increase cell motility, causing aggregation streams to break up. The pulses of cyclic AMP (cAMP) that mediate aggregation cause a transient translocation of Akt/protein kinase B (Akt/PKB) to the leading edge of the plasma membrane and a concomitant activation of the kinase activity, which in turn stimulates motility. We found that countin− cells (which lack bioactive CF) and wild-type cells starved in the presence of anticountin antibodies (which block CF activity) showed a decreased level of cAMP-stimulated Akt/PKB membrane translocation and kinase activity compared to parental wild-type cells. Recombinant countin has the bioactivity of CF, and a 1-min treatment of cells with recombinant countin potentiated Akt/PKB translocation to membranes and Akt/PKB activity. Western blotting of total cell lysates indicated that countin does not affect the total level of Akt/PKB. Fluorescence microscopy of cells expressing an Akt/PKB pleckstrin homology domain-green fluorescent protein (PH-GFP) fusion protein indicated that recombinant countin and anti-countin antibodies do not obviously alter the distribution of Akt/PKB PH-GFP when it translocates to the membrane. Our data indicate that CF increases motility by potentiating the cAMP-stimulated activation and translocation of Akt/PKB. PMID:15470246

Differentially expressed circulating microRNAs in the development of acute diabetic Charcot foot.

PubMed

Pasquier, Jennifer; Ramachandran, Vimal; Abu-Qaoud, Moh'd Rasheed; Thomas, Binitha; Benurwar, Manasi J; Chidiac, Omar; Hoarau-Véchot, Jessica; Robay, Amal; Fakhro, Khalid; Menzies, Robert A; Jayyousi, Amin; Zirie, Mahmoud; Al Suwaidi, Jassim; Malik, Rayaz A; Talal, Talal K; Najafi-Shoushtari, Seyed Hani; Rafii, Arash; Abi Khalil, Charbel

2018-06-05

Charcot foot (CF) is a rare complication of Type 2 diabetes (T2D). We assessed circulating miRNAs in 17 patients with T2D and acute CF (G1), 17 patients with T2D (G2) and equivalent neuropathy and 17 patients with T2D without neuropathy (G3) using the high-throughput miRNA expression profiling. 51 significantly deregulated miRNAs were identified in G1 versus G2, 37 in G1 versus G3 and 64 in G2 versus G3. Furthermore, we demonstrated that 16 miRNAs differentially expressed between G1 versus G2 could be involved in osteoclastic differentiation. Among them, eight are key factors involved in CF pathophysiology. Our data reveal that CF patients exhibit an altered expression profile of circulating miRNAs.

Freshwater Sediment Characterization Factors of Copper Oxide Nanoparticles

NASA Astrophysics Data System (ADS)

Pu, Yubing; Laratte, Bertrand; Ionescu, Rodica Elena

2017-01-01

Wide use of engineered nanoparticles (ENPs) is likely to result in the eventually accumulation of ENPs in sediment. The benthic organisms living in sediments may suffer relatively high toxic effects of ENPs. This study has selected copper oxide nanoparticles (nano-CuO) as a research object. To consider the impacts of spatial heterogeneity on ENPs toxicity, the characterization factor (CF) derived from life cycle assessment (LCA) methodology is used as an indicator in this study. A nano-specific fate model has been used to calculate the freshwater sediment fate factor (FF) of nano-CuO. A literature survey of the nano-CuO toxicology values has been performed to calculate the effect factor (EF). Seventeen freshwater sediment CFs of nano-CuO are proposed as recommended values for subcontinental regions. The region most likely to be affected by nano-CuO is northern Australia (CF of 21.01·103 CTUe, comparative toxic units) and the least likely is northern Europe and northern Canada (CF of 8.55·103 CTUe). These sediment CFs for nano-CuO could be used in the future when evaluating the ecosystem impacts of products containing nano-CuO by LCA method.

Reference intervals and percentiles for carotid-femoral pulse wave velocity in a healthy population aged between 9 and 87 years.

PubMed

Diaz, Alejandro; Zócalo, Yanina; Bia, Daniel; Wray, Sandra; Fischer, Edmundo Cabrera

2018-04-01

There is little information regarding age-related reference intervals (RIs) of carotid-femoral pulse wave velocity (cfPWV) for large healthy populations in South America. The aims of this study were to determine cfPWV RIs and percentiles in a cohort of healthy children, adolescents, and adults and to generate year-to-year percentile curves and body-height percentile curves for children and adolescents. cfPWV was measured in 1722 healthy participants with no cardiovascular risk factors (9-87 years, 60% men). First, RIs were evaluated for males and females through correlation and covariate analysis. Then, mean and standard deviation age-related equations were obtained for cfPWV using parametric regression methods based on fractional polynomials and age-specific (year-to-year) percentile curves that were defined using the standard normal distribution. Age-specific first, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th, and 99th percentile curves were calculated. Finally, height-related cfPWV percentile curves for children and adolescents (<21 years) were established. After adjusting for age and blood pressure differences with respect to females, males showed higher cfPWV levels (6.60 vs 6.45 m/s; P < .01). Thus, specific RIs for males and females were reported. The study provides the largest database to date concerning cfPWV in healthy people from Argentina. Specific RIs and percentiles of cfPWV are now available according to age and sex. Specific percentiles of cfPWV according to body height were reported for people younger than 21 years. ©2018 Wiley Periodicals, Inc.

Exosome and Microvesicle-Enriched Fractions Isolated from Mesenchymal Stem Cells by Gradient Separation Showed Different Molecular Signatures and Functions on Renal Tubular Epithelial Cells.

PubMed

Collino, Federica; Pomatto, Margherita; Bruno, Stefania; Lindoso, Rafael Soares; Tapparo, Marta; Sicheng, Wen; Quesenberry, Peter; Camussi, Giovanni

2017-04-01

Several studies have suggested that extracellular vesicles (EVs) released from mesenchymal stem cells (MSCs) may mediate MSC paracrine action on kidney regeneration. This activity has been, at least in part, ascribed to the transfer of proteins/transcription factors and different RNA species. Information on the RNA/protein content of different MSC EV subpopulations and the correlation with their biological activity is currently incomplete. The aim of this study was to evaluate the molecular composition and the functional properties on renal target cells of MSC EV sub-populations separated by gradient floatation. The results demonstrated heterogeneity in quantity and composition of MSC EVs. Two peaks of diameter were observed (90-110 and 170-190 nm). The distribution of exosomal markers and miRNAs evaluated in the twelve gradient fractions showed an enrichment in fractions with a flotation density of 1.08-1.14 g/mL. Based on this observation, we evaluated the biological activity on renal cell proliferation and apoptosis resistance of low (CF1), medium (CF2) and high (CF3) floatation density fractions. EVs derived from all fractions, were internalized by renal cells, CF1 and CF2 but not CF3 fraction stimulated significant cell proliferation. CF2 also inhibited apoptosis on renal tubular cells submitted to ischemia-reperfusion injury. Comparative miRNomic and proteomic profiles reveal a cluster of miRNAs and proteins common to all three fractions and an enrichment of selected molecules related to renal regeneration in CF2 fraction. In conclusion, the CF2 fraction enriched in exosomal markers was the most active on renal tubular cell proliferation and protection from apoptosis.

Dams, floodplain land use, and riparian forest conservation in the semiarid Upper Colorado River Basin, USA

USGS Publications Warehouse

Andersen, D.C.; Cooper, D.J.; Northcott, K.

2007-01-01

Land and water resource development can independently eliminate riparian plant communities, including Fremont cottonwood forest (CF), a major contributor to ecosystem structure and functioning in semiarid portions of the American Southwest. We tested whether floodplain development was linked to river regulation in the Upper Colorado River Basin (UCRB) by relating the extent of five developed land-cover categories as well as CF and other natural vegetation to catchment reservoir capacity, changes in total annual and annual peak discharge, and overall level of mainstem hydrologic alteration (small, moderate, or large) in 26 fourth-order subbasins. We also asked whether CF appeared to be in jeopardy at a regional level. We classified 51% of the 57,000 ha of alluvial floodplain examined along >2600 km of mainstem rivers as CF and 36% as developed. The proportion developed was unrelated to the level of mainstem hydrologic alteration. The proportion classified as CF was also independent of the level of hydrologic alteration, a result we attribute to confounding effects from development, the presence of time lags, and contrasting effects from flow alteration in different subbasins. Most CF (68% by area) had a sparse canopy (???5% cover), and stands with >50% canopy cover occupied <1% of the floodplain in 15 subbasins. We suggest that CF extent in the UCRB will decline markedly in the future, when the old trees on floodplains now disconnected from the river die and large areas change from CF to non-CF categories. Attention at a basinwide scale to the multiple factors affecting cottonwood patch dynamics is needed to assure conservation of these riparian forests. ?? 2007 Springer Science+Business Media, LLC.

Compressive force induces osteoclast differentiation via prostaglandin E(2) production in MC3T3-E1 cells.

PubMed

Sanuki, Rina; Shionome, Chieko; Kuwabara, Akiko; Mitsui, Narihiro; Koyama, Yuki; Suzuki, Naoto; Zhang, Fan; Shimizu, Noriyoshi; Maeno, Masao

2010-04-01

In orthodontic tooth movement, prostaglandin E(2) (PGE(2)) released from osteoblasts can alter the normal process of bone remodeling. We previously showed that compressive force (CF) controls bone formation by stimulating the production of PGE(2) and Ep2 and/or Ep4 receptors in osteoblasts. The present study was undertaken to examine the effect of CF on the production of PGE(2), cyclooxygenase-2 (COX-2), macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) using osteoblastic MC3T3-E1 cells and to examine the indirect effect of CF on osteoclast differentiation using RAW264.7 cells as osteoclast precursors. MC3T3-E1 cells were cultured with or without continuous CF (1.0 or 3.0 g/cm(2)) for 24 hr, and PGE(2) production was determined using ELISA. The expression of COX-2, M-CSF, RANKL, and OPG genes and proteins was determined using real-time PCR and ELISA, respectively. Osteoclast differentiation was estimated using tartrate-resistant acid phosphatase (TRAP) staining of RAW 264.7 cells cultured for 10 days with conditioned medium from CF-treated MC3T3-E1 cells and soluble RANKL. As CF increased, PGE(2) production and the expression of COX-2, M-CSF, and RANKL increased, whereas OPG expression decreased. The number of TRAP-positive cells increased as CF increased. Celecoxib, a specific inhibitor of COX-2, blocked the stimulatory effect of CF on TRAP staining and the production of PGE(2), M-CSF, RANKL, and OPG. These results suggest that CF induces osteoclast differentiation by increasing M-CSF production and decreasing OPG production via PGE(2) in osteoblasts.

EPAC expression and function in cardiac fibroblasts and myofibroblasts

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

Olmedo, Ivonne; Muñoz, Claudia; Guzmán, Nancy

In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF weremore » treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in cardiac fibroblast. • PKA regulates collagen gel contraction in cardiac myofibroblast.« less

Developing a model for cystic fibrosis sociomicrobiology based on antibiotic and environmental stress.

PubMed

Lopes, Susana Patrícia; Azevedo, Nuno Filipe; Pereira, Maria Olívia

2017-12-01

Cystic fibrosis (CF) infections are invariably biofilm-mediated and polymicrobial, being safe to assume that a myriad of factors affects the sociomicrobiology within the CF infection site and modulate the CF community dynamics, by shaping their social activities, overall functions, virulence, ultimately affecting disease outcome. This work aimed to assess changes in the dynamics (particularly on the microbial composition) of dual-/three-species biofilms involving CF-classical (Pseudomonas aeruginosa) and unusual species (Inquilinus limosus and Dolosigranulum pigrum), according to variable oxygen conditions and antibiotic exposure. Low fluctuations in biofilm compositions were observed across distinct oxygen environments, with dual-species biofilms exhibiting similar relative proportions and P. aeruginosa and/or D. pigrum populations dominating three-species consortia. Once exposed to antibiotics, biofilms displayed high resistance profiles, and microbial compositions, distributions, and microbial interactions significantly challenged. The antibiotic/oxygen environment supported such fluctuations, which enhanced for three-species communities. In conclusion, antibiotic therapy hugely disturbed CF communities' dynamics, inducing significant compositional changes on multispecies consortia. Clearly, multiple perturbations may disturb this dynamic, giving rise to various microbiological scenarios in vivo, and affecting disease phenotype. Therefore, an appreciation of the ecological/evolutionary nature within CF communities will be useful for the optimal use of current therapies and for newer breakthroughs on CF antibiotherapy. Copyright © 2017 Elsevier GmbH. All rights reserved.

Ultra-accurate collaborative information filtering via directed user similarity

NASA Astrophysics Data System (ADS)

Guo, Q.; Song, W.-J.; Liu, J.-G.

2014-07-01

A key challenge of the collaborative filtering (CF) information filtering is how to obtain the reliable and accurate results with the help of peers' recommendation. Since the similarities from small-degree users to large-degree users would be larger than the ones in opposite direction, the large-degree users' selections are recommended extensively by the traditional second-order CF algorithms. By considering the users' similarity direction and the second-order correlations to depress the influence of mainstream preferences, we present the directed second-order CF (HDCF) algorithm specifically to address the challenge of accuracy and diversity of the CF algorithm. The numerical results for two benchmark data sets, MovieLens and Netflix, show that the accuracy of the new algorithm outperforms the state-of-the-art CF algorithms. Comparing with the CF algorithm based on random walks proposed by Liu et al. (Int. J. Mod. Phys. C, 20 (2009) 285) the average ranking score could reach 0.0767 and 0.0402, which is enhanced by 27.3% and 19.1% for MovieLens and Netflix, respectively. In addition, the diversity, precision and recall are also enhanced greatly. Without relying on any context-specific information, tuning the similarity direction of CF algorithms could obtain accurate and diverse recommendations. This work suggests that the user similarity direction is an important factor to improve the personalized recommendation performance.

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease.

PubMed

Ayoub, Fares; Trillo-Alvarez, Cesar; Morelli, Giuseppe; Lascano, Jorge

2018-01-27

To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis (CF) patients with hepatic steatosis as compared to normal CF controls. We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging (ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls. Data was collected on 114 patients meeting inclusion criteria. Seventeen patients (14.9%) were found to have hepatic steatosis on imaging. Being overweight (BMI > 25) ( P = 0.019) and having a higher ppFEV1 (75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level (27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes. Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher ppFEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.

Malabsorption Blood Test: Assessing Fat Absorption in Patients with Cystic Fibrosis and Pancreatic Insufficiency

PubMed Central

Mascarenhas, Maria R.; Mondick, John; Barrett, Jeffrey S.; Wilson, Martha; Stallings, Virginia A.; Schall, Joan I.

2015-01-01

The Malabsorption Blood Test (MBT), consisting of pentadecanoic acid (PA), a free fatty acid and triheptadecanoic acid (THA), a triglyceride that requires pancreatic lipase for absorption of the heptadecanoic acid (HA), was developed to assess fat malabsorption in patients with cystic fibrosis (CF) and pancreatic insufficiency (PI). The objective was to construct a population pharmacokinetic (PK) model to describe PA and HA disposition in healthy subjects and CF subjects. A model was simultaneously fit to PA and HA concentrations, consisting of one compartment disposition and a transit model to describe absorption. PA bioavailability estimates for CF subjects without pancreatic enzyme administration [1.07 (0.827,1.42)] and with enzymes [0.88 (0.72,1.09)] indicated PA absorption comparable to healthy subjects. HA bioavailability in CF without enzyme administration was 0.0292 (0.0192,0.0459), and with enzymes increased to 0.606 (0.482,0.823). In CF, compared to taking enzymes with the MBT, HA bioavailability was further decreased by factors of 0.829 (0.664,0.979) and 0.78 (0.491,1.13) with enzymes taken 30 and 60 minutes after MBT, respectively. The MBT detected differences in fat absorption in subjects with CF with and without enzyme administration and with changes in enzyme timing. Future studies will address application of the MBT in CF and other malabsorption diagnoses. PMID:25689042

Cracking process of Fe-26Cr-1Mo during low cycle corrosion fatigue

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

Wang, J.Q.; Li, J.; Wang, Z.F.

1994-12-01

The corrosion fatigue (CF) life has been divided classically into the initiation'' and propagation'' periods. Usually, the crack initiation process dominates the component lifetime under the low cycle CF condition because the crack propagates rapidly one initiated. Despite much work done on the research of the CF crack initiation mechanisms, however, a full understanding of crack initiation is still lacking. There are some limitations in explaining the CF crack initiation in an aqueous solution using the above four mechanisms individually. And, it is difficult to conduct experiments in which one mechanism along can be examined. Although CF is complicated, itmore » is possible to reproduce a specific experiment condition which will have the dominant factor affecting the CF crack initiation. Once the cracks initiate on the smooth metal surface, their coalescence, micropropagation and macropropagation will take place successively. The initiated cracks propagate first in the range of several grains, and the behavior of the microcrack propagation is different from that of macrocrack propagation. For Fe-26Cr-1Mo ferritic stainless steel, the fundamental research work of straining electrode has been done by many investigators, but the observation of the material surface at different deformation processes has not been reported. In the present study, the detailed observation of the cracking process of the material has been carried out in low cycle CF.« less

FOXO1 content is reduced in cystic fibrosis and increases with IGF-I treatment.

PubMed

Smerieri, Arianna; Montanini, Luisa; Maiuri, Luigi; Bernasconi, Sergio; Street, Maria E

2014-10-08

Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF). The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-), whereas winged helix forkhead (FOX)O1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I) increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes.

Epidemiology of nontuberculous mycobacteria (NTM) amongst individuals with cystic fibrosis (CF).

PubMed

Viviani, Laura; Harrison, Michael J; Zolin, Anna; Haworth, Charles S; Floto, R Andres

2016-09-01

Infection by nontuberculous mycobacteria (NTM) in patients with cystic fibrosis (CF) is often associated with significant morbidity. Limited, conflicting results are published regarding risk factors for pulmonary NTM disease. We analysed factors potentially associated with NTM in a large population of European patients with CF. We investigated associations between presence of NTM and various factors for patients registered in the European Cystic Fibrosis Society Patient Registry. 374 (2.75%) of 13,593 patients studied had at least one positive NTM culture within the study year. Age- and FEV1-adjusted odds of NTM infection was more than 2.5 times higher (95%CI: 1.79; 3.60) in patients infected by Stenotrophomonas maltophilia than in patients not infected (p<0.0001), 2.36 times higher (95%CI: 1.80;3.08) in patients with ABPA than without (p<0.0001), 1.79 times higher (95%CI: 1.34; 2.38) in patients who use bronchodilators than in patients who don't (p<0.0001), 1.49 times higher (95%CI: 1.18; 1.89) in patients who use inhaled antibiotics than in patients who don't (p=0.001), and 1.30 times higher (95%CI: 1.02; 1.66) in patients who use rhDNase than in patients who don't (p=0.032). NTM-positive cultures in individuals with CF are associated with distinct clinical variables. Improved data collection identifying risk factors for NTM infection will allow more focused screening strategies, and influence therapeutic choices and infection control measures in high-risk patients. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Detection of qnrVC6, within a new genetic context, in a NDM-1-producing Citrobacter freundii clinical isolate from Uruguay.

PubMed

Bado, Inés; Ezdra, Romina Papa; Cordeiro, Nicolás; Outeda, Matilde; Caiata, Leticia; García-Fulgueiras, Virginia; Seija, Verónica; Vignoli, Rafael

2018-03-08

The objective of the present study was to characterise the mechanisms underlying quinolone and oxyimino-cephalosporin resistance in a Citrobacter freundii clinical isolate obtained from the ICU in Uruguay's University Hospital. Citrobacter freundii strain CF638 was isolated from a urine culture. Identification and susceptibility testing were performed using the VITEK ® 2 system, and MIC determination and disc diffusion assay, respectively. Resistance genes and mobile genetic elements were identified, by PCR and sequencing. Plasmid transfer was assessed by conjugation; plasmid, size was estimated by treatment with S1 and PFGE. Plasmid incompatibility, group and toxin-antitoxin systems were sought by PCR. Strain CF638 showed a multi-drug resistant profile, including, resistance to carbapenemes and quinolones. Transconjugant TcCF638, harbouring a ∼200 kb IncA/C plasmid, also showed resistance to all β-lactams, (except for aztreonam), and diminished susceptibility to ciprofloxacin. PCR, assays were positive for bla NDM-1 and qnrVC in CF638 and TcCF638. Two different class 1 integrons were detected, In127 and In907. In127, featured the genetic array: aadA2-ltr2. Conversely, complex In907 featured, two variable regions (VR); VR-1 consisted of aadB-bla OXA-10 -aadA1cc, whereas, VR-2, featured a gene qnrVC6 108 bp downstream from the ISCR1 and 45 bp, upstream from the qacEΔ1. Expression of qnrVC6 would be on account of a, putative promoter region, detected using the Neural Network Promoter, Prediction program. To the best of our knowledge this constitutes the first report of a qnrVC gene within a complex class 1 integron, and the first report as well of the occurrence of such gene in an NDM-1-producing enterobacterial clinical isolate. Copyright © 2018. Published by Elsevier Ltd.

Enterococcus faecalis Sex Pheromone cCF10 Enhances Conjugative Plasmid Transfer In Vivo.

PubMed

Hirt, Helmut; Greenwood-Quaintance, Kerryl E; Karau, Melissa J; Till, Lisa M; Kashyap, Purna C; Patel, Robin; Dunny, Gary M

2018-02-13

Cell-cell communication mediated by peptide pheromones (cCF10 [CF]) is essential for high-frequency plasmid transfer in vitro in Enterococcus faecalis To examine the role of pheromone signaling in vivo , we established either a CF-producing (CF+) recipient or a recipient producing a biologically inactive variant of CF (CF- recipient) in a germfree mouse model 3 days before donor inoculation and determined transfer frequencies of the pheromone-inducible plasmid pCF10. Plasmid transfer was detected in the upper and middle sections of the intestinal tract 5 h after donor inoculation and was highly efficient in the absence of antibiotic selection. The transconjugant/donor ratio reached a maximum level approaching 1 on day 4 in the upper intestinal tract. Plasmid transfer was significantly lower with the CF- recipient. While rescue of the CF- mating defect by coculture with CF+ recipients is easily accomplished in vitro , no extracellular complementation occurred in vivo This suggests that most pheromone signaling in the gut occurs between recipient and donor cells in very close proximity. Plasmid-bearing cells (donors plus transconjugants) steadily increased in the population from 0.1% after donor inoculation to about 10% at the conclusion of the experiments. This suggests a selective advantage of pCF10 carriage distinct from antibiotic resistance or bacteriocin production. Our results demonstrate that pheromone signaling is required for efficient pCF10 transfer in vivo In the absence of CF+ recipients, a low level of transfer to CF- recipients occurred in the gut. This may result from low-level host-mediated induction of the donors in the gastrointestinal (GI) tract, similar to that previously observed in serum. IMPORTANCE Horizontal gene transfer is a major factor in the biology of Enterococcus faecalis , an important nosocomial pathogen. Previous studies showing efficient conjugative plasmid transfer in the gastrointestinal (GI) tracts of experimental animals did not examine how the enterococcal sex pheromone response impacts the efficiency of transfer. Our study demonstrates for the first time pheromone-enhanced, high-frequency plasmid transfer of E. faecalis plasmid pCF10 in a mouse model in the absence of antibiotic or bacteriocin selection. Pheromone production by recipients dramatically increased plasmid transfer in germfree mice colonized initially with recipients, followed by donors. The presence of a coresident community of common gut microbes did not significantly reduce in vivo plasmid transfer between enterococcal donors and recipients. In mice colonized with enterococcal recipients, we detected plasmid transfer in the intestinal tract within 5 h of addition of donors, before transconjugants could be cultured from feces. Surprisingly, pCF10 carriage provided a competitive fitness advantage unrelated to antibiotic resistance or bacteriocin production. Copyright © 2018 Hirt et al.

Luminosity and redshift dependence of the covering factor of active galactic nuclei viewed with WISE and Sloan digital sky survey

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

Toba, Y.; Matsuhara, H.; Oyabu, S.

2014-06-10

In this work, we investigate the dependence of the covering factor (CF) of active galactic nuclei (AGNs) on the mid-infrared (MIR) luminosity and the redshift. We constructed 12 and 22 μm luminosity functions (LFs) at 0.006 ≤z ≤ 0.3 using Wide-field Infrared Survey Explorer (WISE) data. Combining the WISE catalog with Sloan Digital Sky Survey (SDSS) spectroscopic data, we selected 223,982 galaxies at 12 μm and 25,721 galaxies at 22 μm for spectroscopic classification. We then identified 16,355 AGNs at 12 μm and 4683 AGNs at 22 μm by their optical emission lines and cataloged classifications in the SDSS. Followingmore » that, we estimated the CF as the fraction of Type 2 AGN in all AGNs whose MIR emissions are dominated by the active nucleus (not their host galaxies) based on their MIR colors. We found that the CF decreased with increasing MIR luminosity, regardless of the choice of Type 2 AGN classification criteria, and the CF did not change significantly with redshift for z ≤ 0.2. Furthermore, we carried out various tests to determine the influence of selection bias and confirmed that similar dependences exist, even when taking these uncertainties into account. The luminosity dependence of the CF can be explained by the receding torus model, but the 'modified' receding torus model gives a slightly better fit, as suggested by Simpson.« less

Vitamin K status in cystic fibrosis patients with liver cirrhosis.

PubMed

Krzyżanowska, Patrycja; Drzymała-Czyż, Sławomira; Pogorzelski, Andrzej; Duś-Żuchowska, Monika; Skorupa, Wojciech; Bober, Lyudmyla; Sapiejka, Ewa; Oralewska, Beata; Rohovyk, Nataliya; Moczko, Jerzy; Nowak, Jan; Wenska-Chyży, Ewa; Rachel, Marta; Lisowska, Aleksandra; Walkowiak, Jarosław

2017-06-01

The available data on the influence of liver cirrhosis on vitamin K status in CF patients is scarce. Therefore, the aims of the present study were to assess the prevalence of vitamin K deficiency in cirrhotic CF subjects and to determine whether it correlates with liver cirrhosis. The study group comprised of 27 CF patients with and 63 without liver cirrhosis. Vitamin K status was assessed using prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). PIVKA-II concentrations were higher in cirrhotic than in non-cirrhotic CF patients (median [1st-3rd quartile]: 3.2ng/ml [1.0-10.0] vs. 1.3ng/ml [0.2-2.6], p=0.0029). However, the differences in u-OC percentages between the studied groups did not reach the level of significance (49.4% [7.0-73.8] vs. 8.0% [2.6-59.1], p=0.0501). Based on multiple linear regression analysis the dose of vitamin K and F508del mutation were potentially defined as determinants of vitamin K deficiency. Liver cirrhosis was not documented to be an independent risk factor. In CF patients with liver cirrhosis vitamin K deficiency is not only more frequent, but also more severe. However, not liver cirrhosis, but the presence of a F508del CFTR mutation constitutes an independent risk factor for vitamin K deficiency. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Lung Transplantation in Cystic Fibrosis and the Impact of Extracorporeal Circulation.

PubMed

Jauregui, Alberto; Deu, Maria; Romero, Laura; Roman, Antonio; Moreno, Antonio; Armengol, Manuel; Solé, Juan

2018-03-10

Lung disease is the major cause of death among cystic fibrosis (CF) patients, affecting 80% of the population. The impact of extracorporeal circulation (ECC) during transplantation has not been fully clarified. This study aimed to evaluate the outcomes of lung transplantation for CF in a single center, and to assess the impact of ECC on survival. We performed a retrospective observational study of all trasplanted CF patients in a single center between 1992 and 2011. During this period, 64 lung transplantations for CF were performed. Five- and 10-year survival of trasplanted patients was 56.7% and 41.3%, respectively. Pre-transplantation supplemental oxygen requirements and non-invasive mechanical ventilation (NIMV) do not seem to affect survival (P=.44 and P=.63, respectively). Five- and 10-year survival among patients who did not undergo ECC during transplantation was 75.69% and 49.06%, respectively, while in those did undergo ECC during the procedure, 5- and 10-year survival was 34.14% and 29.87%, respectively (P=.001). PaCO 2 is an independent risk factor for the need for ECC. The survival rates of CF patients undergoing lung transplantation in our hospital are similar to those described in international registries. Survival is lower among patients receiving ECC during the procedure. PaCO 2 is a risk factor for the need for ECC during lung transplantation. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Analysis of linear energy transfers and quality factors of charged particles produced by spontaneous fission neutrons from 252Cf and 244Pu in the human body.

PubMed

Endo, Akira; Sato, Tatsuhiko

2013-04-01

Absorbed doses, linear energy transfers (LETs) and quality factors of secondary charged particles in organs and tissues, generated via the interactions of the spontaneous fission neutrons from (252)Cf and (244)Pu within the human body, were studied using the Particle and Heavy Ion Transport Code System (PHITS) coupled with the ICRP Reference Phantom. Both the absorbed doses and the quality factors in target organs generally decrease with increasing distance from the source organ. The analysis of LET distributions of secondary charged particles led to the identification of the relationship between LET spectra and target-source organ locations. A comparison between human body-averaged mean quality factors and fluence-averaged radiation weighting factors showed that the current numerical conventions for the radiation weighting factors of neutrons, updated in ICRP103, and the quality factors for internal exposure are valid.

Quantitative analysis of cell-free DNA in ovarian cancer.

PubMed

Shao, Xuefeng; He, Yan; Ji, Min; Chen, Xiaofang; Qi, Jing; Shi, Wei; Hao, Tianbo; Ju, Shaoqing

2015-12-01

The aim of the present study was to investigate the association between cell-free DNA (cf-DNA) levels and clinicopathological characteristics of patients with ovarian cancer using a branched DNA (bDNA) technique, and to determine the value of quantitative cf-DNA detection in assisting with the diagnosis of ovarian cancer. Serum specimens were collected from 36 patients with ovarian cancer on days 1, 3 and 7 following surgery, and additional serum samples were also collected from 22 benign ovarian tumor cases, and 19 healthy, non-cancerous ovaries. bDNA techniques were used to detect serum cf-DNA concentrations. All data were analyzed using SPSS version 18.0. The cf-DNA levels were significantly increased in the ovarian cancer group compared with those of the benign ovarian tumor group and healthy ovarian group (P<0.01). Furthermore, cf-DNA levels were significantly increased in stage III and IV ovarian cancer compared with those of stages I and II (P<0.01). In addition, cf-DNA levels were significantly increased on the first day post-surgery (P<0.01), and subsequently demonstrated a gradual decrease. In the ovarian cancer group, the area under the receiver operating characteristic curve of cf-DNA and the sensitivity were 0.917 and 88.9%, respectively, which was higher than those of cancer antigen 125 (0.724, 75%) and human epididymis protein 4 (0.743, 80.6%). There was a correlation between the levels of serum cf-DNA and the occurrence and development of ovarian cancer in the patients evaluated. bDNA techniques possessed higher sensitivity and specificity than other methods for the detection of serum cf-DNA in patients exhibiting ovarian cancer, and bDNA techniques are more useful for detecting cf-DNA than other factors. Thus, the present study demonstrated the potential value for the use of bDNA as an adjuvant diagnostic method for ovarian cancer.

Diabetes in Cystic Fibrosis: Multicenter Screening Results Based on Current Guidelines

PubMed Central

Scheuing, Nicole; Holl, Reinhard W.; Dockter, Gerd; Fink, Katharina; Junge, Sibylle; Naehrlich, Lutz; Smaczny, Christina; Staab, Doris; Thalhammer, Gabriela; van Koningsbruggen-Rietschel, Silke; Ballmann, Manfred

2013-01-01

Background Published estimates on age-dependent frequency of diabetes in cystic fibrosis (CF) vary widely, and are based mostly on older data. However, CF treatment and prevention of comorbidities changed over recent years. In many studies, definition of cystic fibrosis-related diabetes (CFRD) is not in line with current guideline recommendations. Therefore, we evaluated age-dependent occurrence of glucose abnormalities and associated risk factors in CF patients who participated in a multicenter screening program using oral glucose tolerance tests (OGTT). Methods Between 2001 and 2010, 43 specialized CF centers from Germany and Austria serially performed 5,179 standardized OGTTs in 1,658 clinically stable, non-pregnant CF patients with no prior steroid medication or lung transplantation. Age-dependent occurrence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT, one (DGT) or two consecutive (CFRD) diabetic OGTTs was analyzed, using Kaplan Meier curves. Cox proportional-hazards models were created to elucidate the influence of sex or underweight. Results At baseline/last OGTT, median age was 15.9 years/18.2 years and 30.6%/31.8% of patients were underweight. 25% of patients showed IFG at age 14.3 years; IGT at age 16.3 years; IFG+IGT combined at age 17.7 years. DGT was observed in 25% of patients at age 22.6 years; CFRD at age 34.5 years. Females had a 3.54 [95% CI 1.23–10.18] times higher risk for CFRD; risk for DGT was 2.21 [1.22–3.98] times higher. Underweight was a risk factor for IGT (HR [95% CI]: 1.38 [1.11–1.71]) and IFG+IGT (1.43 [1.11–1.83]), and in males also for DGT (1.49 [1.09–2.04]). Conclusions/Significance If confirmation of diabetes by a second test is required, as recommended in current guidelines, age at CFRD diagnosis was higher compared to most previous studies. However, known risk factors for glucose abnormalities in CF were confirmed. Confirmation of diabetic OGT by a repeat test is important for a consistent diagnosis of CFRD. PMID:24324701

An adaptive beamforming method for ultrasound imaging based on the mean-to-standard-deviation factor.

PubMed

Wang, Yuanguo; Zheng, Chichao; Peng, Hu; Chen, Qiang

2018-06-12

The beamforming performance has a large impact on image quality in ultrasound imaging. Previously, several adaptive weighting factors including coherence factor (CF) and generalized coherence factor (GCF) have been proposed to improved image resolution and contrast. In this paper, we propose a new adaptive weighting factor for ultrasound imaging, which is called signal mean-to-standard-deviation factor (SMSF). SMSF is defined as the mean-to-standard-deviation of the aperture data and is used to weight the output of delay-and-sum (DAS) beamformer before image formation. Moreover, we develop a robust SMSF (RSMSF) by extending the SMSF to the spatial frequency domain using an altered spectrum of the aperture data. In addition, a square neighborhood average is applied on the RSMSF to offer a more smoothed square neighborhood RSMSF (SN-RSMSF) value. We compared our methods with DAS, CF, and GCF using simulated and experimental synthetic aperture data sets. The quantitative results show that SMSF results in an 82% lower full width at half-maximum (FWHM) but a 12% lower contrast ratio (CR) compared with CF. Moreover, the SN-RSMSF leads to 15% and 10% improvement, on average, in FWHM and CR compared with GCF while maintaining the speckle quality. This demonstrates that the proposed methods can effectively improve the image resolution and contrast. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhancement of ionization efficiency of mass spectrometric analysis from non-electrospray ionization friendly solvents with conventional and novel ionization techniques.

PubMed

Jiang, Ping; Lucy, Charles A

2015-10-15

Electrospray ionization mass spectrometry (ESI-MS) has significantly impacted the analysis of complex biological and petroleum samples. However ESI-MS has limited ionization efficiency for samples in low dielectric and low polarity solvents. Addition of a make-up solvent through a T union or electrospray solvent through continuous flow extractive desorption electrospray ionization (CF-EDESI) enable ionization of analytes in non-ESI friendly solvents. A conventional make-up solvent addition setup was used and a CF-EDESI source was built for ionization of nitrogen-containing standards in hexane or hexane/isopropanol. Factors affecting the performance of both sources have been investigated and optimized. Both the make-up solvent addition and CF-EDESI improve the ionization efficiency for heteroatom compounds in non-ESI friendly solvents. Make-up solvent addition provides higher ionization efficiency than CF-EDESI. Neither the make-up solvent addition nor the CF-EDESI eliminates ionization suppression of nitrogen-containing compounds caused by compounds of the same chemical class. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of fiber-matrix adhesion on the creep behavior of CF/PPS composites: temperature and physical aging characterization

NASA Astrophysics Data System (ADS)

Motta Dias, M. H.; Jansen, K. M. B.; Luinge, J. W.; Bersee, H. E. N.; Benedictus, R.

2016-06-01

The influence of fiber-matrix adhesion on the linear viscoelastic creep behavior of `as received' and `surface modified' carbon fibers (AR-CF and SM-CF, respectively) reinforced polyphenylene sulfide (PPS) composite materials was investigated. Short-term tensile creep tests were performed on ±45° specimens under six different isothermal conditions, 40, 50, 60, 65, 70 and 75 °C. Physical aging effects were evaluated on both systems using the short-term test method established by Struik. The results showed that the shapes of the curves were affected neither by physical aging nor by the test temperature, allowing then superposition to be made. A unified model was proposed with a single physical aging and temperature-dependent shift factor, a_{T,te}. It was suggested that the surface treatment carried out in SM-CF/PPS had two major effects on the creep response of CF/PPS composites at a reference temperature of 40 °C: a lowering of the initial compliance of about 25 % and a slowing down of the creep response of about 1.1 decade.

Effects of Consumptive Water Use on Biodiversity in Wetlands of International Importance

PubMed Central

2013-01-01

Wetlands are complex ecosystems that harbor a large diversity of species. Wetlands are among the most threatened ecosystems on our planet, due to human influences such as conversion and drainage. We assessed impacts from water consumption on the species richness of waterbirds, nonresidential birds, water-dependent mammals, reptiles and amphibians in wetlands, considering a larger number of taxa than previous life cycle impact assessment methods. Effect factors (EF) were derived for 1184 wetlands of international importance. EFs quantify the number of global species-equivalents lost per m2 of wetland area loss. Vulnerability and range size of species were included to reflect conservation values. Further, we derived spatially explicit characterization factors (CFs) that distinguish between surface water and groundwater consumption. All relevant watershed areas that are contributing to feeding the respective wetlands were determined for CF applications. In an example of rose production, we compared damages of water consumption in Kenya and The Netherlands. In both cases, the impact was largest for waterbirds. The total impact from water consumption in Kenya was 67 times larger than in The Netherlands, due to larger species richness and species’ vulnerability in Kenya, as well as more arid conditions and larger amounts of water consumed. PMID:24087849

Effects of consumptive water use on biodiversity in wetlands of international importance.

PubMed

Verones, Francesca; Saner, Dominik; Pfister, Stephan; Baisero, Daniele; Rondinini, Carlo; Hellweg, Stefanie

2013-01-01

Wetlands are complex ecosystems that harbor a large diversity of species. Wetlands are among the most threatened ecosystems on our planet, due to human influences such as conversion and drainage. We assessed impacts from water consumption on the species richness of waterbirds, nonresidential birds, water-dependent mammals, reptiles and amphibians in wetlands, considering a larger number of taxa than previous life cycle impact assessment methods. Effect factors (EF) were derived for 1184 wetlands of international importance. EFs quantify the number of global species-equivalents lost per m(2) of wetland area loss. Vulnerability and range size of species were included to reflect conservation values. Further, we derived spatially explicit characterization factors (CFs) that distinguish between surface water and groundwater consumption. All relevant watershed areas that are contributing to feeding the respective wetlands were determined for CF applications. In an example of rose production, we compared damages of water consumption in Kenya and The Netherlands. In both cases, the impact was largest for waterbirds. The total impact from water consumption in Kenya was 67 times larger than in The Netherlands, due to larger species richness and species' vulnerability in Kenya, as well as more arid conditions and larger amounts of water consumed.

Measurements of intracellular calcium signals in polarized primary cultures of normal and cystic fibrosis human airway epithelia.

PubMed

Ribeiro, Carla M P

2011-01-01

The airways are continuously challenged by a variety of stimuli including bacteria, viruses, allergens, and inflammatory factors that act as agonists for G protein-coupled receptors (GPCR). Intracellular calcium (Ca(2+) (i)) mobilization in airway epithelia in response to extracellular stimuli regulates key airway innate defense functions, e.g., Ca(2+)-activated Cl(-) secretion, ciliary beating, mucin secretion, and inflammatory responses. Because Ca(2+) (i) mobilization in response to luminal stimuli is larger in CF vs. normal human airway epithelia, alterations in Ca(2+) (i) signals have been associated with the pathogenesis of CF airway disease. Hence, assessment of Ca(2+) (i) signaling has become an important area of CF research. This chapter will focus on measurements of cytoplasmic and mitochondrial Ca(2+) signals resulting from GPCR activation in polarized primary cultures of normal and CF human bronchial epithelia (HBE).

Ecological Risk Assessment of Metals Contamination in the Sediments of Natural Urban Wetlands in Dry Tropical Climate.

PubMed

Rana, Vivek; Maiti, Subodh Kumar; Jagadevan, Sheeja

2016-09-01

The pollution load due to metal contamination in the sediments of urban wetlands (Dhanbad, India) due to illegal release of domestic and industrial wastewater was studied by using various geochemical indices, such as contamination factor (Cf), degree of contamination (Cd), modified degree of contamination (mCd), pollution load index (PLI) and geoaccumulation index (Igeo) for Cu, Co, Cd, Cr and Mn. Cluster analysis (CA) and Principal component analysis (PCA) of metals present in wetland sediments were carried out to assess their origin and relationship with each other. The Cf values for different metals in the wetlands under investigation indicated low to very high level of pollution (Cf ranged between 0.02 and 14.15) with highest Cf (14.15) for Cd. The wetland receiving both domestic and industrial wastewater had the highest values of Cd, mCd and PLI as 17.48, 3.49 and 1.03 respectively.

Infection in cystic fibrosis: impact of the environment and climate.

PubMed

Ramsay, K A; Stockwell, R E; Bell, S C; Kidd, T J

2016-01-01

In many countries numbers of adults with cystic fibrosis (CF) exceed that of children, with median survival predicted to surpass 50 years. Increasing longevity is, in part, due to intensive therapies including eradication of early infection and suppressive therapies and pulmonary exacerbations. Initial infections with common CF pathogens are thought to arise from the natural environment. We review the impact of climate and environment on infection in CF. Specifically, several studies indicate that higher ambient temperatures, proximity to the equator and the summer season may be linked to the increased prevalence of Pseudomonas aeruginosa in people with CF. The environment may also play an important role in the acquisition of Gram negative organisms other than P. aeruginosa. There is emerging data suggesting that climatic and environmental factors are likely to impact on the risk of infection with NTM and fungi in people which are found extensively throughout the natural environment.

Methodological Variables in the Analysis of Cell-Free DNA.

PubMed

Bronkhorst, Abel Jacobus; Aucamp, Janine; Pretorius, Piet J

2016-01-01

In recent years, cell-free DNA (cfDNA) analysis has received increasing amounts of attention as a potential non-invasive screening tool for the early detection of genetic aberrations and a wide variety of diseases, especially cancer. However, except for some prenatal tests and BEAMing, a technique used to detect mutations in various genes of cancer patients, cfDNA analysis is not yet routinely applied in clinical practice. Although some confusing biological factors inherent to the in vivo setting play a key part, it is becoming increasingly clear that this struggle is mainly due to the lack of an analytical consensus, especially as regards quantitative analyses of cfDNA. In order to use quantitative analysis of cfDNA with confidence, process optimization and standardization are crucial. In this work we aim to elucidate the most confounding variables of each preanalytical step that must be considered for process optimization and equivalence of procedures.

Development and evaluation of event-specific quantitative PCR method for genetically modified soybean A2704-12.

PubMed

Takabatake, Reona; Akiyama, Hiroshi; Sakata, Kozue; Onishi, Mari; Koiwa, Tomohiro; Futo, Satoshi; Minegishi, Yasutaka; Teshima, Reiko; Mano, Junichi; Furui, Satoshi; Kitta, Kazumi

2011-01-01

A novel real-time PCR-based analytical method was developed for the event-specific quantification of a genetically modified (GM) soybean event; A2704-12. During the plant transformation, DNA fragments derived from pUC19 plasmid were integrated in A2704-12, and the region was found to be A2704-12 specific. The pUC19-derived DNA sequences were used as primers for the specific detection of A2704-12. We first tried to construct a standard plasmid for A2704-12 quantification using pUC19. However, non-specific signals appeared with both qualitative and quantitative PCR analyses using the specific primers with pUC19 as a template, and we then constructed a plasmid using pBR322. The conversion factor (C(f)), which is required to calculate the amount of the genetically modified organism (GMO), was experimentally determined with two real-time PCR instruments, the Applied Biosystems 7900HT and the Applied Biosystems 7500. The determined C(f) values were both 0.98. The quantitative method was evaluated by means of blind tests in multi-laboratory trials using the two real-time PCR instruments. The limit of quantitation for the method was estimated to be 0.1%. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSD(R)), and the determined bias and RSD(R) values for the method were each less than 20%. These results suggest that the developed method would be suitable for practical analyses for the detection and quantification of A2704-12.

Selection of Suitable DNA Extraction Methods for Genetically Modified Maize 3272, and Development and Evaluation of an Event-Specific Quantitative PCR Method for 3272.

PubMed

Takabatake, Reona; Masubuchi, Tomoko; Futo, Satoshi; Minegishi, Yasutaka; Noguchi, Akio; Kondo, Kazunari; Teshima, Reiko; Kurashima, Takeyo; Mano, Junichi; Kitta, Kazumi

2016-01-01

A novel real-time PCR-based analytical method was developed for the event-specific quantification of a genetically modified (GM) maize, 3272. We first attempted to obtain genome DNA from this maize using a DNeasy Plant Maxi kit and a DNeasy Plant Mini kit, which have been widely utilized in our previous studies, but DNA extraction yields from 3272 were markedly lower than those from non-GM maize seeds. However, lowering of DNA extraction yields was not observed with GM quicker or Genomic-tip 20/G. We chose GM quicker for evaluation of the quantitative method. We prepared a standard plasmid for 3272 quantification. The conversion factor (Cf), which is required to calculate the amount of a genetically modified organism (GMO), was experimentally determined for two real-time PCR instruments, the Applied Biosystems 7900HT (the ABI 7900) and the Applied Biosystems 7500 (the ABI7500). The determined Cf values were 0.60 and 0.59 for the ABI 7900 and the ABI 7500, respectively. To evaluate the developed method, a blind test was conducted as part of an interlaboratory study. The trueness and precision were evaluated as the bias and reproducibility of the relative standard deviation (RSDr). The determined values were similar to those in our previous validation studies. The limit of quantitation for the method was estimated to be 0.5% or less, and we concluded that the developed method would be suitable and practical for detection and quantification of 3272.

Lung Infections Associated with Cystic Fibrosis

PubMed Central

Lyczak, Jeffrey B.; Cannon, Carolyn L.; Pier, Gerald B.

2002-01-01

While originally characterized as a collection of related syndromes, cystic fibrosis (CF) is now recognized as a single disease whose diverse symptoms stem from the wide tissue distribution of the gene product that is defective in CF, the ion channel and regulator, cystic fibrosis transmembrane conductance regulator (CFTR). Defective CFTR protein impacts the function of the pancreas and alters the consistency of mucosal secretions. The latter of these effects probably plays an important role in the defective resistance of CF patients to many pathogens. As the modalities of CF research have changed over the decades from empirical histological studies to include biophysical measurements of CFTR function, the clinical management of this disease has similarly evolved to effectively address the ever-changing spectrum of CF-related infectious diseases. These factors have led to the successful management of many CF-related infections with the notable exception of chronic lung infection with the gram-negative bacterium Pseudomonas aeruginosa. The virulence of P. aeruginosa stems from multiple bacterial attributes, including antibiotic resistance, the ability to utilize quorum-sensing signals to form biofilms, the destructive potential of a multitude of its microbial toxins, and the ability to acquire a mucoid phenotype, which renders this microbe resistant to both the innate and acquired immunologic defenses of the host. PMID:11932230

Effects of continuous and pulsatile flows generated by ventricular assist devices on renal function and pathology.

PubMed

Miyamoto, Takuma; Karimov, Jamshid H; Fukamachi, Kiyotaka

2018-03-01

Continuous-flow (CF) left ventricular assist devices (LVADs) are widely used to treat end-stage heart failure. Despite substantial improvement in clinical results, numerous complications remain associated with this technology. Worsening renal function is one, associated with morbidity and mortality in patients supported by CF LVADs. The effects of CF LVAD support on renal function have been investigated since the mid-1990s by many research groups. Area covered: We review the current status of LVAD therapy, experimental results regarding the effects of types of flow generated by LVADs on renal function and pathology, changes in renal function after LVAD implant, the influence of renal function on outcomes, and risk factors for renal dysfunction post implant. This information was obtained through online databases and direct extraction of single studies. Expert commentary: Immediately after CF LVAD implantation, renal function improves temporarily as patients recover from the kidneys' previously low perfusion and congestive state. However, many studies have shown that this initially recovered renal function gradually declines during long-term CF LVAD support. Although it is known that CF LVAD support adversely affects renal function over the long term, just how it does has not yet been clearly defined in terms of clinical symptoms or signs.

Fungal infections and treatment in cystic fibrosis.

PubMed

Middleton, Peter G; Chen, Sharon C-A; Meyer, Wieland

2013-11-01

This review summarizes some of the important recent findings concerning fungal airway infections in patients with cystic fibrosis (CF). For many years, both researchers and clinicians have focused on the problems in CF caused by chronic bacterial airway infection with organisms such as Haemophilus, Staphylococcus and Pseudomonas. However, until recently, the lack of sensitive culture techniques to isolate fungi in sputum, bronchoalveolar lavage fluid and other respiratory tract samples has limited the recognition of fungal species and their possible role in CF airway infections. Recent studies using fungal-selective culture media and molecular techniques have shown a plethora of different fungal species in the sputum expectorated from CF patients. Cross-sectional studies have shown associations between Aspergillus and Candida in the sputum and worse lung function. The presence of allergic bronchopulmonary aspergillosis is likely to be a negative prognostic factor, but whether simple fungal colonization itself indicates future problems is not clear. Current research is now examining these epidemiological associations to try to determine the clinical implications. This will help determine whether fungal colonization/infection is associated with worse outcome in CF patients. At present, there is no conclusive evidence that fungal organisms cause respiratory decline. Recent studies of antifungal therapy in CF patients have reported differing results, so further investigations in this area are needed.

An assessment of potential impact of alternative fluorocarbons on tropospheric ozone

NASA Technical Reports Server (NTRS)

Niki, Hiromi

1990-01-01

While the chlorofuorocarbons (CFCs) such as CFC-11 (CFCl3) and CFC-12 (CF2Cl2) are chemically inert in the troposphere, the hydrogen-containing halocarbons being considered as their replacements can, to a large extent, be removed in the troposphere by the HO radical. These alternative halocarbons include the hydrochlorofluorocarbons (HCFCs) 123 (CF3CHCl2), 141b (CFCl2CH3), 142b (CF2ClCH3), 22 (CHF2Cl), and 124 (CF3CHFCl) and the hydrofluorocarbons (HCFs) 134a (CF3CH2F), 152a (CHF2CH3) and 125 (CF3CHF2). Listed are the rate constants (k) for the HO radical reaction of these compounds and their estimated chemical lifetimes in the troposphere. In this table, values of the lifetimes of these selected HCFCs and HCFs are seen to vary by more than a factor of more than ten ranging from 1.6 years for HFC 152a and HCFC 125 to as long as 28 years for HFC 125. Clearly, from the standpoint of avoiding or minimizing impact on stratospheric O3, those halocarbons with short tropospheric lifetimes are the desirable alternates. However, potential environmental consequences of their degradation in the troposphere should be assessed and taken into account in the selection process.

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease

PubMed Central

Ayoub, Fares; Trillo-Alvarez, Cesar; Morelli, Giuseppe; Lascano, Jorge

2018-01-01

AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis (CF) patients with hepatic steatosis as compared to normal CF controls. METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging (ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls. RESULTS Data was collected on 114 patients meeting inclusion criteria. Seventeen patients (14.9%) were found to have hepatic steatosis on imaging. Being overweight (BMI > 25) (P = 0.019) and having a higher ppFEV1 (75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level (27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes. CONCLUSION Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher ppFEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis. PMID:29399276

Modeling cystic fibrosis disease progression in patients with the rare CFTR mutation P67L.

PubMed

MacKenzie, Isobel E R; Paquette, Valerie; Gosse, Frances; George, Sheenagh; Chappe, Frederic; Chappe, Valerie

2017-05-01

The progression of cystic fibrosis (CF) in patients with the rare mutation P67L was examined to determine if it induced a milder form of CF compared to the common severe ΔF508 mutation. Parameters of lung function, level of bacterial infection, nutritional status and hospitalization were used to represent CF progression. Age at diagnosis and pancreatic status were used to assess CF presentation. Analysis of data from the CF Canada Registry collected over a 15-year period included 266 ΔF508/ΔF508 homozygote patients from CF clinics in Atlantic Canada and 26 compound heterozygote patients with the rare P67L mutation from clinics across Canada. Late age at diagnosis, high incidence of pancreatic sufficiency, maintained Body Mass Index (BMI) with age, delayed life-threatening bacterial infection, and fewer days in hospital were observed for P67L heterozygote patients included in this study. Although the decline of lung function did not differ from ΔF508 homozygotes, the fact that a greater proportion of P67L heterozygotes live to an older age suggests that lung function is not the primary factor determining CF progression for P67L heterozygote patients. The P67L mutation is associated with a mild disease, even when combined with the severe ΔF508 mutation. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Effects of different diets on the dietary attractability and selectivity of Chinese shrimp, Fenneropenaeus chinensis

NASA Astrophysics Data System (ADS)

Huang, Guoqiang; Dong, Shuanglin; Wang, Fang

2005-01-01

Attractabilities of different diets and dietary selectivity of Chinese shrimp, Fenneropenaeus chinensis were studied through behavior observation and feeding experiment, respectively. The five diets used in the experiment are: Fish Flesh (FF), Shrimp Flesh (SF), Clam Foot (CF), Polychaete Worm (PW), and Formulated Diet (FD). No significant differences of attractability exist between any two different diets when every two natural diets or all five diets are provided simultaneously. On the other hand, significant differences of attractability exist between FD and every single natural diet when they are provided simultaneously. Results of behavioral observation indicate that natural diets are more attractive than FD. In feeding experiment, Chinese shrimp has distinct selectivity on different diets. It positively selects CF and PW, negatively selects FF and SF, and excludes FD absolutely. The results of the present studies indicate that the dietary selectivity of shrimp was based not only on the attractabilities of the diets, but also on the responses such as growth and food conversion.

[Insights into cystic fibrosis-related bone disease].

PubMed

Braun, C; Bacchetta, J; Reix, P

2016-08-01

With the increasing life expectancy of patients with cystic fibrosis (CF), prevalence of late complications such as CF-related bone disease (CFBD) has increased. It was initially described in 24% of the adult population with CF and has also been reported in the pediatric population. CFBD is multifactorial and progresses in different steps. Both decreased bone formation and increased bone resorption (in different amounts) are observed. CFBD is likely primitive (directly related to the CFTR defect itself), but is also worsened by acquired secondary factors such as lung infections, chronic inflammation, denutrition, vitamin deficiency, and decreased physical activity. CFBD may be clinically apparent (i.e., mainly vertebral and costal fractures), or clinically asymptomatic (therefore corresponding to abnormalities in bone density and architecture). CFBD management mainly aims to prevent the occurrence of fractures. Prevention and regular monitoring of bone disease as early as 8 years of age is of the utmost importance, as is the control of possible secondary deleterious CFBD factors. New radiological tools, such as high-resolution peripheral quantitative computed tomography, allow an accurate evaluation of cortical and trabecular bone micro-architecture in addition to compartmental density; as such, they will likely improve the assessment of the bone fracture threat in CF patients in the near future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Modifier genes in Mendelian disorders: the example of cystic fibrosis

PubMed Central

Cutting, Garry R.

2011-01-01

In the past three decades, scientists have had immense success in identifying genes and their variants that contribute to an array of diseases. While the identification of such genetic variants has informed our knowledge of the etiologic bases of diseases, there continues to be a substantial gap in our understanding of the factors that modify disease severity. Monogenic diseases provide an opportunity to identify modifiers as they have uniform etiology, detailed phenotyping of affected individuals, and familial clustering. Cystic fibrosis (CF) is among the more common life-shortening recessive disorders that displays wide variability in clinical features and survival. Considerable progress has been made in elucidating the contribution of genetic and nongenetic factors to CF. Allelic variation in CFTR, the gene responsible for CF, correlates with some aspects of the disease. However, lung function, neonatal intestinal obstruction, diabetes, and anthropometry display strong genetic control independent of CFTR, and candidate gene studies have revealed genetic modifiers underlying these traits. The application of genome-wide techniques holds great promise for the identification of novel genetic variants responsible for the heritable features and complications of CF. Since the genetic modifiers are known to alter the course of disease, their protein products become immediate targets for therapeutic intervention. PMID:21175684

In vitro wear, surface roughness and hardness of propanal-containing and diacetyl-containing novel composites and copolymers based on bis-GMA analogs.

PubMed

Prakki, Anuradha; Cilli, Renato; Mondelli, Rafael Francisco Lia; Kalachandra, Sid

2008-03-01

To evaluate the effect of two additives, aldehyde or diketone, on the wear, roughness and hardness of bis-GMA-based composites/copolymers containing TEGDMA, propoxylated bis-GMA (CH(3)bis-GMA) or propoxylated fluorinated bis-GMA (CF(3)bis-GMA). Fifteen experimental composites and 15 corresponding copolymers were prepared combining bis-GMA and TEGDMA, CH(3)bis-GMA or CF(3)bis-GMA, with aldehyde (24 mol% and 32 mol%) or diketone (24 mol% and 32 mol%) totaling 30 groups. For composites, hybrid treated filler (barium aluminosilicate glass/pyrogenic silica; 60 wt%) was added to monomer mixtures. Photopolymerization was affected by 0.2 wt% each of camphorquinone and N,N-dimethyl-p-toluidine. Wear (W) test was conducted in a toothbrushing abrasion machine (n=6) and quantified using a profilometer. Surface roughness (R) changes, before and after abrasion test, were determined using a rugosimeter. Microhardness (H) measurements were performed for dry and wet samples using a Knoop microindenter (n=6). Data were analyzed by one-way ANOVA and Tukey's test (alpha=0.05). Incorporation of additives led to improved W and H values for bis-GMA/TEGDMA and bis-GMA/CH(3)bis-GMA systems. Additives had no significant effect on the W and H changes of bis-GMA/CF(3)bis-GMA. With regard to R changes, additives produced decreased values for bis-GMA/CH(3)bis-GMA and bis-GMA/CF(3)bis-GMA composites. Bis-GMA/TEGDMA and bis-GMA/CH(3)bis-GMA copolymers with additives became smoother after abrasion test. The findings correlate with additives ability to improve degree of conversion of some composites/copolymers thereby enhancing mechanical properties.

Arthroprotective Effects of Cf-02 Sharing Structural Similarity with Quercetin.

PubMed

Liu, Feng-Cheng; Lu, Jeng-Wei; Chien, Chiao-Yun; Huang, Hsu-Shan; Lee, Chia-Chung; Lien, Shiu-Bii; Lin, Leou-Chyr; Chen, Liv Weichien; Ho, Yi-Jung; Shen, Min-Chung; Ho, Ling-Jun; Lai, Jenn-Haung

2018-05-14

In this study, we synthesized hundreds of analogues based on the structure of small-molecule inhibitors (SMIs) that were previously identified in our laboratory with the aim of identifying potent yet safe compounds for arthritis therapeutics. One of the analogues was shown to share structural similarity with quercetin, a potent anti-inflammatory flavonoid present in many different fruits and vegetables. We investigated the immunomodulatory effects of this compound, namely 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2 H -benzo[ e ][1,3]oxazine-2,4(3 H )-dione (Cf-02), in a side-by-side comparison with quercetin. Chondrocytes were isolated from pig joints or the joints of patients with osteoarthritis that had undergone total knee replacement surgery. Several measures were used to assess the immunomodulatory potency of these compounds in tumor necrosis factor (TNF-α)-stimulated chondrocytes. Characterization included the protein and mRNA levels of molecules associated with arthritis pathogenesis as well as the inducible nitric oxide synthase (iNOS)⁻nitric oxide (NO) system and matrix metalloproteinases (MMPs) in cultured chondrocytes and proteoglycan, and aggrecan degradation in cartilage explants. We also examined the activation of several important transcription factors, including nuclear factor-kappaB (NF-κB), interferon regulatory factor-1 (IRF-1), signal transducer and activator of transcription-3 (STAT-3), and activator protein-1 (AP-1). Our overall results indicate that the immunomodulatory potency of Cf-02 is fifty-fold more efficient than that of quercetin without any indication of cytotoxicity. When tested in vivo using the induced edema method, Cf-02 was shown to suppress inflammation and cartilage damage. The proposed method shows considerable promise for the identification of candidate disease-modifying immunomodulatory drugs and leads compounds for arthritis therapeutics.

Dissociative electron attachment and vibrational excitation of CF{sub 3}Cl: Effect of two vibrational modes revisited

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

Tarana, Michal; JILA, University of Colorado and NIST, Boulder, Colorado 80309-0440; Houfek, Karel

We present a study of dissociative electron attachment and vibrational excitation processes in electron collisions with the CF{sub 3}Cl molecule. The calculations are based on the two-dimensional nuclear dynamics including the C-Cl symmetric stretch coordinate and the CF{sub 3} symmetric deformation (umbrella) coordinate. The complex potential energy surfaces are calculated using the ab initio R-matrix method. The results for dissociative attachment and vibrational excitation of the umbrella mode agree quite well with experiment whereas the cross section for excitation of the C-Cl symmetric stretch vibrations is about a factor-of-three too low in comparison with experimental data.

Cross-Fostering Implications for Pig Mortality, Welfare and Performance.

PubMed

Calderón Díaz, Julia A; García Manzanilla, Edgar; Diana, Alessia; Boyle, Laura A

2018-01-01

This study aimed to (1) identify cross-fostering (CF) practices employed on a commercial farm; (2) characterize CF pigs according to litter of origin traits, and (3) investigate the implications of CF practices on pig mortality, performance and welfare. This was an observational study whereby pigs were managed according to normal farming practice. Pigs ( n = 1,016) born within 1 week were classified as non-CF (NCF); CF during the first (CFW1) and second or third (CFW2+) weeks of lactation. Pigs were individually weighed and inspected for the presence of tail (TL), ear (EL) and body lesions (BL) at weaning (7.03 ± 1.61 kg) and at the end of the first (12.9 ± 3.03 kg) and second (31.9 ± 5.50 kg) weaner and grower (66.3 ± 9.12 kg) stages. Mortality was recorded through to slaughter (c. 115 kg). At slaughter, TL were scored and carcass characteristics, presence of pleurisy, enzootic pneumonia, pericarditis and heart condemnations were recorded. 40.8% of CF pigs were CFW1; ANOVA tests revealed these were born to sows with a higher number of piglets born alive than NCF pigs (14.6 ± 2.61 and 12.8 ± 2.68, respectively). The remaining 59.2% of CF pigs were CFW2+; these were, on average, 0.14 kg lighter at birth than NCF pigs. Therefore, a nested case control design was retrospectively applied whereby pigs with complete records to slaughter, were matched for these variables to investigate associations between CF weeks, welfare and performance traits. Growth performance did not differ between CF week ( P > 0.05); however, CFW2+ carcasses were 4.9 kg lighter ( P < 0.05) compared with NCF and CFW1 pigs. EL were more likely in CFW1 compared to NCF and CFW2+ ( P < 0.05) pigs. To investigate the effect of CF week on the risk of mortality, all 1,016 pigs were used. CF pigs were at higher risk of death ( P < 0.05) with similar odds in CFW1 and CFW2+ pigs compared with NCF pigs, although other underlying factors could contribute to this result. Performance and health traits were similar between CF weeks. Early cross-fostering appeared to influence the presence of ear lesions but the mechanism is likely indirect and difficult to explain.

Transformation of carbon tetrachloride and chloroform by trichloroethene respiring anaerobic mixed cultures and supernatant.

PubMed

Vickstrom, Kyle E; Azizian, Mohammad F; Semprini, Lewis

2017-09-01

Carbon tetrachloride (CT) and chloroform (CF) were transformed in batch reactor experiments conducted with anaerobic dechlorinating cultures and supernatant (ADC + S) harvested from continuous flow reactors. The Evanite (EV) and Victoria/Stanford (VS) cultures, capable of respiring trichloroethene (TCE), 1,2-cis-dichloroethene (cDCE), and vinyl chloride (VC) to ethene (ETH), were grown in continuous flow reactors receiving an influent feed of saturated TCE (10 mM; 60 mEq) and formate (45 mM; 90 mEq) but no CT or CF. Cells and supernatant were harvested from the chemostats and inoculated into batch reactors at the onset of each experiment. CT transformation was complete following first order kinetics with CF, DCM and CS 2 as the measurable transformation products, representing 20-40% of the original mass of CT, with CO 2 likely the unknown transformation product. CF was transformed to DCM and likely CO 2 at an order of magnitude rate lower than CT, while DCM was not further transformed. An analytical first order model including multiple key reactions effectively simulated CT transformation, product formation and transformation, and provided reasonable estimates of transformation rate coefficients. Biotic and abiotic treatments indicated that CT was mainly transformed via abiotic processes. However, the presence of live cells was associated with the transformation of CF to DCM. In biotic tests both TCE and CT were simultaneously transformed, with TCE transformed to ETH and approximately 15-53% less CF formed via CT transformation. A 14-day exposure to CF (CF max  = 1.4 μM) reduced all rates of chlorinated ethene respiration by a factor of 10 or greater. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cystic Fibrosis Revisited - a Review Study.

PubMed

Klimova, Blanka; Kuca, Kamil; Novotny, Michal; Maresova, Petra

2017-01-01

Cystic fibrosis (CF) is an incurable, chronic disease, which causes severe damages to respiratory and digestive tracts. It is the most common genetically inherited disease among caucasians. This disease is caused by defects in CF genes, the so-called mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene population. At present over 100,000 people suffer from this disease worldwide. The purpose of this review study is to describe the pathophysiology of CF and provide the latest information on its diagnosis and treatment therapies with respect to the improvement of patient's quality of life and emphasis on targeted specialized care. The methodological approaches include a method of literature review of available sources exploring the issue of cystic fibrosis both from a global and specific perspective point of view. A search was performed in the databases PubMed, MEDLINE, Web of Science, Scopus, Springer and ScienceDirect. Furthermore, other sources cited in the analyzed studies were also examined. On the basis of evaluation of these literature sources, the research issue was explored. The main benefits (e.g., specialized centres for the treatment of CF exist or a new breakthrough in the gene therapy of CF has been made) and limitations (e.g., comorbidity of CF, lifelong and costly treatment, or adverse impact on patient's and caregiver's quality of life) in the treatment of narcolepsy are highlighted. CF requires an integrated treatment approach in specialized CF centers, involving various factors contributing to a better patient's state of health in the form of relevant and well-balanced non-pharmacological and pharmacological therapies. In addition, further large scale clinical trials are needed in order to develop compounds that are aimed at the most common classes of CFTR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Environmental allergies and respiratory morbidities in cystic fibrosis.

PubMed

Collaco, Joseph M; Morrow, Christopher B; Green, Deanna M; Cutting, Garry R; Mogayzel, Peter J

2013-09-01

Cystic fibrosis (CF) is characterized by recurrent respiratory infections and progressive lung disease. Although environmental factors account for 50% of the variation in CF lung function, few specific exposures have been identified. Studies using small study samples focusing on environmental allergies in CF have had inconsistent results. Our objective was to examine the role of environmental allergies in upper and lower respiratory tract morbidities in CF. A total of 1,321 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of environmental allergies. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track outcomes. Within the study sample 14% reported environmental allergies. Environmental allergies were associated with a higher risk of sinus disease (adjusted OR: 2.68; P < 0.001) and nasal polyps (adjusted OR: 1.74; P = 0.003). Environmental allergies were also associated with a more rapid decline in lung function (additional -1.1%/year; P = 0.001). However, allergies were associated with a later median age of acquisition of Pseudomonas aeruginosa (6.6 years vs. 4.4 years; log rank P = 0.027). The reported use of common allergy medications, anti-histamines and leukotriene inhibitors, did not alter the frequency of respiratory morbidities. Environmental allergies are associated with an increased risk of sinus disease and nasal polyps and a more rapid decline in CF lung function, but may have a protective effect against the acquisition of P. aeruginosa. Prospective studies are needed to confirm these associations which have implications for more aggressive management of allergies. Copyright © 2012 Wiley Periodicals, Inc.

Environmental Allergies and Respiratory Morbidities in Cystic Fibrosis

PubMed Central

Collaco, Joseph M.; Morrow, Christopher B.; Green, Deanna M.; Cutting, Garry R.; Mogayzel, Peter J.

2012-01-01

SUMMARY Background Cystic fibrosis (CF) is characterized by recurrent respiratory infections and progressive lung disease. Although environmental factors account for 50% of the variation in CF lung function, few specific exposures have been identified. Studies using small study samples focusing on environmental allergies in CF have had inconsistent results. Our objective was to examine the role of environmental allergies in upper and lower respiratory tract morbidities in CF. Methods A total of 1321 subjects with CF were recruited through the U.S. CF Twin-Sibling Study. Questionnaires were used to determine the presence/absence of environmental allergies. Questionnaires, chart review, and U.S. CF Foundation Patient Registry data were used to track outcomes. Results Within the study sample 14% reported environmental allergies. Environmental allergies were associated with a higher risk of sinus disease (adjusted OR: 2.68; p<0.001) and nasal polyps (adjusted OR: 1.74; p=0.003). Environmental allergies were also associated with a more rapid decline in lung function (additional −1.1%/year; p=0.001). However, allergies were associated with a later median age of acquisition of Pseudomonas aeruginosa (6.6 yo vs. 4.4 yo; log rank p=0.027). The reported use of common allergy medications, anti-histamines and leukotriene inhibitors, did not alter the frequency of respiratory morbidities. Conclusions Environmental allergies are associated with an increased risk of sinus disease and nasal polyps and a more rapid decline in CF lung function, but may have a protective effect against the acquisition of P. aeruginosa. Prospective studies are needed to confirm these associations which have implications for more aggressive management of allergies. PMID:23143815

Meconium ileus in patients with cystic fibrosis is not a risk factor for clinical deterioration and survival: the Israeli Multicenter Study.

PubMed

Efrati, Ori; Nir, Judith; Fraser, Drora; Cohen-Cymberknoh, Malena; Shoseyov, David; Vilozni, Daphna; Modan-Moses, Dalit; Levy, Ran; Szeinberg, Amir; Kerem, Eitan; Rivlin, Joseph

2010-02-01

Patients with cystic fibrosis (CF) presenting with meconium ileus (MI) tend to have worse outcomes than those without MI. We evaluated the clinical characteristics and survival rates among Israeli patients with CF with and without MI after a prolonged follow-up (15-30 years). A multicenter retrospective study. Forty-nine patients with CF, representing 13.8% of all patients with CF in Israel, presented with MI (current age 17.4 +/- 7.9 years) between 1975 and 2006. They were compared with 38 patients with CF (current age 19.3 +/- 6.5 years) without MI matched by sex and CF transmembrane conductance regulator mutation. A total of 66.2% of patients with MI and 73.6% without MI were followed for a prolonged period (24.9 +/- 2.7 years). Of the patients with MI, 31 were managed operatively, whereas 18 were treated successfully with gastrograffin enema, with similar clinical outcomes. Five patients in the MI group and 3 in the control group died during the study period. Bacterial colonization, z score of body mass index, and pulmonary function tests were similar in patients with and without MI in the long term. In younger patients, many clinical parameters were more prevalent in patients with MI (P = 0.004). However, these differences disappeared after the long-term follow-up (up to 31-years). Patients with CF presenting with MI had similar pulmonary function and nutritional status, as well as survival rates as did the control patients without MI. The distinct genetic mutation found in our population may explain in part the favorable results compared with other studies. In addition, it seems that early diagnosis and treatment of MI in patients with CF may be beneficial, subsequently lowering morbidity, and increasing survival.

Pretransplant Aspergillus colonization of cystic fibrosis patients and the incidence of post-lung transplant invasive aspergillosis.

PubMed

Luong, Me-Linh; Chaparro, Cecilia; Stephenson, Anne; Rotstein, Coleman; Singer, Lianne G; Waters, Valerie; Azad, Sassan; Keshavjee, Shaf; Tullis, Elizabeth; Husain, Shahid

2014-02-15

Invasive aspergillosis (IA) is an important cause of morbidity and mortality among patients undergoing lung transplant. Cystic fibrosis-lung transplant recipients (CF-LTRs) may be at greater risk of IA following lung transplantation because of the presence of Aspergillus in their airways before transplantation. This study evaluated the impact of pretransplant Aspergillus colonization on the risk for IA among CF-LTRs. A single-center retrospective cohort study of CF-LTRs was conducted between 2006 and 2010. Respiratory tract cultures before transplantation were reviewed to identify patients with pretransplant Aspergillus colonization. Patients with positive Aspergillus sputum culture or positive bronchoalvelolar lavage (BAL) galactomannan after transplantation were classified as having colonization or disease according to the International Society of Heart and Lung Transplantation criteria. A total of 93 CF patients underwent lung transplantation. Seventy percent (65/93) of CF-LTRs had pretransplant Aspergillus colonization. Thirty-six patients had positive intraoperative Aspergillus culture from the native lung BAL. Overall, 22.5% (20/93) of CF-LTRs developed IA. Median time to IA was 42 days following transplantation. Positive intraoperative Aspergillus culture (OR 4.36, 95% CI 1.35-14.05, P=0.01) and treatment for acute cellular rejection within 90 days after transplantation (OR 3.53, 95% CI 1.03-12.15, P=0.05) were independent risk factors for IA. Antifungal prophylaxis was administered to 61% (57/93) of CF-LTRs. One-year mortality rate was 16% (15/93). IA was not associated with increased risk of death (OR 2.10, 95% CI 0.62-7.06, P=0.23). Pretransplant Aspergillus colonization is frequent among CF-LTRs and a positive intraoperative Aspergillus culture produced a fourfold higher risk of developing IA.

The effect of medium viscosity on kinetics of ATP hydrolysis by the chloroplast coupling factor CF1.

PubMed

Malyan, Alexander N

2016-05-01

The coupling factor CF1 is a catalytic part of chloroplast ATP synthase which is exposed to stroma whose viscosity is many-fold higher than that of reaction mixtures commonly used to measure kinetics of CF1-catalyzed ATP hydrolysis. This study is focused on the effect of medium viscosity modulated by sucrose or bovine serum albumin (BSA) on kinetics of Ca(2+)- and Mg(2+)-dependent ATP hydrolysis by CF1. These agents were shown to reduce the maximal rate of Ca(2+)-dependent ATPase without changing the apparent Michaelis constant (К m), thus supporting the hypothesis on viscosity dependence of CF1 activity. For the sulfite- and ethanol-stimulated Mg(2+)-dependent reaction, the presence of sucrose increased К m without changing the maximal rate that is many-fold as high as that of Ca(2+)-dependent hydrolysis. The hydrolysis reaction was shown to be stimulated by low concentrations of BSA and inhibited by its higher concentrations, with the increasing maximal reaction rate estimated by extrapolation. Sucrose- or BSA-induced inhibition of the Mg(2+)-dependent ATPase reaction is believed to result from diffusion-caused deceleration, while its BSA-induced stimulation is probably caused by optimization of the enzyme structure. Molecular mechanisms of the inhibitory effect of viscosity are discussed. Taking into account high protein concentrations in the chloroplast stroma, it was suggested that kinetic parameters of ATP hydrolysis, and probably those of ATP synthesis in vivo as well, must be quite different from measurements taken at a viscosity level close to that of water.

In Vitro Analysis of Pseudomonas aeruginosa Virulence Using Conditions That Mimic the Environment at Specific Infection Sites.

PubMed

Colmer-Hamood, J A; Dzvova, N; Kruczek, C; Hamood, A N

2016-01-01

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes chronic lung infection in patients with cystic fibrosis (CF) and acute systemic infections in severely burned patients and immunocompromised patients including cancer patients undergoing chemotherapy and HIV infected individuals. In response to the environmental conditions at specific infection sites, P. aeruginosa expresses certain sets of cell-associated and extracellular virulence factors that produce tissue damage. Analyzing the mechanisms that govern the production of these virulence factors in vitro requires media that closely mimic the environmental conditions within the infection sites. In this chapter, we review studies based on media that closely resemble three in vivo conditions, the thick mucus accumulated within the lung alveoli of CF patients, the serum-rich wound bed and the bloodstream. Media resembling the CF alveolar mucus include standard laboratory media supplemented with sputum obtained from CF patients as well as prepared synthetic mucus media formulated to contain the individual components of CF sputum. Media supplemented with serum or individual serum components have served as surrogates for the soluble host components of wound infections, while whole blood has been used to investigate the adaptation of pathogens to the bloodstream. Studies using these media have provided valuable information regarding P. aeruginosa gene expression in different host environments as varying sets of genes were differentially regulated during growth in each medium. The unique effects observed indicate the essential role of these in vitro media that closely mimic the in vivo conditions in providing accurate information regarding the pathogenesis of P. aeruginosa infections. Copyright © 2016 Elsevier Inc. All rights reserved.

Employment and work disability in adults with cystic fibrosis.

PubMed

Laborde-Castérot, Hervé; Donnay, Carole; Chapron, Jeanne; Burgel, Pierre-Régis; Kanaan, Reem; Honoré, Isabelle; Dusser, Daniel; Choudat, Dominique; Hubert, Dominique

2012-03-01

As a result of prolonged survival, more patients with cystic fibrosis (CF) participate in the labour force. The aim of this study was to evaluate their education, occupation levels and risk factors for work disability. 207 patients answered a self-administered questionnaire about their educational level and work status. Independently, medical records were reviewed for illness severity indicators. 39 patients (19%) were students, 117 (57%) were in the labour force, 13 (6%) were seeking employment and 38 (18%) were inactive. CF patients had a higher educational level and were more likely to hold skilled jobs and to work part time than the general population. FEV1 and educational level were the strongest predictive factors of disability. Many CF patients have access to professional life. Their higher educational levels improve the chances of attaining employment, which highlights the need for career counselling. Working part time helps to maintain employment despite declining health. Copyright © 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Inverse Calibration Free fs-LIBS of Copper-Based Alloys

NASA Astrophysics Data System (ADS)

Smaldone, Antonella; De Bonis, Angela; Galasso, Agostino; Guarnaccio, Ambra; Santagata, Antonio; Teghil, Roberto

2016-09-01

In this work the analysis by Laser Induced Breakdown Spectroscopy (LIBS) technique of copper-based alloys having different composition and performed with fs laser pulses is presented. A Nd:Glass laser (Twinkle Light Conversion, λ = 527 nm at 250 fs) and a set of bronze and brass certified standards were used. The inverse Calibration-Free method (inverse CF-LIBS) was applied for estimating the temperature of the fs laser induced plasma in order to achieve quantitative elemental analysis of such materials. This approach strengthens the hypothesis that, through the assessment of the plasma temperature occurring in fs-LIBS, straightforward and reliable analytical data can be provided. With this aim the capability of the here adopted inverse CF-LIBS method, which is based on the fulfilment of the Local Thermodynamic Equilibrium (LTE) condition, for an indirect determination of the species excitation temperature, is shown. It is reported that the estimated temperatures occurring during the process provide a good figure of merit between the certified and the experimentally determined composition of the bronze and brass materials, here employed, although further correction procedure, like the use of calibration curves, can be demanded. The reported results demonstrate that the inverse CF-LIBS method can be applied when fs laser pulses are used even though the plasma properties could be affected by the matrix effects restricting its full employment to unknown samples provided that a certified standard having similar composition is available.

Comprehensive vacuum ultraviolet photoionization study of the CF3• trifluoromethyl radical using synchrotron radiation

NASA Astrophysics Data System (ADS)

Dossmann (Soldi-Lose), Héloïse; Garcia, Gustavo A.; Nahon, Laurent; de Miranda, Barbara K. C.; Alcaraz, Christian

2012-05-01

The trifluoromethyl radical, CF3•, is studied for the first time by means of threshold photoelectron spectroscopy (TPES). The radical is produced in the gas phase using the flash-pyrolysis technique from hexafluoroethane as a precursor. CF3+ total ion yield and mass-selected TPES of the radical are recorded using a spectrometer based upon velocity map imaging and Wiley-McLaren time-of-flight coupled to the synchrotron radiation. The high resolution of the instrument and of the photons allows the observation of rich vibrational progressions in the TPES of CF3•. By using Franck-Condon factors computed by Bowman and coworkers, we have been able to simulate the TPES. The initial vibrational temperature of the radical beam has been evaluated at 350 ± 70 K. The structures have been identified as transitions between (n1,n2) and (n1+,n2+) vibrational levels of CF3 and CF3+ with small excitation of the breathing mode, ν1+, and large excitation (n2+ = 10-26) of the umbrella mode, ν2+, in the cation. From the energy separation between the two resolved peaks of each band, a value of 994 ± 16 cm-1 has been derived for the ν1+ breathing frequency of CF3+. For the high-lying n2+ levels, the apparent ν2+ umbrella spacing, 820 ± 14 cm-1, is fairly constant. Taking into account the ν2+ anharmonicity calculated by Bowman and coworkers, we have deduced ν2+ = 809 ± 14 cm-1, and semi-empirical estimations of the adiabatic ionization energy IEad.(CF3•) are proposed in good agreement with most of previous works. A value of the vertical ionization potential, IEvert.(CF3•) = 11.02 eV, has been derived from the observation of a photoelectron spectrum recorded at a fixed photon energy of 12 eV.

The luminosity function for different morphological types in the CfA Redshift Survey

NASA Technical Reports Server (NTRS)

Marzke, Ronald O.; Geller, Margaret J.; Huchra, John P.; Corwin, Harold G., Jr.

1994-01-01

We derive the luminosity function for different morphological types in the original CfA Redshift Survey (CfA1) and in the first two slices of the CfA Redshift Survey Extension (CfA2). CfA1 is a complete sample containing 2397 galaxies distributed over 2.7 steradians with m(sub z) less than or equal 14.5. The first two complete slices of CfA2 contain 1862 galaxies distributed over 0.42 steradians with m(sub z)=15.5. The shapes of the E-S0 and spiral luminosity functions (LF) are indistinguishable. We do not confirm the steeply decreasing faint end in the E-S0 luminosity function found by Loveday et al. for an independent sample in the southern hemisphere. We demonstrate that incomplete classification in deep redshift surveys can lead to underestimates of the faint end of the elliptical luminosity function and could be partially responsible for the difference between the CfA survey and other local field surveys. The faint end of the LF for the Magellanic spirals and irregulars is very steep. The Sm-Im luminosity function is well fit by a Schechter function with M*=-18.79, alpha=-1.87, and phi*=0.6x10(exp -3) for M(sub z) less than or equal to -13. These galaxies are largely responsible for the excess at the faint end of the general CfA luminosity function. The abundance of intrinsically faint, blue galaxies nearby affects the interpretation of deep number counts. The dwarf population increases the expected counts at B=25 in a no-evolution, q(sub 0)=0.05 model by a factor of two over standard no-evolution estimates. These dwarfs change the expected median redshift in deep redshift surveys by less than 10 percent . Thus the steep Sm-Im LF may contribute to the reconciliation of deep number counts with deep redshift surveys.

Cystic fibrosis liver disease - from diagnosis to risk factors.

PubMed

Ciucă, Ioana Mihaiela; Pop, Liviu; Tămaş, Liviu; Tăban, Sorina

2014-01-01

Cystic fibrosis (CF) is the most frequent monogenic genetic disease, autosomal recessive transmitted, characterized by an impressive clinical polymorphism and appreciative fatal prospective. Liver disease is the second non-pulmonary cause of death in cystic fibrosis, which, with increasing life expectancy, became an important management problem. Predisposing factors like male gender, pancreatic insufficiency, meconium ileus and severe mutation are incriminated to influence the occurrence of cystic fibrosis associated liver disease (CFLD). Our study included 174 patients with CF, monitored in the National Cystic Fibrosis Centre, Timisoara, Romania. They were routinely followed-up by clinical assessment, liver biochemical tests, ultrasound examinations and other methods like transient elastography, biopsy, in selected cases. Sixty-six patients, with median age at diagnosis 4.33 years, diagnosed with CFLD, without significant gender gap. CFLD was frequent in patients aged over eight years, with meconium ileus history, carriers of severe mutations (p=0.002). Pancreatic insufficiency, although present in 75% of patients with CFLD was not confirmed as risk factor, not male gender, in our study. CF children older than eight years, carriers of a severe genotype, with a positive history of meconium ileus, were more likely predisposed to CFLD.

Noninvasive detection of activating estrogen receptor 1 (ESR1) mutations in estrogen receptor-positive metastatic breast cancer.

PubMed

Guttery, David S; Page, Karen; Hills, Allison; Woodley, Laura; Marchese, Stephanie D; Rghebi, Basma; Hastings, Robert K; Luo, Jinli; Pringle, J Howard; Stebbing, Justin; Coombes, R Charles; Ali, Simak; Shaw, Jacqueline A

2015-07-01

Activating mutations in the estrogen receptor 1 (ESR1) gene are acquired on treatment and can drive resistance to endocrine therapy. Because of the spatial and temporal limitations of needle core biopsies, our goal was to develop a highly sensitive, less invasive method of detecting activating ESR1 mutations via circulating cell-free DNA (cfDNA) and tumor cells as a "liquid biopsy." We developed a targeted 23-amplicon next-generation sequencing (NGS) panel for detection of hot-spot mutations in ESR1, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), tumor protein p53 (TP53), fibroblast growth factor receptor 1 (FGFR1), and fibroblast growth factor receptor 2 (FGFR2) in 48 patients with estrogen receptor-α-positive metastatic breast cancer who were receiving systemic therapy. Selected mutations were validated using droplet digital PCR (ddPCR). Nine baseline cfDNA samples had an ESR1 mutation. NGS detected 3 activating mutations in ESR1, and 3 hot-spot mutations in PIK3CA, and 3 in TP53 in baseline cfDNA, and the ESR1 p.D538G mutation in 1 matched circulating tumor cell sample. ddPCR analysis was more sensitive than NGS and identified 6 additional baseline cfDNA samples with the ESR1 p.D538G mutation at a frequency of <1%. In serial blood samples from 11 patients, 4 showed changes in cfDNA, 2 with emergence of a mutation in ESR1. We also detected a low frequency ESR1 mutation (1.3%) in cfDNA of 1 primary patient who was thought to have metastatic disease but was clear by scans. Early identification of ESR1 mutations by liquid biopsy might allow for cessation of ineffective endocrine therapies and switching to other treatments, without the need for tissue biopsy and before the emergence of metastatic disease. © 2015 American Association for Clinical Chemistry.

Continuous alternating inhaled antibiotic therapy in CF: A single center retrospective analysis.

PubMed

Van de Kerkhove, C; Goeminne, P C; Kicinski, M; Nawrot, T S; Lorent, N; Van Bleyenbergh, P; De Boeck, K; Dupont, L J

2016-11-01

The efficacy of inhaled antibiotics to treat chronic Pseudomonas aeruginosa pulmonary infection in patients with cystic fibrosis (CF) has been well established. Few data are available on the value of continuous alternating inhaled antibiotic therapy (CAIT), a strategy increasingly used in the management of CF. To investigate the effect of CAIT on clinical outcome in adult CF patients treated at the University Hospital Leuven. Patients with a documented CF diagnosis who received inhaled antibiotics between March 2010 and January 2015 were retrospectively evaluated. In patients receiving CAIT patient characteristics, recorded spirometry data and number of IV antibiotic days were collected retrospectively at fixed time intervals, from 6months before to one year after the start of the 2nd inhaled antibiotic. For patients on inhaled antibiotic monotherapy (IAMT), the same data were obtained at similar intervals during the study period. A total of 49 of 89 patients using chronic inhaled antibiotic therapy received CAIT. Patients receiving CAIT had a lower baseline FEV 1 and were more likely to be homozygous for F508del compared to patients receiving IAMT. FEV 1 deteriorated on average by a factor of 0.904 per year (95% CI: 0.851-0.960) prior to the start of CAIT. The initiation of CAIT was associated with an average improvement in FEV 1 by a factor of 1.148 per year (95% CI: 1.068-1.236, p=0.0002). The analysis of specific types of antibiotics revealed evidence of positive effects of adding COLI to TOBI and COLI to AZLI. We found no effect of the initiation of CAIT on the number of IV antibiotic days (p=0.80). CF patients with more advanced lung disease are more likely to receive CAIT. In this patient group, CAIT was associated with a significant improvement in FEV 1 . Further data are warranted to identify the value of CAIT. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Rapid point-of-care testing for epidermal growth factor receptor gene mutations in patients with lung cancer using cell-free DNA from cytology specimen supernatants.

PubMed

Asaka, Shiho; Yoshizawa, Akihiko; Saito, Kazusa; Kobayashi, Yukihiro; Yamamoto, Hiroshi; Negishi, Tatsuya; Nakata, Rie; Matsuda, Kazuyuki; Yamaguchi, Akemi; Honda, Takayuki

2018-06-01

Epidermal growth factor receptor (EGFR) mutations are associated with responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC). Our previous study revealed a rapid point-of-care system for detecting EGFR mutations. This system analyzes cell pellets from cytology specimens using droplet-polymerase chain reaction (d-PCR), and has a reaction time of 10 min. The present study aimed to validate the performance of the EGFR d-PCR assay using cell-free DNA (cfDNA) from supernatants obtained from cytology specimens. Assay results from cfDNA supernatant analyses were compared with those from cell pellets for 90 patients who were clinically diagnosed with, or suspected of having, lung cancer (80 bronchial lavage fluid samples, nine pleural effusion samples and one spinal fluid sample). EGFR mutations were identified in 12 and 15 cases using cfDNA supernatants and cell pellets, respectively. The concordance rates between cfDNA-supernatant and cell‑pellet assay results were 96.7% [kappa coefficient (K)=0.87], 98.9% (K=0.94), 98.9% (K=0.79) and 98.9% (K=0.79) for total EGFR mutations, L858R, E746_A750del and T790M, respectively. All 15 patients with EGFR mutation-positive results, as determined by EGFR d-PCR assay using cfDNA supernatants or cell pellets, also displayed positive results by conventional EGFR assays using tumor tissue or cytology specimens. Notably, EGFR mutations were even detected in five cfDNA supernatants for which the cytological diagnoses of the corresponding cell pellets were 'suspicious for malignancy', 'atypical' or 'negative for malignancy.' In conclusion, this rapid point-of-care system may be considered a promising novel screening method that may enable patients with NSCLC to receive EGFR-TKI therapy more rapidly, whilst also reserving cell pellets for additional morphological and molecular analyses.

Factors Affecting Parent-Child Relationships One Year After Positive Newborn Screening for Cystic Fibrosis or Congenital Hypothyroidism

PubMed Central

Tluczek, Audrey; Clark, Roseanne; McKechnie, Anne Chevalier; Brown, Roger L.

2014-01-01

Objective Examine factors that mediate parent-infant relationships 12 months after positive newborn screening (NBS). Method We examined effects of infant diagnosis, parents’ perceptions of child vulnerability and child attachment, parental depression and anxiety on parent-infant feeding interactions for 131 mothers and 118 fathers of 131 infants whose NBS and diagnostics confirmed cystic fibrosis (CF, n=23), congenital hypothyroidism (CH, n=35), CF carrier status (CF-C, n=38), or healthy, normal NBS (H, n=35). Results Separate composite indicator structural equation models for mothers and fathers showed neonatal diagnosis was not associated with increased anxiety or depression. In comparison to the H group, CF group parents reported higher perceptions of child vulnerability (p< 0.001, p=0.002); and CF-C group fathers viewed their children as more attached (p=0.021). High maternal perception of child vulnerability was associated with low perceptions of child attachment (p=0.001) which was associated with task-oriented feeding behavior (p=0.016, p=0.029). Parental task-oriented feeding behavior was associated with less positive (p< 0.001, p< 0.001) and more negative interactions (p< 0.001, p= 0.001) with their infants. High paternal perception of child vulnerability was associated with negative parent interactions (p< 0.001). High parental affective involvement and verbalization was associated with high infant affective expressiveness, communicative skills, and social responsiveness (mothers’ p< 0.001, fathers’ p< 0.001). High parental negative affect and/or inconsistent and intrusive behavior was associated with infant dysregulation and irritability (mothers’ p< 0.001, fathers’ p< 0.001). Conclusion The severity of conditions identified through NBS can affect parents’ perceptions of their child’s vulnerability and attachment. Infant feeding problems in the context of chronic health conditions, like CF, could represent signs of more deeply rooted concerns regarding the parent-child relationship that merit additional clinical evaluation. PMID:25493463

Animal and management factors influencing grower and finisher pig performance and efficiency in European systems: a meta-analysis.

PubMed

Douglas, S L; Szyszka, O; Stoddart, K; Edwards, S A; Kyriazakis, I

2015-07-01

A meta-analysis on the effects of management and animal-based factors on the performance and feed efficiency of growing pigs can provide information on single factor and interaction effects absent in individual studies. This study analysed the effects of such factors on average daily gain (ADG), feed intake (FI) and feed conversion ratio (FCR) of grower and finisher pigs. The multivariate models identified significant effects of: (1) bedding (P<0.01), stage of growth (P<0.001) and the interaction bedding×lysine (P<0.001) on ADG. ADG was higher on straw compared with no bedding (710 v. 605 g/day). (2) FI was significantly affected by stage of growth (P<0.01), bedding (P<0.01), group composition (P<0.05), group size (P<0.01), feed CP content (P<0.01), ambient temperature (P<0.01) and the interaction between floor space and feed energy content (P<0.001). Pigs housed on straw had a lower FI in comparison with those without (1.44 v. 2.04 kg/day); a higher FI was seen for pigs separated by gender in comparison with mixed groups (2.05 v. 1.65 kg/day); FI had a negative linear relationship with group size, the CP content of the feed and ambient temperature. (3) Stage of growth (P<0.001), feed CP (P<0.001) and lysine content (P<0.001), ambient temperature (P<0.001) and feed crude fibre (CF) content (P<0.01) significantly affected FCR; there were no significant interactions between any factors on this trait. There was an improvement in FCR at higher ambient temperatures, increased feed CP and lysine content, but a deterioration of FCR at higher CF contents. For ADG, the interaction of bedding×lysine was caused by pigs housed without bedding (straw) having higher ADG when on a feed lower in lysine, whereas those with bedding had a higher ADG when on a feed higher in lysine. Interaction effects on FI were caused by animals with the least amount of floor space having a higher FI when given a feed with a low metabolisable energy (ME) content, in contrast to all other pigs, which showed a higher FI with increased ME content. The meta-analysis confirmed the significant effect of several well-known factors on the performance and efficiency of grower and finisher pigs, the effects of some less established ones and, importantly, the interactions between such factors.

Plasma ultrafiltrates from Fanconi Anemia patients induces chromosomal breakages in donor lymphocytes

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

Emerit, I.; Levy, A.; Pagano, G.

1994-09-01

The present study investigated the occurrence, if any, of transferable clastogenic activity in the plasma from Fanconi Anemia (FA) patients and their families. A total of 13 FA homozygotes, 25 parents, and 12 siblings were studied for their: (a) spontaneous and DEB-induced chromosomal instability, and (b) induction of chromosomal breaks in peripheral blood lymphocytes (PBL) from healthy donors, following exposure to plasma ultrafiltrates from FA subjects, their parents or siblings. Plasma was ultrafiltered through membranes with a cutoff at 10,000 daltons (YM 10 Amicon) and 0.25 ml-aliquote added to PBL from 14 healthy donors. DEB test provided FA confirmatory diagnosis.more » The occurrence of clastogenic factors (CF) was evident in all FA patients, except for one. In two out of three patients, who died during this study, very high CF levels were observed. Clastogenic activity was significantly higher in male than in female patients (p<0.05). No correlation was observed between CF data and spontaneous or DEB-induced chromosomal instability. Ultrafiltrates from parents and siblings showed less CF than FA homozygotes; however, concentration by ultrafiltration through YM 2 (3x to 5x) led to excess clastogenic activity. The control plasmas were lacking CF even after an 8x concentration. The present data suggest that CF formation in the plasma of FA patients is consistent with an in vivo prooxident state in FA.« less

A novel strategy for highly efficient isolation and analysis of circulating tumor-specific cell-free DNA from lung cancer patients using a reusable conducting polymer nanostructure.

PubMed

Lee, HyungJae; Jeon, SeungHyun; Seo, Jin-Suck; Goh, Sung-Ho; Han, Ji-Youn; Cho, Youngnam

2016-09-01

We have developed a reusable nanostructured polypyrrole nanochip and demonstrated its use in the electric field-mediated recovery of circulating cell-free DNA (cfDNA) from the plasma of lung cancer patients. Although cfDNA has been recognized and widely studied as a versatile and promising biomarker for the diagnosis and prognosis of cancers, the lack of efficient strategies to directly isolate cfDNA from the plasma has become a great hindrance to its potential clinical use. As a proof-of-concept study, we demonstrated a technique for the rapid and efficient isolation of cfDNA with high yield and purity. In particular, the synergistic effects of the electro-activity and the nanostructured features of the polypyrrole polymer enabled repeated retrieval of cfDNA using a single platform. Moreover, polypyrrole nanochip facilitated the amplification of tumor-specific DNA fragments from the plasma samples of patients with lung cancer characterized by mutations in exons 21 of the epidermal growth factor receptor gene (EGFR). Overall, the proposed polypyrrole nanochip has enormous potential for industrial and clinical applications with significantly enhanced efficiency in the recovery of tumor-associated circulating cfDNA. This may ultimately contribute to more robust and reliable evaluation of gene mutations in peripheral blood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Application of face centred central composite design to optimise compression force and tablet diameter for the formulation of mechanically strong and fast disintegrating orodispersible tablets.

PubMed

Pabari, Ritesh M; Ramtoola, Zebunnissa

2012-07-01

A two factor, three level (3(2)) face centred, central composite design (CCD) was applied to investigate the main and interaction effects of tablet diameter and compression force (CF) on hardness, disintegration time (DT) and porosity of mannitol based orodispersible tablets (ODTs). Tablet diameters of 10, 13 and 15 mm, and CF of 10, 15 and 20 kN were studied. Results of multiple linear regression analysis show that both the tablet diameter and CF influence tablet characteristics. A negative value of regression coefficient for tablet diameter showed an inverse relationship with hardness and DT. A positive value of regression coefficient for CF indicated an increase in hardness and DT with increasing CF as a result of the decrease in tablet porosity. Interestingly, at the larger tablet diameter of 15 mm, while hardness increased and porosity decreased with an increase in CF, the DT was resistant to change. The optimised combination was a tablet of 15 mm diameter compressed at 15 kN showing a rapid DT of 37.7s and high hardness of 71.4N. Using these parameters, ODTs containing ibuprofen showed no significant change in DT (ANOVA; p>0.05) irrespective of the hydrophobicity of the ibuprofen. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of COPD treatments on MRP1-mediated transport in bronchial epithelial cells

PubMed Central

van der Deen, Margaretha; Homan, Sandra; Timmer-Bosscha, Hetty; Scheper, Rik J; Timens, Wim; Postma, Dirkje S; de Vries, Elisabeth G

2008-01-01

Background Smoking is the principle risk factor for development of chronic obstructive pulmonary disease (COPD). Multidrug resistance-associated protein 1 (MRP1) is known to protect against toxic compounds and oxidative stress, and might play a role in protection against smoke-induced disease progression. We questioned whether MRP1-mediated transport is influenced by pulmonary drugs that are commonly prescribed in COPD. Methods The immortalized human bronchial epithelial cell line 16HBE14o− was used to analyze direct in vitro effects of budesonide, formoterol, ipratropium bromide and N-acetylcysteine (NAC) on MRP1-mediated transport. Carboxyfluorescein (CF) was used as a model MRP1 substrate and was measured with functional flow cytometry. Results Formoterol had a minor effect, whereas budesonide concentration-dependently decreased CF transport by MRP1. Remarkably, addition of formoterol to the highest concentration of budesonide increased CF transport. Ipratropium bromide inhibited CF transport at low concentrations and tended to increase CF transport at higher levels. NAC increased CF transport by MRP1 in a concentration-dependent manner. Conclusions Our data suggest that, besides their positive effects on respiratory symptoms, budesonide, formoterol, ipratropium bromide, and NAC modulate MRP1 activity in bronchial epithelial cells. Further studies are required to assess whether stimulation of MRP1 activity is beneficial for long-term treatment of COPD. PMID:18990976

Joint carbon footprint assessment and data envelopment analysis for the reduction of greenhouse gas emissions in agriculture production.

PubMed

Rebolledo-Leiva, Ricardo; Angulo-Meza, Lidia; Iriarte, Alfredo; González-Araya, Marcela C

2017-09-01

Operations management tools are critical in the process of evaluating and implementing action towards a low carbon production. Currently, a sustainable production implies both an efficient resource use and the obligation to meet targets for reducing greenhouse gas (GHG) emissions. The carbon footprint (CF) tool allows estimating the overall amount of GHG emissions associated with a product or activity throughout its life cycle. In this paper, we propose a four-step method for a joint use of CF assessment and Data Envelopment Analysis (DEA). Following the eco-efficiency definition, which is the delivery of goods using fewer resources and with decreasing environmental impact, we use an output oriented DEA model to maximize production and reduce CF, taking into account simultaneously the economic and ecological perspectives. In another step, we stablish targets for the contributing CF factors in order to achieve CF reduction. The proposed method was applied to assess the eco-efficiency of five organic blueberry orchards throughout three growing seasons. The results show that this method is a practical tool for determining eco-efficiency and reducing GHG emissions. Copyright © 2017 Elsevier B.V. All rights reserved.

CF60 Concrete Composition Design and Application on Fudiankou Xijiang Super Large Bridge

NASA Astrophysics Data System (ADS)

Qiu, Yi Mei; Wen, Sen Yuan; Chen, Jun Xiang

2018-06-01

Guangxi Wuzhou City Ring Road Fudiankou Xijiang super large bridge CF60 concrete is a new multi-phase composite high-performance concrete, this paper for the Fudiankou Xijiang bridge structure and characteristics of the project, in accordance with the principle of local materials and technical specification requirements, combined with the site conditions of CF60 engineering high performance concrete component materials, proportion and the technical performance, quantify the main physical and mechanical performance index. Analysis main influencing factors of the technical indicators, reasonable adjustment of concrete mix design parameters, and the use of technical means of admixture and multi-function composite admixture of concrete, obtain the optimal proportion of good work, process, mechanical properties stability and durability of engineering properties, recommend and verification of concrete mix; to explore the CF60 high performance concrete Soil in the Fudiankou Xijiang bridge application technology, detection and tracking the quality of concrete construction, concrete structure during the construction of the key technology and control points is proposed, evaluation of CF60 high performance concrete in the actual engineering application effect and benefit to ensure engineering quality of bridge structure and service life, and super long span bridge engineering construction to provide basis and reference.

CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease.

PubMed

Fernandez Fernandez, Elena; de Santi, Chiara; De Rose, Virginia; Greene, Catherine M

2018-05-11

Obstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are causes of high morbidity and mortality worldwide. CF is a multiorgan genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterized by progressive chronic obstructive lung disease. Most cases of COPD are a result of noxious particles, mainly cigarette smoke but also other environmental pollutants. Areas covered: Although the pathogenesis and pathophysiology of CF and COPD differ, they do share key phenotypic features and because of these similarities there is great interest in exploring common mechanisms and/or factors affected by CFTR mutations and environmental insults involved in COPD. Various molecular, cellular and clinical studies have confirmed that CFTR protein dysfunction is common in both the CF and COPD airways. This review provides an update of our understanding of the role of dysfunctional CFTR in both respiratory diseases. Expert Commentary: Drugs developed for people with CF to improve mutant CFTR function and enhance CFTR ion channel activity might also be beneficial in patients with COPD. A move toward personalized therapy using, for example, microRNA modulators in conjunction with CFTR potentiators or correctors, could enhance treatment of both diseases.

Altered Sputum Microstructure as a Marker of Airway Obstruction in Cystic Fibrosis Patients

NASA Astrophysics Data System (ADS)

Duncan, Gregg; Jung, James; West, Natalie; Boyle, Michael; Suk, Jung Soo; Hanes, Justin

In the lungs of cystic fibrosis (CF) patients, highly viscoelastic mucus remains stagnant in the lung leading to obstructed airways prone to recurrent infections. Bulk-fluid rheological measurement is primarily used to assess the pathological features of mucus. However, this approach is limited in detecting microscopic properties on the length scale of pathogens and immune cells. We have shown in prior work based on the transport of muco-inert nanoparticles (MIP) in CF sputum that patients can carry significantly different microstructural properties. In this study, we aimed to determine the factors leading to variations between patients in sputum microstructure and their clinical implications. The microrheological properties of CF sputum were measured using multi-particle tracking experiments of MIP. MIP were made by grafting polyethylene glycol onto the surface of polystyrene nanoparticles which prior work has shown prevents adhesion to CF sputum. Biochemical analyses show that sputum microstructure was significantly altered by elevated mucin and DNA content. Reduction in sputum pore size is characteristic of patients with obstructed airways as indicated by measured pulmonary function tests. Our microstructural read-out may serve as a novel biomarker for CF.

Trends in the epidemiological aspects and mortality of alcoholic liver disease in Korea in the decade between 2000 and 2009.

PubMed

Bang, Hyung-Ae; Kwon, Young-Hwan; Lee, Myeong-Jin; Lee, Won-Chang

2015-02-01

Alcohol consumption and related alcohol liver disease (ALD) have substantially increased in Korea during the last decade. The objective of this study was to evaluate the trends in the epidemiological aspects and mortality rate (MR) of Korea in the decade between 2000 and 2009. The raw data analyzed in this study were obtained from the website of "the ALD" managed by Korea Center for Disease Control and Prevention (KCDC), Korea Public Health Association (KPHA), and statistics website of Statistics Korea. The data analyses were performed using Excel 2007 statistical software (Microsoft Corp., USA). The amount of alcohol-consumption-per-capita-per-year (ACCY) in Korea was 8.38 L in 2000 and 8.54 L in 2009. The most taken alcoholic beverage was soju, followed by beer. There were a total of 1,403 case-fatalities (CF) with an MR of 2.98 per 100,000 populations of ALD in 2000, while a total of 3,588 CF with an MR of 7.21 in 2009 (P < 0.01). The CF and MR of ALD in males were significantly higher than those in females (P < 0.01). In over 40-year-old age groups, the CF and MR were significantly increased (P < 0.01). Moreover, occupational classification revealed that the mistress/students/jobless (MSJ) were the most risky group. The comparison of overall CF and MR of ALD by six key classifications (International Classification of Diseases (ICD)) showed that alcoholic cirrhosis (229 CF and 16.3%) in 2000 tended to be increased in 2009 (2,803 CF and 78.1%), while alcoholic fibrosis and sclerosis (607 CF and 43.3%) in 2000 significantly decreased in 2009 (120 CF and 3.3%), respectively. ALD is one of the most severe diseases in Korea, as indicated by its high CF and MR in this study. As over-consumption of alcoholic beverages is relatively common in Korea, more efforts should be made toward prevention of ALD by raising awareness of the risk factors of ALD by public health education.

Trends in the Epidemiological Aspects and Mortality of Alcoholic Liver Disease in Korea in the Decade Between 2000 and 2009

PubMed Central

Bang, Hyung-Ae; Kwon, Young-Hwan; Lee, Myeong-Jin; Lee, Won-Chang

2015-01-01

Background Alcohol consumption and related alcohol liver disease (ALD) have substantially increased in Korea during the last decade. The objective of this study was to evaluate the trends in the epidemiological aspects and mortality rate (MR) of Korea in the decade between 2000 and 2009. Methods The raw data analyzed in this study were obtained from the website of “the ALD” managed by Korea Center for Disease Control and Prevention (KCDC), Korea Public Health Association (KPHA), and statistics website of Statistics Korea. The data analyses were performed using Excel 2007 statistical software (Microsoft Corp., USA). Results The amount of alcohol-consumption-per-capita-per-year (ACCY) in Korea was 8.38 L in 2000 and 8.54 L in 2009. The most taken alcoholic beverage was soju, followed by beer. There were a total of 1,403 case-fatalities (CF) with an MR of 2.98 per 100,000 populations of ALD in 2000, while a total of 3,588 CF with an MR of 7.21 in 2009 (P < 0.01). The CF and MR of ALD in males were significantly higher than those in females (P < 0.01). In over 40-year-old age groups, the CF and MR were significantly increased (P < 0.01). Moreover, occupational classification revealed that the mistress/students/jobless (MSJ) were the most risky group. The comparison of overall CF and MR of ALD by six key classifications (International Classification of Diseases (ICD)) showed that alcoholic cirrhosis (229 CF and 16.3%) in 2000 tended to be increased in 2009 (2,803 CF and 78.1%), while alcoholic fibrosis and sclerosis (607 CF and 43.3%) in 2000 significantly decreased in 2009 (120 CF and 3.3%), respectively. Conclusion ALD is one of the most severe diseases in Korea, as indicated by its high CF and MR in this study. As over-consumption of alcoholic beverages is relatively common in Korea, more efforts should be made toward prevention of ALD by raising awareness of the risk factors of ALD by public health education. PMID:25436025

Behavior of a Liquid Bridge between Nonparallel Hydrophobic Surfaces.

PubMed

Ataei, Mohammadmehdi; Chen, Huanchen; Amirfazli, Alidad

2017-12-26

When a liquid bridge is formed between two nonparallel identical surfaces, it can move along the surfaces. Literature indicates that the direction of bridge movement is governed by the wettability of surfaces. When the surfaces are hydrophilic, the motion of the bridge is always toward the cusp (intersection of the plane of the two bounding surfaces). On the other hand, the movement is hitherto thought to be always pointing away from the cusp when the surfaces are hydrophobic. In this study, through experiments, numerical simulations, and analytical reasoning, we demonstrate that for hydrophobic surfaces, wettability is not the only factor determining the direction of the motion. A new geometrical parameter, i.e., confinement (cf), was defined as the ratio of the distance of the farthest contact point of the bridge to the cusp, and that of the closest contact point to the cusp. The direction of the motion depends on the amount of confinement (cf). When the distance between the surfaces is large (resulting in a small cf), the bridge tends to move toward the cusp through a pinning/depinning mechanism of contact lines. When the distance between the surfaces is small (large cf), the bridge tends to move away from the cusp. For a specific system, a maximum cf value (cf max ) exists. A sliding behavior (i.e., simultaneous advancing on the wider side and receding on the narrower side) can also be seen when a liquid bridge is compressed such that the cf exceeds the cf max . Contact angle hysteresis (CAH) is identified as an underpinning phenomenon that together with cf fundamentally explains the movement of a trapped liquid between two hydrophobic surfaces. If there is no CAH, however, i.e., the case of ideal hydrophobic surfaces, the cf will be a constant; we show that the bridge slides toward the cusp when it is stretched, while it slides away from the cusp when it is compressed (note sliding motion is different from motion due to pinning/depinning mechanism of contact lines). As such, the displacement is only related to geometrical parameters such as the amount of compression (or stretching) and the dihedral angle between the surfaces.

Development of High-Activity Para- to Ortho-Hydrogen Conversion Catalysts. Volume 2

DTIC Science & Technology

1989-09-28

Proc. Roy. Soc. London AllO, 464 (1925). 2 1929 Para- and ortho-hydrogen, Barmois, E., La Nature No. 2820, 400-1 (1929) C.A. 24,, 1020b. K. F...U.S. At. Energy Comm. LA -2719, 40 pp. (1962); cf. 3. Chem. Eng. Data 7, 179(1962). C.A. 58, 10750g. Schmidt number for normal hydrogen and...A-L);- p 181-9; in Eng. Briones, A. G.; Garcia de la Banda, J. F.; Inst. Quim. Fis. Quim., Madrid, Anales Real. Soc. Espan. Fis. Quim. (Madrid); Ser

Doping, Ionic Conductivity and Photothermal Stability of Functionalized DNA for Solar Energy Conversion and Electrochromic Applications

DTIC Science & Technology

2011-06-01

and coworkers 1,2,3,4 . They are renewable and biodegradable materials, recovered from waste in food industry (fruits, animal and fish meat waste) and...charges leads to the change of its absorption spectrum, or in other words to a change of its color . However in most cases the electrolyte used is in...electrodes (cf. Fig. 25). CeO2- TiO2 BK7 BK7 SOLID ELECTROLYTE ITO WO3 ITO Fig. 25. Structure of the used electrochromic cell 21 Figure 26

Microbial BOD sensors based on Zr (IV)-loaded collagen fiber.

PubMed

Zhao, Lei; He, Li; Chen, Shujuan; Zou, Likou; Zhou, Kang; Ao, Xiaolin; Liu, Shuliang; Hu, Xinjie; Han, Guoquan

2017-03-01

Biochemical oxygen demand (BOD) sensors based on Zr (IV)-loaded collagen fiber (ZrCF), a novel material with great porous structure, were developed. This novel material shows adsorbability by microorganisms. Saccharomyces cerevisiae and Escherichia coli were used for the construction of BOD sensors. Factors affecting BOD sensor performance were examined. The ZrCF-based BOD sensor showed different sensitivities and linear response ranges with different biofilm densities. The amount of microorganisms strongly affected the performance of the BOD sensor. Poor permeability of previously reported immobilization carriers were greatly circumvented by ZrCF. The service life of the ZrCF-based BOD sensor was more than 42 days. The immobilized microorganisms can be stored for more than 6 months under 4°C in PB solution. There was good correlation between the results of the sensor method and the standard 5-day BOD method in the determination of pure organic substrates and real water samples. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial variations in shear stress in a 3-D bifurcation model at low Reynolds numbers.

PubMed

Rouhanizadeh, Mahsa; Lin, Tiantian C; Arcas, Diego; Hwang, Juliana; Hsiai, Tzung K

2005-10-01

Real-time wall shear stress is difficult to monitor precisely because it varies in space and time. Microelectromechanical systems sensor provides high spatial resolution to resolve variations in shear stress in a 3-D bifurcation model for small-scaled hemodynamics. At low Reynolds numbers from 1.34 to 6.7 skin friction coefficients (C(f)) varied circumferentially by a factor of two or more within the bifurcation. At a Reynolds number of 6.7, the C(f) value at the lateral wall of the bifurcation along the 270 degree plane was 7.1, corresponding to a shear stress value of 0.0061 dyn/cm(2). Along the 180 degree plane, C(f) was 13 or 0.0079 dyn/cm(2), and at the medial wall along the 90 degree plane, C(f) was 10.3 or 0.0091 dyn/cm(2). The experimental skin friction coefficients correlated with values derived from the Navier-Stokes solutions.

Retrograde Signaling from Progranulin to Sort1 Counteracts Synapse Elimination in the Developing Cerebellum.

PubMed

Uesaka, Naofumi; Abe, Manabu; Konno, Kohtarou; Yamazaki, Maya; Sakoori, Kazuto; Watanabe, Takaki; Kao, Tzu-Huei; Mikuni, Takayasu; Watanabe, Masahiko; Sakimura, Kenji; Kano, Masanobu

2018-02-21

Elimination of redundant synapses formed early in development and strengthening of necessary connections are crucial for shaping functional neural circuits. Purkinje cells (PCs) in the neonatal cerebellum are innervated by multiple climbing fibers (CFs) with similar strengths. A single CF is strengthened whereas the other CFs are eliminated in each PC during postnatal development. The underlying mechanisms, particularly for the strengthening of single CFs, are poorly understood. Here we report that progranulin, a multi-functional growth factor implicated in the pathogenesis of frontotemporal dementia, strengthens developing CF synaptic inputs and counteracts their elimination from postnatal day 11 to 16. Progranulin derived from PCs acts retrogradely onto its putative receptor Sort1 on CFs. This effect is independent of semaphorin 3A, another retrograde signaling molecule that counteracts CF synapse elimination. We propose that progranulin-Sort1 signaling strengthens and maintains developing CF inputs, and may contribute to selection of single "winner" CFs that survive synapse elimination. Copyright © 2018 Elsevier Inc. All rights reserved.

Colonoscopic screening shows increased early incidence and progression of adenomas in cystic fibrosis

PubMed Central

Niccum, David E.; Billings, Joanne L.; Dunitz, Jordan M.; Khoruts, Alexander

2018-01-01

Background Colorectal cancer is an emerging problem in cystic fibrosis (CF). The goal of this study was to evaluate adenoma detection by systematic colonoscopic screening and surveillance. Methods We analyzed prospectively collected results of colonoscopies initiated at age 40 years from 88 CF patients at a single Cystic Fibrosis Center. We also reviewed results of diagnostic colonoscopies from 27 patients aged 30–39 years performed during the same time period at the Center. Results The incidence of polyp detection increased markedly after age 40 in CF patients. Greater than 50% were found to have adenomatous polyps; approximately 25% had advanced adenomas as defined by size and/or histopathology; 3% were found to have colon cancer. Multivariate analysis demonstrated specific risk factors for adenoma formation and progression. Conclusions Early screening and more frequent surveillance should be considered in patients with CF due to early incidence and progression of adenomas in this patient population. PMID:26851188

Oxygen isotope analysis of phosphate: improved precision using TC/EA CF-IRMS.

PubMed

LaPorte, D F; Holmden, C; Patterson, W P; Prokopiuk, T; Eglington, B M

2009-06-01

Oxygen isotope values of biogenic apatite have long demonstrated considerable promise for paleothermometry potential because of the abundance of material in the fossil record and greater resistance of apatite to diagenesis compared to carbonate. Unfortunately, this promise has not been fully realized because of relatively poor precision of isotopic measurements, and exceedingly small size of some substrates for analysis. Building on previous work, we demonstrate that it is possible to improve precision of delta18O(PO4) measurements using a 'reverse-plumbed' thermal conversion elemental analyzer (TC/EA) coupled to a continuous flow isotope ratio mass spectrometer (CF-IRMS) via a helium stream [Correction made here after initial online publication]. This modification to the flow of helium through the TC/EA, and careful location of the packing of glassy carbon fragments relative to the hot spot in the reactor, leads to narrower, more symmetrically distributed CO elution peaks with diminished tailing. In addition, we describe our apatite purification chemistry that uses nitric acid and cation exchange resin. Purification chemistry is optimized for processing small samples, minimizing isotopic fractionation of PO4(-3) and permitting Ca, Sr and Nd to be eluted and purified further for the measurement of delta44Ca and 87Sr/86Sr in modern biogenic apatite and 143Nd/144Nd in fossil apatite. Our methodology yields an external precision of +/- 0.15 per thousand (1sigma) for delta18O(PO4). The uncertainty is related to the preparation of the Ag3PO4 salt, conversion to CO gas in a reversed-plumbed TC/EA, analysis of oxygen isotopes using a CF-IRMS, and uncertainty in constructing calibration lines that convert raw delta18O data to the VSMOW scale. Matrix matching of samples and standards for the purpose of calibration to the VSMOW scale was determined to be unnecessary. Our method requires only slightly modified equipment that is widely available. This fact, and the demonstrated improvement in precision, should help to make apatite paleothermometry far more accessible to paleoclimate researchers. Copyright 2009 John Wiley & Sons, Ltd.

The Enantiomers of 4-Amino-3-fluorobutanoic Acid as Substrates for γ-Aminobutyric Acid Aminotransferase. Conformational Probes for GABA Binding†

PubMed Central

Clift, Michael; Ji, Haitao; Deniau, Gildas P.; O’Hagan, David; Silverman, Richard B.

2008-01-01

γ-Aminobutyric acid aminotransferase (GABA-AT), a pyridoxal 5’-phosphate dependent enzyme, catalyzes the degradation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) to succinic semialdehyde with concomitant conversion of pyridoxal 5’-phosphate (PLP) to pyridoxamine 5’-phosphate (PMP). The enzyme then catalyzes the conversion of α-ketoglutarate to the excitatory neurotransmitter L-glutamate. Racemic 4-amino-3-fluorobutanoic acid (3-F-GABA) was shown previously to act as a substrate for GABA-AT, not for transamination, but for HF elimination. Here we report studies of the reaction catalyzed by GABA-AT on (R)- and (S)-3-F-GABA. Neither enantiomer is a substrate for transamination. Very little elimination from the (S)-enantiomer was detected using a coupled enzyme assay; The rate of elimination of HF from the (R)-enantiomer is at least 10 times greater than that for the (S)-enantiomer. The (R)-enantiomer is about 20 times more efficient as a substrate for GABA-AT catalyzed HF elimination than GABA is a substrate for transamination. The (R)-enantiomer also inhibits the transamination of GABA 10 times more effectively than the (S)-enantiomer. Using a combination of computer modeling and the knowledge that vicinal C-F and C-NH3+ bonds have a strong preference to align gauche rather than anti to each other, it is concluded that on binding of free 3-F-GABA to GABA-AT the optimal conformation places the C-NH3+ and C-F bonds gauche in the (R)-enantiomer but anti in the (S)-enantiomer. Furthermore, the dynamic binding process and the bioactive conformation of GABA bound to GABA-AT have been inferred based on the different biological behavior of the two enantiomers of 3-F-GABA when they bind to the enzyme. The present study suggests that the C-F bond can be utilized as a conformational probe to explore the dynamic binding process and provide insight into the bioactive conformation of substrates, which cannot be easily determined by other biophysical approaches. PMID:17988152

Organic rankine cycle fluid

DOEpatents

Brasz, Joost J.; Jonsson, Ulf J.

2006-09-05

A method of operating an organic rankine cycle system wherein a liquid refrigerant is circulated to an evaporator where heat is introduced to the refrigerant to convert it to vapor. The vapor is then passed through a turbine, with the resulting cooled vapor then passing through a condenser for condensing the vapor to a liquid. The refrigerant is one of CF.sub.3CF.sub.2C(O)CF(CF.sub.3).sub.2, (CF.sub.3).sub.2 CFC(O)CF(CF.sub.3).sub.2, CF.sub.3(CF.sub.2).sub.2C(O)CF(CF.sub.3).sub.2, CF.sub.3(CF.sub.2).sub.3C(O)CF(CG.sub.3).sub.2, CF.sub.3(CF.sub.2).sub.5C(O)CF.sub.3, CF.sub.3CF.sub.2C(O)CF.sub.2CF.sub.2CF.sub.3, CF.sub.3C(O)CF(CF.sub.3).sub.2.

VAPOR PRESSURES, LIQUID MOLAR VOLUMES, VAPOR NON- IDEALITY, AND CRITICAL PROPERTIES OF CF3OCF2CF2CF3, c-CF2CF2CF2CF2O, CF3OCF2OCF3, AND CF3OCF2CF2H

EPA Science Inventory

New measurements of the thermophysical properties of CF3OCF2CF2CF3 and c -CF2CF2CF2CF2O are reported from T ≈ 235 K to the critical region. Liquid-phase volumetric results for CF3OCF2OCF3 and CF3OCF2CF2H (235 < T/K < 303) are reported to supplement the information already availab...

ONR (Office of Naval Research) Far East Scientific Information Bulletin. Volume 14, Number 2, April-June 1989

DTIC Science & Technology

1989-06-01

tions on either side of the stoichiometric 4V) have been aluminized by using a pack composition. Four factors are considered cementation process. Cyclic...However, in this new applica- tion GPCF is expanding into fiber- (1) Improving CF strength by designing reinforced cements and concretes. Carbon new...called hybrid composite. portland cement matrix. CF provides: (2) Enhancing the energy-absorbing • Chemical inertness to acid and alkali mechanism of

Cognitive function of children with cystic fibrosis: deleterious effect of early malnutrition.

PubMed

Koscik, Rebecca L; Farrell, Philip M; Kosorok, Michael R; Zaremba, Kathleen M; Laxova, Anita; Lai, Hui-Chuan; Douglas, Jeff A; Rock, Michael J; Splaingard, Mark L

2004-06-01

Patients who have cystic fibrosis (CF) and experience delayed diagnosis by traditional methods have greater nutritional insult compared with peers diagnosed via neonatal screening. The objective of this study was to evaluate cognitive function in children with CF and the influence of both early diagnosis through neonatal screening and the potential effect of early malnutrition. Cognitive assessment data were obtained for 89 CF patients (aged 7.3-17 years) during routine clinic visits. Patients had been enrolled in either the screened (N = 42) or traditional diagnosis (control) group (N = 47) of the Wisconsin CF Neonatal Screening Project. The Test of Cognitive Skills, Second Edition was administered to generate the Cognitive Skills Index (CSI) and cognitive factor scores (Verbal, Nonverbal, and Memory). Cognitive scores in the overall study population were similar to normative data (CSI mean [standard deviation]: 102.5 [16.6]; 95% confidence interval: 99.1-105.9). The mean (standard deviation) CSI scores for the screened and control groups were 104.4 (14.4) and 99.8 (18.5), respectively. Significantly lower cognitive scores correlated with indicators of malnutrition and unfavorable family factors such as single parents, lower socioeconomic status, and less parental education. Our analyses revealed lower cognitive scores in patients with low plasma alpha-tocopherol (alpha-T) levels at diagnosis. In addition, patients in the control group who also had vitamin E deficiency at diagnosis (alpha-T < 300 microg/dl) showed significantly lower CSI scores in comparison with alpha-T-sufficient control subjects and both deficient and sufficient alpha-T subsets of screened patients. Results suggest that prevention of prolonged malnutrition by early diagnosis and nutritional therapy, particularly minimizing the duration of vitamin E deficiency, is associated with better cognitive functioning in children with CF.

Selective gene amplification to detect the T790M mutation in plasma from patients with advanced non-small cell lung cancer (NSCLC) who have developed epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance.

PubMed

Nishikawa, Shingo; Kimura, Hideharu; Koba, Hayato; Yoneda, Taro; Watanabe, Satoshi; Sakai, Tamami; Hara, Johsuke; Sone, Takashi; Kasahara, Kazuo; Nakao, Shinji

2018-03-01

The epidermal growth factor receptor (EGFR) T790M mutation is associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). However, tissues for the genotyping of the EGFR T790M mutation can be difficult to obtain in a clinical setting. The aims of this study were to evaluate a blood-based, non-invasive approach to detecting the EGFR T790M mutation in advanced NSCLC patients using the PointMan™ EGFR DNA enrichment kit, which is a novel method for the selective amplification of specific genotype sequences. Blood samples were collected from NSCLC patients who had activating EGFR mutations and who were resistant to EGFR-TKI treatment. Using cell-free DNA (cfDNA) from plasma, EGFR T790M mutations were amplified using the PointMan™ enrichment kit, and all the reaction products were confirmed using direct sequencing. The concentrations of plasma DNA were then determined using quantitative real-time PCR. Nineteen patients were enrolled, and 12 patients (63.2%) were found to contain EGFR T790M mutations in their cfDNA, as detected by the kit. T790M mutations were detected in tumor tissues in 12 cases, and 11 of these cases (91.7%) also exhibited the T790M mutation in cfDNA samples. The concentrations of cfDNA were similar between patients with the T790M mutation and those without the mutation. The PointMan™ kit provides a useful method for determining the EGFR T790M mutation status in cfDNA.

Clinical application of dual photon absorptiometry (DPA) at the lumbar spine (LS) in the diagnosis of osteoporosis

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

Wahner, H.W.; Dunn, W.L.; Riggs, B.L.

This study evaluates the effectiveness of DPA to separate patients with osteoporosis (greater than 2 spinal fractures, normal Ca, P, absence of drugs, and metabolic bone disease) from a normal population. Performance criteria for the instrument have been described previously. Data was obtained from a prospective study of 105 normal women, 75 patients with osteoporosis and a retrospective study of 300 patients with osteoporosis seen in 1982/83. The results were as follows: (1) Area density (gm/cm/sup 2/) was found superior to mass (gm) due to the occasional problem to clearly identify the boundaries of L1-4. (2) Separation of the twomore » populations was best when L1-L4,L2-L4, L3 alone or 10 paths over the mid lumbar area were used. One pass was not acceptable. (3) Compression fractures (CF) in the LS showed an increase in area density initially but area density may be undistinguishable from intact vertebrae later. To correct for this loss of bone area a factor predicting the area of lumbar vertebrae and based on patients actual height and weight was introduced and tested. (4) In the retrospective study a negative correlation was found between number of thoracic spine CF and bone mineral values in the LS. (5) A fracture threshold value of BM defined as the level below which 95% of all patients with CF were found was determined to be 0.98 g/cm2. Sixty-five percent of patients with two or more spinal CF could be separated from the normal population (outside 2SD). By using a correction factor for height loss this could be further increased to about 70%. CF in the LS may falsely elevate bone mineral values.« less

Iron-Regulated Expression of Alginate Production, Mucoid Phenotype, and Biofilm Formation by Pseudomonas aeruginosa

PubMed Central

Wiens, Jacinta R.; Vasil, Adriana I.; Schurr, Michael J.; Vasil, Michael L.

2014-01-01

ABSTRACT Pseudomonas aeruginosa strains of non-cystic fibrosis (non-CF) origin do not produce significant amounts of extracellular alginate and are nonmucoid. In CF, such isolates can become mucoid through mutation of one of the genes (mucA, mucB, mucC, or mucD) that produce regulatory factors that sequester AlgU, required for increased expression of alginate genes. Mutation of the muc genes in the nonmucoid PAO1, PA14, PAKS-1, and Ps388 strains led to increased levels of extracellular alginate and an obvious mucoid phenotype, but only under iron-limiting growth conditions (≤5 µM), not under iron-replete conditions (≥10 µM). In contrast, >50% of P. aeruginosa isolates from chronic CF pulmonary infections expressed increased levels of alginate and mucoidy both under iron-limiting and iron-replete conditions (i.e., iron-constitutive phenotype). No single iron regulatory factor (e.g., Fur, PvdS) was associated with this loss of iron-regulated alginate expression and mucoidy in these CF isolates. However, the loss of only pyoverdine production, or its uptake, abrogated the ability of P. aeruginosa to produce a robust biofilm that represents the Psl-type of biofilm. In contrast, we show that mutation of the pyoverdine and pyochelin biosynthesis genes and the pyoverdine receptor (FpvA) lead to iron-constitutive expression of the key alginate biosynthesis gene, algD, and an explicitly mucoid phenotype in both iron-limiting and iron-replete conditions. These data indicate that alginate production and mucoidy, in contrast to other types of biofilms produced by P. aeruginosa, are substantially enhanced under iron limitation. These results also have compelling implications in relation to the use of iron chelators in the treatment of P. aeruginosa CF infections. PMID:24496793

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

PubMed

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

2017-03-01

Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to <200 days and decreasing mortality on the waitlist. A current challenge is the wait for the waitlist-the time between the patient's transplant-eligible diagnosis and waitlist registration. We investigated whether sociodemographic (age, sex, race, insurance, marital status, median household income) and clinical (forced expiratory volume in 1 second [FEV 1 ] percent of predicted, body mass index, depression/anxiety, alcohol/substance misuse, absolute/relative contraindications) factors influenced referral and waitlist registration. We conducted a retrospective cohort study through chart review of hospitalized patients on the University of Chicago general medicine service from 2006 to 2014 who met transplant-eligible criteria and ICD-9 billing codes for cystic fibrosis (CF) and pulmonary fibrosis (PF). We analyzed the times from transplant eligibility to referral, work-up and waitlisting using Kaplan-Meier curves and log-rank tests. Overall, the referral rate for transplant-eligible patients was 64%. Of those referred, approximately 36% reach the lung transplant waitlist. Referred CF patients were significantly more likely to reach the transplant waitlist than PF patients (CF 60% vs PF 22%, p < 0.05). In addition, CF patients had a shorter wait from transplant eligibility to waitlist than PF patients (329 vs 2,369 days, respectively [25th percentile], p < 0.05). Patients with PF and CF both faced delays from eligibility to referral and waitlist. Quality improvement efforts are needed to better identify and refer appropriate patients for lung transplant evaluation. Targeted interventions may facilitate more efficient evaluation completion and waitlist appearance. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Pathophysiology and Genetics of Bronchiectasis Unrelated to Cystic Fibrosis.

PubMed

Nikolic, Aleksandra

2018-05-12

Bronchiectasis is characterized by deregulated inflammatory response and recurrent bacterial infection resulting in progressive lung damage and an irreversible dilatation of bronchi and bronchioles. Generally accepted model of the development of bronchiectasis is the "vicious cycle hypothesis" that proposes compromising of the mucociliary clearance by an initial event, which leads to the infection of the respiratory tract followed by further impairment of mucociliary function, bacterial proliferation, and more inflammation. Bronchiectasis is a very common symptom in patients with cystic fibrosis (CF), while bronchiectasis unrelated to CF is heterogeneous pathology of unknown cause with a large number of potential contributory factors and poorly understood pathogenesis. It is presumed that bronchiectasis unrelated to CF is a multifactorial condition predisposed by genetic factors. Different molecules have been implicated in the onset and development of idiopathic bronchiectasis, as well as modulation of the disease severity and response to therapy. Most of these molecules are involved in the processes that contribute to the homeostasis of the lung tissue, especially mucociliary clearance, protease-antiprotease balance, and immunomodulation. Evaluation of the studies performed towards investigation of the role these molecules play in bronchiectasis identifies genetic variants that may be of potential importance for clinical management of the disease, and also of interest for future research efforts. This review focuses on the molecules with major roles in lung homeostasis and their involvement in bronchiectasis unrelated to CF.

Professional quality of life normative benchmarks.

PubMed

De La Rosa, Gabriel M; Webb-Murphy, Jennifer A; Fesperman, Susan F; Johnston, Scott L

2018-03-01

Those responsible for the care of trauma survivors can experience both beneficial and detrimental consequences resulting from their professional demands. Research has demonstrated that among professional caregivers, compassion satisfaction (CS), burnout (BO), and compassion fatigue (CF) are important factors contributing to professional quality of life. The current research aims to provide normative information regarding the factors contributing to professional quality of life among those who interact with survivors of trauma. The Professional Quality of Life (ProQOL) Scale is a widely used measure of CS, BO, and CF. The most recent iteration of the ProQOL manual provides normative data to assist in the interpretation of scores. However, a review of the literature reporting raw scores on the ProQOL suggests that mean scores and cutoff scores for the 25th and 75th percentiles may be misleading. A review of 30 studies (total sample size of 5,612) was conducted and normative values are presented. The mean (standard deviation) level of CS, CF, and BO were 37.7 (6.5), 16.7 (5.7), and 22.8 (5.4), respectively. Values gathered from the literature review tend to align well with one another and suggest that within a given sample, CS scores tend to be higher than BO scores, and BO scores tend to be slightly higher than CF scores. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Highly effective cystic fibrosis clinical research teams: critical success factors.

PubMed

Retsch-Bogart, George Z; Van Dalfsen, Jill M; Marshall, Bruce C; George, Cynthia; Pilewski, Joseph M; Nelson, Eugene C; Goss, Christopher H; Ramsey, Bonnie W

2014-08-01

Bringing new therapies to patients with rare diseases depends in part on optimizing clinical trial conduct through efficient study start-up processes and rapid enrollment. Suboptimal execution of clinical trials in academic medical centers not only results in high cost to institutions and sponsors, but also delays the availability of new therapies. Addressing the factors that contribute to poor outcomes requires novel, systematic approaches tailored to the institution and disease under study. To use clinical trial performance metrics data analysis to select high-performing cystic fibrosis (CF) clinical research teams and then identify factors contributing to their success. Mixed-methods research, including semi-structured qualitative interviews of high-performing research teams. CF research teams at nine clinical centers from the CF Foundation Therapeutics Development Network. Survey of site characteristics, direct observation of team meetings and facilities, and semi-structured interviews with clinical research team members and institutional program managers and leaders in clinical research. Critical success factors noted at all nine high-performing centers were: 1) strong leadership, 2) established and effective communication within the research team and with the clinical care team, and 3) adequate staff. Other frequent characteristics included a mature culture of research, customer service orientation in interactions with study participants, shared efficient processes, continuous process improvement activities, and a businesslike approach to clinical research. Clinical research metrics allowed identification of high-performing clinical research teams. Site visits identified several critical factors leading to highly successful teams that may help other clinical research teams improve clinical trial performance.

Characterization of the major proteins of tubers of yam bean (Pachyrhizus ahipa).

PubMed

Forsyth, Jane L; Shewry, Peter R

2002-03-27

Tubers of six accessions of ahipa (Pachyrhizus ahipa) contained between 0.77 and 1.34% nitrogen on a dry weight basis. This corresponds to 4.8 to 8.4% crude protein based on a nitrogen to protein conversion factor of 6.25; but detailed analysis of AC230 showed that although 93% of the total N was extracted with buffer containing 1.0 M NaCl, about a third of this was lost on dialysis. It was calculated, therefore, that salt-soluble proteins comprise about 60% of the total tuber nitrogen, with low-molecular-mass nitrogenous components comprising a further 30%. Electophoretic analysis of the salt-soluble proteins showed similar patterns of components in the six accessions, with none being present in amounts sufficiently high to suggest a role as storage proteins. Furthermore, light microscopy failed to show significant deposits of protein within the tuber cells. Five "major" protein bands, which together accounted for about 19% of the total salt-soluble protein fraction were purified and subjected to N-terminal amino acid sequencing. Comparison of these with sequences in protein databases revealed similarities to alpha-amylases, chitinases and chitin binding proteins, cysteine proteinases (including major components from P. erosus tubers), a tuberization-specific protein from potato, and proteins induced in soybean and pea by stress or the plant hormone abscisic acid, respectively. It was concluded that the primary roles of these proteins are probably in aspects of tuber metabolism and development and/or conferring protection to pests and pathogens, and that true storage proteins are not present. The absence of storage proteins is consistent with the biological role of the tubers as storage organs for carbohydrates (cf cassava tuberous roots) rather than as propagules (cf yam and potato tubers).

Technical feasibility and validation of a coronary artery calcium scoring system using CT coronary angiography images.

PubMed

Pavitt, Christopher W; Harron, Katie; Lindsay, Alistair C; Zielke, Sayeh; Ray, Robin; Gordon, Daniel; Rubens, Michael B; Padley, Simon P; Nicol, Edward D

2016-05-01

We validate a novel CT coronary angiography (CCTA) coronary calcium scoring system. Calcium was quantified on CCTA images using a new patient-specific attenuation threshold: mean + 2SD of intra-coronary contrast density (HU). Using 335 patient data sets a conversion factor (CF) for predicting CACS from CCTA scores (CCTAS) was derived and validated in a separate cohort (n = 168). Bland-Altman analysis and weighted kappa for MESA centiles and Agatston risk groupings were calculated. Multivariable linear regression yielded a CF: CACS = (1.185 × CCTAS) + (0.002 × CCTAS × attenuation threshold). When applied to CCTA data sets there was excellent correlation (r = 0.95; p < 0.0001) and agreement (mean difference -10.4 [95% limits of agreement -258.9 to 238.1]) with traditional calcium scores. Agreement was better for calcium scores below 500; however, MESA percentile agreement was better for high risk patients. Risk stratification was excellent (Agatston groups k = 0.88 and MESA centiles k = 0.91). Eliminating the dedicated CACS scan decreased patient radiation exposure by approximately one-third. CCTA calcium scores can accurately predict CACS using a simple, individualized, semiautomated approach reducing acquisition time and radiation exposure when evaluating patients for CAD. This method is not affected by the ROI location, imaging protocol, or tube voltage strengthening its clinical applicability. • Coronary calcium scores can be reliably determined on contrast-enhanced cardiac CT • This score can accurately risk stratify patients • Elimination of a dedicated calcium scan reduces patient radiation by a third.

VAPOR PRESSURES, LIQUID MOLAR VOLUMES, VAPOR NON- IDEALITIES, AND CRITICAL PROPERTIES OF SOME FLUORINATED ETHERS: CF3OCF2OCF3, CF3OCF2 CF2H, c-CF2CF2CF2O, CF3OCF2H, AND CF3OCH3; AND OF CCl3F AND CF2ClH

EPA Science Inventory

Vapor pressures, compressibilities, expansivities, and molar volumes of the liquid phase have been measured between room temperature and the critical temperature for a series of fluorinated ethers: CF3OCF2OCF3, CF3OCF2CF2H, c-CF2CF2CF2O, CF3OCF2H, and CF3OCH3. Vapor-phase non-ide...

Psychological interventions to reduce suicidality in high-risk patients with major depression: a randomized controlled trial.

PubMed

Celano, C M; Beale, E E; Mastromauro, C A; Stewart, J G; Millstein, R A; Auerbach, R P; Bedoya, C A; Huffman, J C

2017-04-01

Positive psychological constructs have been associated with reduced suicidal ideation, and interventions to cultivate positive feelings have the potential to reduce suicide risk. This study compares the efficacy of a 6-week, telephone-based positive psychology (PP) intervention against a cognition-focused (CF) control intervention among patients recently hospitalized for depression and suicidal ideation or behavior. A total of 65 adults with a current major depressive episode reporting suicidal ideation or a recent suicide attempt were enrolled from participating in-patient psychiatric units. Prior to discharge, participants were randomized to the PP (n = 32) or CF (n = 33) intervention. In both interventions, participants received a treatment manual, performed weekly PP (e.g. gratitude letter) or CF (e.g. recalling daily events) exercises, and completed weekly one-on-one telephone sessions over 6 weeks. Between-group differences in hopelessness (primary outcome), depression, suicidality and positive psychological constructs at 6 and 12 weeks were tested using mixed-effects models accounting for intensity of post-hospitalization psychiatric treatment. Compared with PP, the CF intervention was associated with significantly greater improvements in hopelessness at 6 weeks (β = -3.15, 95% confidence interval -6.18 to -0.12, effect size = -0.84, p = 0.04), but not 12 weeks. Similarly, the CF intervention led to greater improvements in depression, suicidal ideation, optimism and gratitude at 6 and 12 weeks. Contrary to our hypothesis, the CF intervention was superior to PP in improving hopelessness, other suicide risk factors and positive psychological constructs during a key post-discharge period among suicidal patients with depression. Further study of this CF intervention is warranted in populations at high suicide risk.

Psychological interventions to reduce suicidality in high-risk patients with major depression: a randomized controlled trial

PubMed Central

Celano, C. M.; Beale, E. E.; Mastromauro, C. A.; Stewart, J. G.; Millstein, R. A.; Auerbach, R. P.; Bedoya, C. A.; Huffman, J. C.

2016-01-01

Background Positive psychological constructs have been associated with reduced suicidal ideation, and interventions to cultivate positive feelings have the potential to reduce suicide risk. This study compares the efficacy of a 6-week, telephone-based positive psychology (PP) intervention against a cognition-focused (CF) control intervention among patients recently hospitalized for depression and suicidal ideation or behavior. Method A total of 65 adults with a current major depressive episode reporting suicidal ideation or a recent suicide attempt were enrolled from participating in-patient psychiatric units. Prior to discharge, participants were randomized to the PP (n = 32) or CF (n = 33) intervention. In both interventions, participants received a treatment manual, performed weekly PP (e.g. gratitude letter) or CF (e.g. recalling daily events) exercises, and completed weekly one-on-one telephone sessions over 6 weeks. Between-group differences in hopelessness (primary outcome), depression, suicidality and positive psychological constructs at 6 and 12 weeks were tested using mixed-effects models accounting for intensity of post-hospitalization psychiatric treatment. Results Compared with PP, the CF intervention was associated with significantly greater improvements in hopelessness at 6 weeks (β = −3.15, 95% confidence interval −6.18 to −0.12, effect size = −0.84, p = 0.04), but not 12 weeks. Similarly, the CF intervention led to greater improvements in depression, suicidal ideation, optimism and gratitude at 6 and 12 weeks. Conclusions Contrary to our hypothesis, the CF intervention was superior to PP in improving hopelessness, other suicide risk factors and positive psychological constructs during a key post-discharge period among suicidal patients with depression. Further study of this CF intervention is warranted in populations at high suicide risk. PMID:27876105

Designing a SCAR molecular marker for monitoring Trichoderma cf. harzianum in experimental communities.

PubMed

Pérez, Gabriel; Verdejo, Valentina; Gondim-Porto, Clarissa; Orlando, Julieta; Carú, Margarita

2014-11-01

Several species of the fungal genus Trichoderma establish biological interactions with various micro- and macro-organisms. Some of these interactions are relevant in ecological terms and in biotechnological applications, such as biocontrol, where Trichoderma could be considered as an invasive species that colonizes a recipient community. The success of this invasion depends on multiple factors, which can be assayed using experimental communities as study models. Therefore, the aim of this work is to develop a species-specific sequence-characterized amplified region (SCAR) marker to monitor the colonization and growth of T. cf. harzianum when it invades experimental communities. For this study, 16 randomly amplified polymorphic DNA (RAPD) primers of 10-mer were used to generate polymorphic patterns, one of which generated a band present only in strains of T. cf. harzianum. This band was cloned, sequenced, and five primers of 20-23 mer were designed. Primer pairs 2F2/2R2 and 2F2/2R3 successfully and specifically amplified fragments of 278 and 448 bp from the T. cf. harzianum BpT10a strain DNA, respectively. Both primer pairs were also tested against the DNA from 14 strains of T. cf. harzianum and several strains of different fungal genera as specificity controls. Only the DNA from the strains of T. cf. harzianum was successfully amplified. Moreover, primer pair 2F2/2R2 was assessed by quantitative real-time polymerase chain reaction (PCR) using fungal DNA mixtures and DNA extracted from fungal experimental communities as templates. T. cf. harzianum was detectable even when as few as 100 copies of the SCAR marker were available or even when its population represented only 0.1% of the whole community.

Designing a SCAR molecular marker for monitoring Trichoderma cf. harzianum in experimental communities* #

PubMed Central

Pérez, Gabriel; Verdejo, Valentina; Gondim-Porto, Clarissa; Orlando, Julieta; Carú, Margarita

2014-01-01

Several species of the fungal genus Trichoderma establish biological interactions with various micro- and macro-organisms. Some of these interactions are relevant in ecological terms and in biotechnological applications, such as biocontrol, where Trichoderma could be considered as an invasive species that colonizes a recipient community. The success of this invasion depends on multiple factors, which can be assayed using experimental communities as study models. Therefore, the aim of this work is to develop a species-specific sequence-characterized amplified region (SCAR) marker to monitor the colonization and growth of T. cf. harzianum when it invades experimental communities. For this study, 16 randomly amplified polymorphic DNA (RAPD) primers of 10-mer were used to generate polymorphic patterns, one of which generated a band present only in strains of T. cf. harzianum. This band was cloned, sequenced, and five primers of 20–23 mer were designed. Primer pairs 2F2/2R2 and 2F2/2R3 successfully and specifically amplified fragments of 278 and 448 bp from the T. cf. harzianum BpT10a strain DNA, respectively. Both primer pairs were also tested against the DNA from 14 strains of T. cf. harzianum and several strains of different fungal genera as specificity controls. Only the DNA from the strains of T. cf. harzianum was successfully amplified. Moreover, primer pair 2F2/2R2 was assessed by quantitative real-time polymerase chain reaction (PCR) using fungal DNA mixtures and DNA extracted from fungal experimental communities as templates. T. cf. harzianum was detectable even when as few as 100 copies of the SCAR marker were available or even when its population represented only 0.1% of the whole community. PMID:25367789

On the generation of a bubbly universe - A quantitative assessment of the CfA slice

NASA Technical Reports Server (NTRS)

Ostriker, J. P.; Strassler, M. J.

1989-01-01

A first attempt is made to calculate the properties of the matter distribution in a universe filled with overlapping bubbles produced by multiple explosions. Each spherical shell follows the cosmological Sedov-Taylor solution until it encounters another shell. Thereafter, mergers are allowed to occur in pairs on the basis of N-body results. At the final epoch, the matrix of overlapping shells is populated with 'galaxies' and the properties of slices through the numerically constructed cube compare well with CfA survey results for specified initial conditions. A statistic is found which measures the distance distribution from uniformly distributed points to the nearest galaxies on the projected plane which appears to provide a good measure of the bubbly character of the galaxy distribution. In a quantitative analysis of the CfA 'slice of the universe', a very good match is found between simulation and the real data for final average bubble radii of (13.5 + or - 1.5)/h Mpc with formal filling factor 1.0-1.5 or actual filling factor of 65-80 percent.

Characterization of unusual bacteria isolated from respiratory secretions of cystic fibrosis patients and description of Inquilinus limosus gen. nov., sp. nov.

PubMed

Coenye, Tom; Goris, Johan; Spilker, Theodore; Vandamme, Peter; LiPuma, John J

2002-06-01

Using a polyphasic approach (including cellular protein and fatty acid analysis, biochemical characterization, 16S ribosomal DNA sequencing, and DNA-DNA hybridizations), we characterized 51 bacterial isolates recovered from respiratory secretions of cystic fibrosis (CF) patients. Our analyses showed that 24 isolates belong to taxa that have so far not (or only rarely) been reported from CF patients. These taxa include Acinetobacter sp., Bordetella hinzii, Burkholderia fungorum, Comamonas testosteroni, Chryseobacterium sp., Herbaspirillum sp., Moraxella osloensis, Pandoraea genomospecies 4, Ralstonia gilardii, Ralstonia mannitolilytica, Rhizobium radiobacter, and Xanthomonas sp. In addition, one isolate most likely represents a novel Ralstonia species, whereas nine isolates belong to novel taxa within the alpha-PROTEOBACTERIA: Eight of these latter isolates are classified into the novel genus Inquilinus gen. nov. as Inquilinus limosus gen. nov., sp. nov., or as Inquilinus sp. The remaining 17 isolates are characterized as members of the family ENTEROBACTERIACEAE: The recovery of these species suggests that the CF lung is an ecological niche capable of supporting the growth of a wide variety of bacteria rarely seen in clinical samples. Elucidation of the factors that account for the association between these unusual species and the respiratory tract of CF patients may provide important insights into the pathophysiology of CF infection. Because accurate identification of these organisms in the clinical microbiology laboratory may be problematic, the present study highlights the utility of reference laboratories capable of identifying unusual species recovered from CF sputum.

Microbiome in the pathogenesis of cystic fibrosis and lung transplant-related disease.

PubMed

Cribbs, Sushma K; Beck, James M

2017-01-01

Significant advances in culture-independent methods have expanded our knowledge about the diversity of the lung microbial environment. Complex microorganisms and microbial communities can now be identified in the distal airways in a variety of respiratory diseases, including cystic fibrosis (CF) and the posttransplantation lung. Although there are significant methodologic concerns about sampling the lung microbiome, several studies have now shown that the microbiome of the lower respiratory tract is distinct from the upper airway. CF is a disease characterized by chronic airway infections that lead to significant morbidity and mortality. Traditional culture-dependent methods have identified a select group of pathogens that cause exacerbations in CF, but studies using bacterial 16S rRNA gene-based microarrays have shown that the CF microbiome is an intricate and dynamic bacterial ecosystem, which influences both host immune health and disease pathogenesis. These microbial communities can shift with external influences, including antibiotic exposure. In addition, there have been a number of studies suggesting a link between the gut microbiome and respiratory health in CF. Compared with CF, there is significantly less knowledge about the microbiome of the transplanted lung. Risk factors for bronchiolitis obliterans syndrome, one of the leading causes of death, include microbial infections. Lung transplant patients have a unique lung microbiome that is different than the pretransplanted microbiome and changes with time. Understanding the host-pathogen interactions in these diseases may suggest targeted therapies and improve long-term survival in these patients. Published by Elsevier Inc.

Strong incidence of Pseudomonas aeruginosa on bacterial rrs and ITS genetic structures of cystic fibrosis sputa

PubMed Central

Pages-Monteiro, Laurence; Marti, Romain; Commun, Carine; Alliot, Nolwenn; Bardel, Claire; Meugnier, Helene; Perouse-de-Montclos, Michele; Reix, Philippe; Durieu, Isabelle; Durupt, Stephane; Vandenesch, Francois; Freney, Jean; Cournoyer, Benoit; Doleans-Jordheim, Anne

2017-01-01

Cystic fibrosis (CF) lungs harbor a complex community of interacting microbes, including pathogens like Pseudomonas aeruginosa. Meta-taxogenomic analysis based on V5-V6 rrs PCR products of 52 P. aeruginosa-positive (Pp) and 52 P. aeruginosa-negative (Pn) pooled DNA extracts from CF sputa suggested positive associations between P. aeruginosa and Stenotrophomonas and Prevotella, but negative ones with Haemophilus, Neisseria and Burkholderia. Internal Transcribed Spacer analyses (RISA) from individual DNA extracts identified three significant genetic structures within the CF cohorts, and indicated an impact of P. aeruginosa. RISA clusters Ip and IIIp contained CF sputa with a P. aeruginosa prevalence above 93%, and of 24.2% in cluster IIp. Clusters Ip and IIIp showed lower RISA genetic diversity and richness than IIp. Highly similar cluster IIp RISA profiles were obtained from two patients harboring isolates of a same P. aeruginosa clone, suggesting convergent evolution in the structure of their microbiota. CF patients of cluster IIp had received significantly less antibiotics than patients of clusters Ip and IIIp but harbored the most resistant P. aeruginosa strains. Patients of cluster IIIp were older than those of Ip. The effects of P. aeruginosa on the RISA structures could not be fully dissociated from the above two confounding factors but several trends in these datasets support the conclusion of a strong incidence of P. aeruginosa on the genetic structure of CF lung microbiota. PMID:28282386

First-trimester contingent screening for trisomies 21, 18 and 13 by biomarkers and maternal blood cell-free DNA testing.

PubMed

Nicolaides, K H; Syngelaki, A; Poon, L C; Gil, M M; Wright, D

2014-01-01

To examine potential performance of screening for trisomies by cell-free (cf) DNA testing in maternal blood contingent on results of first-line testing by combinations of fetal translucency thickness (NT), fetal heart rate (FHR), ductus venosus pulsatility index (DV PIV), and serum-free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF) and α-fetoprotein (AFP). Performance was estimated for firstly, screening by cfDNA in all pregnancies and secondly, cfDNA testing contingent on results of first-line testing by combinations of ultrasound and biochemical markers. In first-line screening by cfDNA testing, the detection rate for trisomy 21 and trisomies 18 or 13 would be 99 and 96%, respectively, after invasive testing in 1% of the population. In contingent screening, a detection rate of 98% for trisomy 21 and 96% for trisomy 18 or 13, at an invasive testing rate of 0.7%, can be achieved by carrying out cfDNA testing in about 35, 20 and 11% of cases identified by first-line screening with the combined test alone (age, NT, FHR, β-hCG, PAPP-A), the combined test plus PLGF and AFP and the combined test plus PLGF, AFP and DV PIV, respectively. Effective first-trimester screening for trisomies can be achieved by contingent screening incorporating biomarkers and cfDNA testing. © 2013 S. Karger AG, Basel.

Prodrugs of herpes simplex thymidine kinase inhibitors.

PubMed

Yanachkova, Milka; Xu, Wei-Chu; Dvoskin, Sofya; Dix, Edward J; Yanachkov, Ivan B; Focher, Federico; Savi, Lida; Sanchez, M Dulfary; Foster, Timothy P; Wright, George E

2015-04-01

Because guanine-based herpes simplex virus thymidine kinase inhibitors are not orally available, we synthesized various 6-deoxy prodrugs of these compounds and evaluated them with regard to solubility in water, oral bioavailability, and efficacy to prevent herpes simplex virus-1 reactivation from latency in a mouse model. Organic synthesis was used to prepare compounds, High Performance Liquid Chromatography (HPLC) to analyze hydrolytic conversion, Mass Spectrometry (MS) to measure oral bioavailability, and mouse latent infection and induced reactivation to evaluate the efficacy of a specific prodrug. Aqueous solubilities of prodrugs were improved, oxidation of prodrugs by animal cytosols occurred in vitro, and oral absorption of the optimal prodrug sacrovir™ (6-deoxy-mCF3PG) in the presence of the aqueous adjuvant Soluplus® and conversion to active compound N(2)-[3-(trifluoromethyl)pheny])guanine (mCF3PG) were accomplished in mice. Treatment of herpes simplex virus-1 latent mice with sacrovir™ in 1% Soluplus in drinking water significantly suppressed herpes simplex virus-1 reactivation and viral genomic replication. Ad libitum oral delivery of sacrovir™ was effective in suppressing herpes simplex virus-1 reactivation in ocularly infected latent mice as measured by the numbers of mice shedding infectious virus at the ocular surface, numbers of trigeminal ganglia positive for infectious virus, number of corneas that had detectable infectious virus, and herpes simplex virus-1 genome copy numbers in trigeminal ganglia following reactivation. These results demonstrate the statistically significant effect of the prodrug on suppressing herpes simplex virus-1 reactivation in vivo. © The Author(s) 2015.

Association of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer

PubMed Central

Stover, Daniel G.; Parsons, Heather A.; Ha, Gavin; Freeman, Samuel S.; Barry, William T.; Guo, Hao; Choudhury, Atish D.; Gydush, Gregory; Reed, Sarah C.; Rhoades, Justin; Rotem, Denisse; Hughes, Melissa E.; Dillon, Deborah A.; Partridge, Ann H.; Wagle, Nikhil; Krop, Ian E.; Getz, Gad; Golub, Todd R.; Love, J. Christopher; Winer, Eric P.; Tolaney, Sara M.; Lin, Nancy U.

2018-01-01

Purpose Cell-free DNA (cfDNA) offers the potential for minimally invasive genome-wide profiling of tumor alterations without tumor biopsy and may be associated with patient prognosis. Triple-negative breast cancer (TNBC) is characterized by few mutations but extensive somatic copy number alterations (SCNAs), yet little is known regarding SCNAs in metastatic TNBC. We sought to evaluate SCNAs in metastatic TNBC exclusively via cfDNA and determine if cfDNA tumor fraction is associated with overall survival in metastatic TNBC. Patients and Methods In this retrospective cohort study, we identified 164 patients with biopsy-proven metastatic TNBC at a single tertiary care institution who received prior chemotherapy in the (neo)adjuvant or metastatic setting. We performed low-coverage genome-wide sequencing of cfDNA from plasma. Results Without prior knowledge of tumor mutations, we determined tumor fraction of cfDNA for 96.3% of patients and SCNAs for 63.9% of patients. Copy number profiles and percent genome altered were remarkably similar between metastatic and primary TNBCs. Certain SCNAs were more frequent in metastatic TNBCs relative to paired primary tumors and primary TNBCs in publicly available data sets The Cancer Genome Atlas and METABRIC, including chromosomal gains in drivers NOTCH2, AKT2, and AKT3. Prespecified cfDNA tumor fraction threshold of ≥ 10% was associated with significantly worse metastatic survival (median, 6.4 v 15.9 months) and remained significant independent of clinicopathologic factors (hazard ratio, 2.14; 95% CI, 1.4 to 3.8; P < .001). Conclusion We present the largest genomic characterization of metastatic TNBC to our knowledge, exclusively from cfDNA. Evaluation of cfDNA tumor fraction was feasible for nearly all patients, and tumor fraction ≥ 10% is associated with significantly worse survival in this large metastatic TNBC cohort. Specific SCNAs are enriched and prognostic in metastatic TNBC, with implications for metastasis, resistance, and novel therapeutic approaches. PMID:29298117

Breathing pattern and chest wall volumes during exercise in patients with cystic fibrosis, pulmonary fibrosis and COPD before and after lung transplantation.

PubMed

Wilkens, H; Weingard, B; Lo Mauro, A; Schena, E; Pedotti, A; Sybrecht, G W; Aliverti, A

2010-09-01

Pulmonary fibrosis (PF), cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) often cause chronic respiratory failure (CRF). In order to investigate if there are different patterns of adaptation of the ventilatory pump in CRF, in three groups of lung transplant candidates with PF (n=9, forced expiratory volume in 1 s (FEV(1))=37+/-3% predicted, forced vital capacity (FVC)=32+/-2% predicted), CF (n=9, FEV(1)=22+/-3% predicted, FVC=30+/-3% predicted) and COPD (n=21, FEV(1)=21+/-1% predicted, FVC=46+/-2% predicted), 10 healthy controls and 16 transplanted patients, total and compartmental chest wall volumes were measured by opto-electronic plethysmography during rest and exercise. Three different breathing patterns were found during CRF in PF, CF and COPD. Patients with COPD were characterised by a reduced duty cycle at rest and maximal exercise (34+/-1%, p<0.001), while patients with PF and CF showed an increased breathing frequency (49+/-6 and 34+/-2/min, respectively) and decreased tidal volume (0.75+/-0.10 and 0.79+/-0.07 litres) (p<0.05). During exercise, end-expiratory chest wall and rib cage volumes increased significantly in patients with COPD and CF but not in those with PF. End-inspiratory volumes did not increase in CF and PF. The breathing pattern of transplanted patients was similar to that of healthy controls. There are three distinct patterns of CRF in patients with PF, CF and COPD adopted by the ventilatory pump to cope with the underlying lung disease that may explain why patients with PF and CF are prone to respiratory failure earlier than patients with COPD. After lung transplantation the chronic adaptations of the ventilatory pattern to advanced lung diseases are reversible and indicate that the main contributing factor is the lung itself rather than systemic effects of the disease.

Neutrophil Extracellular Trap (NET)-Mediated Killing of Pseudomonas aeruginosa: Evidence of Acquired Resistance within the CF Airway, Independent of CFTR

PubMed Central

Young, Robert L.; Malcolm, Kenneth C.; Kret, Jennifer E.; Caceres, Silvia M.; Poch, Katie R.; Nichols, David P.; Taylor-Cousar, Jennifer L.; Saavedra, Milene T.; Randell, Scott H.; Vasil, Michael L.; Burns, Jane L.; Moskowitz, Samuel M.; Nick, Jerry A.

2011-01-01

The inability of neutrophils to eradicate Pseudomonas aeruginosa within the cystic fibrosis (CF) airway eventually results in chronic infection by the bacteria in nearly 80 percent of patients. Phagocytic killing of P. aeruginosa by CF neutrophils is impaired due to decreased cystic fibrosis transmembrane conductance regulator (CFTR) function and virulence factors acquired by the bacteria. Recently, neutrophil extracellular traps (NETs), extracellular structures composed of neutrophil chromatin complexed with granule contents, were identified as an alternative mechanism of pathogen killing. The hypothesis that NET-mediated killing of P. aeruginosa is impaired in the context of the CF airway was tested. P. aeruginosa induced NET formation by neutrophils from healthy donors in a bacterial density dependent fashion. When maintained in suspension through continuous rotation, P. aeruginosa became physically associated with NETs. Under these conditions, NETs were the predominant mechanism of killing, across a wide range of bacterial densities. Peripheral blood neutrophils isolated from CF patients demonstrated no impairment in NET formation or function against P. aeruginosa. However, isogenic clinical isolates of P. aeruginosa obtained from CF patients early and later in the course of infection demonstrated an acquired capacity to withstand NET-mediated killing in 8 of 9 isolates tested. This resistance correlated with development of the mucoid phenotype, but was not a direct result of the excess alginate production that is characteristic of mucoidy. Together, these results demonstrate that neutrophils can kill P. aeruginosa via NETs, and in vitro this response is most effective under non-stationary conditions with a low ratio of bacteria to neutrophils. NET-mediated killing is independent of CFTR function or bacterial opsonization. Failure of this response in the context of the CF airway may occur, in part, due to an acquired resistance against NET-mediated killing by CF strains of P. aeruginosa. PMID:21909403

Association of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer.

PubMed

Stover, Daniel G; Parsons, Heather A; Ha, Gavin; Freeman, Samuel S; Barry, William T; Guo, Hao; Choudhury, Atish D; Gydush, Gregory; Reed, Sarah C; Rhoades, Justin; Rotem, Denisse; Hughes, Melissa E; Dillon, Deborah A; Partridge, Ann H; Wagle, Nikhil; Krop, Ian E; Getz, Gad; Golub, Todd R; Love, J Christopher; Winer, Eric P; Tolaney, Sara M; Lin, Nancy U; Adalsteinsson, Viktor A

2018-02-20

Purpose Cell-free DNA (cfDNA) offers the potential for minimally invasive genome-wide profiling of tumor alterations without tumor biopsy and may be associated with patient prognosis. Triple-negative breast cancer (TNBC) is characterized by few mutations but extensive somatic copy number alterations (SCNAs), yet little is known regarding SCNAs in metastatic TNBC. We sought to evaluate SCNAs in metastatic TNBC exclusively via cfDNA and determine if cfDNA tumor fraction is associated with overall survival in metastatic TNBC. Patients and Methods In this retrospective cohort study, we identified 164 patients with biopsy-proven metastatic TNBC at a single tertiary care institution who received prior chemotherapy in the (neo)adjuvant or metastatic setting. We performed low-coverage genome-wide sequencing of cfDNA from plasma. Results Without prior knowledge of tumor mutations, we determined tumor fraction of cfDNA for 96.3% of patients and SCNAs for 63.9% of patients. Copy number profiles and percent genome altered were remarkably similar between metastatic and primary TNBCs. Certain SCNAs were more frequent in metastatic TNBCs relative to paired primary tumors and primary TNBCs in publicly available data sets The Cancer Genome Atlas and METABRIC, including chromosomal gains in drivers NOTCH2, AKT2, and AKT3. Prespecified cfDNA tumor fraction threshold of ≥ 10% was associated with significantly worse metastatic survival (median, 6.4 v 15.9 months) and remained significant independent of clinicopathologic factors (hazard ratio, 2.14; 95% CI, 1.4 to 3.8; P < .001). Conclusion We present the largest genomic characterization of metastatic TNBC to our knowledge, exclusively from cfDNA. Evaluation of cfDNA tumor fraction was feasible for nearly all patients, and tumor fraction ≥ 10% is associated with significantly worse survival in this large metastatic TNBC cohort. Specific SCNAs are enriched and prognostic in metastatic TNBC, with implications for metastasis, resistance, and novel therapeutic approaches.

Life cycle assessment of milk production from commercial dairy farms: the influence of management tactics.

PubMed

Yan, M-J; Humphreys, J; Holden, N M

2013-07-01

Little consideration has been given to how farm management, specifically tactics used to implement the management strategy, may influence the carbon footprint (CF) and land use for milk produced on commercial farms. In this study, the CF and land use of milk production from 18 Irish commercial dairy farms were analyzed based on foreground data from a 12-mo survey capturing management tactics and background data from the literature. Large variation was found in farm attributes and management tactics; for example, up to a 1.5-fold difference in fertilizer nitrogen input was used to support the same stocking density, and up to a 3.5-fold difference in concentrate fed for similar milk output per cow. However, the coefficient of variation for milk CF between farms only varied by 13% and for land use by 18%. The overall CF and overall land use of the milk production from the 18 dairy farms was 1.23±0.04kg of CO2 Eq and 1.22±0.05 m(2) per kilogram of energy-corrected milk. Milk output per cow, economic allocation between exports of milk and liveweight, and on-farm diesel use per ha were found to be influential factors on milk CF, whereas the fertilizer N rate, milk output per cow, and economic allocation between exports of milk and liveweight were influential on land use. Effective sward management of white clover within a few farms appeared to lower the CF but increased on-farm land use. It was concluded that a combination of multiple tactics determines CF and land use for milk production on commercial dairy farms and, although these 2 measures of environmental impact are correlated, a farm with a low CF did not always have low land use and vice versa. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Respiratory viruses in healthy infants and infants with cystic fibrosis: a prospective cohort study.

PubMed

Korten, Insa; Kieninger, Elisabeth; Klenja, Shkipe; Mack, Ines; Schläpfer, Njima; Barbani, Maria Teresa; Regamey, Nicolas; Kuehni, Claudia E; Hilty, Markus; Frey, Urs; Gorgievski, Meri; Casaulta, Carmen; Latzin, Philipp

2018-01-01

Acute viral respiratory tract infections in children with cystic fibrosis (CF) are known causes of disease exacerbation. The role of viral infections during infancy is, however, less known, although early infancy is thought to be a crucial period for CF disease development.We prospectively assessed symptomatic and asymptomatic viral detection in the first year of life in infants with CF and healthy controls. In a prospective cohort study, we included 31 infants with CF from the Swiss Cystic Fibrosis Infant Lung Development Cohort and 32 unselected, healthy infants from the Basel Bern Infant Lung Development Cohort and followed them throughout the first year of life. Respiratory symptoms were assessed by weekly telephone interviews. Biweekly nasal swabs were analysed for 10 different viruses and two atypical bacteria with real-time seven duplex PCR (CF=561, controls=712). Infants with CF and healthy controls showed similar numbers of swabs positive for virus (mean 42% vs 44%; OR 0.91, 95% CI 0.66 to 1.26, p=0.6). Virus-positive swabs were less often accompanied by respiratory symptoms in infants with CF (17% vs 23%; OR 0.64, 95% CI 0.43 to 0.95, p=0.026). This finding was pronounced for symptomatic human rhinovirus detection (7% vs 11%; OR 0.52, 95% CI 0.31 to 0.9, p=0.02). Viral detection is not more frequent in infants with CF and respiratory symptoms during viral detection occur even less often than in healthy controls. It is likely an interplay of different factors such as local epithelial properties and immunological mechanisms that contribute to our findings. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Understanding the Pathogenicity of Burkholderia contaminans, an Emerging Pathogen in Cystic Fibrosis.

PubMed

Nunvar, Jaroslav; Kalferstova, Lucie; Bloodworth, Ruhi A M; Kolar, Michal; Degrossi, Jose; Lubovich, Silvina; Cardona, Silvia T; Drevinek, Pavel

2016-01-01

Several bacterial species from the Burkholderia cepacia complex (Bcc) are feared opportunistic pathogens that lead to debilitating lung infections with a high risk of developing fatal septicemia in cystic fibrosis (CF) patients. However, the pathogenic potential of other Bcc species is yet unknown. To elucidate clinical relevance of Burkholderia contaminans, a species frequently isolated from CF respiratory samples in Ibero-American countries, we aimed to identify its key virulence factors possibly linked with an unfavorable clinical outcome. We performed a genome-wide comparative analysis of two isolates of B. contaminans ST872 from sputum and blood culture of a female CF patient in Argentina. RNA-seq data showed significant changes in expression for quorum sensing-regulated virulence factors and motility and chemotaxis. Furthermore, we detected expression changes in a recently described low-oxygen-activated (lxa) locus which encodes stress-related proteins, and for two clusters responsible for the biosynthesis of antifungal and hemolytic compounds pyrrolnitrin and occidiofungin. Based on phenotypic assays that confirmed changes in motility and in proteolytic, hemolytic and antifungal activities, we were able to distinguish two phenotypes of B. contaminans that coexisted in the host and entered her bloodstream. Whole genome sequencing revealed that the sputum and bloodstream isolates (each representing a distinct phenotype) differed by over 1,400 mutations as a result of a mismatch repair-deficient hypermutable state of the sputum isolate. The inferred lack of purifying selection against nonsynonymous mutations and the high rate of pseudogenization in the derived isolate indicated limited evolutionary pressure during evolution in the nutrient-rich, stable CF sputum environment. The present study is the first to examine the genomic and transcriptomic differences between longitudinal isolates of B. contaminans. Detected activity of a number of putative virulence factors implies a genuine pathogenic nature of this novel Bcc species.

Turning eating psychopathology risk factors into action. The pervasive effect of body image-related cognitive fusion.

PubMed

Ferreira, Cláudia; Palmeira, Lara; Trindade, Inês A

2014-09-01

Body image dissatisfaction and unfavourable social comparisons are significant risk factors to eating psychopathology. Nevertheless, the impact of these negative experiences depends on the cognitive and emotional processes involved. Previous research has shown that cognitive fusion is a nuclear process linked to psychological inflexibility, but its role on body image and eating difficulties remains unclear. This study aims to explore a model of the mediational role of body image-related cognitive fusion (CF-BI) on the relationship between body dissatisfaction, unfavourable social comparisons, and eating psychopathology in a sample of 345 female students. Results from path analyses show that the impact of unfavourable social comparisons on eating psychopathology is fully mediated by CF-BI. Moreover, CF-BI also revealed a mediational effect on the relationship between body image dissatisfaction and the severity of eating symptoms, in spite of the fact that a direct effect of body dissatisfaction still exists. The tested model highlights the crucial role that cognitive fusion, in the specific domain of body image, plays in the relationship between risk factors and the severity of disordered eating attitudes and behaviours. Furthermore, these findings present empirical support for the relevance of addressing acceptance and cognitive defusion techniques to prevent and treat eating disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential Responses of Neotropical Mountain Forests to Climate Change during the Last Millenium

NASA Astrophysics Data System (ADS)

Figueroa-Rangel, B. L.; Olvera Vargas, M.

2013-05-01

The long-term perspective in the conservation of mountain ecosystems using palaeoecological and paleoclimatological techniques are providing with crucial information for the understanding of the temporal range and variability of ecological pattern and processes. This perception is contributing with means to anticipate future conditions of these ecosystems, especially their response to climate change. Neotropical mountain forests, created by a particular geological and climatic history in the Americas, represent one of the most distinctive ecosystems in the tropics which are constantly subject to disturbances included climate change. Mexico due to its geographical location between the convergence of temperate and tropical elements, its diverse physiography and climatic heterogeneity, contains neotropical ecosystems with high biodiversity and endemicity whose structure and taxonomical composition have changed along centurial to millennial scales. Different neotropical forests expand along the mountain chains of Mexico with particular responses along spatial and temporal scales. Therefore in order to capture these scales at fine resolution, sedimentary sequences from forest hollows were retrieved from three forest at different altitudes within 10 km; Pine forest (PF), Transitional forest (TF) and Cloud forest (CF). Ordination techniques were used to relate changes in vegetation with the environment every ~60 years. The three forests experience the effect of the dry stage ~AD 800-1200 related to the Medieval Warm Period reported for several regions of the world. CF contracted, PF expanded while the TF evolved from CF to a community dominated by dry-resistant epiphytes. Dry periods in PF and TF overlapped with the increase in fire occurrences while a dissimilar pattern took place in CF. Maize, Asteraceae and Poaceae were higher during dry intervals while epiphytes decreased. A humid period ~1200-1450 AD was associated with an expansion and a high taxa turnover in CF. During periods of aridity, temporal heterogeneity in the abundance of individual taxa was crucial in the determination of forest resilience following climate change, where some taxa disappeared for hundreds years and then reappeared when humidity returns. Given the global climate change prediction for neotropical forests where drier environments are expected, the long-term resilience of these ecosystems may be greatly reduced. Fire was determined as an essential natural component of the PF. Consequently conservation and management strategies should always regard fire as an important tool for its present and future perpetuation. CF is a vulnerable community, distinctive in temporal taxa composition, therefore site-specificity protection schemes are crucial for its future preservation.TF was a CF in the past developing into a Pinus-Carpinus-Quercus forest today. Given the present-day predictions of global warming, the goal in this forest is to avoid its conversion into an open-land establishing strict protection schemes.

Deregulation of the growth hormone/insulin-like growth factor-1 axis in adults with cystic fibrosis.

PubMed

Pascucci, C; De Biase, R V; Savi, D; Quattrucci, S; Isidori, A M; Lubrano, C; Gnessi, L; Lenzi, A

2018-05-01

Patients with cystic fibrosis (CF) present with signs and symptoms that overlap with those of adult growth hormone deficiency (GHD) syndrome: loss of muscle mass, bone fragility and lower stress tolerance. In literature, the prevalence of GHD in pediatric CF patients is higher than general population, but these studies have been performed on children with growth delay. To our knowledge, there are no studies on adult patients. The aim of this paper is to evaluate GH-IGF1 axis in an adult CF population. Fifty clinically stable adult patients, 30 males; age 36 ± 2 years; BMI 21.39 ± 0.22 kg/m 2 and FEV 1 67 ± 4% were studied. Data regarding glycometabolic status and results of pituitary, thyroid, parathyroid, gonadal and adrenal function tests were recorded. All patients underwent a GH releasing hormone (GHRH) + Arginine stimulation test to confirm a GHD. GHRH + Arginine test revealed the presence of GHD in 16 patients (32%); specifically 7 patients had a severe deficiency and 9 a partial deficiency. Adult patients with CF may show GHD. These patients should be followed over time to assess if the GHD could impact the clinical progression of CF.

Synthesis and photophysical studies of blue phosphorescent Ir(III) complexes with dimethylphenylphospine.

PubMed

Ham, Ho-Wan; Jung, Kyung-Yoon; Kim, Young-Sik

2012-02-01

New blue emitting mixed ligand iridium(III) complexes comprising one cyclometalating, two phosphines trans to each other such as Ir{(CF3)2Meppy}(PPhMe3)2(H)(L) [L = CI, NCMe, CN] [(CF3)2Meppy = 2-(3', 5'-bis-trifluoromethylphenyl)-4-methylpyridine] were synthesized and studied to tune the phosphorescence wavelength to the deep blue region and to enhance the luminescence efficiencies. To achieve deep blue emission, the trifluoromethyl group substituted on the phenyl ring and the methyl group substituted on the pyridyl ring increased HOMO-LUMO gap and achieved the hypsochromic shift. To gain insight into the factors responsible for the emission color change and the different luminescence efficiency, we investigate the electron-withdrawing capabilities of ancillary ligands using the DFT and TD-DFT calculations on the ground and excited states of the complexes. From these results, we discuss how the ancillary ligand influences the emission peak as well as the metal to ligand charge transfer (MLCT) transition efficiency. The maximum emission spectra of Ir{(CF3)2Meppy}(PPhMe3)2(H)(Cl), [Ir{(CF3),Meppy)(PPhMe3),(H)(NCMe)]+ and Ir{(CF3)2Meppy}(PPhMe3)2(H)(CN) were in the ranges of 441, 435, 434 nm, respectively.

Complementary Feeding Strategies to Facilitate Acceptance of Fruits and Vegetables: A Narrative Review of the Literature.

PubMed

Nicklaus, Sophie

2016-11-19

Complementary feeding (CF), which should begin after exclusive breastfeeding for six months, according to the World Health Organization (WHO), or after four months and before six months according to the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN), is a period when the infant implicitly learns what, when, how, and how much to eat. At the onset of CF, the brain and the gut are still developing and maturing, and food experiences contribute to shaping brain connections involved in food hedonics and in the control of food intake. These learning processes are likely to have a long-term impact. Children's consumption of fruit and vegetables (FV) is below recommendations in many countries. Thus, it is crucial to establish preferences for FV early, when infants are learning to eat. The development of food preferences mainly starts when infants discover their first solid foods. This narrative review summarizes the factors that influence FV acceptance at the start of the CF period: previous milk feeding experience; timing of onset of CF; repeated exposures to the food; variety of foods offered as of the start of the CF period; quality and sensory properties of the complementary foods; quality of the meal time context; and parental responsive feeding.

Complementary Feeding Strategies to Facilitate Acceptance of Fruits and Vegetables: A Narrative Review of the Literature

PubMed Central

Nicklaus, Sophie

2016-01-01

Complementary feeding (CF), which should begin after exclusive breastfeeding for six months, according to the World Health Organization (WHO), or after four months and before six months according to the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN), is a period when the infant implicitly learns what, when, how, and how much to eat. At the onset of CF, the brain and the gut are still developing and maturing, and food experiences contribute to shaping brain connections involved in food hedonics and in the control of food intake. These learning processes are likely to have a long-term impact. Children’s consumption of fruit and vegetables (FV) is below recommendations in many countries. Thus, it is crucial to establish preferences for FV early, when infants are learning to eat. The development of food preferences mainly starts when infants discover their first solid foods. This narrative review summarizes the factors that influence FV acceptance at the start of the CF period: previous milk feeding experience; timing of onset of CF; repeated exposures to the food; variety of foods offered as of the start of the CF period; quality and sensory properties of the complementary foods; quality of the meal time context; and parental responsive feeding. PMID:27869776

Burnout, compassion fatigue, and compassion satisfaction among staff in community-based mental health services.

PubMed

Rossi, Alberto; Cetrano, Gaia; Pertile, Riccardo; Rabbi, Laura; Donisi, Valeria; Grigoletti, Laura; Curtolo, Cristina; Tansella, Michele; Thornicroft, Graham; Amaddeo, Francesco

2012-12-30

Providing care to individuals with complex mental health needs can be stressful. However, little research has focused on the emotional, cognitive, and physical consequences of providing mental health care. The aim of this study is to assess burnout (BO), compassion fatigue (CF) and compassion satisfaction (CS) among staff at the four community-based mental health services (CMHS) of Verona, Italy. All staff were asked to complete anonymously the Professional Quality of Life Scale, the General Health Questionnaire, and a socio-demographic questionnaire. In total 260 staff participated (a response rate of 84%). Psychiatrists and social workers were the professionals with the highest levels of BO and CF. Workers with psychological distress reported both higher BO and CF scores, and lower levels of CS. A significant increase in the BO and CF scores was also detected for each extra year spent working in a CMHS. A higher level of CF was associated with female and having been experienced one negative life event in the previous year. These findings are useful for health managers and team leaders to identify factors affecting the professional quality of life of mental healthcare staff, and can provide a rationale for detecting staff at risk for developing negative work-related outcomes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Mitigation of nitrous oxide (N2 O) emission from swine wastewater treatment in an aerobic bioreactor packed with carbon fibers.

PubMed

Yamashita, Takahiro; Yamamoto-Ikemoto, Ryoko; Yokoyama, Hiroshi; Kawahara, Hirofumi; Ogino, Akifumi; Osada, Takashi

2015-03-01

Mitigation of nitrous oxide (N2 O) emission from swine wastewater treatment was demonstrated in an aerobic bioreactor packed with carbon fibers (CF reactor). The CF reactor had a demonstrated advantage in mitigating N2 O emission and avoiding NOx (NO3  + NO2 ) accumulation. The N2 O emission factor was 0.0003 g N2 O-N/gTN-load in the CF bioreactor compared to 0.03 gN2 O-N/gTN-load in an activated sludge reactor (AS reactor). N2 O and CH4 emissions from the CF reactor were 42 g-CO2 eq/m(3) /day, while those from the AS reactor were 725 g-CO2 eq/m(3) /day. The dissolved inorganic nitrogen (DIN) in the CF reactor removed an average of 156 mg/L of the NH4 -N, and accumulated an average of 14 mg/L of the NO3 -N. In contrast, the DIN in the AS reactor removed an average 144 mg/L of the NH4 -N and accumulated an average 183 mg/L of the NO3 -N. NO2 -N was almost undetectable in both reactors. © 2014 Japanese Society of Animal Science.

The relationship between serum YKL-40 levels and arterial stiffness in patients with ankylosing spondylitis.

PubMed

Kucukali Turkyilmaz, Aysegul; Devrimsel, Gul; Serdaroglu Beyazal, Munevver; Kirbas, Aynur; Cicek, Yuksel; Capkin, Erhan; Karkucak, Murat; Gokmen, Ferhat

2017-01-01

Serum YKL-40 plays roles in inflammatory and vascular processes. Our aim was to evaluate serum YKL-40 levels in patients with ankylosing spondylitis (AS) and to investigate their potential relationship with arterial stiffness based on carotid-femoral pulse wave velocity (CF-PWV). Forty-three patients with AS and 41 healthy controls with no history or current signs of cardiovascular disease were included in the study. All patients were administered nonsteroidal anti-inflammatory drugs (NSAIDs), and none were prescribed anti-tumor necrosis factor agents. Serum YKL-40 levels were measured. CF-PWV and intima-media thickness of the common carotid artery (IMT-C) were evaluated. The mean age of AS patients was 34.6 ± 10.2 years and of controls was 36.3 ± 9.0 years. CF-PWV was significantly higher in AS patients than in controls (8.2±2.7 vs.7.0±1.6 m/s, respectively; P=0.015). However, the IMT-C was not significantly different between AS patients and controls (0.6±0.3 vs. 0.5±0.2 mm, P=0.501). YKL-40 levels were significantly higher in AS patients than in controls (78.9±37.9 vs. 58.4±21.2 ng/mL, P=0.003) and were strongly correlated with CF-PWV (r=0.773, P < 0.001) and IMT-C (r=0.548, P < 0.001). A multiple linear regression analysis revealed that CF-PWV could be explained by serum YKL-40 levels and IMT-C (adjusted R²= 0.707, P=0.013 and P=0.001, respectively). AS patients with a higher disease activity score had higher YKL-40 levels, IMT-C, and CF-PWV than did those with a lower disease activity score (P < 0.001, P=0.008, and P < 0.001, respectively) Conclusion: AS patients had higher serum YKL-40 levels, CF-PWV, and IMT-C than did healthy controls. Additionally, there was an association between increased CF-PWV and serum YKL-40 levels. Therefore, we conclude that CF-PWV and YKL-40 levels may be used for early diagnosis of atherosclerosis in AS patients.

Effect of endurance exercise on respiratory muscle function in patients with cystic fibrosis.

PubMed

Reilly, Charles C; Ward, Katie; Jolley, Caroline J; Frank, Lucy A; Elston, Caroline; Moxham, John; Rafferty, Gerrard F

2012-03-15

During exercise, patients with cystic fibrosis (CF) dynamically hyperinflate, which imposes both elastic and threshold loads on the inspiratory muscles and places them at a mechanical disadvantage due to muscle shortening. Conversely, dynamic hyperinflation imposes a progressively resistive load and lengthens the expiratory muscles potentially increasing their susceptibility to develop low frequency fatigue (LFF). The aim of the study was to determine whether high intensity endurance exercise leads to the development of LFF in either the diaphragm or expiratory abdominal wall muscles in patients with CF. Ten patients and ten healthy individuals were studied. Twitch transdiaphragmatic pressure (TwP(di)) and twitch abdominal pressure (TwT(10)) were measured before and after exhaustive endurance cycle exercise at 80% of their previously determined maximum work rate. There was no difference in TwP(di) or TwT(10) at 20, 40 or 60 min post exercise compared to pre-exercise resting values in any of the participants, indicating that overt LFF of the respiratory muscles did not develop. Copyright © 2012 Elsevier B.V. All rights reserved.

A novel perovskite solar cell design using aligned TiO2 nano-bundles grown on a sputtered Ti layer and a benzothiadiazole-based, dopant-free hole-transporting material.

PubMed

Ameen, Sadia; Nazim, M; Akhtar, M Shaheer; Nazeeruddin, Mohammad Khaja; Shin, Hyung-Shik

2017-11-16

This work highlights the utilization of a novel hole-transporting material (HTM) derived from benzothiadiazole: 4-(3,5-bis(trifluoromethyl)phenyl)-7-(5'-hexyl-[2,2'-bithiophen]-5-yl)benzo[c][1,2,5]thiadiazole (CF-BTz-ThR) and aligned TiO 2 nano-bundles (TiO 2 NBs) as the electron transporting layer (ETL) for perovskite solar cells (PSCs). The aligned TiO 2 NBs were grown on titanium (Ti)-coated FTO substrates using a facile hydrothermal method. The newly designed CF-BTz-ThR molecule with suitable highest occupied molecular orbital (HOMO) favored the effective hole injection from perovskite deposited aligned TiO 2 NBs thin film. The PSCs demonstrated a power conversion efficiency (PCE) of ∼15.4% with a short circuit current density (J sc ) of ∼22.42 mA cm -2 and an open circuit voltage (V oc ) of ∼1.02 V. The efficiency data show the importance of proper molecular engineering whilst highlighting the advantages of dopant-free HTMs in PSCs.

Preparation of new crosslinking agents and additives for use in polymer electrolyte membranes (PEMs) for fuel cell applications

NASA Astrophysics Data System (ADS)

Zhou, Yangliu

The most commonly used proton conductive membrane in polymer electrolyte membrane fuel cells (PEMFC) and direct methanol fuel cells (DMFC) studies to date is DuPont's NafionRTM, which is a perfluorinated copolymer of tetrafluoroethylene (TFE) and perfluorovinyl ether with a pendant sulfonic acid group. A focus of this work is to find ways to improve the performance of NafionRTM membranes. Crosslinking the TFE chains of fluorinated ionomeric copolymers to improve their thermal and mechanical stability is a proven route to this goal. A straightforward synthetic route to perfluorinated divinyl ethers of the formula CF2=CFO(CF 2)3[OCF(CF3)CF2]mOCF=CF 2 (m = 0-1) has been demonstrated. The compounds CF2=CFO(CF 2)3OCF=CF2 and CF2=CFO(CF2) 3OCF(CF3)CF2OCF=CF2 were prepared and characterized by GC-MS, 13C and 19F NMR, and gas-IR spectroscopy. Synthetic routes to fluorosulfato-tetrafluoropropionyl fluoride [FSO3CF2CF2C(O)F] and difluoromalonyl difluoride [F(O)CCF2C(O)F] with improved yields were found. The second focus of the dissertation was the development of fluorous triarylphosphines for use as new doping materials for the modification of NafionRTM membranes and for use as ligands in catalysts for biphasic catalysis. The synthesis and characterization of a series of new polyhexafluoropropylene oxide derivatives for preparation of fluorous triarylphosphines and phosphonium salts was studied, such as F[CF(CF3)CF2O] 4CF(CF3)CH2CH2I, F[CF(CF3)CF 2O]4CF(CF3)CH=CH2, F[CF(CF3)CF 2O]4CF(CF3) CH2CH2C6H5, and F[CF(CF 3)CF2O]4CF(CF3)CH2CH 2C6H4Br. In a separate study, the photochlorination of 2,2,3,3-tetrafluoro-1-propanol (HCF2CF2CH2OH) and 2,2,3,3-tetrafluoropropyl 2,2,3,3-tetrafluoropropionate [HCF2CF2C(O)OCH2 CF2CF2H] with super diazo blue light (lambda max = 420 nm) were investigated. The photochemical products are different from those obtained under mercury light (lambda = 253.7nm). A new compound ClCF2CF2C(O)OC(H)ClCF2CF2Cl was prepared and characterized by GC-MS, elemental analysis, 1H, 13C and 19F NMR, and gas-IR spectroscopy.

Reliable Multi-Label Learning via Conformal Predictor and Random Forest for Syndrome Differentiation of Chronic Fatigue in Traditional Chinese Medicine

PubMed Central

Wang, Huazhen; Liu, Xin; Lv, Bing; Yang, Fan; Hong, Yanzhu

2014-01-01

Objective Chronic Fatigue (CF) still remains unclear about its etiology, pathophysiology, nomenclature and diagnostic criteria in the medical community. Traditional Chinese medicine (TCM) adopts a unique diagnostic method, namely ‘bian zheng lun zhi’ or syndrome differentiation, to diagnose the CF with a set of syndrome factors, which can be regarded as the Multi-Label Learning (MLL) problem in the machine learning literature. To obtain an effective and reliable diagnostic tool, we use Conformal Predictor (CP), Random Forest (RF) and Problem Transformation method (PT) for the syndrome differentiation of CF. Methods and Materials In this work, using PT method, CP-RF is extended to handle MLL problem. CP-RF applies RF to measure the confidence level (p-value) of each label being the true label, and then selects multiple labels whose p-values are larger than the pre-defined significance level as the region prediction. In this paper, we compare the proposed CP-RF with typical CP-NBC(Naïve Bayes Classifier), CP-KNN(K-Nearest Neighbors) and ML-KNN on CF dataset, which consists of 736 cases. Specifically, 95 symptoms are used to identify CF, and four syndrome factors are employed in the syndrome differentiation, including ‘spleen deficiency’, ‘heart deficiency’, ‘liver stagnation’ and ‘qi deficiency’. The Results CP-RF demonstrates an outstanding performance beyond CP-NBC, CP-KNN and ML-KNN under the general metrics of subset accuracy, hamming loss, one-error, coverage, ranking loss and average precision. Furthermore, the performance of CP-RF remains steady at the large scale of confidence levels from 80% to 100%, which indicates its robustness to the threshold determination. In addition, the confidence evaluation provided by CP is valid and well-calibrated. Conclusion CP-RF not only offers outstanding performance but also provides valid confidence evaluation for the CF syndrome differentiation. It would be well applicable to TCM practitioners and facilitate the utilities of objective, effective and reliable computer-based diagnosis tool. PMID:24918430

Effects of TiO{sub 2} addition on ionic conductivity of PVC/PEMA blend based composite polymer electrolyte

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

Subban, R. H. Y.; Facultyof Applied Sciences Universiti Teknologi MARA40450 Shah Alam Selangor Malaysia; Sukri, Nursyazwani

2015-08-28

PVC/PEMA blend based polymer electrolytes with lithium bistrifluoromethane sulfonimide (LiN(CF{sub 3}SO{sub 2}){sub 2}) and PVC/PEMA/(LiN(CF{sub 3}SO{sub 2}){sub 2}-TiO{sub 2} films were prepared by solution cast technique. The sample containing 35 wt. % LiN(CF{sub 3}SO{sub 2}){sub 2} exhibited the highest conductivity of 1.75 × 10{sup −5} Scm{sup −1}. The conductivity of the sample increased to 2.12 × 10{sup −5} Scm{sup −1} and 4.61 × 10{sup −5} Scm{sup −1} when 4 wt. % and 10 wt. % of titanium dioxide (TiO{sub 2}) was added to the sample at 65 wt. % PVC/PEMA-35 wt. % LiN(CF{sub 3}SO{sub 2}){sub 2} composition respectively. The lowmore » increase in conductivity is attributed to two competing factors: increase in crystallinity as accounted by X-Ray diffraction (XRD) and decrease in glass transition temperature as accounted by differential scanning calorimetry (DSC)« less

Cation-enhanced capillary electrophoresis separation of atropoisomer anions.

PubMed

Na, Yun-Cheol; Berthod, Alain; Armstrong, Daniel W

2015-12-01

CE was used to study the separation of the atropoisomers of four phosphoric acids and two sulfonic acids and the enantiomers of two phosphoric acids. All solutes are in their anionic forms in aqueous electrolytes. The chiral additives were two hydroxypropyl cyclodextrins (CDs) and cyclofructan 6 (CF6). The CDs were able to separate four solutes and the CF6 additive could separate only one: 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate (BHP). Since CF6 is able to bind with cations, nitrate of alkaline metals, Ba(2+) , and Pb(2+) were added, greatly improving the BHP separation at the expense of longer migration times. There seems to be a link between CF6-cation-binding constants and BHP resolution factors. Cation additions were also performed with CD selectors that are less prone to form complexes with cations. Significant improvements of enantiomer or atropoisomer separations were observed also associated with longer migration times. It is speculated that the anionic solutes associate with the added cations forming larger entities better differentiated by CDs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Theoretical research on the spin-Hamiltonian parameters of the rhombic W5+ centers in CaWO4:Y3+ crystal

NASA Astrophysics Data System (ADS)

Mei, Yang; Wei, Cheng-Fu; Zheng, Wen-Chen

2016-02-01

Detailed theoretical calculations for the spin-Hamiltonian parameters (g factors gi and hyperfine structure constants Ai, where i=x, y, z) of the rhombic W5+ center in CaWO4:Y3+ crystal are performed by using the high-order perturbation formulas for d1 ions in rhombic tetrahedral clusters with the ground state |dz2>. These formulas consist of the contributions from two mechanisms, the crystal-field (CF) mechanism connected with CF excited states in the vastly-used CF theory and the frequently-neglected charge-transfer (CT) mechanism related to CT excited states. The calculated results agree well with the experimental values. The calculations indicate that for W5+ ion (or other high valence state dn ions) in crystals, the model calculations of spin-Hamiltonian parameters should take both the CF and CT mechanisms into account. The signs of hyperfine structure constants Ai are suggested and the forming (or defect model) of rhombic W5+ center in CaWO4:Y3+ crystal is confirmed from the calculations.

The crunch factor's role in golf-related low back pain.

PubMed

Cole, Michael H; Grimshaw, Paul N

2014-05-01

The golf swing exposes the spine to complex torsional, compressive, and shearing loads that increase a player's risk of injury. The crunch factor (CF) has been described as a measure to evaluate the risk of low back injuries in golfers and is based on the notion that lateral flexion and axial trunk rotation jointly contribute to spinal degeneration. However, few studies have evaluated the appropriateness of this measure in golfers with low back pain (LBP). To objectively examine the usefulness of the CF as a measure for assessing the risk of low back injury in golfers. Field-based research using a cross-sectional design. This research used three-dimensional motion analysis to assess the golf swings of 12 golfers with LBP and 15 asymptomatic controls. Three-dimensional kinematics were derived using Vicon Motus, and the CF was calculated as the instantaneous product of axial trunk rotation velocity and lateral trunk flexion angle. Maximum CFs and their timings were not significantly different between the symptomatic and asymptomatic groups. Furthermore, for those golfers who produced higher CFs (irrespective of the group), the increased magnitude could not be attributed to an increased axial angular trunk velocity or lateral flexion angle, but rather to a concomitant increase in both of these variables. The findings suggested that although the fundamental concepts that underpin the CF seem sensible, this measure does not appear to be sensitive enough to distinguish golfers with LBP from the asymptomatic players. Copyright © 2014 Elsevier Inc. All rights reserved.

Trihalomethanes in Lisbon indoor swimming pools: occurrence, determining factors, and health risk classification.

PubMed

Silva, Zelinda Isabel; Rebelo, Maria Helena; Silva, Manuela Manso; Alves, Ana Martins; Cabral, Maria da Conceição; Almeida, Ana Cristina; Aguiar, Fátima Rôxo; de Oliveira, Anabela Lopes; Nogueira, Ana Cruz; Pinhal, Hermínia Rodrigues; Aguiar, Pedro Manuel; Cardoso, Ana Sofia

2012-01-01

Characterization of water quality from indoor swimming pools, using chorine-based disinfection techniques, was performed during a 6-mo period to study the occurrence, distribution, and concentration factors of trihalomethanes (THM). Several parameters such as levels of water THM, water and air chloroform, water bromodichloromethane (BDCM), water dibromochloromethane (DBCM), water bromoform (BF), free residual chlorine (FrCl), pH, water and air temperature, and permanganate water oxidizability (PWO) were determined in each pool during that period. Chloroform (CF(W)) was the THM detected at higher concentrations in all pools, followed by BDCM, DBCM, and BF detected at 99, 34, and 6% of the samples, respectively. Water THM concentrations ranged from 10.1 to 155 μg/L, with 6.5% of the samples presenting values above 100 μg/L (parametric value established in Portuguese law DL 306/2007). In this study, air chloroform (CF(Air)) concentrations ranged from 45 to 373 μg/m³ with 24% of the samples presenting values above 136 μg/m³ (considered high exposure value). Several significant correlations were observed between total THM and other parameters, namely, CF(W), CF(Air), FrCl, water temperature (T(W)), and PWO. These correlations indicate that FrCl, T(W) and PWO are parameters that influence THM formation. The exposure criterion established for water THM enabled the inclusion of 67% of Lisbon pools in the high exposure group, which reinforces the need for an improvement in pool water quality.

Effect of dairy farming system, herd, season, parity, and days in milk on modeling of the coagulation, curd firming, and syneresis of bovine milk.

PubMed

Bittante, G; Cipolat-Gotet, C; Malchiodi, F; Sturaro, E; Tagliapietra, F; Schiavon, S; Cecchinato, A

2015-04-01

The objectives of this study were to characterize the variation in curd firmness model parameters obtained from coagulating bovine milk samples, and to investigate the effects of the dairy system, season, individual farm, and factors related to individual cows (days in milk and parity). Individual milk samples (n = 1,264) were collected during the evening milking of 85 farms representing different environments and farming systems in the northeastern Italian Alps. The dairy herds were classified into 4 farming system categories: traditional system with tied animals (29 herds), modern dairy systems with traditional feeding based on hay and compound feed (30 herds), modern dairy system with total mixed ration (TMR) that included silage as a large proportion of the diet (9 herds), and modern dairy system with silage-free TMR (17 herds). Milk samples were analyzed for milk composition and coagulation properties, and parameters were modeled using curd firmness measures (CFt) collected every 15 s from a lacto-dynamographic analysis of 90 min. When compared with traditional milk coagulation properties (MCP), the curd firming measures showed greater variability and yielded a more accurate description of the milk coagulation process: the model converged for 93.1% of the milk samples, allowing estimation of 4 CFt parameters and 2 derived traits [maximum CF (CF(max)) and time from rennet addition to CF(max) (t(max))] for each sample. The milk samples whose CFt equations did not converge showed longer rennet coagulation times obtained from the model (RCT(eq)) and higher somatic cell score, and came from less-productive cows. Among the sources of variation tested for the CFt parameters, dairy herd system yielded the greatest differences for the contrast between the traditional farm and the 3 modern farms, with the latter showing earlier coagulation and greater instant syneresis rate constant (k(SR)). The use of TMR yielded a greater tmax because of a higher instant curd-firming rate constant (k(CF)). Season of sampling was found to be very important, yielding higher values during winter for all traits except k(CF) and k(SR). All CFt traits were affected by individual cow factors. For parity, milk produced by first-lactation cows showed higher k(CF) and k(SR), but delays in achieving CF(max). With respect to stage of lactation, RCT(eq) and potential asymptotic CF increased during the middle of lactation and stabilized thereafter, whereas the 2 instant rate constants presented the opposite pattern, with the lowest (k(CF)) and highest (k(SR)) values occurring in mid lactation. The new challenge offered by prolonging the test interval and individual modeling of milk technological properties allowed us to study the effects of parameters related to the environment and to individual cows. This novel strategy may be useful for investigating the genetic variability of these new coagulation traits. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Prevalence of Secondary Traumatic Stress Among Psychiatric Nurses in Greece.

PubMed

Mangoulia, Polyxeni; Koukia, Evmorfia; Alevizopoulos, George; Fildissis, George; Katostaras, Theofanis

2015-10-01

The aim of this study was to investigate the prevalence of secondary traumatic stress/compassion fatigue (STS/CF), burnout (BO) and compassion satisfaction (CS) in psychiatric nurses, and their risk factors. The Professional Quality of Life Scale (ProQOL R-IV) and a demographic and work related characteristics questionnaire were distributed to 174 psychiatric nurses in 12 public hospitals in Greece. The majority of participants were at the high risk category for STS/CF (44.8%) and BO (49.4%), while only 8.1% of nurses expressed high potential for CS. Awareness of the factors associated with STS may help nurses to prevent or offset the development of this condition. Copyright © 2015 Elsevier Inc. All rights reserved.

User Needs in the Development of a Health App Ecosystem for Self-Management of Cystic Fibrosis: User-Centered Development Approach.

PubMed

Floch, Jacqueline; Zettl, Annabel; Fricke, Lena; Weisser, Tina; Grut, Lisbet; Vilarinho, Thomas; Stav, Erlend; Ascolese, Antonio; Schauber, Cornelia

2018-05-08

Digital self-management in cystic fibrosis (CF) is foreseen as a means toward better understanding of the disease and its treatment and better adherence to the treatment. Mobile apps hold the potential to provide access to information, motivate, and strengthen compliance. However, to deliver high-quality apps, the development should be based on thorough knowledge about user needs. Empirical research on the user-centered development of mobile apps for health care is, however, still limited. The aim of this research is to develop and evaluate an app ecosystem for self-management in CF. It targets not only those directly affected by CF but also parents and health care professionals involved in the treatment. This paper covers the first step of the design process that aims to analyze the context and the user requirements. The primary research question is as follows: what digital support has the potential to usefully support persons with CF and their caregivers in the CF care? To answer this question, we address two preliminary questions: what important factors in everyday life affect the care of persons with CF? and how is the CF care delivered today and what are the limitations of CF care services? The overall research adopts a user-centered design approach in which future users are involved in the development process from the very beginning to ensure that the apps developed best suit the potential users. The research presented in the paper follows an interpretative case study research strategy seeking to understand the concerns and needs of persons with CF and their caregivers. Data were collected through semistructured qualitative interviews involving 74 participants in seven European countries and from internet forums. The results of the analysis phase show a strong need for individuality of the digital support, as well as for its adaptability to different contexts. The paper presents the concerns and needs of the participants in the study and extracts a set of relevant features for a self-management app ecosystem. Education, enzyme dosage calculation, nutrition management, treatment organization, health diary, treatment follow-up, practical guidelines for treatment, communication with doctors, and communication with peers are foreseen as useful features. The results indicate the readiness for self-management in the CF care even in countries that provide well-functioning health care services for CF care. The large diversity of user requirements identified reflects the crucial role user integration plays in developing apps for a chronic condition such as CF. The need for personalization stemming from the individuality of the patients and the need for communication with health care professionals support the idea of an app ecosystem for the self-management of CF. ©Jacqueline Floch, Annabel Zettl, Lena Fricke, Tina Weisser, Lisbet Grut, Thomas Vilarinho, Erlend Stav, Antonio Ascolese, Cornelia Schauber. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 08.05.2018.

The Influence of Genetics on Cystic Fibrosis Phenotypes

PubMed Central

Knowles, Michael R.; Drumm, Mitchell

2012-01-01

Technological advances in genetics have made feasible and affordable large studies to identify genetic variants that cause or modify a trait. Genetic studies have been carried out to assess variants in candidate genes, as well as polymorphisms throughout the genome, for their associations with heritable clinical outcomes of cystic fibrosis (CF), such as lung disease, meconium ileus, and CF-related diabetes. The candidate gene approach has identified some predicted relationships, while genome-wide surveys have identified several genes that would not have been obvious disease-modifying candidates, such as a methionine sulfoxide transferase gene that influences intestinal obstruction, or a region on chromosome 11 proximate to genes encoding a transcription factor and an apoptosis controller that associates with lung function. These unforeseen associations thus provide novel insight into disease pathophysiology, as well as suggesting new therapeutic strategies for CF. PMID:23209180

The mean density and two-point correlation function for the CfA redshift survey slices

NASA Technical Reports Server (NTRS)

De Lapparent, Valerie; Geller, Margaret J.; Huchra, John P.

1988-01-01

The effect of large-scale inhomogeneities on the determination of the mean number density and the two-point spatial correlation function were investigated for two complete slices of the extension of the Center for Astrophysics (CfA) redshift survey (de Lapparent et al., 1986). It was found that the mean galaxy number density for the two strips is uncertain by 25 percent, more so than previously estimated. The large uncertainty in the mean density introduces substantial uncertainty in the determination of the two-point correlation function, particularly at large scale; thus, for the 12-deg slice of the CfA redshift survey, the amplitude of the correlation function at intermediate scales is uncertain by a factor of 2. The large uncertainties in the correlation functions might reflect the lack of a fair sample.

Role of Contact Force Sensing in Catheter Ablation of Cardiac Arrhythmias: Evolution or History Repeating Itself?

PubMed

Ariyarathna, Nilshan; Kumar, Saurabh; Thomas, Stuart P; Stevenson, William G; Michaud, Gregory F

2018-06-01

Adequate catheter-tissue contact facilitates efficient heat energy transfer to target tissue. Tissue contact is thus critical to achieving lesion transmurality and success of radiofrequency (RF) ablation procedures, a fact recognized more than 2 decades ago. The availability of real-time contact force (CF)-sensing catheters has reinvigorated the field of ablation biophysics and optimized lesion formation. The ability to measure and display CF came with the promise of dramatic improvement in safety and efficacy; however, CF quality was noted to have just as important an influence on lesion formation as absolute CF quantity. Multiple other factors have emerged as key elements influencing effective lesion formation, including catheter stability, lesion contiguity and continuity, lesion density, contact homogeneity across a line of ablation, spatiotemporal dynamics of contact governed by cardiac and respiratory motion, contact directionality, and anatomic wall thickness, in addition to traditional ablation indices of power and RF duration. There is greater appreciation of surrogate markers as a guide to lesion formation, such as impedance fall, loss of pace capture, and change in unipolar electrogram morphology. In contrast, other surrogates such as tactile feedback, catheter motion, and electrogram amplitude are notably poor predictors of actual contact and lesion formation. This review aims to contextualize the role of CF sensing in lesion formation with respect of the fundamental principles of biophysics of RF ablation and summarize the state-of-the-art evidence behind the role of CF in optimizing lesion formation. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Oxidative stress modulates the expression of genes involved in cell survival in ΔF508 cystic fibrosis airway epithelial cells.

PubMed

Voisin, Grégory; Bouvet, Guillaume F; Legendre, Pierre; Dagenais, André; Massé, Chantal; Berthiaume, Yves

2014-09-01

Although cystic fibrosis (CF) pathophysiology is explained by a defect in CF transmembrane conductance regulator (CFTR) protein, the broad spectrum of disease severity is the consequence of environmental and genetic factors. Among them, oxidative stress has been demonstrated to play an important role in the evolution of this disease, with susceptibility to oxidative damage, decline of pulmonary function, and impaired lung antioxidant defense. Although oxidative stress has been implicated in the regulation of inflammation, its molecular outcomes in CF cells remain to be evaluated. To address the question, we compared the gene expression profile in NuLi-1 cells with wild-type CFTR and CuFi-1 cells homozygous for ΔF508 mutation cultured at air-liquid interface. We analyzed the transcriptomic response of these cell lines with microarray technology, under basal culture conditions and after 24 h oxidative stress induced by 15 μM 2,3-dimethoxy-1,4-naphtoquinone. In the absence of oxidative conditions, CuFi-1 gene profiling showed typical dysregulated inflammatory responses compared with NuLi-1. In the presence of oxidative conditions, the transcriptome of CuFi-1 cells reflected apoptotic transcript modulation. These results were confirmed in the CFBE41o- and corrCFBE41o- cell lines as well as in primary culture of human CF airway epithelial cells. Altogether, our data point to the influence of oxidative stress on cell survival functions in CF and identify several genes that could be implicated in the inflammation response observed in CF patients. Copyright © 2014 the American Physiological Society.

What does low-intensity rTMS do to the cerebellum?

PubMed

Morellini, N; Grehl, S; Tang, A; Rodger, J; Mariani, J; Lohof, A M; Sherrard, R M

2015-02-01

Non-invasive stimulation of the human cerebellum, such as by transcranial magnetic stimulation (TMS), is increasingly used to investigate cerebellar function and identify potential treatment for cerebellar dysfunction. However, the effects of TMS on cerebellar neurons remain poorly defined. We applied low-intensity repetitive TMS (LI-rTMS) to the mouse cerebellum in vivo and in vitro and examined the cellular and molecular sequelae. In normal C57/Bl6 mice, 4 weeks of LI-rTMS using a complex biomimetic high-frequency stimulation (BHFS) alters Purkinje cell (PC) dendritic and spine morphology; the effects persist 4 weeks after the end of stimulation. We then evaluated whether LI-rTMS could induce climbing fibre (CF) reinnervation to denervated PCs. After unilateral pedunculotomy in adult mice and 2 weeks sham or BHFS stimulation, VGLUT2 immunohistochemistry was used to quantify CF reinnervation. In contrast to sham, LI-rTMS induced CF reinnervation to the denervated hemicerebellum. To examine potential mechanisms underlying the LI-rTMS effect, we verified that BHFS could induce CF reinnervation using our in vitro olivocerebellar explants in which denervated cerebellar tissue is co-cultured adjacent to intact cerebella and treated with brain-derived neurotrophic factor (BDNF) (as a positive control), sham or LI-rTMS for 2 weeks. Compared with sham, BDNF and BHFS LI-rTMS significantly increased CF reinnervation, without additive effect. To identify potential underlying mechanisms, we examined intracellular calcium flux during the 10-min stimulation. Complex high-frequency stimulation increased intracellular calcium by release from intracellular stores. Thus, even at low intensity, rTMS modifies PC structure and induces CF reinnervation.

Symposium 6: Young people, artificial nutrition and transitional care. The nutritional challenges of the young adult with cystic fibrosis: transition.

PubMed

Morton, Alison M

2009-11-01

Cystic fibrosis (CF) is a complex multisystem disorder affecting mainly the gastrointestinal tract and respiratory system. Intestinal malabsorption occurs in approximately 90% of patients. In the past, malnutrition was an inevitable consequence of disease progression, leading to poor growth, impaired respiratory muscle function, decreased exercise tolerance and immunological impairment. A positive association between body weight and height and survival has been widely reported. The energy requirements of patients with CF vary widely and generally increase with age and disease severity. For many young adults requirements will be 120-150% of the age-related estimated average requirement. To meet these energy needs patients are encouraged to eat a high-fat high-energy diet with appropriate pancreatic enzyme supplements. Many patients are unable to achieve an adequate intake as a result of a variety of factors including chronic poor appetite, infection-related anorexia, gastro-oesophageal reflux and abdominal pain. Oral energy supplements and enteral tube feeding are widely used. Nutritional support has been shown to improve nutritional status and stabilise or slow the rate of decline in lung function. With such emphasis on nutritional intake and nutritional status throughout life, poor adherence to therapies and issues relating to body image are emerging. The median survival of patients with CF is increasing. CF is now considered a life-limiting disease of adulthood rather than a terminal childhood illness. With increased longevity new challenges are emerging that include the transition of young adults with CF to adult services, CF-related diabetes, disordered eating, osteoporosis, liver disease and transplantation.

The effects of resistance exercise training on arterial stiffness in metabolic syndrome.

PubMed

DeVallance, E; Fournier, S; Lemaster, K; Moore, C; Asano, S; Bonner, D; Donley, D; Olfert, I M; Chantler, P D

2016-05-01

Arterial stiffness is a strong independent risk factor for cardiovascular disease and is elevated in individuals with metabolic syndrome (MetS). Resistance training is a popular form of exercise that has beneficial effects on muscle mass, strength, balance and glucose control. However, it is unknown whether resistance exercise training (RT) can lower arterial stiffness in patients with MetS. Thus, the aim of this study was to examine whether a progressive RT program would improve arterial stiffness in MetS. A total of 57 subjects (28 healthy sedentary subjects; 29 MetS) were evaluated for arterial structure and function, including pulse wave velocity (cfPWV: arterial stiffness), before and after an 8-week period of RT or continuation of sedentary lifestyle. We found that 8 weeks of progressive RT increased skeletal muscle strength in both Con and MetS, but did not change arterial stiffness in either MetS (cfPWV; Pre 7.9 ± 0.4 m/s vs. Post 7.7 ± 0.4 m/s) or healthy controls (cfPWV; Pre 6.9 ± 0.3 m/s vs. Post 7.0 ± 0.3 m/s). However, when cfPWV is considered as a continuous variable, high baseline measures of cfPWV tended to show a decrease in cfPWV following RT. Eight weeks of progressive RT did not decrease the group mean values of arterial stiffness in individuals with MetS or healthy controls.

Preanalytical blood sample workup for cell-free DNA analysis using Droplet Digital PCR for future molecular cancer diagnostics.

PubMed

van Ginkel, Joost H; van den Broek, Daan A; van Kuik, Joyce; Linders, Dorothé; de Weger, Roel; Willems, Stefan M; Huibers, Manon M H

2017-10-01

In current molecular cancer diagnostics, using blood samples of cancer patients for the detection of genetic alterations in plasma (cell-free) circulating tumor DNA (ctDNA) is an emerging practice. Since ctDNA levels in blood are low, highly sensitive Droplet Digital PCR (ddPCR) can be used for detecting rare mutational targets. In order to perform ddPCR on blood samples, a standardized procedure for processing and analyzing blood samples is necessary to facilitate implementation into clinical practice. Therefore, we assessed the technical sample workup procedure for ddPCR on blood plasma samples. Blood samples from healthy individuals, as well as lung cancer patients were analyzed. We compared different methods and protocols for sample collection, storage, centrifugation, isolation, and quantification. Cell-free DNA (cfDNA) concentrations of several wild-type targets and BRAF and EGFR-mutant ctDNA concentrations quantified by ddPCR were primary outcome measurements. Highest cfDNA concentrations were measured in blood collected in serum tubes. No significant differences in cfDNA concentrations were detected between various time points of up to 24 h until centrifugation. Highest cfDNA concentrations were detected after DNA isolation with the Quick cfDNA Serum & Plasma Kit, while plasma isolation using the QIAamp Circulating Nucleic Acid Kit yielded the most consistent results. DdPCR results on cfDNA are highly dependent on multiple factors during preanalytical sample workup, which need to be addressed during the development of this diagnostic tool for cancer diagnostics in the future. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Total DNA input is a crucial determinant of the sensitivity of plasma cell-free DNA EGFR mutation detection using droplet digital PCR

PubMed Central

Zhao, Jing; Chen, Minjiang; Zhang, Li; Li, Longyun; Wang, Mengzhao

2017-01-01

We evaluated the use of droplet digital PCR (ddPCR) to detect plasma cell-free DNA (cfDNA) epidermal growth factor receptor (EGFR) mutations in advanced non-small cell lung cancer (NSCLC) patients. Compared with tumor-tissue-based detection, the sensitivity of ddPCR for detecting plasma cfDNA tyrosine kinase inhibitor (TKI)-sensitizing EGFR mutations was 61.3%, the specificity was 96.7%, and the consistency rate was 81.4% (?=0.605, 95% confidence interval: 0.501-0.706, p <0.0001). The sensitivity declined from 82.6% to 46.7% with decreasing cfDNA inputs (p=0.028). The plasma cfDNA concentration correlated with gender (males vs.females =11.69 ng/mL vs. 9.508 ng/mL; p=0.044), EGFR mutation status (tumor-tissue EGFR mutation-positive (EGFR M+) vs. EGFR mutation-negative (EGFR M-) = 9.61 ng/mL vs. 12.82 ng/mL; p =0.049) and specimen collection time (=2 years vs. >2 years=13.83 ng/mL vs. 6.575 ng/mL; p <0.001), and was greater in tumor-tissue EGFR M+ / plasma EGFR M+ patients than in tumor-tissue EGFR M+/plasma EGFR M- patients (11.61 vs. 7.73 ng/mL, respectively; p=0.003). Thus total cfDNA input crucially influences the sensitivity of plasma cfDNA EGFR mutation testing with ddPCR. Such analysis could be an effective supplemental test for advanced NSCLC patients. PMID:28052016

Adherence to airway clearance therapy in pediatric cystic fibrosis: Socioeconomic factors and respiratory outcomes.

PubMed

Oates, Gabriela R; Stepanikova, Irena; Gamble, Stephanie; Gutierrez, Hector H; Harris, William T

2015-12-01

The evidence linking socioeconomic status (SES) and adherence in cystic fibrosis (CF) is inconclusive and focused on medication uptake. We examined associations between SES, adherence to airway clearance therapy (ACT), and CF respiratory outcomes. Socioeconomic, clinical, and adherence data of CF patients (N = 110) at a single CF Center were evaluated in this cross-sectional observational study. SES was operationalized as maternal and paternal education and household income. Adherence to ACT was measured with utilization data from the high-frequency chest wall oscillation (HFCWO) device over 4-6 weeks. Statistical modeling was used to test three hypotheses: (H1) Higher SES is associated with higher ACT adherence; (H2) Higher SES is associated with better respiratory outcomes; and (H3) ACT adherence mediates the relationship between SES and respiratory outcomes. In multinomial logistic regression, maternal college education, annual income >$50,000, and more adults in the household were independently related to better adherence (P < 0.05). Paternal college education, income >$100,000, and lack of exposure to smoking were independently related to higher lung function (P < 0.05). Current adherence to ACT with HFCWO was not associated with lung function over 12 months. SES is associated both with ACT adherence and respiratory outcomes in pediatric CF patients. However, the link between SES and respiratory outcomes in this study was not mediated by adherence to ACT with HFCWO. These data emphasize the importance of socioeconomic resources and household environment for CF health. Family socio-demographic profiles can help identify patients at increased risk for ACT nonadherence. © 2015 Wiley Periodicals, Inc.

Association between competitive food and beverage policies in elementary schools and childhood overweight/obesity trends: differences by neighborhood socioeconomic resources.

PubMed

Sanchez-Vaznaugh, Emma V; Sánchez, Brisa N; Crawford, Patricia B; Egerter, Susan

2015-05-01

To our knowledge, few published studies have examined the influence of competitive food and beverage (CF&B) policies on student weight outcomes; none have investigated disparities in the influence of CF&B policies on children's body weight by school neighborhood socioeconomic resources. To investigate whether the association between CF&B policies and population-level trends in childhood overweight/obesity differed by school neighborhood income and education levels. This cross-sectional study, from July 2013 to October 2014, compared overweight/obesity prevalence trends before (2001-2005) and after (2006-2010) implementation of CF&B policies in public elementary schools in California. The study included 2 700 880 fifth-grade students in 5362 public schools from 2001 to 2010. California CF&B policies (effective July 1, 2004, and July 1, 2007) and school neighborhood income and education levels. Overweight/obesity defined as a body mass index at or greater than the 85th percentile for age and sex. Overall rates of overweight/obesity ranged from 43.5% in 2001 to 45.8% in 2010. Compared with the period before the introduction of CF&B policies, overweight/obesity trends changed in a favorable direction after the policies took effect (2005-2010); these changes occurred for all children across all school neighborhood socioeconomic levels. In the postpolicy period, these trends differed by school neighborhood socioeconomic advantage. From 2005-2010, trends in overweight/obesity prevalence leveled off among students at schools in socioeconomically disadvantaged neighborhoods but declined in socioeconomically advantaged neighborhoods. Students in the lowest-income neighborhoods experienced zero or near zero change in the odds of overweight/obesity over time: the annual percentage change in overweight/obesity odds was 0.1% for females (95% CI, -0.7 to 0.9) and -0.3% for males (95% CI, -1.1 to 0.5). In contrast, in the highest-income neighborhoods, the annual percentage decline in the odds of overweight was 1.2% for females (95% CI, 0.4 to 1.9) and 1.0% for males (95% CI, 0.3 to 1.8). Findings were similar for school neighborhood education. Our study found population-level improvements in the prevalence of childhood overweight/obesity that coincided with the period following implementation of statewide CF&B policies (2005-2010). However, these improvements were greatest at schools in the most advantaged neighborhoods. This suggests that CF&B policies may help prevent child obesity; however, the degree of their effectiveness is likely to depend on socioeconomic and other contextual factors in school neighborhoods. To reduce disparities and prevent obesity, school policies and environmental interventions must address relevant contextual factors in school neighborhoods.

Geochemical assessment of heavy metals pollution in surface sediments of Vellar and Coleroon estuaries, southeast coast of India.

PubMed

Nethaji, S; Kalaivanan, R; Arya Viswam; Jayaprakash, M

2017-02-15

Surface sediments were collected from Vellar and Coleroon estuaries for determine sediment texture, calcium carbonate, organic matter and heavy metals. Pollution indices such as pollution load index (PLI), contamination factor (CF), enrichment factor (EF) and geo-accumulation index (I geo ) were done for this study to know the level of heavy metals pollution in the estuarine ecosystem. Pearson correlation matrix and factor were used to assess the relationship and source of heavy metals in the estuarine sediments. The results of PLI values reveal that the study area was polluted by all the heavy metals. The calculated values of CF and I geo followed the decreasing order Cu>Ni>Pb>Co>Cr>Zn>Mn>Fe and illustrate that Cu, Ni and Pb are contaminated due to anthropogenic sources in both estuaries. Correlation and factor analysis suggest that FeMn oxyhydroxides, organic matter and fine particles are responsible for high concentration of heavy metals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Barriers to carrier testing for adult cystic fibrosis sibs: the importance of not knowing.

PubMed

Fanos, J H; Johnson, J P

1995-10-23

Early experience in centers offering population screening for cystic fibrosis (CF) has shown that few of the public are taking advantage of the offer [Miller, 1993: New Scientist 139:6]. There is similar low utilization among adult CF sibs [Fanos and Johnson, 1993: Am J Hum Genet 53:A51]. The purpose of this study was to identify factors motivating or interfering with the pursuit of carrier testing in adult CF sibs. Eighty-four adult CF sibs and their spouses, drawn from Children's Hospital, Oakland, CA, and Children's Hospital, Boston, MA, were interviewed for about an hour, and qualitative material was coded on various themes. Structural and psychological barriers to the transmission of genetic information were identified: 1) sibs encountered difficulty in obtaining information concerning availability of testing; 2) parental guilt and blame prevents parents from discussing genetic issues with the sib; 3) sibs rarely discuss testing with each other; 4) the CF patient or parent often has difficulty with the implications of the sib seeking carrier testing; 5) family and individual myths about carrier status influence the sib's decision to seek testing; 6) statistical odds have lost meaning in families where the rare has already occurred; 7) the sib fears loss of interpersonal desirability; and 8) carrier status can serve an important function in binding guilt. Remaining unaware of their carrier status may serve significant psychological functions for individuals at risk.

Expression pattern of Chlamys farreri sox2 in eggs, embryos and larvae of various stages

NASA Astrophysics Data System (ADS)

Liang, Shaoshuai; Ma, Xiaoshi; Han, Tiantian; Yang, Dandan; Zhang, Zhifeng

2015-08-01

The SOX2 protein is an important transcription factor functioning during the early development of animals. In this study, we isolated a full-length cDNA sequence of scallop Chlamys farreri sox2, Cf-sox2 which was 2194 bp in length with a 981 bp open reading frame encoding 327 amino acids. With real-time PCR analysis, it was detected that Cf-sox2 was expressed in unfertilized oocytes, fertilized eggs and all the tested embryos and larvae. The expression level increased significantly ( P < 0.01) in embryos from 2-cell to blastula, and then decreased significantly ( P < 0.01) and reached the minimum in umbo larva. Moreover, location of the Cf-sox2 expression was revealed using whole mount in situ hybridization technique. Positive hybridization signal could be detected in the central region of unfertilized oocytes and fertilized eggs, and then strong signals dispersed throughout the embryos from 2-cell to gastrula. During larval development, the signals were concentrated and strong signals were restricted to 4 regions of viscera mass in veliger larva. In umbo larva, weak signals could be detected in regions where presumptive visceral and pedal ganglia may be formed. The expression pattern of Cf-sox2 during embryogenesis was similar to that of mammal sox2, which implied that Cf-SOX2 may participate in the regulation of early development of C. farreri.

Associations of Dairy Intake with Arterial Stiffness in Brazilian Adults: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

PubMed

Ribeiro, Amanda Gomes; Mill, José Geraldo; Cade, Nágela Valadão; Velasquez-Melendez, Gustavo; Matos, Sheila Maria Alvim; Molina, Maria Del Carmen Bisi

2018-05-31

Recent studies have suggested the possible effect of dairy product intake on cardiovascular risk markers, including arterial stiffness. Our aim was to investigate whether dairy food intake is associated with arterial stiffness, which we assessed by carotid-femoral pulse wave velocity (cfPWV) and pulse pressure (PP) in a cross-sectional analysis of baseline data (2008⁻2010; n = 12,892) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Dairy consumption was evaluated with a validated food-frequency questionnaire (FFQ) by computing servings per day for total and subgroups of dairy products. Dairy consumption was described in four categories (≤1 serving/day to >4 servings/day). Covariance analysis (ANCOVA) was used to compare cfPWV across increasing intake of dairy food, adjusting for confounding factors, including non-dairy food groups. The intake of total dairy was inversely associated with cfPWV and PP (-0.13 m/s and -1.3 mmHg, from the lowest and to the highest category of dairy intake). Low-fat dairy, fermented dairy and cheese showed an inverse relationship with cfPWV and PP. These findings suggest a beneficial effect of dairy consumption to reduce arterial stiffness. However, further evidence from longitudinal studies or long-term intervention is needed to support reduction of cfPWV and PP mediating the beneficial effects of dairy products on cardiovascular health.

Theoretical insight into OH- and Cl-initiated oxidation of CF3OCH(CF3)2 and CF3OCF2CF2H & fate of CF3OC(X•)(CF3)2 and CF3OCF2CF2X• radicals (X=O, O2)

PubMed Central

Bai, Feng-Yang; Ma, Yuan; Lv, Shuang; Pan, Xiu-Mei; Jia, Xiu-Juan

2017-01-01

In this study, the mechanistic and kinetic analysis for reactions of CF3OCH(CF3)2 and CF3OCF2CF2H with OH radicals and Cl atoms have been performed at the CCSD(T)//B3LYP/6-311++G(d,p) level. Kinetic isotope effects for reactions CF3OCH(CF3)2/CF3OCD(CF3)2 and CF3OCF2CF2H/CF3OCF2CF2D with OH and Cl were estimated so as to provide the theoretical estimation for future laboratory investigation. All rate constants, computed by canonical variational transition state theory (CVT) with the small-curvature tunneling correction (SCT), are in reasonable agreement with the limited experimental data. Standard enthalpies of formation for the species were also calculated. Atmospheric lifetime and global warming potentials (GWPs) of the reaction species were estimated, the large lifetimes and GWPs show that the environmental impact of them cannot be ignored. The organic nitrates can be produced by the further oxidation of CF3OC(•)(CF3)2 and CF3OCF2CF2• in the presence of O2 and NO. The subsequent decomposition pathways of CF3OC(O•)(CF3)2 and CF3OCF2CF2O• radicals were studied in detail. The derived Arrhenius expressions for the rate coefficients over 230–350 K are: k T(1) = 5.00 × 10−24T3.57 exp(−849.73/T), k T(2) = 1.79 × 10−24T4.84 exp(−4262.65/T), kT(3) = 1.94 × 10−24 T4.18 exp(−884.26/T), and k T(4) = 9.44 × 10−28T5.25 exp(−913.45/T) cm3 molecule−1 s−1. PMID:28067283

Theoretical insight into OH- and Cl-initiated oxidation of CF3OCH(CF3)2 and CF3OCF2CF2H & fate of CF3OC(X•)(CF3)2 and CF3OCF2CF2X• radicals (X=O, O2)

NASA Astrophysics Data System (ADS)

Bai, Feng-Yang; Ma, Yuan; Lv, Shuang; Pan, Xiu-Mei; Jia, Xiu-Juan

2017-01-01

In this study, the mechanistic and kinetic analysis for reactions of CF3OCH(CF3)2 and CF3OCF2CF2H with OH radicals and Cl atoms have been performed at the CCSD(T)//B3LYP/6-311++G(d,p) level. Kinetic isotope effects for reactions CF3OCH(CF3)2/CF3OCD(CF3)2 and CF3OCF2CF2H/CF3OCF2CF2D with OH and Cl were estimated so as to provide the theoretical estimation for future laboratory investigation. All rate constants, computed by canonical variational transition state theory (CVT) with the small-curvature tunneling correction (SCT), are in reasonable agreement with the limited experimental data. Standard enthalpies of formation for the species were also calculated. Atmospheric lifetime and global warming potentials (GWPs) of the reaction species were estimated, the large lifetimes and GWPs show that the environmental impact of them cannot be ignored. The organic nitrates can be produced by the further oxidation of CF3OC(•)(CF3)2 and CF3OCF2CF2• in the presence of O2 and NO. The subsequent decomposition pathways of CF3OC(O•)(CF3)2 and CF3OCF2CF2O• radicals were studied in detail. The derived Arrhenius expressions for the rate coefficients over 230-350 K are: k T(1) = 5.00 × 10-24T3.57 exp(-849.73/T), k T(2) = 1.79 × 10-24T4.84 exp(-4262.65/T), kT(3) = 1.94 × 10-24 T4.18 exp(-884.26/T), and k T(4) = 9.44 × 10-28T5.25 exp(-913.45/T) cm3 molecule-1 s-1.

Atmospheric Chemistry of (CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3.

PubMed

Østerstrøm, Freja From; Wallington, Timothy J; Sulbaek Andersen, Mads P; Nielsen, Ole John

2015-10-22

Smog chambers with in situ FTIR detection were used to measure rate coefficients in 700 Torr of air and 296 ± 2 K of: k(Cl+(CF3)2CHOCH3) = (5.41 ± 1.63) × 10(-12), k(Cl+(CF3)2CHOCHO) = (9.44 ± 1.81) × 10(-15), k(Cl+CF3C(O)OCH3) = (6.28 ± 0.98) × 10(-14), k(OH+(CF3)2CHOCH3) = (1.86 ± 0.41) × 10(-13), and k(OH+(CF3)2CHOCHO) = (2.08 ± 0.63) × 10(-14) cm(3) molecule(-1) s(-1). The Cl atom initiated oxidation of (CF3)2CHOCH3 gives (CF3)2CHOCHO in a yield indistinguishable from 100%. The OH radical initiated oxidation of (CF3)2CHOCH3 gives the following products (molar yields): (CF3)2CHOCHO (76 ± 8)%, CF3C(O)OCH3 (16 ± 2)%, CF3C(O)CF3 (4 ± 1)%, and C(O)F2 (45 ± 5)%. The primary oxidation product (CF3)2CHOCHO reacts with Cl atoms to give secondary products (molar yields): CF3C(O)CF3 (67 ± 7)%, CF3C(O)OCHO (28 ± 3)%, and C(O)F2 (118 ± 12)%. CF3C(O)OCH3 reacts with Cl atoms to give: CF3C(O)OCHO (80 ± 8)% and C(O)F2 (6 ± 1)%. Atmospheric lifetimes of (CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3 were estimated to be 62 days, 1.5 years, and 220 days, respectively. The 100-year global warming potentials (GWPs) for (CF3)2CHOCH3, (CF3)2CHOCHO, and CF3C(O)OCH3 are estimated to be 6, 121, and 46, respectively. A comprehensive description of the atmospheric fate of (CF3)2CHOCH3 is presented.

Growing normally in an urban environment: positive deviance among slum children of Vadodara, India.

PubMed

Kanani, Shubhada; Popat, Kamal

2012-05-01

To assess factors contributing to positive deviance among the urban poor of Vadodara city. Mothers of sixty 6-18 mo old children- 30 each in positive deviant (PD: normal by weight-age) and negative deviant (ND: grade II by weight-age) groups-were interviewed through home visits using semi-structured questionnaires. Factors contributing significantly to PD (p < 0.01): PD children (vs. ND), were older (12-18 mo vs. 6-11 mo); families were smaller (5-7 vs. >7 members), of lower parity (1-2 vs. 3-4), greater birth interval (>3 y vs. 1-2 y); received colostrum (96% vs. 26%), breastfed at least 8-9 times/d (86% vs. 20%); were started on complementary feeds (CF) at 6-8 mo (53% vs. 23%); given thicker consistency CF (73% vs. 36%); fed actively (40% vs. 23%), fewer had diarrhea episodes in past 15 d (26% vs. 83%). Mean calorie intake (% RDA) from CF among PD was significantly higher than in ND (68% vs.42%). Factors contributing to PD in urban poor families are similar to those reported in rural India; which implies that ICDS-Health services for both urban and rural poor need to ensure that national IYCF guidelines-healthcare recommendations are followed by communities. Further research relating PD to desirable complementary feeding and hygiene-healthcare practices in rural and urban areas is required.

Burkholderia cenocepacia K56-2 trimeric autotransporter adhesin BcaA binds TNFR1 and contributes to induce airway inflammation.

PubMed

Mil-Homens, Dalila; Pinto, Sandra N; Matos, Rute G; Arraiano, Cecília; Fialho, Arsenio M

2017-04-01

Chronic lung disease caused by persistent bacterial infections is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). CF pathogens acquire antibiotic resistance, overcome host defenses, and impose uncontrolled inflammation that ultimately may cause permanent damage of lungs' airways. Among the multiple CF-associated pathogens, Burkholderia cenocepacia and other Burkholderia cepacia complex bacteria have become prominent contributors of disease progression. Here, we demonstrate that BcaA, a trimeric autotransporter adhesin (TAA) from the epidemic strain B. cenocepacia K56-2, is a tumor necrosis factor receptor 1-interacting protein able to regulate components of the tumor necrosis factor signaling pathway and ultimately leading to a significant production of the proinflammatory cytokine IL-8. Notably, this study is the first to demonstrate that a protein belonging to the TAA family is involved in the induction of the inflammatory response during B. cenocepacia infections, contributing to the success of the pathogen. Moreover, our results reinforce the relevance of the TAA BcaA as a multifunctional protein with a major role in B. cenocepacia virulence. © 2016 John Wiley & Sons Ltd.

Perceived Quality of Work Life and Risk for Compassion Fatigue Among Oncology Nurses: A Mixed-Methods Study.

PubMed

Denigris, Jami; Fisher, Kathleen; Maley, MaryKay; Nolan, Elizabeth

2016-05-01

To examine factors that influenced the nurse's perceived quality of work life and risk for compassion fatigue (CF). The specific aims of the study were to describe the (a) relationship among nurse characteristics and perceived quality of work life, (b) relationship between personal life stress and perceived quality of work life, and (c) the nurse's beliefs about his or her risk for CF.
. A descriptive, mixed-methods study.
. A hematology-oncology unit in a large urban teaching hospital in Pennsylvania.
. 20 oncology nurses. 
. Descriptive study using questionnaires and in-depth interviews. The variables were nurse characteristics, personal life stress, and quality of work life. Data were analyzed descriptively and thematically. Scores on the self-report questionnaires were compared to themes.
. Personal life stressors, measured by combining the Impact of Events Scale and Life Events Scale, identified powerful or severe impacts on well-being for 30% of nurse respondents in this study, theoretically placing them at risk for CF. However, qualitative data did not complement the results of the Life Events Scale, and 55% of the nurses described their overall work experiences as "life-affirming and rewarding." The participants provided multiple sources of their work-related stress, including subcategories of communication breakdown, work environment/institution, and care-driven factors. 
. Overall, oncology nurses experienced positive reinforcement at work and they had little concern about individual or organizational effectiveness. Positive experiences offset the negative and balanced out the risk for CF.
. The identification of personal and social contributors, as well as solutions to work-related stress, supports the philosophical premises (i.e., conceptual model) that the circumstances that place a nurse at risk for CF are socially constructed. Nurses can achieve greater empathy through self-understanding and translate this learning to patient care.

Enhancement of tritium concentrations on uptake by marine biota: experience from UK coastal waters.

PubMed

Hunt, G J; Bailey, T A; Jenkinson, S B; Leonard, K S

2010-03-01

Concentrations of tritium in sea water and marine biota as reported over the last approximately 10 years from monitoring programmes carried out by this laboratory under contract to the UK Food Standards Agency are reviewed from three areas: near Cardiff; Sellafield; and Hartlepool. Near Cardiff, enhancement of concentration factors (CFs) above an a priori value of approximately 1 have already been studied, and attributed to compounds containing organically bound tritium in local radioactive waste discharges. Further data for Cardiff up to 2006 are reported in this note. Up to 2001, CFs increased to values of more than approximately 7000 in flounders and approximately 4000 in mussels, but have subsequently reduced; this variability could be due to changes in the organic constitution of compounds discharged. Near Sellafield and Hartlepool, enhancements to the tritium concentration factor are observed but they are relatively small compared with those near Cardiff. Near Sellafield, plaice and mussels appear to have a CF for tritium of approximately 10; in some cases concentrations of tritium in winkles are below detection limits and positively measured values indicate a CF of approximately 3. The variation could be due to mechanisms of uptake by the different organisms. Near Hartlepool there were only a few cases where tritium was positively measured. These data give a value of approximately 5 for the CF in plaice (on the basis of two samples); approximately 15 in winkles (eight samples); and > 45 in mussels (two samples). Any differences between the behaviours at Sellafield and Hartlepool would need to be confirmed by improved measurements. Possible causes are the organic composition of the effluent and differences in environmental behaviour and uptake by organisms near the two sites. These potential causes need further investigation. It is emphasised that results from tritium analyses are heavily method dependent; thus comparison with results from other programmes needs to take this into account. Further, the results for enhancement of CF will also depend on the definition of CF itself.

Epidemic Pseudomonas aeruginosa infection in patients with cystic fibrosis is not a risk factor for poor clinical Outcomes following lung transplantation.

PubMed

Pritchard, Julia; Thakrar, Mitesh V; Somayaji, Ranjani; Surette, Michael G; Rabin, Harvey R; Helmersen, Doug; Lien, Dale; Purighalla, Swathi; Waddell, Barbara; Parkins, Michael D

2016-05-01

Epidemic strains of Pseudomonas aeruginosa (ePA) causing infection in cystic fibrosis (CF) have been commonly identified from clinics around the world. ePA disproportionally impacts CF patient pre-transplant outcomes manifesting in increased exacerbation frequency, worsened treatment burden and increased rate of lung function decline, and disproportionally leads to death and/or transplantation. As other CF factors such as pre-transplant infection with multi-resistant organisms, and isolation of P. aeruginosa in the post transplant graft, may impact post-transplant outcomes, we sought to determine if infection with ePA similarly adversely impact post-transplant outcomes. Between 1991-2014, 53 CF patients from our center received lung transplants. Bacterial strain typing was performed retrospectively on isolates collected prior to transplantation. Comprehensive chart reviews were performed to obtain baseline patient characteristics and post-transplant outcomes. Of the 53 transplanted patients, 57% of patients were infected with ePA prior to transplant; the other 43% of patients had unique strains of P. aeruginosa. Mean age at transplant was 29.0years for ePA and 33.3years for unique (p=0.04). There were no differences in overall survival (HR=0.75, 95% CI 0.31-1.79), bronchiolitis obliterans syndrome (BOS) free survival (HR 1.43, 95% CI 0.54-4.84) or all other assessed outcomes including exacerbation frequency, chronic renal failure, acute cellular rejections, Aspergillus infection, airway stenosis, and post-transplant lymphoproliferative disorder. Unlike pre-transplant outcomes, CF patients infected with ePA do not experience worse post-transplant outcomes than those infected with unique strains. Therefore, lung transplantation should be considered for all patients with P. aeruginosa infection and end stage lung disease, irrespective of infection with ePA. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Flavonoids eupatorin and sinensetin present in Orthosiphon stamineus leaves inhibit inflammatory gene expression and STAT1 activation.

PubMed

Laavola, Mirka; Nieminen, Riina; Yam, Mun Fei; Sadikun, Amirin; Asmawi, Mohd Zaini; Basir, Rusliza; Welling, Jukka; Vapaatalo, Heikki; Korhonen, Riku; Moilanen, Eeva

2012-05-01

Cytokines and other inflammatory mediators, such as prostaglandin E₂ (PGE₂) and nitric oxide (NO) produced by cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), respectively, activate and drive inflammation and therefore serve as targets for anti-inflammatory drug development. Orthosiphon stamineus is an indigenous medicinal plant of Southeast Asia that has been traditionally used in the treatment of rheumatoid arthritis, gout, and other inflammatory disorders. The present study investigated the anti-inflammatory properties of Orthosiphon stamineus leaf chloroform extract (CE), its flavonoid-containing CE fraction 2 (CF2), and the flavonoids eupatorin, eupatorin-5-methyl ether (TMF), and sinensetin, identified from the CF2. It was found that CE (20 and 50 µg/mL) and CF2 (20 and 50 µg/mL) inhibited iNOS expression and NO production, as well as PGE₂ production. Eupatorin and sinensetin inhibited iNOS and COX-2 expression and the production of NO (IC₅₀ 5.2 µM and 9.2 µM for eupatorin and sinensetin, respectively) and PGE₂ (IC₅₀ 5.0 µM and 2.7 µM for eupatorin and sinensetin, respectively) in a dose-dependent manner. The extracts and the compounds also inhibited tumor necrosis factor α (TNF-α) production (IC₅₀ 5.0 µM and 2.7 µM for eupatorin and sinensetin, respectively). Eupatorin and sinensetin inhibited lipopolysaccharide (LPS)-induced activation of transcription factor signal transducers and activators of transcription 1α (STAT1α). Furthermore, eupatorin (50 mg/kg i. p.) and sinensetin (50 mg/kg i. p.) inhibited carrageenan-induced paw inflammation in mice. The results suggest that CE and CF2, as well as the known constituents of CF2, i.e., eupatorin and sinensetin, have meaningful anti-inflammatory properties which may be utilized in the development of novel anti-inflammatory treatments. Georg Thieme Verlag KG Stuttgart · New York.

Brome isotope selective control of CF3Br molecule clustering by IR laser radiation in gas-dynamic expansion of CF3Br - Ar mixture

NASA Astrophysics Data System (ADS)

Apatin, V. M.; Lokhman, V. N.; Makarov, G. N.; Ogurok, N.-D. D.; Ryabov, E. A.

2018-02-01

We report the results of research on the experimental control of CF3Br molecule clustering under gas-dynamic expansion of the CF3Br - Ar mixture at a nozzle exit by using IR laser radiation. A cw CO2 laser is used for exciting molecules and clusters in the beam and a time-of-flight mass-spectrometer with laser UV ionisation of particles for their detection. The parameters of the gas above the nozzle are determined (compositions and pressure) at which intensive molecule clustering occurs. It is found that in the case of the CF3Br gas without carrier when the pressure P0 above the nozzle does not exceed 4 atm, molecular clusters actually are not generated in the beam. If the gas mixture of CF3Br with argon is used at a pressure ratio 1 : N, where N >= 3, and the total pressure above the nozzle is P0 >= 2 atm, then there occurs molecule clustering. We study the dependences of the efficiency of suppressing the molecule clustering on parameters of the exciting pulse, gas parameters above the nozzle, and on a distance of the molecule irradiation zone from the nozzle exit section. It is shown that in the case of resonant vibrational excitation of gas-dynamically cooled CF3Br molecules at the nozzle exit one can realise isotope-selective suppression of molecule clustering with respect to bromine isotopes. With the CF3Br - Ar mixtures having the pressure ratio 1 : 3 and 1 : 15, the enrichment factors obtained with respect to bromine isotopes are kenr ≈ 1.05 ± 0.005 and kenr ≈ 1.06 ± 0.007, respectively, under jet irradiation by laser emission in the 9R(30) line (1084.635 cm-1). The results obtained let us assume that this method can be used to control clustering of molecules comprising heavy element isotopes, which have a small isotopic shift in IR absorption spectra.

Serum lipid level and lifestyles are associated with carotid femoral pulse wave velocity among adults: 4.4-year prospectively longitudinal follow-up of a clinical trial.

PubMed

Zhao, XiaoXiao; Wang, Hongyu; Bo, LiuJin; Zhao, Hongwei; Li, Lihong; Zhou, Yingyan

2018-01-01

Lifestyle modifications are recommended as the initial treatment for high blood pressure. The influence of dyslipidemia might be via moderate arterial stiffness, which results in hypertension and cardiovascular disease. We used data from a subgroup of the lifestyle, level of serum lipids/carotid femoral-pulse wave velocity (CF-PWV) Susceptibility BEST Study, a population-based study of community-dwelling adults aged 45-75 years. The serum lipid level and CF-PWV were measured at baseline, and lifestyle such as smoking status, sleeping habits, and the level of oil or salt intake was determined with the use of a validated questionnaire during follow-up. Arterial stiffness was determined as CF-PWV using an electrocardiogram after a mean follow-up of 4.4 years. Regression coefficients (95% CIs), adjusted for demographics, risk factors, cholesterol, and triglycerides (TGs), were calculated by linear regression. Logistic regression analysis was used to identify the association between the variables with CF-PWV independently. In the results, glucose and total cholesterol (TC) were associated with higher CF-PWV (p = 0.000) and lower-destiny lipoprotein was associated with lower CF-PWV (p = 0.001) after adjustments for age, sex, mean arterial pressure, and heart rate. There were significant associations observed for current salt intake in relation to CF-PWV (p-trend = 0.038) without adjustment. This association was retained after adjustments for covariates and had statistical significance (p-trend = 0.048) in model 3, which adjusted age, sex, baseline CF-PWV, mean arterial pressure, heart rate waist circumference, education, smoking status, physical activity, diabetes mellitus (DM), heart disease, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, TGs, antihypertensive medicine, nitrate medicine, and antiplatelet medicine. Linear regression showed statistically significant associations between LDL and CF-PWV in the fully adjusted models (model 1 p = 0.010, model 2 p = 0.020, model 3 p = 0.017). Logistic regression analysis showed that CF-PWV was independently associated with age (p = 0.000), TC (p = 0.000), TGs (p = 0.000), and homo-cysteine (p = 0.000), and their odds ratios were 0.781, 3.424, 0.075, and 1.046, respectively. Our results showed a positive association between LDL and arterial stiffness, and suggested that less smoking status, sleeping disorder, and salt intake were associated with less arterial stiffness.

Dietary intake of energy-dense, nutrient-poor and nutrient-dense food sources in children with cystic fibrosis.

PubMed

Sutherland, Rosie; Katz, Tamarah; Liu, Victoria; Quintano, Justine; Brunner, Rebecca; Tong, Chai Wei; Collins, Clare E; Ooi, Chee Y

2018-04-30

Prescription of a high-energy, high-fat diet is a mainstay of nutrition management in cystic fibrosis (CF). However, families may be relying on energy-dense, nutrient-poor (EDNP) foods rather than nutrient-dense (ND) foods to meet dietary targets. We aimed to evaluate the relative contribution of EDNP and ND foods to the usual diets of children with CF and identify sociodemographic factors associated with higher EDNP intakes. This is a cross-sectional comparison of children with CF aged 2-18 years and age- and gender-matched controls. Dietary intake was assessed using the Australian Child and Adolescent Eating Survey (ACAES) food frequency questionnaire. Children with CF (n = 80: 37 males; mean age 9.3 years) consumed significantly more EDNP foods than controls (mean age 9.8 years) in terms of both total energy (median [IQR]: 1301 kcal/day (843-1860) vs. 686 kcal/day (480-1032); p < 0.0001), and as a proportion of energy intake (median [IQR]: 44% (34-51) vs. 31% (24-43); p < 0.0001). Although children with CF met their estimated energy requirements (median [IQR]: 158% (124-187) vs. 112% (90-137); p < 0.0001) and their diets were high in fat (median [IQR]: 38% (35-41) vs. 34% (32-36); p < 0.0001), this was largely attributable to EDNP foods. High EDNP intakes (≥10 serves/day) were associated with socioeconomic disadvantage (p = 0.01) and rural residential location (p = 0.03). The energy- and fat-dense CF diet is primarily achieved by overconsumption of EDNP foods, rather than ND sources. This dietary pattern may not be optimal for the future health of children with CF, who are now expected to survive well into adulthood. Copyright © 2018 European Cystic Fibrosis Society. All rights reserved.

Prevalence of Virulence Genes Among Bulgarian Nosocomial and Cystic Fibrosis Isolates of Pseudomonas Aeruginosa

PubMed Central

Mitov, Ivan; Strateva, Tanya; Markova, Boyka

2010-01-01

The aim of this study was to evaluate the prevalence of some virulence genes among 202 Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients (n=42) and non-CF in-patients (n=160) and to analyze the values according to the patient groups, infection localization and antimicrobial resistance. The following frequencies in all studied strains were established: algD (encoding GDP-mannose 6-dehydrogenase AlgD) – 91.1%, pilB (type IV fimbrial biogenesis protein PilB) – 23.8%, nan1 (neuraminidase) – 21.3%, lasB (elastase LasB) – 100%, plcH (haemolytic phospholipase C precursor) – 91.6%, exoS (exoenzyme S) – 62.4%, and exoU (exoenzyme U) – 30.2%. The prevalence of nan1 was significantly higher (P<0.01) in CF isolates (38.1%) than that in non-CF isolates (16.9%). The nan1–positive CF strains were cultured from 16 patients with recurrent lung exacerbations. This study revealed a statistically significant difference (P<0.01) between the portion of multidrug-resistant (MDR) nosocomial P. aeruginosa strains containing a large number (≥5) of virulence genes (38.1%) and the respective part of non-MDR isolates (17.6%). Moreover, pilB, exoU and nan1 manifested a higher spread (P<0.001) among MDR than in non-MDR strains (respectively, 39.1% vs. 13.2%; 40.2% vs. 17.7% and 26.1% vs. 4.4%). In conclusion, the dissemination of nan1 in CF isolates was moderate and correlated with the lower proportion of patients with lung exacerbations. The molecular-genetic detection of this gene may be used as an indirect measure of CF pulmonary disease evolution. Simultaneous determination of virulence factors and antimicrobial resistance is the contemporary approach for examination of the microbiological aspects of infections caused by P. aeruginosa. PMID:24031533

Down-regulation of IL-8 by high-dose vitamin D is specific to hyperinflammatory macrophages and involves mechanisms beyond up-regulation of DUSP1

PubMed Central

Dauletbaev, N; Herscovitch, K; Das, M; Chen, H; Bernier, J; Matouk, E; Bérubé, J; Rousseau, S; Lands, L C

2015-01-01

Background and Purpose There is current interest in vitamin D as a potential anti-inflammatory treatment for chronic inflammatory lung disease, including cystic fibrosis (CF). Vitamin D transcriptionally up-regulates the anti-inflammatory gene DUSP1, which partly controls production of the inflammatory chemokine IL-8. IL-8 is overabundant in CF airways, potentially due to hyperinflammatory responses of CF macrophages. We tested the ability of vitamin D metabolites to down-regulate IL-8 production in CF macrophages. Experimental Approach CF and healthy monocyte-derived macrophages (MDM) were treated with two vitamin D metabolites, 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), or paricalcitol, synthetic analogue of 1,25(OH)2D3. 25OHD3 was tested at doses of 25–150 nM, whereas 1,25(OH)2D3 and paricalcitol at doses of up to 100 nM. IL-8 was stimulated by bacterial virulence factors. As potential anti-inflammatory mechanism of vitamin D metabolites, we assessed up-regulation of DUSP1. Key Results MDM from patients with CF and some healthy donors showed excessive production of stimulated IL-8, highlighting their hyperinflammatory phenotype. Vitamin D metabolites down-regulated stimulated IL-8 only in those hyperinflammatory MDM, and only when used at high doses (>100 nM for 25OHD3, or >1 nM for 1,25(OH)2D3 and paricalcitol). The magnitude of IL-8 down-regulation by vitamin D metabolites or paricalcitol was moderate (∼30% vs. >70% by low-dose dexamethasone). Transcriptional up-regulation of DUSP1 by vitamin D metabolites was seen in all tested MDM, regardless of IL-8 down-regulation. Conclusions and Implications Vitamin D metabolites and their analogues moderately down-regulate IL-8 in hyperinflammatory macrophages, including those from CF. This down-regulation appears to go through DUSP1-independent mechanisms. PMID:26178144

Down-regulation of IL-8 by high-dose vitamin D is specific to hyperinflammatory macrophages and involves mechanisms beyond up-regulation of DUSP1.

PubMed

Dauletbaev, N; Herscovitch, K; Das, M; Chen, H; Bernier, J; Matouk, E; Bérubé, J; Rousseau, S; Lands, L C

2015-10-01

There is current interest in vitamin D as a potential anti-inflammatory treatment for chronic inflammatory lung disease, including cystic fibrosis (CF). Vitamin D transcriptionally up-regulates the anti-inflammatory gene DUSP1, which partly controls production of the inflammatory chemokine IL-8. IL-8 is overabundant in CF airways, potentially due to hyperinflammatory responses of CF macrophages. We tested the ability of vitamin D metabolites to down-regulate IL-8 production in CF macrophages. CF and healthy monocyte-derived macrophages (MDM) were treated with two vitamin D metabolites, 25-hydroxyvitamin D3 (25OHD3 ) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), or paricalcitol, synthetic analogue of 1,25(OH)2 D3 . 25OHD3 was tested at doses of 25-150 nM, whereas 1,25(OH)2 D3 and paricalcitol at doses of up to 100 nM. IL-8 was stimulated by bacterial virulence factors. As potential anti-inflammatory mechanism of vitamin D metabolites, we assessed up-regulation of DUSP1. MDM from patients with CF and some healthy donors showed excessive production of stimulated IL-8, highlighting their hyperinflammatory phenotype. Vitamin D metabolites down-regulated stimulated IL-8 only in those hyperinflammatory MDM, and only when used at high doses (>100 nM for 25OHD3 , or >1 nM for 1,25(OH)2 D3 and paricalcitol). The magnitude of IL-8 down-regulation by vitamin D metabolites or paricalcitol was moderate (∼30% vs. >70% by low-dose dexamethasone). Transcriptional up-regulation of DUSP1 by vitamin D metabolites was seen in all tested MDM, regardless of IL-8 down-regulation. Vitamin D metabolites and their analogues moderately down-regulate IL-8 in hyperinflammatory macrophages, including those from CF. This down-regulation appears to go through DUSP1-independent mechanisms. © 2015 The British Pharmacological Society.

Hemoglobin A1c levels and aortic arterial stiffness: the Cardiometabolic Risk in Chinese (CRC) study.

PubMed

Liang, Jun; Zhou, Na; Teng, Fei; Zou, Caiyan; Xue, Ying; Yang, Manqing; Song, Huaidong; Qi, Lu

2012-01-01

The American Diabetes Association (ADA) recently published new clinical guidelines in which hemoglobin A1c (HbA1c) was recommended as a diagnostic test for diabetes. The present study was to investigate the association between HbA1c and cardiovascular risk, and compare the associations with fasting glucose and 2-hour oral glucose tolerance test (2 h OGTT). The study samples are from a community-based health examination survey in central China. Carotid-to-femoral pulse wave velocity (cfPWV) and HbA1c were measured in 5,098 men and women. After adjustment for age, sex, and BMI, the levels of HbA1c were significantly associated with an increasing trend of cfPWV in a dose-dependent fashion (P for trend <0.0001). The associations remained significant after further adjustment for blood pressure, heart rate, and lipids (P = 0.004), and the difference in cfPWV between the highest and the lowest quintiles of HbA1c was 0.31 m/s. Fasting glucose and 2 h OGTT were not associated with cfPWV in the multivariate analyses. HbA1c showed additive effects with fasting glucose or 2 h OGTT on cfPWV. In addition, age and blood pressure significantly modified the associations between HbA1c and cfPWV (P for interactions <0.0001 for age; and  = 0.019 for blood pressure). The associations were stronger in subjects who were older (≥60 y; P for trend = 0.004) and had higher blood pressure (≥120 [systolic blood pressure]/80 mmHg [diastolic blood pressure]; P for trend = 0.028) than those who were younger and had lower blood pressure (P for trend >0.05). HbA1c was related to high cfPWV, independent of conventional cardiovascular risk factors. Senior age and high blood pressure might amplify the adverse effects of HbA1c on cardiovascular risk.

Pulmonary function disparities exist and persist in Hispanic patients with cystic fibrosis: A longitudinal analysis.

PubMed

McGarry, Meghan E; Neuhaus, John M; Nielson, Dennis W; Burchard, Esteban; Ly, Ngoc P

2017-12-01

Hispanic patients with cystic fibrosis (CF) have decreased life expectancy compared to non-Hispanic white patients. Pulmonary function is a main predictor of life expectancy in CF. Ethnic differences in pulmonary function in CF have been understudied. The objective was to compare longitudinal pulmonary function between Hispanic and non-Hispanic white patients with CF. This cohort study of 15 018 6-25 years old patients in the CF Foundation Patient Registry from 2008 to 2013 compared FEV 1 percent predicted and longitudinal change in FEV 1 percent predicted in Hispanic to non-Hispanic white patients. We used linear mixed effects models with patient-specific slopes and intercepts, adjusting for 14 demographic and clinical variables. We did sub-analyses by CFTR class, F508del copies, and PERT use. Hispanic patients had lower FEV 1 percent predicted (79.9%) compared with non-Hispanic white patients (85.6%); (-5.8%, 95%CI -6.7% to -4.8%, P < 0.001), however, there was no difference in FEV 1 decline over time. Patients on PERT had a larger difference between Hispanic and non-Hispanic white patients in FEV 1 percent predicted than patients not on PERT (-6.0% vs -4.1%, P = 0.02). The ethnic difference in FEV 1 percent predicted was not statistically significant between CFTR classes (Class I-III: -6.1%, Class IV-V: -5.9%, Unclassified: -5.7%, P > 0.05) or between F508del copies (None: -7.6%, Heterozygotes: -5.6%, Homozygotes: -5.3%, P > 0.05). Disparities in pulmonary function exist in Hispanic patients with CF early in life and then persist without improving or worsening over time. It is valuable to investigate the factors contributing to pulmonary function in Hispanic patients with CF. © 2017 Wiley Periodicals, Inc.

Substrate biochemistry control on the pathways for the formation of soil organic matter

NASA Astrophysics Data System (ADS)

Almeida, L. F.; Hurtarte, L. C.; Souza, I. F.; Barros, E. M.; Vergutz, L.; Silva, I. R.

2017-12-01

Linking plant litter biochemistry, its decomposition and soil organic matter (SOM) formation is not straightforward. To address this issue, we evaluated the decomposition of four biochemical fractions operationally defined as i) hot-water extractable (HWE), ii) total solvent (acetone) extractable (TSE), iii) acid-base (HNO3-KOH) unhydrolyzable cellulosic fraction (CF), and iv) acid(H2SO4) unhydrolyzable (AUR) and the transfer of C from these fractions to SOM. Each biochemical fraction was Soxhlet-extracted from isotopically labeled (13C) leaves, twigs, bark and roots of eucalypt plants (120 days old). The molecular composition of each fraction was inferred from thermochemolysis with tertamethylammonium (TMAH), followed by gas chromatography coupled o mass spectrometry (GC-MS). For the incubation, we collected soil samples from the topsoil (0-20 cm) of a sandy-clay loam, kaolinitic Typic Hapludox (Haplic Ferralsol). Four plant organs and four biochemical fractions were arranged into a (4 4) + 1 factorial scheme, including one control treatment (soil only). The samples were incubated at 80% of their water-holding capacity and kept under controlled temperature (25 ºC). The decomposition of the biochemical fractions was monitored by determining the CO2 concentration into the headspace of the vials. Finished the incubation, soil samples were submitted to density followed by particle-size fractionation. HWE and CF was decomposed at faster rates than TSE and AUR throughout the incubation. The soil fraction <53 µm retained a significantly higher proportion of the initial input of HWE (32%) and AUR (31%) than TSE (19%) or CF (15%). Light fraction organic matter (LFOM) with density <1.8 g cm-3, retained a significant proportion of AUR (37%) and TSE (32%) while CF was mostly lost as CO2 (79%). Selective preservation of organic materials (e.g., long-chain lipids) within AUR and TSE fractions appears to be a significant pathway for SOM formation. A microbial-driven pathway cannot be ruled out for any biochemical fraction, but seems more relevant for HWE and CF. In short-term, substrate biochemistry exerts a strong influence on the conversion of eucalypt litter fractions into either CO2 or SOM. Such results warrant the relevance of field-based study to link plant litter biochemistry and SOM formation in long-term.

Throat Swabs and Sputum Culture as Predictors of P. aeruginosa or S. aureus Lung Colonization in Adult Cystic Fibrosis Patients.

PubMed

Seidler, Darius; Griffin, Mary; Nymon, Amanda; Koeppen, Katja; Ashare, Alix

2016-01-01

Due to frequent infections in cystic fibrosis (CF) patients, repeated respiratory cultures are obtained to inform treatment. When patients are unable to expectorate sputum, clinicians obtain throat swabs as a surrogate for lower respiratory cultures. There is no clear data in adult subjects demonstrating the adequacy of throat swabs as a surrogate for sputum or BAL. Our study was designed to determine the utility of throat swabs in identifying lung colonization with common organisms in adults with CF. Adult CF subjects (n = 20) underwent bronchoscopy with BAL. Prior to bronchoscopy, a throat swab was obtained. A sputum sample was obtained from subjects who were able to spontaneously expectorate. All samples were sent for standard microbiology culture. Using BAL as the gold standard, we found the positive predictive value for Pseudomonas aeruginosa to be 100% in both sputum and throat swab compared to BAL. However, the negative predictive value for P. aeruginosa was 60% and 50% in sputum and throat swab, respectively. Conversely, the positive predictive value for Staphylococcus aureus was 57% in sputum and only 41% in throat swab and the negative predictive value of S. aureus was 100% in sputum and throat swab compared to BAL. Our data show that positive sputum and throat culture findings of P. aeruginosa reflect results found on BAL fluid analysis, suggesting these are reasonable surrogates to determine lung colonization with P. aeruginosa. However, sputum and throat culture findings of S. aureus do not appear to reflect S. aureus colonization of the lung.

Formation and chemical reactivity of carbon fibers prepared by defluorination of graphite fluoride

NASA Technical Reports Server (NTRS)

Hung, Ching-Cheh

1994-01-01

Defluorination of graphite fluoride (CFX) by heating to temperatures of 250 to 450 C in chemically reactive environments was studied. This is a new and possibly inexpensive process to produce new carbon-based materials. For example, CF 0.68 fibers, made from P-100 carbon fibers, can be defluorinated in BrH2C-CH = CH-CH2Br (1,4-dibromo-2butene) heated to 370 C, and graphitized to produce fibers with an unusually high modulus and a graphite layer structure that is healed and cross-linked. Conversely, a sulfur-doped, visibly soft carbon fiber was produced by defluorinating CF 0.9 fibers, made from P-25, in sulfur (S) vapor at 370 C and then heating to 660 C in nitrogen (N2). Furthermore, defluorination of the CF 0.68 fibers in bromine (Br2) produced fragile, structurally damaged carbon fibers. Heating these fragile fibers to 1100 C in N2 caused further structural damage, whereas heating to 150 C in bromoform (CHBr3) and then to 1100 C in N2 healed the structural defects. The defluorination product of CFX, tentatively called activated graphite, has the composition and molecular structure of graphite, but is chemically more reactive. Activated graphite is a scavenger of manganese (Mn), and can be intercalated with magnesium (Mg). Also, it can easily collect large amounts of an alloy made from copper (Cu) and type 304 stainless steel to form a composite. Finally, there are indications that activated graphite can wet metals or ceramics, thereby forming stronger composites with them than the pristine carbon fibers can form.

Burkholderia cepacia complex in cystic fibrosis in the post-epidemic period: multilocus sequence typing-based approach.

PubMed

Fila, Libor; Dřevínek, Pavel

2017-11-01

Cystic fibrosis (CF) patients in the Czech Republic suffered in the late 1990s from an epidemic with ST32 strain of Burkholderia cepacia complex (Bcc). Cohort segregation of Bcc and of ST32 positive patients was introduced in 1999 and 2002, respectively. We performed a study to evaluate the molecular epidemiology of Bcc infection after implementation of these infection control measures. Patients attending the Prague CF adult Centre from 2000 to 2015 were included in the present study. Demographic data and microbial statuses were collected from patient records. All Bcc isolates were analyzed using multilocus sequence typing (MLST). The prevalences of epidemic strain ST32 and of other Bcc strains were calculated. Ninety out of 227 CF patients were infected with Bcc during the study period. The prevalence of ST32 cases significantly decreased from 46.5% in 2000-2001 to 10.4% in 2014-2015 (P < 0.001) due to occurrence of only one new case in 2003, as well as to the death of 72% of ST32-infected patients. Conversely, there was a significant increase in prevalence of other Bcc strains, which rose from 0 to 14.9% (P = 0.015) and of transient infections. A micro-epidemic of infection with ST630 strain was observed in 2014 in lung transplant patients hospitalized in intensive care unit. The prevalence of epidemic strain ST32 decreased, whereas that of non-clonal strains of Bcc increased. Routine use of MLST allowed early detection of new and potentially epidemic strains.

Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation.

PubMed

Sampaziotis, Fotios; de Brito, Miguel Cardoso; Madrigal, Pedro; Bertero, Alessandro; Saeb-Parsy, Kourosh; Soares, Filipa A C; Schrumpf, Elisabeth; Melum, Espen; Karlsen, Tom H; Bradley, J Andrew; Gelson, William Th; Davies, Susan; Baker, Alastair; Kaser, Arthur; Alexander, Graeme J; Hannan, Nicholas R F; Vallier, Ludovic

2015-08-01

The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening.

[Dehydration and metabolic alkalosis: an unusual presentation of cystic fibrosis in an infant].

PubMed

Aranzamendi, Roberto J; Breitman, Fanny; Asciutto, Carolina; Delgado, Norma; Castaños, Claudio

2008-10-01

Cystic fibrosis (CF) may present during neonatal period with classic clinic symptoms related to the disease. The severity of the disease is multifactorial, one of the factors depends on the level of activity of the CFTR protein, which is related with the mutation type that affects the patient. An infant is presented who developed recurrent episodes of vomiting, anorexia, weight loss, dehydration and electrolyte abnormalities, such as metabolic alkalosis, hyponatremia, hypokalemia and hypochloremia. CF was diagnosed after the third episode showing an unusual and not very publicized presentation of the disease. Mutations !F 508 and 2789+5G-A were found. CF should be considered in patients of any age, but particularly in infants, presenting with anorexia, vomiting, failure to thrive, that are associated with recurrent episodes of hyponatremic hypochloremic, dehydration with metabolic alkalosis unexplained by other causes, even in the absence of respiratory or gastrointestinal symptoms or failure to thrive.

The effect of interaural fluctuation rate on correlation change discrimination.

PubMed

Goupell, Matthew J; Litovsky, Ruth Y

2014-02-01

While bilateral cochlear implants (CIs) provide some binaural benefits, these benefits are limited compared to those observed in normal-hearing (NH) listeners. The large frequency-to-electrode allocation bandwidths (BWs) in CIs compared to auditory filter BWs in NH listeners increases the interaural fluctuation rate available for binaural unmasking, which may limit binaural benefits. The purpose of this work was to investigate the effect of interaural fluctuation rate on correlation change discrimination and binaural masking-level differences in NH listeners presented a CI simulation using a pulsed-sine vocoder. In experiment 1, correlation-change just-noticeable differences (JNDs) and tone-in-noise thresholds were measured for narrowband noises with different BWs and center frequencies (CFs). The results suggest that the BW, CF, and/or interaural fluctuation rate are important factors for correlation change discrimination. In experiment 2, the interaural fluctuation rate was systematically varied and dissociated from changes in BW and CF by using a pulsed-sine vocoder. Results indicated that the interaural fluctuation rate did not affect correlation change JNDs for correlated reference noises; however, slow interaural fluctuations increased correlation change JNDs for uncorrelated reference noises. In experiment 3, the BW, CF, and vocoder pulse rate were varied while interaural fluctuation rate was held constant. JNDs increased for increasing BW and decreased for increasing CF. In summary, relatively fast interaural fluctuation rates are not detrimental for detecting changes in interaural correlation. Thus, limiting factors to binaural benefits in CI listeners could be a result of other temporal and/or spectral deficiencies from electrical stimulation.

75 FR 22693 - Airworthiness Directives; General Electric Company (GE) CF34-1A, CF34-3A, and CF34-3B Series...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

..., Aerospace Engineer, Engine Certification Office, FAA, Engine & Propeller Directorate, 12 New England... Directives; General Electric Company (GE) CF34-1A, CF34-3A, and CF34-3B Series Turbofan Engines; Correction... to GE CF34-1A, CF34-3A, and CF34-3B series turbofan engines. The docket number is incorrect in all...

Parent and Child Perceptions of a Self-Regulated, Home-Based Exercise Program for Children with Cystic Fibrosis

PubMed Central

Happ, Mary Beth; Hoffman, Leslie A.; Higgins, Linda W.; DiVirgilio, Dana; Orenstein, David M.

2014-01-01

Background Despite recognized benefits, many children with cystic fibrosis (CF) do not consistently participate in physical activities. There is little empirical literature regarding the feelings and attitudes of children with CF toward exercise programs, parental roles in exercise, or factors influencing exercise experiences during research participation. Objectives To describe the exercise experiences of children with CF and their parents during participation in a six-month program of self-regulated, home-based exercise. Methods This qualitative descriptive study nested within a randomized controlled trial of a self-regulated, home-based exercise program used serial semi-structured interviews conducted individually at two and six months with 11 purposively selected children with CF and their parent(s). Results Six boys and five girls, ages 10–16, and parents (nine mothers, four fathers) participated in a total of 44 interviews. Five major thematic categories describing child and parent perceptions and experience of the bicycle exercise program were identified in the transcripts: (a) motivators; (b) barriers; (c) effort/work; (d) exercise routine; (e) sustaining exercise. Research participation, parent-family participation, health benefits, and the child’s personality traits were primary motivators. Competing activities, priorities and responsibilities were the major barriers to implementing the exercise program as prescribed. Motivation waned and the novelty wore off for several (approximately half) parent-child dyads, who planned to decrease or stop the exercise program after the study ended. Discussion We identified motivators and barriers to a self-regulated, home-based exercise program for children with CF that can be addressed in planning future exercise interventions to maximize the health benefits for children with CF and the feasibility and acceptability to the children and their families. PMID:23995464

Parent and child perceptions of a self-regulated, home-based exercise program for children with cystic fibrosis.

PubMed

Happ, Mary Beth; Hoffman, Leslie A; Higgins, Linda W; Divirgilio, Dana; DiVirgilio, Dana; Orenstein, David M

2013-01-01

Despite recognized benefits, many children with cystic fibrosis (CF) do not consistently participate in physical activities. There is little empirical literature regarding the feelings and attitudes of children with CF toward exercise programs, parental roles in exercise, or factors influencing exercise experiences during research participation. The aim of this study is to describe the exercise experiences of children with CF and their parents during participation in a 6-month program of self-regulated, home-based exercise. This qualitative descriptive study was nested within a randomized controlled trial of a self-regulated, home-based exercise program and used serial semistructured interviews conducted individually at 2 and 6 months with 11 purposively selected children with CF and their parent(s). Six boys and five girls, ages 10-16 years, and parents(nine mothers, four fathers) participated in a total of 44 interviews. Five major thematic categories describing child and parent perceptions and experience of the bicycle exercise program were identified in the transcripts: (a) motivators, (b) barriers, (c) effort/work, (d) exercise routine, and (e) sustaining exercise. Research participation, parent-family participation, health benefits, and the child's personality traits were the primary motivators. Competing activities, priorities, and responsibilities were the major barriers in implementing the exercise program as prescribed. Motivation waned, and the novelty wore off for several (approximately half) parent-child dyads, who planned to decrease or stop the exercise program after the study ended. We identified motivators and barriers to a self-regulated, home-based exercise program for children with CF that can be addressed in planning future exercise interventions to maximize the health benefits for children with CF and the feasibility and acceptability to the children and their families.

A prospective analysis of unplanned patient-initiated contacts in an adult cystic fibrosis centre.

PubMed

Burnet, Espérie; Hubert, Dominique; Champreux, Juliette; Honoré, Isabelle; Kanaan, Reem; Panzo, Rosewilta; Burgel, Pierre-Régis

2018-05-07

Timely response should be provided when patients contact the cystic fibrosis (CF) centre in between scheduled visits. Little data exist on unplanned patient-initiated contacts in CF adults. A two-stage prospective study was undertaken from 1 January to 31 December 2015 at Cochin Hospital, Paris (France). The first stage included all adults (≥18 years) who initiated unplanned contacts to the CF centre over four months. Four physicians and three nurses systematically recorded unplanned patient-initiated contacts. The data was analysed to determine why and how patients contacted the CF centre and time spent responding to their request(s). The second stage (one physician, three nurses) lasted twelve months and explored whether high contact frequency was associated with disease severity, using multivariate logistic regression. In the first stage, 259 of 410 patients (63%) initiated at least one unplanned contact, corresponding to 1067 contacts over 4 months. Patients favoured email with physicians (61% of contacts) and telephone with nurses (87% of contacts). Total time spent by the 7 caregivers on providing responses was 8 h/work week. Reasons for contacting the CF centre varied greatly, but <20% of contacts were directly related to symptom management. In the second stage, 180 of 212 patients (85%) initiated 1876 contacts over 12 months. Factors associated with ≥5 contacts/year were female sex, FEV 1  ≤ 30% predicted, ≥5 physician visits/year, and ≥ 1 hospital admission/year. Answering unplanned patient-initiated contacts represented a significant workload for CF caregivers. Increased disease severity was associated with high contact frequency. Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Occurrence of Pseudomonas aeruginosa in waters: implications for patients with cystic fibrosis (CF).

PubMed

Caskey, S; Stirling, J; Moore, J E; Rendall, J C

2018-06-01

Chronic Pseudomonas aeruginosa infection is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). Current understanding of risk factors for acquisition is limited and so the aim of this study was to examine a large sample of environmental waters from diverse sources. Environmental water samples (n = 7904) from jacuzzis, hydrants, swimming pools, hot tubs, plunge pools, bottled natural mineral water, taps, springs, ice machines, water coolers, bores and showers were examined for the presence of P. aeruginosa. Pseudomonas aeruginosa was detected in 524/7904 (6·6%) waters examined. Hot tubs (51/243; 20·9%), tap water (3/40; 8%) and jacuzzis (432/5811; 7·4%) were the most likely environments where P. aeruginosa was isolated. Pseudomonas aeruginosa was isolated from bottled water (2/67; 3%). Our study highlights the ubiquitous nature of P. aeruginosa in the environment. Given CF patients are frequently counselled to make lifestyle changes to minimize P. aeruginosa exposure, these results have important implications. In particular, the occurrence of P. aeruginosa in tap water highlights the need to disinfect the CF patients' nebulizer after each use. This study examined a large number of water sources (n = 7904) over a 9-year period for the presence of Pseudomonas aeruginosa. The study highlighted that jacuzzis (n = 5811; 7% positive) and hot tubs had the highest occurrence of this organism (n = 243, 21% positive). Patients with cystic fibrosis (CF) are interested in knowing what water environments are likely to be contaminated with this organism, as this bacterium is an important cause of increased morbidity and mortality in such patients. With such information, CF patients and parents may make informed decisions about lifestyle choice and water environment avoidance. © 2018 The Society for Applied Microbiology.

A novel method for blood volume estimation using trivalent chromium in rabbit models.

PubMed

Baby, Prathap Moothamadathil; Kumar, Pramod; Kumar, Rajesh; Jacob, Sanu S; Rawat, Dinesh; Binu, V S; Karun, Kalesh M

2014-05-01

Blood volume measurement though important in management of critically ill-patients is not routinely estimated in clinical practice owing to labour intensive, intricate and time consuming nature of existing methods. The aim was to compare blood volume estimations using trivalent chromium [(51)Cr(III)] and standard Evans blue dye (EBD) method in New Zealand white rabbit models and establish correction-factor (CF). Blood volume estimation in 33 rabbits was carried out using EBD method and concentration determined using spectrophotometric assay followed by blood volume estimation using direct injection of (51)Cr(III). Twenty out of 33 rabbits were used to find CF by dividing blood volume estimation using EBD with blood volume estimation using (51)Cr(III). CF is validated in 13 rabbits by multiplying it with blood volume estimation values obtained using (51)Cr(III). The mean circulating blood volume of 33 rabbits using EBD was 142.02 ± 22.77 ml or 65.76 ± 9.31 ml/kg and using (51)Cr(III) was estimated to be 195.66 ± 47.30 ml or 89.81 ± 17.88 ml/kg. The CF was found to be 0.77. The mean blood volume of 13 rabbits measured using EBD was 139.54 ± 27.19 ml or 66.33 ± 8.26 ml/kg and using (51)Cr(III) with CF was 152.73 ± 46.25 ml or 71.87 ± 13.81 ml/kg (P = 0.11). The estimation of blood volume using (51)Cr(III) was comparable to standard EBD method using CF. With further research in this direction, we envisage human blood volume estimation using (51)Cr(III) to find its application in acute clinical settings.

The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis.

PubMed

Amin, Reshma; Dupuis, Annie; Aaron, Shawn D; Ratjen, Felix

2010-01-01

The relevance of Aspergillus fumigatus in patients with cystic fibrosis (CF) not affected by allergic bronchopulmonary aspergillosis is unclear. Our aim was to determine the effect of persistent infection with A fumigatus on pulmonary exacerbations and lung function in children with CF. This was a retrospective cohort study of patients with CF followed at The Hospital for Sick Children from 1999 to 2006. Persistent A fumigatus infection was defined as the presence of two or more positive sputum or bronchoalveolar cultures for A fumigatus in a given year. The primary outcome measure was the annual number of hospitalizations for pulmonary exacerbations. Two hundred thirty patients with CF were included in the analysis. The FEV(1) of patients persistently infected with A fumigatus was 3.61% (P< or =.0001) lower during the study period compared with uninfected patients. There was a significant interaction between A fumigatus and Pseudomonas aeruginosa on lung function (P=.0006). Patients not infected with either organism had the highest pulmonary function. Persistent A fumigatus infection (relative risk [RR]=1.94, P=.0002) and CF-related diabetes (RR=1.64, P=.028) were associated with an increased risk of pulmonary exacerbations requiring hospitalization, whereas there was no increased risk of pulmonary exacerbations among patients with allergic bronchopulmonary aspergillosis (RR=1.02, P=.94). When adjusted for baseline pulmonary function, none of these variables were associated with a significantly increased risk of pulmonary exacerbations, with only chronic A fumigatus infection trending toward significance (RR=1.40, P=.065). Persistent A fumigatus infection is an independent risk factor for hospital admissions in patients with CF.

From arterial stiffness to kidney graft microvasculature: Mortality and graft survival within a cohort of 220 kidney transplant recipients.

PubMed

Cheddani, Lynda; Radulescu, Camélia; Chaignon, Michel; Karras, Alexandre; Neuzillet, Yann; Duong, Jean-Paul; Tabibzadeh, Nahid; Letavernier, Emmanuel; Delahousse, Michel; Haymann, Jean-Philippe

2018-01-01

Aortic stiffness assessed by carotid-femoral pulse wave velocity (CF-PWV) is a predictor of mortality in several populations. However, little is known in kidney transplant recipients. Our objectives were to evaluate the ability of CF-PWV measured 3 months following transplantation to predict mortality, graft loss and its potential links to measured Glomerular Filtration Rate (mGFR) or kidney graft microvasculature parameters. The study is based on a monocentric retrospective cohort including 220 adult kidney graft recipients evaluated three months after transplantation. CF-PWV measures, clinical, laboratory and histological data performed at 3 (M3) and 12 months (M12) following transplantation were retrospectively collected. The two primary endpoints were all-cause mortality and occurrence of end stage renal disease (ESRD) defined by initiation of dialysis. After a median follow up of 5.5 years [1.9; 8.8], death and graft loss occurred in 10 and 12 patients respectively. M3 CF-PWV was an independent mortality risk factor (HR = 1.29 [1.03; 1.61]; p = 0.03), despite no aortic stiffness variation during the first year of transplantation. Of notice, M3 CF-PWV was not associated with M12 mGFR or ESRD outcome. Graft microcirculation assessed by Banff vascular fibrous intimal thickening score (cv) worsened between M3 and M12 (p = 0.01), but no link was found with CF-PWV, mGFR or ESRD outcome. Surprisingly, acute rejections at M3 were associated after adjustment with mortality (p = 0.03) but not ESRD. Aortic stiffness measured 3 months after kidney transplantation is a strong predictor of mortality with no obvious influence on kidney graft microvasculature or graft loss.

Parent knowledge of disease management in cystic fibrosis: Assessing behavioral treatment management.

PubMed

Nicolais, Christina J; Bernstein, Ruth; Riekert, Kristin A; Quittner, Alexandra L

2018-02-01

Cystic fibrosis (CF) is a life-shortening, burdensome disease requiring complex knowledge to manage the disease. Significant gaps in knowledge have been documented for parents, which may lead to unintentionally poor adherence and insufficient transfer of treatment responsibility from parents to adolescents. There are no current, validated measures of parent knowledge for this population and there are no measures that assess the knowledge required for day-to-day behavioral management of CF. We assessed the psychometric properties of the parent version of the Knowledge of Disease Management-Cystic Fibrosis measure (KDM-CF-P) using data from iCARE (I Change Adherence and Raise Expectations), a randomized control adherence intervention trial. A total of 196 parents in the iCARE standard care/control arm completed 35 items assessing their knowledge of disease management at their 12-month study visit, prior to beginning the intervention. Items were eliminated from the measure if they met the threshold for ceiling effects, were deemed clinically irrelevant, or did not correlate well with their intended scale. Item-to-total correlations, confirmatory factor analysis, discriminant function, reliability, and convergent validity were calculated. The KDM-CF-P (19 items) demonstrated internal consistency of KR20 = 0.60 on each scale and a two-scale structure. Convergent validity for knowledge scores was found with maternal education, family income, and type of medical insurance. Parents correctly answered approximately 85% of items on the KDM-CF-P. The KDM-CF-P psychometrics support a two-scale measure with clinical utility. It is useful for assessing gaps in knowledge that can be remediated through individualized, tailored interventions. © 2017 Wiley Periodicals, Inc.

Heritability of Lung Disease Severity in Cystic Fibrosis

PubMed Central

Vanscoy, Lori L.; Blackman, Scott M.; Collaco, Joseph M.; Bowers, Amanda; Lai, Teresa; Naughton, Kathleen; Algire, Marilyn; McWilliams, Rita; Beck, Suzanne; Hoover-Fong, Julie; Hamosh, Ada; Cutler, Dave; Cutting, Garry R.

2007-01-01

Rationale: Obstructive lung disease, the major cause of mortality in cystic fibrosis (CF), is poorly correlated with mutations in the disease-causing gene, indicating that other factors determine severity of lung disease. Objectives: To quantify the contribution of modifier genes to variation in CF lung disease severity. Methods: Pulmonary function data from patients with CF living with their affected twin or sibling were converted into reference values based on both healthy and CF populations. The best measure of FEV1 within the last year was used for cross-sectional analysis. FEV1 measures collected over at least 4 years were used for longitudinal analysis. Genetic contribution to disease variation (i.e., heritability) was estimated in two ways: by comparing similarity of lung function in monozygous (MZ) twins (∼ 100% gene sharing) with that of dizygous (DZ) twins/siblings (∼ 50% gene sharing), and by comparing similarity of lung function measures for related siblings to similarity for all study subjects. Measurements and Main Results: Forty-seven MZ twin pairs, 10 DZ twin pairs, and 231 sibling pairs (of a total of 526 patients) with CF were studied. Correlations for all measures of lung function for MZ twins (0.82–0.91, p < 0.0001) were higher than for DZ twins and siblings (0.50–0.64, p < 0.001). Heritability estimates from both methods were consistent for each measure of lung function and ranged from 0.54 to 1.0. Heritability estimates generally increased after adjustment for differences in nutritional status (measured as body mass index z-score). Conclusions: Our heritability estimates indicate substantial genetic control of variation in CF lung disease severity, independent of CFTR genotype. PMID:17332481

Constrictive Bronchiolitis in Cystic Fibrosis Adolescents with Refractory Pulmonary Decline.

PubMed

Harris, William T; Boyd, J Todd; McPhail, Gary L; Brody, Alan S; Szczesniak, Rhonda D; Korbee, Leslie L; Baker, Michael L; Clancy, John P

2016-12-01

Refractory lung function decline in association with recurrent pulmonary exacerbations is a common, yet poorly explained finding in cystic fibrosis (CF). To investigate the histopathologic mechanisms of pulmonary deterioration during adolescence and early adulthood, we reviewed clinically-indicated lung biopsy specimens obtained during a period of persistent decline. To determine if peribronchiolar remodeling is prominent in lung biopsy specimens obtained in adolescents with CF refractory to conventional therapy. Six adolescents with CF (mean age, 16.2 y; mean FEV 1 , 52% predicted at biopsy) with significant pulmonary deterioration over 12-24 months (mean FEV 1 decline of 14% predicted/year) despite aggressive intervention underwent computed tomography imaging and ultimately lung biopsy to aid clinical management. In addition to routine clinical evaluation, histopathologic investigation included staining for transforming growth factor-β (TGF-β, a genetic modifier of CF lung disease), collagen deposition (a marker of fibrosis), elastin (to evaluate for bronchiectasis), and α-smooth muscle actin (to identify myofibroblasts). All computed tomography scans demonstrated a mix of bronchiectasis and hyperinflation that was variable across lung regions and within patients. Lung biopsy revealed significant peribronchiolar remodeling, particularly in patients with more advanced disease, with near complete obliteration of the peribronchiolar lumen (constrictive bronchiolitis). Myofibroblast differentiation (a TGF-β-dependent process) was prominent in specimens with significant airway remodeling. Constrictive bronchiolitis is widely present in the lung tissue of adolescents with CF with advanced disease and may contribute to impaired lung function that is refractory to conventional therapy (antibiotics, antiinflammatories, and mucolytics). TGF-β-dependent myofibroblast differentiation is prominent in areas of active fibrogenesis and may foster small airway remodeling in CF lung disease.

Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis

PubMed Central

Shirazi, Fazal; Ferreira, Jose A. G.; Stevens, David A.; Clemons, Karl V.; Kontoyiannis, Dimitrios P.

2016-01-01

Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (p<0.0001). Intracellular ROS levels were elevated (p<0.001) in NMuc-CF-treated Af biofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (p<0.0001) filtrates. Exposure to filtrates resulted in more DNA fragmentation in Af biofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation. PMID:26930399

Biofilm Filtrates of Pseudomonas aeruginosa Strains Isolated from Cystic Fibrosis Patients Inhibit Preformed Aspergillus fumigatus Biofilms via Apoptosis.

PubMed

Shirazi, Fazal; Ferreira, Jose A G; Stevens, David A; Clemons, Karl V; Kontoyiannis, Dimitrios P

2016-01-01

Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) colonize cystic fibrosis (CF) patient airways. Pa culture filtrates inhibit Af biofilms, and Pa non-CF, mucoid (Muc-CF) and nonmucoid CF (NMuc-CF) isolates form an ascending inhibitory hierarchy. We hypothesized this activity is mediated through apoptosis induction. One Af and three Pa (non-CF, Muc-CF, NMuc-CF) reference isolates were studied. Af biofilm was formed in 96 well plates for 16 h ± Pa biofilm filtrates. After 24 h, apoptosis was characterized by viability dye DiBAc, reactive oxygen species (ROS) generation, mitochondrial membrane depolarization, DNA fragmentation and metacaspase activity. Muc-CF and NMuc-CF filtrates inhibited and damaged Af biofilm (p<0.0001). Intracellular ROS levels were elevated (p<0.001) in NMuc-CF-treated Af biofilms (3.7- fold) compared to treatment with filtrates from Muc-CF- (2.5- fold) or non-CF Pa (1.7- fold). Depolarization of mitochondrial potential was greater upon exposure to NMuc-CF (2.4-fold) compared to Muc-CF (1.8-fold) or non-CF (1.25-fold) (p<0.0001) filtrates. Exposure to filtrates resulted in more DNA fragmentation in Af biofilm, compared to control, mediated by metacaspase activation. In conclusion, filtrates from CF-Pa isolates were more inhibitory against Af biofilms than from non-CF. The apoptotic effect involves mitochondrial membrane damage associated with metacaspase activation.

Plasma treatment of polymer dielectric films to improve capacitive energy storage

NASA Technical Reports Server (NTRS)

Yializis, A.; Binder, M.; Mammone, R. J.

1994-01-01

Demand for compact instrumentation, portable field equipment, and new electromagnetic weapons is creating a need for new dielectric materials with higher energy storage capabilities. Recognizing the need for higher energy storage capacitors, the Army Research Lab at Fort Monmouth, NJ, initiated a program a year ago to investigate potential methods for increasing the dielectric strength of polyvinylidene difluoride (PVDF) film, which is the highest energy density material commercially available today. Treatment of small area PVDF films in a CF4/O2 plasma showed that the dielectric strength of PVDF films can be increased by as much as 20 percent when treated in a 96 percent CF4/4 percent O2 plasma. This 44 percent increase in energy storage of a PVDF capacitor is significant considering that the treatment can be implemented in a conventional metallizing chamber, with minimum capital investment. The data shows that improved breakdown strength may be unique to PVDF film and the particular CF4/O2 gas mixture, because PVDF film treated with 100 percent CF4, 100 percent O2, Ar gas plasma, and electron irradiation shows no improvement in breakdown strength. Other data presented includes dissipation factor, dielectric constant, and surface tension measurements.

Serum Iron Level Is Associated with Time to Antibiotics in Cystic Fibrosis.

PubMed

Gifford, Alex H; Dorman, Dana B; Moulton, Lisa A; Helm, Jennifer E; Griffin, Mary M; MacKenzie, Todd A

2015-12-01

Serum levels of hepcidin-25, a peptide hormone that reduces blood iron content, are elevated when patients with cystic fibrosis (CF) develop pulmonary exacerbation (PEx). Because hepcidin-25 is unavailable as a clinical laboratory test, we questioned whether a one-time serum iron level was associated with the subsequent number of days until PEx, as defined by the need to receive systemic antibiotics (ABX) for health deterioration. Clinical, biochemical, and microbiological parameters were simultaneously checked in 54 adults with CF. Charts were reviewed to determine when they first experienced a PEx after these parameters were assessed. Time to ABX was compared in subgroups with and without specific attributes. Multivariate linear regression was used to identify parameters that significantly explained variation in time to ABX. In univariate analyses, time to ABX was significantly shorter in subjects with Aspergillus-positive sputum cultures and CF-related diabetes. Multivariate linear regression models demonstrated that shorter time to ABX was associated with younger age, lower serum iron level, and Aspergillus sputum culture positivity. Serum iron, age, and Aspergillus sputum culture positivity are factors associated with shorter time to subsequent PEx in CF adults. © 2015 Wiley Periodicals, Inc.

Measures of large-scale structure in the CfA redshift survey slices

NASA Technical Reports Server (NTRS)

De Lapparent, Valerie; Geller, Margaret J.; Huchra, John P.

1991-01-01

Variations of the counts-in-cells with cell size are used here to define two statistical measures of large-scale clustering in three 6 deg slices of the CfA redshift survey. A percolation criterion is used to estimate the filling factor which measures the fraction of the total volume in the survey occupied by the large-scale structures. For the full 18 deg slice of the CfA redshift survey, f is about 0.25 + or - 0.05. After removing groups with more than five members from two of the slices, variations of the counts in occupied cells with cell size have a power-law behavior with a slope beta about 2.2 on scales from 1-10/h Mpc. Application of both this statistic and the percolation analysis to simulations suggests that a network of two-dimensional structures is a better description of the geometry of the clustering in the CfA slices than a network of one-dimensional structures. Counts-in-cells are also used to estimate at 0.3 galaxy h-squared/Mpc the average galaxy surface density in sheets like the Great Wall.

Temperature-Dependent Rate Constants and Substituent Effects for the Reactions of Hydroxyl Radicals With Three Partially Fluorinated Ethers

NASA Technical Reports Server (NTRS)

Hsu, K.-J.; DeMore, W. B.

1995-01-01

Rate constants and temperature dependencies for the reactions of OH with CF3OCH3 (HFOC-143a), CF2HOCF2H (HFOC-134), and CF3OCF2H (HFOC-125) were studied using a relative rate technique in the temperature range 298-393 K. The following absolute rate constants were derived: HFOC-143a, 1.9E-12 exp(-1555/T); HFOC-134, 1.9E-12 exp(-2006/T); HFOC-125, 4.7E-13 exp(-2095/T). Units are cm(exp 3)molecule(exp -1) s(exp -1). Substituent effects on OH abstraction rate constants are discussed, and it is shown that the CF3O group has an effect on the OH rate constants similar to that of a fluorine atom. The effects are related to changes in the C-H bond energies of the reactants (and thereby the activation energies) rather than changes in the preexponential factors. On the basis of a correlation of rate constants with bond energies, the respective D(C-H) bond strengths in the three ethers are found to be 102, 104, and 106 kcal/mol, with an uncertainty of about 1 kcal/mol.

Clinical effects of diet supplementation with DHA in pediatric patients suffering from cystic fibrosis.

PubMed

Leggieri, E; De Biase, R V; Savi, D; Zullo, S; Halili, I; Quattrucci, S

2013-08-01

Cystic fibrosis (CF) patients present an altered fatty acid (FA) metabolism characterized by imbalance in the arachidonic/docosohexasenoic acid (AA/DHA) ratio in favour of the former which can contribute to the increase in pulmonary inflammation. The present study aims to assess respiratory, nutritional, clinical and laboratory parameters, and inflammatory markers after six months of DHA supplementation in paediatric patients suffering from CF. A dose of 1 g/10 kg/die was administered to ten CF patients of paediatric age for the first month and 250 mg/10 kg/die for the remaining 5 months. We carried out follow-ups at T0 (baseline), T6 (after six months of the diet) and T12 (six months after supplementation was interrupted) during which respiratory, nutritional, clinical and laboratory parameters were assessed. After six months of DHA supplementation inflammatory marker levels had diminished: interleukin 8 (IL-8) and Tumour Necrosis Factor Alfa (TNF-α) in serum, and calprotectin in stools. In addition, auxometric parameters were improved as was the clinical condition of patients, who tolerated DHA well. Dietetic integration with DHA seems to improve clinical condition and the inflammatory pulmonary and intestinal state of pediatric patients suffering from CF.

The Certification Framework: Risk Assessment for Safety and Effectiveness of Geologic Carbon Sequestration

NASA Astrophysics Data System (ADS)

Oldenburg, C. M.; Nicot, J.; Bryant, S. L.

2008-12-01

Motivated by the dual objectives of (1) encouraging geologic carbon sequestration (GCS) as one of several strategies urgently needed to reduce CO2 emissions, and (2) protecting the environment from unintended CO2 injection-related impacts, we have developed a simple and transparent framework for certifying GCS safety and effectiveness at individual sites. The approach we developed, called the Certification Framework (CF), is proposed as a standard way for project proponents, regulators, and the public to analyze and understand risks and uncertainties of GCS. In the CF, we relate effective trapping to CO2 leakage risk, where we use the standard definition of risk involving the two factors (1) probability of a particular leakage scenario, and (2) impact of that leakage scenario. In short, if the CO2 leakage risk as calculated by the CF is below threshold values for the life of the project, then effective trapping is predicted and the site can be certified. The concept of effective trapping is more general than traditional "no migration" approaches to underground injection regulation. We achieve simplicity in the CF by using (1) wells and faults as the potential leakage pathways, (2) five compartments to represent where impacts can occur (underground sources of drinking water, hydrocarbon and mineral resources, near-surface environment, health and safety, and emission credits and atmosphere), (3) modeled CO2 fluxes and concentrations as proxies for impact to compartments, (4) broad ranges of storage formation properties to generate a catalog of simulated CO2 plumes, and (5) probabilities of intersection of the CO2 plume with the conduits and compartments. In a case study application of the CF for a saline formation GCS site in the Texas Gulf Coast, analysis with the CF suggested the overall leakage risk to be very small, with the largest contribution coming from risk to the near-surface environment due to potential leakage up abandoned wells, depending on the effective permeability assumed for the wells. This result shows that risk could be drastically reduced by locating and monitoring abandoned wells, along with well or leakage mitigation if necessary. By this means, effective trapping can be predicted with greater certainty because both factors of risk (probability of well leakage, and impact of well leakage) can be reduced significantly through surface monitoring and mitigation, if needed.

Atmospheric abundance and global emissions of perfluorocarbons CF4, C2F6 and C3F8 since 1800 inferred from ice core, firn, air archive and in situ measurements

NASA Astrophysics Data System (ADS)

Trudinger, Cathy M.; Fraser, Paul J.; Etheridge, David M.; Sturges, William T.; Vollmer, Martin K.; Rigby, Matt; Martinerie, Patricia; Mühle, Jens; Worton, David R.; Krummel, Paul B.; Steele, L. Paul; Miller, Benjamin R.; Laube, Johannes; Mani, Francis S.; Rayner, Peter J.; Harth, Christina M.; Witrant, Emmanuel; Blunier, Thomas; Schwander, Jakob; O'Doherty, Simon; Battle, Mark

2016-09-01

Perfluorocarbons (PFCs) are very potent and long-lived greenhouse gases in the atmosphere, released predominantly during aluminium production and semiconductor manufacture. They have been targeted for emission controls under the United Nations Framework Convention on Climate Change. Here we present the first continuous records of the atmospheric abundance of CF4 (PFC-14), C2F6 (PFC-116) and C3F8 (PFC-218) from 1800 to 2014. The records are derived from high-precision measurements of PFCs in air extracted from polar firn or ice at six sites (DE08, DE08-2, DSSW20K, EDML, NEEM and South Pole) and air archive tanks and atmospheric air sampled from both hemispheres. We take account of the age characteristics of the firn and ice core air samples and demonstrate excellent consistency between the ice core, firn and atmospheric measurements. We present an inversion for global emissions from 1900 to 2014. We also formulate the inversion to directly infer emission factors for PFC emissions due to aluminium production prior to the 1980s. We show that 19th century atmospheric levels, before significant anthropogenic influence, were stable at 34.1 ± 0.3 ppt for CF4 and below detection limits of 0.002 and 0.01 ppt for C2F6 and C3F8, respectively. We find a significant peak in CF4 and C2F6 emissions around 1940, most likely due to the high demand for aluminium during World War II, for example for construction of aircraft, but these emissions were nevertheless much lower than in recent years. The PFC emission factors for aluminium production in the early 20th century were significantly higher than today but have decreased since then due to improvements and better control of the smelting process. Mitigation efforts have led to decreases in emissions from peaks in 1980 (CF4) or early-to-mid-2000s (C2F6 and C3F8) despite the continued increase in global aluminium production; however, these decreases in emissions appear to have recently halted. We see a temporary reduction of around 15 % in CF4 emissions in 2009, presumably associated with the impact of the global financial crisis on aluminium and semiconductor production.

New biotite and muscovite isotopic reference materials, USGS57 and USGS58, for δ2H measurements–A replacement for NBS 30

USGS Publications Warehouse

Qi, Haiping; Coplen, Tyler B.; Gehre, Matthias; Vennemann, Torsten W.; Brand, Willi A.; Geilmann, Heike; Olack, Gerard; Bindeman, Ilya N.; Palandri, Jim; Huang, Li; Longstaffe, Fred J.

2017-01-01

The advent of continuous-flow isotope-ratio mass spectrometry (CF-IRMS) coupled with a high temperature conversion (HTC) system enabled faster, more cost effective, and more precise δ2H analysis of hydrogen-bearing solids. Accurate hydrogen isotopic analysis by on-line or off-line techniques requires appropriate isotopic reference materials (RMs). A strategy of two-point calibrations spanning δ2H range of the unknowns using two RMs is recommended. Unfortunately, the supply of the previously widely used isotopic RM, NBS 30 biotite, is exhausted. In addition, recent measurements have shown that the determination of δ2H values of NBS 30 biotite on the VSMOW-SLAP isotope-delta scale by on-line HTC systems with CF-IRMS may be unreliable because hydrogen in this biotite may not be converted quantitatively to molecular hydrogen. The δ2HVSMOW-SLAP values of NBS 30 biotite analyzed by on-line HTC systems can be as much as 21 mUr (or ‰) too positive compared to the accepted value of − 65.7 mUr, determined by only a few conventional off-line measurements. To ensure accurate and traceable on-line hydrogen isotope-ratio determinations in mineral samples, we here propose two isotopically homogeneous, hydrous mineral RMs with well-characterized isotope-ratio values, which are urgently needed. The U.S. Geological Survey (USGS) has prepared two such RMs, USGS57 biotite and USGS58 muscovite. The δ2H values were determined by both glassy carbon-based on-line conversion and chromium-based on-line conversion, and results were confirmed by off-line conversion. The quantitative conversion of hydrogen from the two RMs using the on-line HTC method was carefully evaluated in this study. The isotopic compositions of these new RMs with 1-σ uncertainties and mass fractions of hydrogen are:USGS57 (biotite)δ2HVSMOW-SLAP = − 91.5 ± 2.4 mUr (n = 24)Mass fraction hydrogen = 0.416 ± 0.002% (n = 4)Mass fraction water = 3.74 ± 0.02% (n = 4)USGS58 (muscovite)δ2HVSMOW-SLAP = − 28.4 ± 1.6 mUr (n = 24)Mass fraction hydrogen = 0.448 ± 0.002% (n = 4)Mass fraction water = 4.03 ± 0.02% (n = 4).These δ2HVSMOW-SLAP values encompass typical ranges for solid unknowns of crustal and mantle origin and are available to users for recommended two-point calibration.

ORGANIC SCINTILLATOR FOR REAL-TIME NEUTRON DOSIMETRY.

PubMed

Beyer, Kyle A; Di Fulvio, Angela; Stolarczyk, Liliana; Parol, Wiktor; Mojzeszek, Natalia; Kopéc, Renata; Clarke, Shaun D; Pozzi, Sara A

2017-11-15

We developed a radiation detector based on an organic scintillator for spectrometry and dosimetry of out-of-field secondary neutrons from clinical proton beams. The detector consists of an EJ-299-34 crystalline organic scintillator, coupled by fiber optic cable to a silicon photomultiplier (SiPM). Proof of concept measurements were taken with 137Cs and 252Cf, and corresponding simulations were performed in MCNPX-PoliMi. Despite its small size, the detector is able to discriminate between neutron and gamma-rays via pulse shape discrimination. We simulated the response function of the detector to monoenergetic neutrons in the 100 keV-0 MeV range using MCNPX-PoliMi. The measured unfolded 252Cf neutron spectrum is in good agreement with the theoretical Watt fission spectrum. We determined the ambient dose equivalent by folding the spectrum with the fluence-to-ambient dose conversion coefficient, with a 1.4% deviation from theory. Some preliminary proton beam experiments were preformed at the Bronowice Cyclotron Center patient treatment facility using a clinically relevant proton pencil beam for brain tumor and craino-spinal treatment directed at a child phantom. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Association Between Competitive Food and Beverage Policies in Elementary Schools and Childhood Overweight/Obesity Trends

PubMed Central

Sanchez-Vaznaugh, Emma V.; Sánchez, Brisa N.; Crawford, Patricia B.; Egerter, Susan

2015-01-01

IMPORTANCE To our knowledge, few published studies have examined the influence of competitive food and beverage (CF&B) policies on student weight outcomes; none have investigated disparities in the influence of CF&B policies on children’s body weight by school neighborhood socioeconomic resources. OBJECTIVE To investigate whether the association between CF&B policies and population-level trends in childhood overweight/obesity differed by school neighborhood income and education levels. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study, from July 2013 to October 2014, compared overweight/obesity prevalence trends before (2001–2005) and after (2006–2010) implementation of CF&B policies in public elementary schools in California. The study included 2 700 880 fifth-grade students in 5362 public schools from 2001 to 2010. EXPOSURES California CF&B policies (effective July 1, 2004, and July 1, 2007) and school neighborhood income and education levels. MAIN OUTCOMES AND MEASURES Overweight/obesity defined as a body mass index at or greater than the 85th percentile for age and sex. RESULTS Overall rates of overweight/obesity ranged from 43.5% in 2001 to 45.8% in 2010. Compared with the period before the introduction of CF&B policies, overweight/obesity trends changed in a favorable direction after the policies took effect (2005–2010); these changes occurred for all children across all school neighborhood socioeconomic levels. In the postpolicy period, these trends differed by school neighborhood socioeconomic advantage. From 2005–2010, trends in overweight/obesity prevalence leveled off among students at schools in socioeconomically disadvantaged neighborhoods but declined in socioeconomically advantaged neighborhoods. Students in the lowest-income neighborhoods experienced zero or near zero change in the odds of overweight/obesity over time: the annual percentage change in overweight/obesity odds was 0.1% for females (95% CI, −0.7 to 0.9) and −0.3% for males (95% CI, −1.1 to 0.5). In contrast, in the highest-income neighborhoods, the annual percentage decline in the odds of overweight was 1.2% for females (95% CI, 0.4 to 1.9) and 1.0% for males (95% CI, 0.3 to 1.8). Findings were similar for school neighborhood education. CONCLUSIONS AND RELEVANCE Our study found population-level improvements in the prevalence of childhood overweight/obesity that coincided with the period following implementation of statewide CF&B policies (2005–2010). However, these improvements were greatest at schools in the most advantaged neighborhoods. This suggests that CF&B policies may help prevent child obesity; however, the degree of their effectiveness is likely to depend on socioeconomic and other contextual factors in school neighborhoods. To reduce disparities and prevent obesity, school policies and environmental interventions must address relevant contextual factors in school neighborhoods. PMID:25938657

Copper-Mediated Fluorination of Arylboronate Esters. Identification of a Copper(III) Fluoride Complex

PubMed Central

Fier, Patrick S.; Luo, Jingwei; Hartwig, John F.

2013-01-01

A method for the direct conversion of arylboronate esters to aryl fluorides under mild conditions with readily available reagents is reported. Tandem reactions have also been developed for the fluorination of arenes and aryl bromides through aryl-boronate ester intermediates. Mechanistic studies suggest that this fluorination reaction occurs through facile oxidation of Cu(I) to Cu(III) followed by rate-limiting transmetallation of a bound arylboronate to Cu(III). Fast C-F reductive elimination is proposed to occur from an aryl-copper(III)-fluoride complex. Cu(III) intermediates have been generated independently and identified by NMR spectroscopy and ESI-MS. PMID:23384209

[Study on the nutrition of alpine meadow based on hyperspectral data].

PubMed

Wang, Xun; Liu, Shu-Jie; Jia, Hai-Feng; Chai, Sha-Tuo; Dang, An-Rong; Liu, Xue-Hua; Hao, Li-Zhuang; Cui, Zhan-Hong

2012-10-01

Remote sensing monitoring of alpine grassland nutritional status is a key factor of grassland reasonable utilization, also a difficulty for dynamic vegetation monitoring. The present paper studies the correlations between vegetation nutrition and hyperspectral data. The results showed that two band ratio models have a significant correlation with biomass, air-DM, P, CF, and CP. MAXR models have a significant correlation with most of nutrition index when selected wavebands equaled five. On the whole, the MAXR model precedes two band ratio models. Using MAXR models to estimate air-DM, P and CF can obtain higher accuracy.

In situ measurement of airway surface liquid [K+] using a ratioable K+-sensitive fluorescent dye.

PubMed

Namkung, Wan; Song, Yuanlin; Mills, Aaron D; Padmawar, Prashant; Finkbeiner, Walter E; Verkman, A S

2009-06-05

The airway surface liquid (ASL) is the thin fluid layer lining airway surface epithelial cells, whose volume and composition are tightly regulated and may be abnormal in cystic fibrosis (CF). We synthesized a two-color fluorescent dextran to measure ASL [K(+)], TAC-Lime-dextran-TMR, consisting of a green-fluorescing triazacryptand K(+) ionophore-Bodipy conjugate, coupled to dextran, together with a red fluorescing tetramethylrhodamine reference chromophore. TAC-Lime-dextran-TMR fluorescence was K(+)-selective, increasing >4-fold with increasing [K(+)] from 0 to 40 mm. In well differentiated human airway epithelial cells, ASL [K(+)] was 20.8 +/- 0.3 mm and decreased by inhibition of the Na(+)/K(+) pump (ouabain), ENaC (amiloride), CF transmembrane conductance regulator (CFTR(inh)-172), or K(+) channels (TEA or XE991). ASL [K(+)] was increased by forskolin but not affected by Na(+)/K(+)/2Cl(-) cotransporter inhibition (bumetanide). Functional and expression studies indicated the involvement of [K(+)] channels KCNQ1, KCNQ3, and KCNQ5 as determinants of ASL [K(+)]. [K(+)] in CF cultures was similar to that in non-CF cultures, suggesting that abnormal ASL [K(+)] is not a factor in CF lung disease. In intact airways, ASL [K(+)] was also well above extracellular [K(+)]: 22 +/- 1 mm in pig trachea ex vivo and 16 +/- 1 mm in mouse trachea in vivo. Our results provide the first noninvasive measurements of [K(+)] in the ASL and indicate the involvement of apical and basolateral membrane ion transporters in maintaining a high ASL [K(+)].

IFN-γ Stimulates Autophagy-Mediated Clearance of Burkholderia cenocepacia in Human Cystic Fibrosis Macrophages

PubMed Central

Assani, Kaivon; Tazi, Mia F.; Amer, Amal O.; Kopp, Benjamin T.

2014-01-01

Burkholderia cenocepacia is a virulent pathogen that causes significant morbidity and mortality in patients with cystic fibrosis (CF), survives intracellularly in macrophages, and uniquely causes systemic infections in CF. Autophagy is a physiologic process that involves engulfing non-functional organelles and proteins and delivering them for lysosomal degradation, but also plays a role in eliminating intracellular pathogens, including B. cenocepacia. Autophagy is defective in CF but can be stimulated in murine CF models leading to increased clearance of B. cenocepacia, but little is known about autophagy stimulation in human CF macrophages. IFN-γ activates macrophages and increases antigen presentation while also inducing autophagy in macrophages. We therefore, hypothesized that treatment with IFN-γ would increase autophagy and macrophage activation in patients with CF. Peripheral blood monocyte derived macrophages (MDMs) were obtained from CF and non-CF donors and subsequently infected with B. cenocepacia. Basal serum levels of IFN-γ were similar between CF and non-CF patients, however after B. cenocepacia infection there is deficient IFN-γ production in CF MDMs. IFN-γ treated CF MDMs demonstrate increased co-localization with the autophagy molecule p62, increased autophagosome formation, and increased trafficking to lysosomes compared to untreated CF MDMs. Electron microscopy confirmed IFN-γ promotes double membrane vacuole formation around bacteria in CF MDMs, while only single membrane vacuoles form in untreated CF cells. Bacterial burden is significantly reduced in autophagy stimulated CF MDMs, comparable to non-CF levels. IL-1β production is decreased in CF MDMs after IFN-γ treatment. Together, these results demonstrate that IFN-γ promotes autophagy-mediated clearance of B. cenocepacia in human CF macrophages. PMID:24798083

Calculation and characteristic analysis on synergistic effect of CF3I gas mixtures

NASA Astrophysics Data System (ADS)

Su, ZHAO; Yunkun, DENG; Yuhao, GAO; Dengming, XIAO

2018-06-01

CF3I is a potential SF6 alternative gas. In order to study the insulation properties and synergistic effects of CF3I/N2 and CF3I/CO2 gas mixtures, two-term approximate Boltzmann equations were used to obtain the ionization coefficient α, attachment coefficient η and the critical equivalent electrical field strength (E/N)cr. The results show that the (E/N)cr of CF3I gas at 300 K is 1.2 times that of SF6 gas, and CF3I/N2 and CF3I/CO2 gas mixtures both have synergistic effect occurred. The synergistic effect coefficient of CF3I/CO2 gas mixture was higher than that of CF3I/N2 gas mixture. But the (E/N)cr of CF3I/N2 is higher than that of CF3I/CO2 under the same conditions. When the content of CF3I exceeds 20%, the (E/N)cr of CF3I/N2 and CF3I/CO2 gas mixture increase linearly with the increasing of CF3I gas content. The breakdown voltage of CF3I/N2 gas mixture is also higher than that of CF3I/CO2 gas mixture in slightly non-uniform electrical field under power frequency voltage, but the synergistic effect coefficients of the two gas mixtures are basically the same.

Purification and Characterization of a Glycerol-Resistant CF0-CF1 and CF1-ATPase from the Halotolerant Alga Dunaliella bardawil1

PubMed Central

Finel, Moshe; Pick, Uri; Selman-Reimer, Susanne; Selman, Bruce R.

1984-01-01

The isolation of the chloroplast ATP synthase complex (CF0-CF1) and of CF1 from Dunaliella bardawil is described. The subunit structure of the D. bardawil ATPase differs from that of the spinach in that the D. bardawil α subunit migrates ahead of the β subunit and ε-migrates ahead of subunit II of CF0 when separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The CF1 isolated from D. bardawil resembles the CF1 isolated from Chladmydomonas reinhardi in that a reversible, Mg2+-dependent ATPase is induced by selected organic solvents. Glycerol stimulates cyclic photophosphorylation catalyzed by D. bardawil thylakoid membranes but inhibits photophosphorylation catalyzed by spinach thylakoid membranes. Glycerol (20%) also stimulates the rate of ATP-Pi exchange catalyzed by D. bardawil CF0-CF1 proteoliposomes but inhibits the activity with the spinach enzyme. The ethanol-activated, Mg2+-ATPase of the D. bardawil CF1 is more resistant to glycerol inhibition than the octylglucoside-activated, Mg2+-ATPase of spinach CF1 or the ethanol-activated, Mg2+-dependent ATPase of the C. reinhardi CF1. Both cyclic photophosphorylation and ATP-Pi exchange catalyzed by D. bardawil CF0-CF1 are more sensitive to high concentrations of NaCl than is the spinach complex. Images Fig. 5 PMID:16663507

Assessment of the anthropogenic influx of metallic pollutants in the Sefidrud delta, Gilan Province, Iran.

PubMed

Rafiei, Behrouz; Ahmadi-Ghomi, Fatemeh; Karimkhani, Afshin

2017-08-15

Understanding the anthropogenic effects on the Sefidrud delta, the concentration of six metals (Cr, Co, Cu, Ni, Pb and Zn) was measured in two sites included the old Sefidrud delta (Amirabad, 23 samples) and the new Sefidrud delta (Kiashahr, 24 samples). Geoaccumulation Index (I geo ), Enrichment Factor (EF), Contamination Factor (CF) and Pollution Load Index (PLI) were used to determine the metal pollution in all sediment samples. Although the EF, I geo , CF and PLI results in the old delta indicate no significant pollution, sediment samples in the new delta show a considerable pollution. Since the sediment source and the lithology of the Sefidrud River drainage basin did not change in the past 500years, the metal pollution in the new delta must be from anthropogenic sources. Copyright © 2017 Elsevier Ltd. All rights reserved.

Usefulness of circulating free DNA for monitoring epidermal growth factor receptor mutations in advanced non-small cell lung cancer patients: a case report

PubMed Central

Gonzalez-Cao, Maria; Ramirez, Santiago Viteri; Ariza, Nuria Jordana; Balada, Ariadna; Garzón, Mónica; Teixidó, Cristina; Karachaliou, Niki; Morales-Espinosa, Daniela; Molina-Vila, Miguel Ángel; Rosell, Rafael

2016-01-01

Genomic analysis of circulating tumor DNA (ctDNA) released from cancer cells into the bloodstream has been proposed as a useful method to capture dynamic changes during the course of the disease. In particular, the ability to monitor epidermal growth factor receptor (EGFR) mutation status in cell-free circulating DNA (cfDNA) isolated from advanced non-small cell lung cancer (NSCLC) patients EGFR can help to the correct management of the disease and overcome the challenges associated with tumor heterogeneity and insufficient biopsied material to perform key molecular diagnosis. Here, we report a case of long term monitorization of EGFR mutation status in cfDNA from peripheral blood in an NSCLC patient in, with excellent correlation with clinical evolution. PMID:27826535

Evaluating the validity of the Work Role Functioning Questionnaire (Canadian French version) using classical test theory and item response theory.

PubMed

Hong, Quan Nha; Coutu, Marie-France; Berbiche, Djamal

2017-01-01

The Work Role Functioning Questionnaire (WRFQ) was developed to assess workers' perceived ability to perform job demands and is used to monitor presenteeism. Still few studies on its validity can be found in the literature. The purpose of this study was to assess the items and factorial composition of the Canadian French version of the WRFQ (WRFQ-CF). Two measurement approaches were used to test the WRFQ-CF: Classical Test Theory (CTT) and non-parametric Item Response Theory (IRT). A total of 352 completed questionnaires were analyzed. A four-factor and three-factor model models were tested and shown respectively good fit with 14 items (Root Mean Square Error of Approximation (RMSEA) = 0.06, Standardized Root Mean Square Residual (SRMR) = 0.04, Bentler Comparative Fit Index (CFI) = 0.98) and with 17 items (RMSEA = 0.059, SRMR = 0.048, CFI = 0.98). Using IRT, 13 problematic items were identified, of which 9 were common with CTT. This study tested different models with fewer problematic items found in a three-factor model. Using a non-parametric IRT and CTT for item purification gave complementary results. IRT is still scarcely used and can be an interesting alternative method to enhance the quality of a measurement instrument. More studies are needed on the WRFQ-CF to refine its items and factorial composition.

Experimental and Estimated Rate Constants for the Reactions of Hydroxyl Radicals with Several Halocarbons

NASA Technical Reports Server (NTRS)

DeMore, W.B.

1996-01-01

Relative rate experiments are used to measure rate constants and temperature dependencies of the reactions of OH with CH3F (41), CH2FCl (31), CH2BrCl (30B1), CH2Br2 (3OB2), CHBr3 (2OB3), CF2BrCHFCl (123aBl(alpha)), and CF2ClCHCl2 (122). Rate constants for additional compounds of these types are estimated using an empirical rate constant estimation method which is based on measured rate constants for a wide range of halocarbons. The experimental data are combined with the estimated and previously reported rate constants to illustrate the effects of F, Cl, and Br substitution on OH rate constants for a series of 19 halomethanes and 25 haloethanes. Application of the estimation technique is further illustrated for some higher hydrofluorocarbons (HFCs), including CHF2CF2CF2CF2H (338pcc), CF3CHFCHFCF2CF3 (43-10mee), CF3CH2CH2CF3 (356ffa), CF3CH2CF2CH2CF3 (458mfcf), CF3CH2CHF2 (245fa), and CF3CH2CF2CH3 (365mfc). The predictions are compared with literature data for these compounds.

Intracavitary moderator balloon combined with (252)Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations.

PubMed

Brandão, S F; Campos, T P R

2015-07-01

This article proposes a combination of californium-252 ((252)Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Dosimetric evaluations were performed on three protocol set-ups: (252)Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0-5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the (252)Cf source, sparing the normal brain tissue. Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis.

The Relationship Between N(Htotal) and E(B-V) at High Galactic Latitude

NASA Astrophysics Data System (ADS)

Doppel, Jessica Erin; Magnani, Loris A.

2017-06-01

We studied the gas-to-dust ratio at high Galactic latitudes (|b| ≥ 20° and 30°). The gas content was measured by the column density of atomic hydrogen from the Leiden/Argentine/Bonn survey and the dust by E(B-V) from the Schlafly et al. (2014) compilation. We do not see significant variation as a function of galactic quadrant or hemisphere. Our results are similar to other studies that used different techniques for deriving N(HI), N(H2), or E(B-V). Like Liszt (2013), we see a higher slope [N(HI)/E(B-V)] if we choose only those points with E(B-V) ≤ 0.1 mag. We also see the break in slope he noted at 0.08 mag. We examined lines of sight that coincided with the Georgia/Harvard Smithsonian CfA high-latitude CO(1-0) surveys. Although at |b| ≥ 30° there were only about 200 CO detections, those points lie systematically below our best fit lines to the data. We can convert the CO line intensities to N(H2) and determine a global CO-H2 conversion factor for the high latitude sky.

Looking beyond Psychopathology: The Dual-Factor Model of Mental Health in Youth

ERIC Educational Resources Information Center

Suldo, Shannon M.; Shaffer, Emily J.

2008-01-01

In a dual-factor model of mental health (cf. Greenspoon & Saklofske, 2001), assessments of positive indicators of wellness (i.e., subjective well-being--SWB) are coupled with traditional negative indicators of illness (i.e., psychopathology) to comprehensively measure mental health. The current study examined the existence and utility of a…

Factors associated with malnutrition in adolescent and adult patients with cystic fibrosis.

PubMed

Barni, Gabriela Cristofoli; Forte, Gabriele Carra; Forgiarini, Luis Felipe; Abrahão, Claudine Lacerda de Oliveira; Dalcin, Paulo de Tarso Roth

2017-01-01

To determine the prevalence of malnutrition in patients attending an adult cystic fibrosis (CF) program and to investigate the associations of malnutrition with the clinical characteristics of those patients. This was a cross-sectional study involving patients with clinically stable CF patients (16 years of age or older). The patients underwent clinical assessment, nutritional assessments, pulmonary function tests, and pancreatic function assessment. They also completed a questionnaire regarding diet compliance. On the basis of their nutritional status, the patients were classified divided into three groups: adequate nutrition; at nutritional risk; and malnutrition. The study has included 73 patients (mean age, 25.6 ± 7.3 years), 40 of whom (54.8%) were female. The mean body mass index was 21.0 ± 3.0 kg/m2 and the mean FEV1 was 59.7 ± 30.6% of predicted. In this sample of patients, 32 (43.8%), 23 (31.5%), and 18 (24.7%) of the patients were allocated to the adequate nutrition, nutritional risk, and malnutrition groups, respectively. The logistic regression analysis identified three independent factors associated with the risk of malnutrition: Shwachman-Kulczycki score, percent predicted FEV1; and age. Malnutrition remains a common complication in adolescents and adults with CF, despite dietary advice. Malnutrition is associated with age, clinical severity, and lung function impairment.

Relevance of multidrug-resistant Pseudomonas aeruginosa infections in cystic fibrosis.

PubMed

Stefani, S; Campana, S; Cariani, L; Carnovale, V; Colombo, C; Lleo, M M; Iula, V D; Minicucci, L; Morelli, P; Pizzamiglio, G; Taccetti, G

2017-09-01

Multidrug-resistant (MDR) Pseudomonas aeruginosa is an important issue for physicians who take care of patients with cystic fibrosis (CF). Here, we review the latest research on how P. aeruginosa infection causes lung function to decline and how several factors contribute to the emergence of antibiotic resistance in P. aeruginosa strains and influence the course of the infection course. However, many aspects of the practical management of patients with CF infected with MDR P. aeruginosa are still to be established. Less is known about the exact role of susceptibility testing in clinical strategies for dealing with resistant infections, and there is an urgent need to find a tool to assist in choosing the best therapeutic strategy for MDR P. aeruginosa infection. One current perception is that the selection of antibiotic therapy according to antibiogram results is an important component of the decision-making process, but other patient factors, such as previous infection history and antibiotic courses, also need to be evaluated. On the basis of the known issues and the best current data on respiratory infections caused by MDR P. aeruginosa, this review provides practical suggestions to optimize the diagnostic and therapeutic management of patients with CF who are infected with these pathogens. Copyright © 2017 Elsevier GmbH. All rights reserved.

[Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis].

PubMed

Su, Fei; Zheng, Ke; Fu, Yiyun; Wu, Qian; Tang, Yuan; Wang, Weiya; Jiang, Lili

2018-05-20

Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy. ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed. The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS). For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.

Aberration compensation between anterior and posterior corneal surfaces after Small incision lenticule extraction and Femtosecond laser-assisted laser in-situ keratomileusis.

PubMed

Li, Xiaojing; Wang, Yan; Dou, Rui

2015-09-01

To investigate the aberration compensation between anterior and posterior corneal surfaces after SMILE and FS-LASIK. Fifty-five subjects (55 eyes) undergoing SMILE and 51 subjects (51 eyes) undergoing FS-LASIK were enrolled in this study. Wavefront aberrations of anterior and posterior corneal surfaces and the whole cornea at 6 mm in diameter were measured using a Scheimpflug Camera preoperatively and one, three and 6 months postoperatively. The compensation factor (CF), where CF = 1 - (aberration of the whole cornea/aberration of anterior corneal surface), was calculated. Spherical aberration of the posterior surface and the whole cornea remained stable after SMILE. However, spherical aberration of posterior surface increased significantly at 6 months in the FS-LASIK group. The total higher-order aberration (tHOA) of the anterior surface and the whole cornea was lower at 6 months than at one and 3 months (p = 0.001 and 0.001, respectively) in the FS-LASIK group. Meanwhile, in the SMILE group, no significant difference in tHOA was found between various postoperative time points. There were significant decreases in the CF of tHOA compared with preoperative values in both groups. The CF of spherical aberration reduced significantly in both groups at 3 and 6 mm in diameter one, three and 6 months postoperatively. Significant decreases in the CF of vertical coma were found at three and 6 months postoperatively in the FS-LASIK group compared with preoperative values at 6 mm in diameter (p = 0.021 and 0.008, respectively). The change in CF (ΔCF) of spherical aberration was smaller in the SMILE group than in the FS-LASIK group at one and 3 months postoperatively (p = 0.003 and p < 0.0001, respectively). The ΔCF of spherical aberration was significantly lower in moderately myopic subjects than in subjects with high myopia at 1 month in the SMILE group (p = 0.041) and at one, three and 6 months in the FS-LASIK group (p = 0.014, 0.020, and 0.004, respectively). The posterior corneal surface plays an important role in compensating for spherical aberration of the anterior corneal surface. The compensation mechanisms of spherical aberration and higher-order aberration between anterior and posterior corneal surfaces were disrupted by the SMILE and the FS-LASIK procedures. The change in the CF of spherical aberration was smaller in the SMILE group compared with the FS-LASIK group, especially in subjects with high myopia. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Theoretical studies on atmospheric chemistry of HFE-245mc and perfluoro-ethyl formate: Reaction with OH radicals, atmospheric fate of alkoxy radical and global warming potential

NASA Astrophysics Data System (ADS)

Lily, Makroni; Baidya, Bidisha; Chandra, Asit K.

2017-02-01

Theoretical studies have been performed on the kinetics, mechanism and thermochemistry of the hydrogen abstraction reactions of CF3CF2OCH3 (HFE-245mc) and CF3CF2OCHO with OH radical using DFT based M06-2X method. IRC calculation shows that both hydrogen abstraction reactions proceed via weakly bound hydrogen-bonded complex preceding to the formation of transition state. The rate coefficients calculated by canonical transition state theory along with Eckart's tunnelling correction at 298 K: k1(CF3CF2OCH3 + OH) = 1.09 × 10-14 and k2(CF3CF2OCHO + OH) = 1.03 × 10-14 cm3 molecule-1 s-1 are in very good agreement with the experimental values. The atmospheric implications of CF3CF2OCH3 and CF3CF2OCHO are also discussed.

Psychometric Properties of a Russian Version of the Cognitive Flexibility Inventory (CFI-R).

PubMed

Kurginyan, Sergey S; Osavolyuk, Ekaterina Y

2018-01-01

The Cognitive Flexibility Inventory (CFI) is a brief self-report measure of the type of cognitive flexibility (CF) necessary to successfully challenge and restructure maladaptive beliefs with more balanced and adaptive thinking; it is particularly popular for use with English speakers. The CFI has recently been translated into five languages (Chinese, Japanese, Iranian, Turkish, and Russian), although estimates of reliability and validity of these translated versions are scarce. This study reports on the factor structure, internal consistency, reliability, and construct validity of the CFI. We adopted the CFI for a Russian-speaking population, using student sample of 445 first and second-year undergraduates ( M = 18.59 years, SD = 1.19) and found that a two-factor model fitted the data well. However, the structure of the CFI was revised because of some modifications, which were made to the original English to match the Russian equivalents of items originally developed to assess the definite aspect of cognitive flexibility. The CFI-R showed good internal consistency and suitable 7-week test-retest reliability. The construct validity of the Russian version of the CFI was studied by computing correlations with other related measures of CF (Attributional Style Questionnaire), depressive symptoms (Beck Depression Inventory), coping (Ways of Coping (Revised), and rigidity (Tomsk Rigidity Questionnaire). Furthermore, to assess whether the construct validity were affected by psychopathology we examined results for non-clinical and clinical samples, using "known-groups" method. The clinical sample reported lower CF than did the non-clinical sample on the CFI-R's total score and its subscales' scores. Findings in the present study suggest that the psychometric properties of the Russian CFI are comparable to the English original, making it appropriate to research assessment of the type of CF in Russian speaking population.

Optimisation of asymmetric flow field-flow fractionation for the characterisation of nanoparticles in coated polydisperse TiO2 with applications in food and feed.

PubMed

Omar, J; Boix, A; Kerckhove, G; von Holst, C

2016-12-01

Titanium dioxide (TiO 2 ) has various applications in consumer products and is also used as an additive in food and feeding stuffs. For the characterisation of this product, including the determination of nanoparticles, there is a strong need for the availability of corresponding methods of analysis. This paper presents an optimisation process for the characterisation of polydisperse-coated TiO 2 nanoparticles. As a first step, probe ultrasonication was optimised using a central composite design in which the amplitude and time were the selected variables to disperse, i.e., to break up agglomerates and/or aggregates of the material. The results showed that high amplitudes (60%) favoured a better dispersion and time was fixed in mid-values (5 min). In a next step, key factors of asymmetric flow field-flow fraction (AF4), namely cross-flow (CF), detector flow (DF), exponential decay of the cross-flow (CF exp ) and focus time (Ft), were studied through experimental design. Firstly, a full-factorial design was employed to establish the statistically significant factors (p < 0.05). Then, the information obtained from the full-factorial design was utilised by applying a central composite design to obtain the following optimum conditions of the system: CF, 1.6 ml min -1 ; DF, 0.4 ml min -1 ; Ft, 5 min; and CF exp , 0.6. Once the optimum conditions were obtained, the stability of the dispersed sample was measured for 24 h by analysing 10 replicates with AF4 in order to assess the performance of the optimised dispersion protocol. Finally, the recovery of the optimised method, particle shape and particle size distribution were estimated.

Aspergillus infection in lung transplant patients: incidence and prognosis.

PubMed

Iversen, M; Burton, C M; Vand, S; Skovfoged, L; Carlsen, J; Milman, N; Andersen, C B; Rasmussen, M; Tvede, M

2007-12-01

Lung transplant recipients experience a particularly high incidence of Aspergillus infection in comparison with other solid-organ transplantations. This study was conducted to determine the incidence of Aspergillus colonisation and invasive aspergillosis, and the impact on long-term survival associated with Aspergillus infection. A retrospective study of 362 consecutive lung transplant patients from a single national centre who were transplanted 1992-2003 were studied. Twenty-seven patients were excluded due to incomplete or missing files. A total of 105/335 (31%) patients had evidence of Aspergillus infection (colonisation or invasion), including 83 (25%) patients with colonisation and 22 (6%) patients with radiographic or histological evidence of invasive disease. Most of the infections occurred within the first 3 months after transplantation. Cystic fibrosis (CF) patients had higher incidences of colonisation and invasive disease [15 (42%) and 4 (11%) of 36 patients] than non-CF patients [68 (23%) and 18 (6%) of 299 patients] (P = 0.01). Invasive aspergillosis was associated with 58% mortality after 2 years, whereas colonisation was not associated with early increased mortality but was associated with increased mortality after 5 years compared to non-infected patients (P < 0.05). An analysis of demographic factors showed that donor age [OR 1.40 per decade (95% CI 1.10-1.80)], ischaemia time [OR 1.17 per hour increase (95% CI 1.01-1.39)], and use of daclizumab versus polyclonal induction [OR 2.05 (95% CI 1.14-3.75)] were independent risk factors for Aspergillus infection. Invasive aspergillosis was associated with early and high mortality in lung transplant patients. Colonisation with Aspergillus was also associated with a significant increase in mortality after 5 years. CF patients have a higher incidence of Aspergillus infection than non-CF patients.

Plasma epidermal growth factor receptor mutation testing with a chip-based digital PCR system in patients with advanced non-small cell lung cancer.

PubMed

Kasahara, Norimitsu; Kenmotsu, Hirotsugu; Serizawa, Masakuni; Umehara, Rina; Ono, Akira; Hisamatsu, Yasushi; Wakuda, Kazushige; Omori, Shota; Nakashima, Kazuhisa; Taira, Tetsuhiko; Naito, Tateaki; Murakami, Haruyasu; Koh, Yasuhiro; Mori, Keita; Endo, Masahiro; Nakajima, Takashi; Yamada, Masanobu; Kusuhara, Masatoshi; Takahashi, Toshiaki

2017-04-01

Epidermal growth factor receptor (EGFR) mutation testing is a companion diagnostic to determine eligibility for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). Recently, plasma-based EGFR testing by digital polymerase chain reaction (dPCR), which enables accurate quantification of target DNA, has shown promise as a minimally invasive diagnostic. Here, we aimed to evaluate the accuracy of a plasma-based EGFR mutation test developed using chip-based dPCR-based detection of 3 EGFR mutations (exon 19 deletions, L858R in exon 21, and T790M in exon 20). Forty-nine patients with NSCLC harboring EGFR-activating mutations were enrolled, and circulating free DNAs (cfDNAs) were extracted from the plasma of 21 and 28 patients before treatment and after progression following EGFR-TKI treatment, respectively. Using reference genomic DNA containing each mutation, the detection limit of each assay was determined to be 0.1%. The sensitivity and specificity of detecting exon 19 deletions and L858R mutations, calculated by comparing the mutation status in the corresponding tumors, were 70.6% and 93.3%, and 66.7% and 100%, respectively, showing similar results compared with previous studies. T790M was detected in 43% of 28 cfDNAs after progression with EGFR-TKI treatment, but in no cfDNAs before the start of the treatment. This chip-based dPCR assay can facilitate detection of EGFR mutations in cfDNA as a minimally invasive method in clinical settings. Copyright © 2017 Elsevier B.V. All rights reserved.

High ambient temperature and risk of intestinal obstruction in cystic fibrosis.

PubMed

Ooi, Chee Y; Jeyaruban, Christina; Lau, Jasmine; Katz, Tamarah; Matson, Angela; Bell, Scott C; Adams, Susan E; Krishnan, Usha

2016-04-01

Distal intestinal obstruction syndrome (DIOS) and constipation in cystic fibrosis (CF) are conditions associated with impaction and/or obstruction by abnormally viscid mucofaecal material within the intestinal lumen. Dehydration has been proposed as a risk factor for DIOS and constipation in CF. The study primarily aimed to determine whether warmer ambient temperature and lower rainfall are risk factors for DIOS and constipation in CF. Hospitalisations for DIOS (incomplete or complete) and/or constipation were retrospectively identified (2000-2012). Genotype, phenotype, temperatures and rainfall data (for the week preceding and season of hospitalisation) were collected. Twenty-seven DIOS (59.3% incomplete; 40.7% complete) and 44 constipation admissions were identified. All admitted patients were pancreatic insufficient. Meconium ileus was significantly more likely in DIOS than constipation (64.7% vs. 33.3%; P = 0.038) and in complete than incomplete DIOS (100% vs. 57.1%; P = 0.04). The maximum temperature of the week before DIOS admission (mean (standard deviation) = 28.0 (5.8) °C) was significantly higher than the maximum temperature of the season of admission (25.2 (3.4) °C; P = 0.002). Similarly, the maximum temperature of the week before hospitalisation for constipation (mean (standard deviation) = 27.9 (6.3) °C) was significantly warmer compared with the season of admission (24.0 (4.1) °C; P < 0.0001). There were no significant differences between levels of rainfall during the week before hospitalisation and the season of admission for both DIOS and constipation. Relatively high ambient temperature may play a role in the pathogenesis of DIOS and constipation in CF. © 2016 The Authors Journal of Paediatrics and Child Health © 2016 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Whey protein processing influences formula-induced gut maturation in preterm pigs.

PubMed

Li, Yanqi; Østergaard, Mette V; Jiang, Pingping; Chatterton, Dereck E W; Thymann, Thomas; Kvistgaard, Anne S; Sangild, Per T

2013-12-01

Immaturity of the gut predisposes preterm infants to nutritional challenges potentially leading to clinical complications such as necrotizing enterocolitis. Feeding milk formulas is associated with greater risk than fresh colostrum or milk, probably due to loss of bioactive proteins (e.g., immunoglobulins, lactoferrin, insulin-like growth factor, transforming growth factor-β) during industrial processing (e.g., pasteurization, filtration, spray-drying). We hypothesized that the processing method for whey protein concentrate (WPC) would affect gut maturation in formula-fed preterm pigs used as a model for preterm infants. Fifty-five caesarean-delivered preterm pigs were distributed into 4 groups given 1 of 4 isoenergetic diets: formula containing conventional WPC (filtration, multi-pasteurization, standard spray-drying) (CF); formula containing gently treated WPC (reduced filtration and pasteurization, gentle spray-drying) (GF); formula containing minimally treated WPC (rennet precipitation, reduced filtration, heat treatment <40°C, freeze-drying) (MF); and bovine colostrum (used as a positive reference group) (BC). Relative to CF, GF, and MF pigs, BC pigs had greater villus heights, lactose digestion, and absorption and lower gut permeability (P < 0.05). MF and BC pigs had greater plasma citrulline concentrations than CF and GF pigs and intestinal interleukin-8 was lower in BC pigs than in the other groups (P < 0.05). MF pigs had lower concentrations of intestinal claudin-4, cleaved caspase-3, and phosphorylated c-Jun than CF pigs (P < 0.05). The conventional and gently treated WPCs had similar efficacy in stimulating proliferation of porcine intestinal epithelial cells. We conclude that processing of WPC affects intestinal structure, function, and integrity when included in formulas for preterm pigs. Optimization of WPC processing technology may be important to preserve the bioactivity and nutritional value of formulas for sensitive newborns.

Effect of Graphene Oxide Mixed Epoxy on Mechanical Properties of Carbon Fiber/Acrylonitrile-Butadiene-Styrene Composites.

PubMed

Wang, Cuicui; Ge, Heyi; Ma, Xiaolong; Liu, Zhifang; Wang, Ting; Zhang, Jingyi

2018-04-01

In this study, the watersoluble epoxy resin was prepared via the ring-opening reaction between diethanolamine and epoxy resin. The modified resin mixed with graphene oxide (GO) as a sizing agent was coated onto carbon fiber (CF) and then the GO-CF reinforced acrylonitrile-butadienestyrene (ABS) composites were prepared. The influences of the different contents of GO on CF and CF/ABS composite were explored. The combination among epoxy, GO sheets and maleic anhydride grafted ABS (ABSMA) showed a synergistic effect on improving the properties of GO-CF and GO-CF/ABS composite. The GO-CF had higher single tensile strength than the commercial CF. The maximum ILSS of GO-CF/ABS composite obtained 19.2% improvement as compared with that of the commercial CF/ABS composite. Such multiscale enhancement method and the synergistic reinforced GO-CF/ABS composite show good prospective applications in many industry areas.

[Effect of mineral N fertilizer reduction and organic fertilizer substitution on soil biological properties and aggregate characteristics in drip-irrigated cotton field.

PubMed

Li, Rui; Tai, Rui; Wang, Dan; Chu, Gui-Xin

2017-10-01

A four year field study was conducted to determine how soil biological properties and soil aggregate stability changed when organic fertilizer and biofertilizer were used to reduce chemical fertilizer application to a drip irrigated cotton field. The study consisted of six fertilization treatments: unfertilized (CK); chemical fertilizer (CF, 300 kg N·hm -2 ; 90 kg P2O5 · hm -2 , 60 kg K2 O·hm -2 ); 80% CF plus 3000 kg·hm -2 organic fertilizer (80%CF+OF); 60% CF plus 6000 kg·hm -2 organic fertilizer (60%CF+OF); 80% CF plus 3000 kg·hm -2 biofertilizer (80%CF+BF); and 60% CF plus 6000 kg·hm -2 biofertilizer (60%CF+BF). The relationships among soil organic C, soil biological properties, and soil aggregate size distribution were determined. The results showed that organic fertilizer and biofertilizer both significantly increased soil enzyme activities. Compared with CF, the biofertilizer treatments increased urease activity by 55.6%-84.0%, alkaline phosphatise activity by 53.1%-74.0%, invertase activity by 15.1%-38.0%, β-glucosidase activity by 38.2%-68.0%, polyphenoloxidase activity by 29.6%-52.0%, and arylsulfatase activity by 35.4%-58.9%. Soil enzyme activity increased as the amount of organic fertilizer and biofertilizer increased (i.e., 60%CF+OF > 80%CF+OF, 60%CF+BF > 80%CF+BF). Soil basal respiration decreased significantly in the order BF > OF > CF > CK. Soil microbial biomass C and N were 22.3% and 43.5% greater, respectively, in 60%CF+BF than in CF. The microbial biomass C:N was significantly lower in 60%CF+BF than in CF. The organic fertilizer and the biofertilizer both improved soil aggregate structure. Soil mass in the >0.25 mm fraction was 7.1% greater in 80%CF+OF and 8.0% greater in (60%CF+OF) than in CF. The geometric mean diameter was 9.2% greater in 80%CF+BF than in 80%CF+OF. Redundancy analysis and cluster analysis both demonstrated that soil aggregate structure and biological activities increased when organic fertilizer and biofertilizer were used to reduce chemical fertilizer application. In conclusion, the organic fertilizer and the biofertilizer significantly increased SOC, soil enzyme activity, and soil microbial biomass C and N. The organic fertilizers also improved soil aggregation. Therefore, soil quality could be improved by using these fertilizers to reduce chemical fertilizer application, especially under drip-irrigation.

Differences in Outcomes between Early and Late Diagnosis of Cystic Fibrosis in the Newborn Screening Era.

PubMed

Coffey, Michael J; Whitaker, Viola; Gentin, Natalie; Junek, Rosie; Shalhoub, Carolyn; Nightingale, Scott; Hilton, Jodi; Wiley, Veronica; Wilcken, Bridget; Gaskin, Kevin J; Ooi, Chee Y

2017-02-01

To evaluate children with cystic fibrosis (CF) who had a late diagnosis of CF (LD-CF) despite newborn screening (NBS) and compare their clinical outcomes with children diagnosed after a positive NBS (NBS-CF). A retrospective review of patients with LD-CF in New South Wales, Australia, from 1988 to 2010 was performed. LD-CF was defined as NBS-negative (negative immunoreactive trypsinogen or no F508del) or NBS-positive but discharged following sweat chloride < 60 mmol/L. Cases of LD-CF were each matched 1:2 with patients with NBS-CF for age, sex, hospital, and exocrine pancreatic status. A total of 45 LD-CF cases were identified (39 NBS-negative and 6 NBS-positive) with 90 NBS-CF matched controls. Median age (IQR) of diagnosis for LD-CF and NBS-CF was 1.35 (0.4-2.8) and 0.12 (0.03-0.2) years, respectively (P <.0001). Estimated incidence of LD-CF was 1 in 45 000 live births. Compared with NBS-CF, LD-CF had more respiratory manifestations at time of diagnosis (66% vs 4%; P <.0001), a higher rate of hospital admission per year for respiratory illness (0.49 vs 0.2; P = .0004), worse lung function (forced expiratory volume in 1 second percentage of predicted, 0.88 vs 0.97; P = .007), and higher rates of chronic colonization with Pseudomonas aeruginosa (47% vs 24%; P = .01). The LD-CF cohort also appeared to be shorter than NBS-CF controls (mean height z-score -0.65 vs -0.03; P = .02). LD-CF, despite NBS, seems to be associated with worse health before diagnosis and worse later growth and respiratory outcomes, thus providing further support for NBS programs for CF. Copyright © 2016 Elsevier Inc. All rights reserved.

Intracavitary moderator balloon combined with 252Cf brachytherapy and boron neutron capture therapy, improving dosimetry in brain tumour and infiltrations

PubMed Central

Brandão, S F

2015-01-01

Objective: This article proposes a combination of californium-252 (252Cf) brachytherapy, boron neutron capture therapy (BNCT) and an intracavitary moderator balloon catheter applied to brain tumour and infiltrations. Methods: Dosimetric evaluations were performed on three protocol set-ups: 252Cf brachytherapy combined with BNCT (Cf-BNCT); Cf-BNCT with a balloon catheter filled with light water (LWB) and the same set-up with heavy water (HWB). Results: Cf-BNCT-HWB has presented dosimetric advantages to Cf-BNCT-LWB and Cf-BNCT in infiltrations at 2.0–5.0 cm from the balloon surface. However, Cf-BNCT-LWB has shown superior dosimetry up to 2.0 cm from the balloon surface. Conclusion: Cf-BNCT-HWB and Cf-BNCT-LWB protocols provide a selective dose distribution for brain tumour and infiltrations, mainly further from the 252Cf source, sparing the normal brain tissue. Advances in knowledge: Malignant brain tumours grow rapidly and often spread to adjacent brain tissues, leading to death. Improvements in brain radiation protocols have been continuously achieved; however, brain tumour recurrence is observed in most cases. Cf-BNCT-LWB and Cf-BNCT-HWB represent new modalities for selectively combating brain tumour infiltrations and metastasis. PMID:25927876

Estimating Effective Dose of Radiation From Pediatric Cardiac CT Angiography Using a 64-MDCT Scanner: New Conversion Factors Relating Dose-Length Product to Effective Dose.

PubMed

Trattner, Sigal; Chelliah, Anjali; Prinsen, Peter; Ruzal-Shapiro, Carrie B; Xu, Yanping; Jambawalikar, Sachin; Amurao, Maxwell; Einstein, Andrew J

2017-03-01

The purpose of this study is to determine the conversion factors that enable accurate estimation of the effective dose (ED) used for cardiac 64-MDCT angiography performed for children. Anthropomorphic phantoms representative of 1- and 10-year-old children, with 50 metal oxide semiconductor field-effect transistor dosimeters placed in organs, underwent scanning performed using a 64-MDCT scanner with different routine clinical cardiac scan modes and x-ray tube potentials. Organ doses were used to calculate the ED on the basis of weighting factors published in 1991 in International Commission on Radiological Protection (ICRP) publication 60 and in 2007 in ICRP publication 103. The EDs and the scanner-reported dose-length products were used to determine conversion factors for each scan mode. The effect of infant heart rate on the ED and the conversion factors was also assessed. The mean conversion factors calculated using the current definition of ED that appeared in ICRP publication 103 were as follows: 0.099 mSv · mGy -1 · cm -1 , for the 1-year-old phantom, and 0.049 mSv · mGy -1 · cm -1 , for the 10-year-old phantom. These conversion factors were a mean of 37% higher than the corresponding conversion factors calculated using the older definition of ED that appeared in ICRP publication 60. Varying the heart rate did not influence the ED or the conversion factors. Conversion factors determined using the definition of ED in ICRP publication 103 and cardiac, rather than chest, scan coverage suggest that the radiation doses that children receive from cardiac CT performed using a contemporary 64-MDCT scanner are higher than the radiation doses previously reported when older chest conversion factors were used. Additional up-to-date pediatric cardiac CT conversion factors are required for use with other contemporary CT scanners and patients of different age ranges.

Dentin bond optimization using the dimethyl sulfoxide-wet bonding strategy: A 2-year in vitro study.

PubMed

Stape, Thiago Henrique Scarabello; Tjäderhane, Leo; Tezvergil-Mutluay, Arzu; Yanikian, Cristiane Rumi Fujiwara; Szesz, Anna Luiza; Loguercio, Alessandro Dourado; Martins, Luís Roberto Marcondes

2016-12-01

This study evaluated a new approach, named dimethyl sulfoxide (DMSO)-wet bonding, to produce more desirable long-term prospects for the ultrafine interactions between synthetic polymeric biomaterials and the inherently hydrated dentin substrate. Sound third molars were randomly restored with/without DMSO pretreatment using a total-etch (Scocthbond Multipurpose: SBMP) and a self-etch (Clearfil SE Bond: CF) adhesive systems. Restored teeth (n=10)/group were sectioned into sticks and submitted to different analyses: micro-Raman determined the degree of conversion inside the hybrid layer (DC); resin-dentin microtensile bond strength and fracture pattern analysis at 24h, 1year and 2 years of aging; and nanoleakage evaluation at 24h and 2 years. DMSO-wet bonding produced significantly higher 24h bond strengths for SBMP that were sustained over the two-year period, with significantly less adhesive failures. Similarly, DMSO-treated CF samples presented significantly higher bond strength than untreated samples at two years. Both adhesives had significant less adhesive failures at 2 years with DMSO. DMSO had no effect on DC of SBMP, but significantly increased the DC of CF. DMSO-treated SBMP samples presented reduced silver uptake compared to untreated samples after aging. Biomodification of the dentin substrate by the proposed strategy using DMSO is a suitable approach to produce more durable hybrid layers with superior ability to withstand hydrolytic degradation over time. Although the active role of DMSO on dentin bond improvement may vary according to monomer composition, its use seems to be effective on both self-etch and etch-and-rinse bonding mechanisms. Copyright © 2016 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

TALEN-mediated generation and genetic correction of disease-specific human induced pluripotent stem cells.

PubMed

Ramalingam, Sivaprakash; Annaluru, Narayana; Kandavelou, Karthikeyan; Chandrasegaran, Srinivasan

2014-01-01

Generation and precise genetic correction of patient-derived hiPSCs have great potential in regenerative medicine. Such targeted genetic manipulations can now be achieved using gene-editing nucleases. Here, we report generation of cystic fibrosis (CF) and Gaucher's disease (GD) hiPSCs respectively from CF (homozygous for CFTRΔF508 mutation) and Type II GD [homozygous for β-glucocerebrosidase (GBA) 1448T>C mutation] patient fibroblasts, using CCR5- specific TALENs. Site-specific addition of loxP-flanked Oct4/Sox2/Klf4/Lin28/Nanog/eGFP gene cassette at the endogenous CCR5 site of patient-derived disease-specific primary fibroblasts induced reprogramming, giving rise to both monoallele (heterozygous) and biallele CCR5-modified hiPSCs. Subsequent excision of the donor cassette was done by treating CCR5-modified CF and GD hiPSCs with Cre. We also demonstrate site-specific correction of sickle cell disease (SCD) mutations at the endogenous HBB locus of patient-specific hiPSCs [TNC1 line that is homozygous for mutated β- globin alleles (βS/βS)], using HBB-specific TALENs. SCD-corrected hiPSC lines showed gene conversion of the mutated βS to the wild-type βA in one of the HBB alleles, while the other allele remained a mutant phenotype. After excision of the loxP-flanked DNA cassette from the SCD-corrected hiPSC lines using Cre, we obtained secondary heterozygous βS/βA hiPSCs, which express the wild-type (βA) transcript to 30-40% level as compared to uncorrected (βS/βS) SCD hiPSCs when differentiated into erythroid cells. Furthermore, we also show that TALEN-mediated generation and genetic correction of disease-specific hiPSCs did not induce any off-target mutations at closely related sites.

Composite fermions on a torus

NASA Astrophysics Data System (ADS)

Pu, Songyang; Wu, Ying-Hai; Jain, J. K.

2017-11-01

We achieve an explicit construction of the lowest Landau level (LLL) projected wave functions for composite fermions in the periodic (torus) geometry. To this end, we first demonstrate how the vortex attachment of the composite fermion (CF) theory can be accomplished in the torus geometry to produce the "unprojected" wave functions satisfying the correct (quasi)periodic boundary conditions. We then consider two methods for projecting these wave functions into the LLL. The direct projection produces valid wave functions but can be implemented only for very small systems. The more powerful and more useful projection method of Jain and Kamilla fails in the torus geometry because it does not preserve the periodic boundary conditions and thus takes us out of the original Hilbert space. We have succeeded in constructing a modified projection method that is consistent with both the periodic boundary conditions and the general structure of the CF theory. This method is valid for a large class of states of composite fermions, called "proper states," which includes the incompressible ground states at electron filling factors ν =n/2 p n +1 , their charged and neutral excitations, and also the quasidegenerate ground states at arbitrary filling factors of the form ν =ν/*2pν*+1 , where n and p are integers and ν* is the CF filling factor. Comparison with exact results known for small systems for the ground and excited states at filling factors ν =1 /3 , 2/5, and 3/7 demonstrates our LLL-projected wave functions to be extremely accurate representations of the actual Coulomb eigenstates. Our construction enables the study of large systems of composite fermions on the torus, thereby opening the possibility of investigating numerous interesting questions and phenomena.

Psychological and educational factors: better predictors of work status than FEV1 in adults with cystic fibrosis.

PubMed

Burker, Eileen J; Sedway, Jan; Carone, Stacia

2004-11-01

Now that more individuals with cystic fibrosis (CF) are living into adulthood, vocational attainment is an increasingly important consideration. Work is a key factor in quality of life. The purpose of the present paper was to evaluate the factors that are associated with work status in 183 adults with CF. Approximately half of the participants were working at the time of evaluation, an impressive figure given that the mean forced expired volume in 1 sec (FEV1) was 31.9%. The average number of hours worked was 32.7 hr/week. The majority of individuals were employed in professional, technical, or managerial occupations (accounting, teaching, law, or social work). A third were employed in clerical and sales occupations, and the remaining individuals were employed in a wide range of other occupations (hotel manager, undercover shopper, artist, or dental technician). Interestingly, FEV1 and age did not differentiate between subjects who were working and those who were not. Individuals who were working had significantly lower depression scores and a higher educational level than those who were not working. Future research is needed to determine whether it is the increased socialization and the resulting social support that may come from a work environment, or a reduction in financial stress because of better income and health benefits that helps to explain this difference. Alternatively, work may serve as a distraction from the symptoms of CF. It is likely that those with higher educational levels had more professional jobs that were more easily modified as health declined. Future research needs to assess how career choices are made, and what factors into a patient's decision to keep working. (c) 2004 Wiley-Liss, Inc.

Forming trifluoromethylmetallates: competition between decarboxylation and C-F bond activation of group 11 trifluoroacetate complexes, [CF3CO2ML]-.

PubMed

Rijs, Nicole J; O'Hair, Richard A J

2012-03-28

A combination of gas-phase 3D quadrupole ion trap mass spectrometry experiments and density functional theory (DFT) calculations have been used to examine the mechanism of thermal decomposition of fluorinated coinage metal carboxylates. The precursor anions, [CF(3)CO(2)MO(2)CCF(3)](-) (M = Cu, Ag and Au), were introduced into the gas-phase via electrospray ionization. Multistage mass spectrometry (MS(n)) experiments were conducted utilizing collision-induced dissociation, yielding a series of trifluoromethylated organometallic species and fluorides via the loss of CO(2), CF(2) or "CF(2)CO(2)". Carboxylate ligand loss was insignificant or absent in all cases. DFT calculations were carried out on a range of potentially competing fragmentation pathways for [CF(3)CO(2)MO(2)CCF(3)](-), [CF(3)CO(2)MCF(3)](-) and [CF(3)CO(2)MF](-). These shed light on possible products and mechanisms for loss of "CF(2)CO(2)", namely, concerted or step-wise loss of CO(2) and CF(2) and a CF(2)CO(2) lactone pathway. The lactone pathway was found to be higher in energy in all cases. In addition, the possibility of forming [CF(3)MCF(3)](-) and [CF(3)MF](-), via decarboxylation is discussed. For the first time the novel fluoride complexes [FMF](-), M = Cu, Ag and Au have been experimentally observed. Finally, the decomposition reactions of [CF(3)CO(2)ML](-) (where L = CF(3) and CF(3)CO(2)) and [CH(3)CO(2)ML](-) (where L = CH(3) and CH(3)CO(2)) are compared.

Photobleaching dynamics in small molecule vs.  polymer organic photovoltaic blends with 1,7-bis-trifluoromethylfullerene

DOE PAGES

Garner, Logan E.; Nellissery Viswanathan, Vinila; Arias, Dylan H.; ...

2018-02-27

Two organic photovoltaic (OPV) donor materials (one polymer and one small molecule) are synthesized from the same constituent building blocks, namely thiophene units, cyclopentathiophene dione (CTD), and cyclopentadithiophene (CPDT). Photobleaching dynamics of these donor materials are then studied under white light illumination in air with blends of PC 70BM and the bistrifluoromethylfullerene 1,7-C 60(CF 3) 2. For both the polymer and small molecule blends, C 60(CF 3) 2 stabilizes the initial rate of photobleaching by a factor of 15 relative to PC70BM. However, once the small molecule:C 60(CF 3) 2 blend bleaches to ~80% of its initial optical density, themore » rate of photobleaching dramatically accelerates, which is not observed in the analagous polymer blend. We probe that phenomenon using time-resovled photoluminescence (TRPL) to measure PL quenching efficiencies at defined intervals during the photobleaching experiments. The data indicates the small molecule donor and C 60(CF 3) 2 acceptor significantly de-mix with time, after which the blend begins to bleach at approximately the same rate as the neat donor sample. The work suggests that perfluoroalkylfullerenes have great potential to stabilize certain OPV active layers toward photodegradation, provided their morphology is stable.« less

Growth phenotypes of Pseudomonas aeruginosa lasR mutants adapted to the airways of cystic fibrosis patients

PubMed Central

D’Argenio, David A.; Wu, Manhong; Hoffman, Lucas R.; Kulasekara, Hemantha D.; Déziel, Eric; Smith, Eric E.; Nguyen, Hai; Ernst, Robert K.; Larson Freeman, Theodore J.; Spencer, David H.; Brittnacher, Mitchell; Hayden, Hillary S.; Selgrade, Sara; Klausen, Mikkel; Goodlett, David R.; Burns, Jane L.; Ramsey, Bonnie W.; Miller, Samuel I.

2009-01-01

Summary The opportunistic pathogen Pseudomonas aeruginosa undergoes genetic change during chronic airway infection of cystic fibrosis (CF) patients. One common change is a mutation inactivating lasR, which encodes a transcriptional regulator that responds to a homoserine lactone signal to activate expression of acute virulence factors. Colonies of lasR mutants visibly accumulated the iridescent intercellular signal 4-hydroxy-2-heptylquinoline. Using this colony phenotype, we identified P. aeruginosa lasR mutants that emerged in the airway of a CF patient early during chronic infection, and during growth in the laboratory on a rich medium. The lasR loss-of-function mutations in these strains conferred a growth advantage with particular carbon and nitrogen sources, including amino acids, in part due to increased expression of the catabolic pathway regulator CbrB. This growth phenotype could contribute to selection of lasR mutants both on rich medium and within the CF airway, supporting a key role for bacterial metabolic adaptation during chronic infection. Inactivation of lasR also resulted in increased β-lactamase activity that increased tolerance to ceftazidime, a widely used β-lactam antibiotic. Loss of LasR function may represent a marker of an early stage in chronic infection of the CF airway with clinical implications for antibiotic resistance and disease progression. PMID:17493132

Photobleaching dynamics in small molecule vs.  polymer organic photovoltaic blends with 1,7-bis-trifluoromethylfullerene

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

Garner, Logan E.; Nellissery Viswanathan, Vinila; Arias, Dylan H.

Two organic photovoltaic (OPV) donor materials (one polymer and one small molecule) are synthesized from the same constituent building blocks, namely thiophene units, cyclopentathiophene dione (CTD), and cyclopentadithiophene (CPDT). Photobleaching dynamics of these donor materials are then studied under white light illumination in air with blends of PC 70BM and the bistrifluoromethylfullerene 1,7-C 60(CF 3) 2. For both the polymer and small molecule blends, C 60(CF 3) 2 stabilizes the initial rate of photobleaching by a factor of 15 relative to PC70BM. However, once the small molecule:C 60(CF 3) 2 blend bleaches to ~80% of its initial optical density, themore » rate of photobleaching dramatically accelerates, which is not observed in the analagous polymer blend. We probe that phenomenon using time-resovled photoluminescence (TRPL) to measure PL quenching efficiencies at defined intervals during the photobleaching experiments. The data indicates the small molecule donor and C 60(CF 3) 2 acceptor significantly de-mix with time, after which the blend begins to bleach at approximately the same rate as the neat donor sample. The work suggests that perfluoroalkylfullerenes have great potential to stabilize certain OPV active layers toward photodegradation, provided their morphology is stable.« less

Hypersonic lateral and directional stability characteristics of aeroassist flight experiment configuration in air and CF4

NASA Technical Reports Server (NTRS)

Micol, John R.; Wells, William L.

1993-01-01

Hypersonic lateral and directional stability characteristics measured on a 60 deg half-angle elliptical cone, which was raked at an angle of 73 deg from the cone centerline and with an ellipsoid nose (ellipticity equal to 2.0 in the symmetry plane), are presented for angles of attack from -10 to 10 deg. The high normal-shock density ratio of a real gas was simulated by tests at a Mach number of 6 in air and CF4 (density ratio equal to 5.25 and 12.0, respectively). Tests were conducted in air at Mach 6 and 10 and in CF4 at Mach 6 to examine the effects of Mach number, Reynolds number, and normal-shock density ratio. Changes in Mach number from 6 to 10 in air or in Reynolds number by a factor of 4 at Mach 6 had a negligible effect on lateral and directional stability characteristics. Variations in normal-shock density ratio had a measurable effect on lateral and directional aerodynamic coefficients, but no significant effect on lateral and directional stability characteristics. Tests in air and CF4 indicated that the configuration was laterally and directionally stable through the test range of angle of attack.

Sleep and Behavior in Cross-Fostering Rats: Developmental and Sex Aspects.

PubMed

Santangeli, Olena; Lehtikuja, Henna; Palomäki, Eeva; Wigren, Henna-Kaisa; Paunio, Tiina; Porkka-Heiskanen, Tarja

2016-12-01

Adverse early-life events induce behavioral psychopathologies and sleep changes in adulthood. In order to understand the molecular level mechanisms by which the maltreatment modifies sleep, valid animal models are needed. Changing pups between mothers at early age (cross-fostering) may satisfyingly model adverse events in human childhood. Cross-fostering (CF) was used to model mild early-life stress in male and female Wistar rats. Behavior and BDNF gene expression in the basal forebrain (BF), cortex, and hypothalamus were assessed during adolescence and adulthood. Spontaneous sleep, sleep homeostasis, and BF extracellular adenosine levels were assessed in adulthood. CF rats demonstrated increased number of REM sleep onsets in light and dark periods of the day. Total REM and NREM sleep duration was also increased during the light period. While sleep homeostasis was not severely affected, basal level of adenosine in the BF of both male and female CF rats was lower than in controls. CF did not lead to considerable changes in behavior. Even when the consequences of adverse early-life events are not observed in tests for anxiety and depression, they leave a molecular mark in the brain, which can act as a vulnerability factor for psychopathologies in later life. Sleep is a sensitive indicator for even mild early-life stress. © 2016 Associated Professional Sleep Societies, LLC.

Accounting for pH heterogeneity and variability in modelling human health risks from cadmium in contaminated land.

PubMed

Gay, J Rebecca; Korre, Anna

2009-07-01

The authors have previously published a methodology which combines quantitative probabilistic human health risk assessment and spatial statistical methods (geostatistics) to produce an assessment, incorporating uncertainty, of risks to human health from exposure to contaminated land. The model assumes a constant soil to plant concentration factor (CF(veg)) when calculating intake of contaminants. This model is modified here to enhance its use in a situation where CF(veg) varies according to soil pH, as is the case for cadmium. The original methodology uses sequential indicator simulation (SIS) to map soil concentration estimates for one contaminant across a site. A real, age-stratified population is mapped across the contaminated area, and intake of soil contaminants by individuals is calculated probabilistically using an adaptation of the Contaminated Land Exposure Assessment (CLEA) model. The proposed improvement involves not only the geostatistical estimation of the contaminant concentration, but also that of soil pH, which in turn leads to a variable CF(veg) estimate which influences the human intake results. The results presented demonstrate that taking pH into account can influence the outcome of the risk assessment greatly. It is proposed that a similar adaptation could be used for other combinations of soil variables which influence CF(veg).

Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid biopsy.

PubMed

Li, Y S; Jiang, B Y; Yang, J J; Zhang, X C; Zhang, Z; Ye, J Y; Zhong, W Z; Tu, H Y; Chen, H J; Wang, Z; Xu, C R; Wang, B C; Du, H J; Chuai, S; Han-Zhang, H; Su, J; Zhou, Q; Yang, X N; Guo, W B; Yan, H H; Liu, Y H; Yan, L X; Huang, B; Zheng, M M; Wu, Y L

2018-04-01

Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM. Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled. A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P < 0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P = 0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression. CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.

Proteomics of Pseudomonas aeruginosa Australian epidemic strain 1 (AES-1) cultured under conditions mimicking the cystic fibrosis lung reveals increased iron acquisition via the siderophore pyochelin.

PubMed

Hare, Nathan J; Soe, Cho Zin; Rose, Barbara; Harbour, Colin; Codd, Rachel; Manos, Jim; Cordwell, Stuart J

2012-02-03

Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). While most CF patients are thought to acquire P. aeruginosa from the environment, person-to-person transmissible strains have been identified in CF clinics worldwide, and the molecular basis for transmissibility remains poorly understood. We undertook a complementary proteomics approach to characterize protein profiles from a transmissible, acute isolate of the Australian epidemic strain 1 (AES-1R), the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1 when grown in an artificial medium that mimics the CF lung environment compared to growth in standard laboratory medium. Proteins elevated in abundance in AES-1R included those involved in methionine and S-adenosylmethionine biosynthesis and in the synthesis of phenazines. Proteomic data were validated by measuring culture supernatant levels of the virulence factor pyocyanin, which is the final product of the phenazine pathway. AES-1R and PAO1 released higher extracellular levels of pyocyanin compared to PA14 when grown in conditions that mimic the CF lung. Proteins associated with biosynthesis of the iron-scavenging siderophore pyochelin (PchDEFGH and FptA) were also present at elevated abundance in AES-1R and at much higher levels than in PAO1, whereas they were reduced in PA14. These protein changes resulted phenotypically in increased extracellular iron acquisition potential and, specifically, elevated pyochelin levels in AES-1R culture supernatants as detected by chrome azurol-S assay and fluorometry, respectively. Transcript analysis of pyochelin genes (pchDFG and fptA) showed they were highly expressed during the early stage of growth in artificial sputum medium (18 h) but returned to basal levels following the establishment of microcolony growth (72 h) consistent with that observed in the CF lung. This provides further evidence that iron acquisition by pyochelin may play a role in the early stages of transmissible CF infection associated with AES-1R.

SU-E-T-90: Accuracy of Calibration of Lithium-6 and -7 Enriched LiF TLDs for Neutron Measurements in High Energy Radiotherapy

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

Keehan, S; Franich, R; Taylor, M

Purpose: To determine the potential error involved in the interpretation of neutron measurements from medical linear accelerators (linacs) using TLD-600H and TLD-700H if standard AmBe and {sup 252}Cf neutron sources are used for calibration without proper inclusion of neutron energy spectrum information. Methods: The Kerma due to neutrons can be calculated from the energy released by various nuclear interactions (elastic and inelastic scatter, (n,α), (n,p), (n,d), (n,t), (n,2n), etc.). The response of each TLD can be considered the sum of the neutron and gamma components; each proportional to the Kerma. Using the difference between the measured TLD responses and themore » ratio of the calculated Kerma for each material, the neutron component of the response can be calculated. The Monte Carlo code MCNP6 has been used to calculate the neutron energy spectra resulting from photonuclear interactions in a Varian 21EX linac. TLDs have been exposed to the mixed (γ-n) field produced by a linac and AmBe and {sup 252}Cf standard neutron sources. Results: For dosimetry of neutrons from AmBe or {sup 252}Cf sources, assuming TLD-700H insensitivity to neutrons will Result in 10% or 20% overestimation of neutron doses respectively.For dosimetry of neutrons produced in a Varian 21EX, applying a calibration factor derived from a standard AmBe or {sup 252}Cf source will Result in an overestimation of neutron fluence, by as much as a factor of 47.The assumption of TLD-700H insensitivity to neutrons produced by linacs leads to a negligible error due to the extremely high Kerma ratio (600H/700H) of 3000 for the assumed neutron spectrum. Conclusion: Lithium-enriched TLDs calibrated with AmBe and/or {sup 252}Cf neutron sources are not accurate for use under the neutron energy spectrum produced by a medical linear accelerator.« less

Granulocyte-Macrophage Colony Stimulatory Factor Enhances the Pro-Inflammatory Response of Interferon-γ-Treated Macrophages to Pseudomonas aeruginosa Infection

PubMed Central

Singh, Sonali; Barr, Helen; Liu, Yi-Chia; Robins, Adrian; Heeb, Stephan; Williams, Paul; Fogarty, Andrew; Cámara, Miguel; Martínez-Pomares, Luisa

2015-01-01

Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF) patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN)-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1) and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human macrophages infected with P. aeruginosa: untreated < treated with GM-CSF < treated with IFN-γ < treated with GM-CSF and IFN-γ. PMID:25706389

Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to Pseudomonas aeruginosa infection.

PubMed

Singh, Sonali; Barr, Helen; Liu, Yi-Chia; Robins, Adrian; Heeb, Stephan; Williams, Paul; Fogarty, Andrew; Cámara, Miguel; Martínez-Pomares, Luisa

2015-01-01

Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF) patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN)-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1) and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human macrophages infected with P. aeruginosa: untreated < treated with GM-CSF < treated with IFN-γ < treated with GM-CSF and IFN-γ.

Up-to-date and projected estimates of survival for people with cystic fibrosis using baseline characteristics: A longitudinal study using UK patient registry data.

PubMed

Keogh, Ruth H; Szczesniak, Rhonda; Taylor-Robinson, David; Bilton, Diana

2018-03-01

Cystic fibrosis (CF) is the most common inherited disease in Caucasians, affecting around 10,000 individuals in the UK today. Prognosis has improved considerably over recent decades with ongoing improvements in treatment and care. Providing up-to-date survival predictions is important for patients, clinicians and health services planning. Flexible parametric survival modelling of UK CF Registry data from 2011 to 2015, capturing 602 deaths in 10,428 individuals. Survival curves were estimated from birth; conditional on reaching older ages; and projected under different assumptions concerning future mortality trends, using baseline characteristics of sex, CFTR genotype (zero, one, two copies of F508del) and age at diagnosis. Male sex was associated with better survival, as was older age at diagnosis, but only in F508del non-homozygotes. Survival did not differ by genotype among individuals diagnosed at birth. Median survival ages at birth in F508del homozygotes were 46years (males) and 41years (females), and similar in non-homozygotes diagnosed at birth. F508del heterozygotes diagnosed aged 5 had median survival ages of 57 (males) and 51 (females). Conditional on survival to 30, median survival age rises to 52 (males) and 49 (females) in homozygotes. Mortality rates decreased annually by 2% during 2006-2015. Future improvements at this rate suggest median survival ages for F508del homozygous babies of 65 (males) and 56 (females). Over half of babies born today, and of individuals aged 30 and above today, can expect to survive into at least their fifth decade. Evidence before this study We searched PubMed with terms "(cystic fibrosis survival) and (projection OR model OR registry OR United Kingdom OR UK)" to identify relevant studies on survival estimates for individuals with cystic fibrosis (CF). We also considered the most recent annual report from the UK Cystic Fibrosis Registry (Cystic Fibrosis Trust, 2016), a review by Buzzetti and colleagues (2009), the chapter on Epidemiology of Cystic Fibrosis by MacNeill (2016), the study of MacKenzie and colleagues (2014), and references therein. There have been many studies of factors associated with survival in CF; most have focused on identifying risk factors, and only a few have presented estimated survival curves, which are the focus of this work. The most recent study of survival in the UK is by Dodge and colleagues (2007), who used data obtained from CF clinics and the national death register, and gave an estimate of survival for babies born in 2003. We found no previous studies that have obtained detailed information on survival using UK Cystic Fibrosis Registry data. Jackson and colleagues obtained survival estimates for the US and Ireland using registry data (Jackson et al., 2011). MacKenzie and colleagues used US Cystic Fibrosis Foundation Patient Registry data from 2000 to 2010 to project survival for children born and diagnosed with CF in 2010, accounting for sex, genotype and age at diagnosis (MacKenzie et al., 2014). Previous studies on estimated survival in CF have become out of date or have not accounted for the full range of patient characteristics available at birth. Few have presented conditional survival estimates (Dodge et al., 2007). Added value of this study This is the first study to yield detailed survival statistics using the UK Cystic Fibrosis Registry, which is one of the largest national CF registries outside of the US and has almost complete coverage of the UK CF population. The primary goal was to leverage the long-term follow-up of the nearly complete UK CF population available in the Registry for the purposes of producing accurate, precise predictions in the modern era of CF care. Estimates are presented from birth and conditional on survival to older ages. These are the first conditional estimates in CF to also account for genotype, sex and age at diagnosis, which were each included in the modelling using a flexible approach. Projections are also provided under different scenarios based on downward trends in mortality rates. Our use of flexible parametric survival models is novel in this field, and our approach could be used to provide modern survival statistics for other chronic diseases and disorders. Implications of all the available evidence Our estimates of future survival in CF under a range of different scenarios are based on data on nearly all individuals living with the disease in the UK in recent times, reflective of a modern era of care, and are most appropriate for the families of babies being born in the present day with CF. Conditional estimates inform patients who have already reached an older age, and their clinicians. Over half of babies born today, and of individuals aged 30years and above alive today, can expect to survive into their fifth decade. Insights based on our survival projections can be used to inform future needs in CF health care provision. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Alkali metal and ammonium fluoro(trifluoroacetato)metallates M'[ M''3(μ3-F)(CF3COO)6(CF3COOH)3], where M' = Li, Na, K, NH4, Rb, or Cs and M'' = Ni or Co. Synthesis and crystal structures

NASA Astrophysics Data System (ADS)

Tereshchenko, D. S.; Morozov, I. V.; Boltalin, A. I.; Karpova, E. V.; Glazunova, T. Yu.; Troyanov, S. I.

2013-01-01

A series of fluoro(trifluoroacetato)metallates were synthesized by crystallization from solutions in trifluoroacetic acid containing nickel(II) or cobalt(II) nitrate hydrates and alkali metal or ammonium fluorides: Li[Ni3(μ3-F)(CF3COO)6(CF3COOH)3](CF3COOH)3 ( I), M'[Ni3(μ3-F)(CF3COO)6(CF3COOH)3] ( M' = Na ( II), NH4 ( IV), Rb ( V), and Cs ( VI)), NH4[Co3(μ3-F) (CF3COO)6(CF3COOH)3] ( III), and Cs[Ni3(μ3-F)(CF3COO)6(CF3COOH)3](CF3COOH)0.5 ( VII). The crystal structures of these compounds were determined by single-crystal X-ray diffraction. All structures contain triangular trinuclear complex anions [ M 3″(μ3-F)(CF3COO)6(CF3COOH)3]- ( M″ = Ni, Co) structurally similar to trinuclear 3d metal oxo carboxylate complexes. The three-coordinated F atom is located at the center of the triangle formed by Ni(II) or Co(II) atoms. The metal atoms are linked in pairs by six bridging trifluoroacetate groups located above and below the plane of the [ M″3 F] triangle. The oxygen atoms of the axial CF3COOH molecules complete the coordination environment of M″ atoms to an octahedron.

Non-Genomic Estrogen Regulation of Ion Transport and Airway Surface Liquid Dynamics in Cystic Fibrosis Bronchial Epithelium

PubMed Central

Saint-Criq, Vinciane; Kim, Sung Hoon; Katzenellenbogen, John A.; Harvey, Brian J.

2013-01-01

Male cystic fibrosis (CF) patients survive longer than females and lung exacerbations in CF females vary during the estrous cycle. Estrogen has been reported to reduce the height of the airway surface liquid (ASL) in female CF bronchial epithelium. Here we investigated the effect of 17β-estradiol on the airway surface liquid height and ion transport in normal (NuLi-1) and CF (CuFi-1) bronchial epithelial monolayers. Live cell imaging using confocal microscopy revealed that airway surface liquid height was significantly higher in the non-CF cells compared to the CF cells. 17β-estradiol (0.1–10 nM) reduced the airway surface liquid height in non-CF and CF cells after 30 min treatment. Treatment with the nuclear-impeded Estrogen Dendrimer Conjugate mimicked the effect of free estrogen by reducing significantly the airway surface liquid height in CF and non-CF cells. Inhibition of chloride transport or basolateral potassium recycling decreased the airway surface liquid height and 17β-estradiol had no additive effect in the presence of these ion transporter inhibitors. 17β-estradiol decreased bumetanide-sensitive transepithelial short-circuit current in non-CF cells and prevented the forskolin-induced increase in ASL height. 17β-estradiol stimulated an amiloride-sensitive transepithelial current and increased ouabain-sensitive basolateral short-circuit current in CF cells. 17β-estradiol increased PKCδ activity in CF and non-CF cells. These results demonstrate that estrogen dehydrates CF and non-CF ASL, and these responses to 17β-estradiol are non-genomic rather than involving the classical nuclear estrogen receptor pathway. 17β-estradiol acts on the airway surface liquid by inhibiting cAMP-mediated chloride secretion in non-CF cells and increasing sodium absorption via the stimulation of PKCδ, ENaC and the Na+/K+ATPase in CF cells. PMID:24223826

Predictors and variation of routine home discharge in critically ill adults with cystic fibrosis.

PubMed

Oud, Lavi; Chan, Yiu Ming

2018-06-01

The short-term outcomes of patients with cystic fibrosis (CF) surviving critical illness were not examined systematically. To determine the factors associated with and variation in rates of routine home discharge among ICU-managed adult CF patients. Predictors of routine home discharge and its hospital-level variation were examined in ICU-managed adults with cystic fibrosis in Texas during 2004-2013. Older age, rural residence, and severity of illness decreased odds of routine home discharge, while hospitalization in facilities accredited as part of the Cystic Fibrosis Foundation Care Center Network nearly doubled the odds of routine home discharge. The median (interquartile) adjusted rate of routine home discharge was 62.0% (31.5-82.5). The identified determinants of routine home discharge can inform clinical decision-making, while the demonstrated wide variation in adjusted across-hospital rates of routine home discharge of ICU-managed adults with CF can provide benchmark data for future quality improvement efforts. Published by Elsevier Inc.

The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing

NASA Astrophysics Data System (ADS)

Zabner, Joseph; Seiler, Michael P.; Launspach, Janice L.; Karp, Philip H.; Kearney, William R.; Look, Dwight C.; Smith, Jeffrey J.; Welsh, Michael J.

2000-10-01

The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface.

The impact of metallic coagulants on the removal of organic compounds from oil sands process-affected water.

PubMed

Pourrezaei, Parastoo; Drzewicz, Przemysław; Wang, Yingnan; Gamal El-Din, Mohamed; Perez-Estrada, Leonidas A; Martin, Jonathan W; Anderson, Julie; Wiseman, Steve; Liber, Karsten; Giesy, John P

2011-10-01

Coagulation/flocculation (CF) by use of alum and cationic polymer polyDADMAC, was performed as a pretreatment for remediation of oil sands process-affected water (OSPW). Various factors were investigated and the process was optimized to improve efficiency of removal of organic carbon and turbidity. Destabilization of the particles occurred through charge neutralization by adsorption of hydroxide precipitates. Scanning electron microscope images revealed that the resultant flocs were compact. The CF process significantly reduced concentrations of naphthenic acids (NAs) and oxidized NAs by 37 and 86%, respectively, demonstrating the applicability of CF pretreatment to remove a persistent and toxic organic fraction from OSPW. Concentrations of vanadium and barium were decreased by 67-78% and 42-63%, respectively. Analysis of surface functional groups on flocs also confirmed the removal of the NAs compounds. Flocculation with cationic polymer compared to alum, caused toxicity toward the benthic invertebrate, Chironoums dilutus, thus application of the polymer should be limited.

Cystic fibrosis.

PubMed

Bye, M R; Ewig, J M; Quittell, L M

1994-01-01

While the care of cystic fibrosis (CF) patients has been mainly the province of pediatricians, great improvements in the therapy and life span of CF patients often results in their transition to care by adult physicians. In this review of CF, we begin with an overview of the epidemiology and genetics of the disease, with a discussion of the recently found ion abnormalities that lead to the clinical manifestations. This is followed by a discussion of the pathophysiology. Methods of diagnosis, ranging from the gold standard, the sweat test, to recent advances based on a greater understanding of the genetics of the disease are reviewed. This is followed by a discussion of therapy primarily geared to the treatment of the respiratory complications, as they are the most common lethal factors of the disease. We point out controversies where they exist. Newer forms of therapy such as lung transplantation are discussed, and we finish with a discussion about future therapeutic modalities, some of which are being approved as the paper is in print.

Anionic poly(amino acid)s dissolve F-actin and DNA bundles, enhance DNase activity, and reduce the viscosity of cystic fibrosis sputum.

PubMed

Tang, Jay X; Wen, Qi; Bennett, Andrew; Kim, Brian; Sheils, Catherine A; Bucki, Robert; Janmey, Paul A

2005-10-01

Bundles of F-actin and DNA present in the sputum of cystic fibrosis (CF) patients but absent from normal airway fluid contribute to the altered viscoelastic properties of sputum that inhibit clearance of infected airway fluid and exacerbate the pathology of CF. Previous strategies to remove these filamentous aggregates have focused on DNase to enzymatically depolymerize DNA to constituent monomers and gelsolin to sever F-actin to small fragments. The high densities of negative surface charge on DNA and F-actin suggest that the bundles of these filaments, which alone exhibit a strong electrostatic repulsion, may be stabilized by multivalent cations such as histones, antimicrobial peptides, and other positively charged molecules prevalent in airway fluid. This study reports that bundles of DNA or F-actin formed after addition of histone H1 or lysozyme are efficiently dissolved by soluble multivalent anions such as polymeric aspartate or glutamate. Addition of poly-aspartate or poly-glutamate also disperses DNA and actin-containing bundles in CF sputum and lowers the elastic moduli of these samples to levels comparable to those obtained after treatment with DNase I or gelsolin. Addition of poly-aspartic acid also increased DNase activity when added to samples containing DNA bundles formed with histone H1. When added to CF sputum, poly-aspartic acid significantly reduced the growth of bacteria, suggesting activation of endogenous antibacterial factors. These findings suggest that soluble multivalent anions have potential alone or in combination with other mucolytic agents to selectively dissociate the large bundles of charged biopolymers that form in CF sputum.

Facile Fabrication of Electrically Conductive Low-Density Polyethylene/Carbon Fiber Tubes for Novel Smart Materials via Multiaxial Orientation.

PubMed

Li, Yijun; Nie, Min; Wang, Qi

2018-01-10

Electromechanical sensors are indispensable components in functional devices and robotics application. However, the fabrication of the sensors still maintains a challenging issue that high percolation threshold and easy failure of conductive network are derived from uniaxial orientation of conductive fillers in practical melt processing. Herein, we reported a facile fabrication method to prepare a multiaxial low-density polyethylene (LDPE)/carbon fibers (CFs) tube with bidirectional controllable electrical conductivity and sensitive strain-responsive performance via rotation extrusion technology. The multidimensional helical flow is confirmed in the reverse rotation extrusion, and the CFs readily respond to the flow field leading to a multiaxial orientation in the LDPE matrix. In contrast to uniaxial LDPE/CF composites, which perform a "head to head" conjunction, multiaxial-orientated CF networks exhibit a unique multilayer structure in which the CFs with distinct orientation direction intersect in the interface, endowing the LDPE/CF composites with a low percolation threshold (15 wt %) to those of the uniaxial ones (∼35 wt %). The angles between two axes play a vital role in determining the density of the conductive networks in the interface, which is predominant in tuning the bending-responsive behaviors with a gauge factor range from 12.5 to 56.3 and the corresponding linear respond region from ∼15 to ∼1%. Such a superior performance of conductive LDPE/CF tube confirms that the design of multiaxial orientation paves a novel way to facile fabrication of advanced cost-effective CF-based smart materials, shedding light on promising applications such as smart materials and intelligent engineering monitoring.

Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolated in serial cultures from the respiratory tract of children with cystic fibrosis.

PubMed

Al-Zubeidi, Duha; Hogan, Patrick G; Boyle, Mary; Burnham, Carey-Ann D; Fritz, Stephanie A

2014-06-01

Little is known about strain relatedness of methicillin-resistant Staphyloccocus aureus (MRSA) isolated at serial time points from the respiratory tract of patients with cystic fibrosis (CF). The objectives are to interrogate the genetic diversity of MRSA recovered in serial cultures from children with CF and to correlate strain relatedness with clinical characteristics. We performed a retrospective analysis of children with CF from whom MRSA was isolated from serial respiratory cultures from 2005 to 2011. Within individual patients, relatedness of isolated strains was determined by repetitive-sequence polymerase chain reaction, and the staphylococcal cassette chromosome mec type of each isolate was characterized. Medical records corresponding to the MRSA cultures were reviewed. We identified 54 CF patients with serial MRSA cultures (145 distinct cultures). Over time, 45 (83%) patients maintained the same strain type and 9 (17%) possessed at least 2 distinct strain types. A total of 91 pairs of isolates were analyzed for strain relatedness. Of these, 81 (89%) were identical and 10 (11%) were distinct strain types. About 117 (83%) isolates were staphylococcal cassette chromosome mec type II, 24 (17%) were staphylococcal cassette chromosome mec type IV and 4 were other types not resolvable with our assay. Clinical factors, including time interval and prescription of antibiotics effective against MRSA between positive cultures, did not correlate with acquisition of a distinct MRSA strain by individual patients. Our data suggest that sustained presence of MRSA in CF patients is most commonly attributable to identical strain types. Acquisition of distinct MRSA strains in the airway is infrequent.

Aspergillus fumigatus Preexposure Worsens Pathology and Improves Control of Mycobacterium abscessus Pulmonary Infection in Mice.

PubMed

Monin, Leticia; Mehta, Shail; Elsegeiny, Waleed; Gopal, Radha; McAleer, Jeremy P; Oury, Tim D; Kolls, Jay; Khader, Shabaana A

2018-03-01

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with Mycobacterium abscessus , which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with Aspergillus fumigatus We established a new mouse model to investigate the relationship between A. fumigatus and M. abscessus pulmonary infections. In this model, animals exposed to A. fumigatus and coinfected with M. abscessus exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with M. abscessus alone. This increased control of M. abscessus infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in M. abscessus control in A. fumigatus -coinfected lungs. Our results demonstrate that A. fumigatus , an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact M. abscessus control in a mouse model. Copyright © 2018 American Society for Microbiology.

Advances in Collaborative Filtering

NASA Astrophysics Data System (ADS)

Koren, Yehuda; Bell, Robert

The collaborative filtering (CF) approach to recommenders has recently enjoyed much interest and progress. The fact that it played a central role within the recently completed Netflix competition has contributed to its popularity. This chapter surveys the recent progress in the field. Matrix factorization techniques, which became a first choice for implementing CF, are described together with recent innovations. We also describe several extensions that bring competitive accuracy into neighborhood methods, which used to dominate the field. The chapter demonstrates how to utilize temporal models and implicit feedback to extend models accuracy. In passing, we include detailed descriptions of some the central methods developed for tackling the challenge of the Netflix Prize competition.

Dose factor entry and display tool for BNCT radiotherapy

DOEpatents

Wessol, Daniel E.; Wheeler, Floyd J.; Cook, Jeremy L.

1999-01-01

A system for use in Boron Neutron Capture Therapy (BNCT) radiotherapy planning where a biological distribution is calculated using a combination of conversion factors and a previously calculated physical distribution. Conversion factors are presented in a graphical spreadsheet so that a planner can easily view and modify the conversion factors. For radiotherapy in multi-component modalities, such as Fast-Neutron and BNCT, it is necessary to combine each conversion factor component to form an effective dose which is used in radiotherapy planning and evaluation. The Dose Factor Entry and Display System is designed to facilitate planner entry of appropriate conversion factors in a straightforward manner for each component. The effective isodose is then immediately computed and displayed over the appropriate background (e.g. digitized image).

Atmospheric chemistry of isoflurane, desflurane, and sevoflurane: kinetics and mechanisms of reactions with chlorine atoms and OH radicals and global warming potentials.

PubMed

Sulbaek Andersen, Mads P; Nielsen, Ole J; Karpichev, Boris; Wallington, Timothy J; Sander, Stanley P

2012-06-21

The smog chamber/Fourier-transform infrared spectroscopy (FTIR) technique was used to measure the rate coefficients k(Cl + CF(3)CHClOCHF(2), isoflurane) = (4.5 ± 0.8) × 10(-15), k(Cl + CF(3)CHFOCHF(2), desflurane) = (1.0 ± 0.3) × 10(-15), k(Cl + (CF(3))(2)CHOCH(2)F, sevoflurane) = (1.1 ± 0.1) × 10(-13), and k(OH + (CF(3))(2)CHOCH(2)F) = (3.5 ± 0.7) × 10(-14) cm(3) molecule(-1) in 700 Torr of N(2)/air diluent at 295 ± 2 K. An upper limit of 6 × 10(-17) cm(3) molecule(-1) was established for k(Cl + (CF(3))(2)CHOC(O)F). The laser photolysis/laser-induced fluorescence (LP/LIF) technique was employed to determine hydroxyl radical rate coefficients as a function of temperature (241-298 K): k(OH + CF(3)CHFOCHF(2)) = (7.05 ± 1.80) × 10(-13) exp[-(1551 ± 72)/T] cm(3) molecule(-1); k(296 ± 1 K) = (3.73 ± 0.08) × 10(-15) cm(3) molecule(-1), and k(OH + (CF(3))(2)CHOCH(2)F) = (9.98 ± 3.24) × 10(-13) exp[-(969 ± 82)/T] cm(3) molecule(-1); k(298 ± 1 K) = (3.94 ± 0.30) × 10(-14) cm(3) molecule(-1). The rate coefficient of k(OH + CF(3)CHClOCHF(2), 296 ± 1 K) = (1.45 ± 0.16) × 10(-14) cm(3) molecule(-1) was also determined. Chlorine atoms react with CF(3)CHFOCHF(2) via H-abstraction to give CF(3)CFOCHF(2) and CF(3)CHFOCF(2) radicals in yields of approximately 83% and 17%. The major atmospheric fate of the CF(3)C(O)FOCHF(2) alkoxy radical is decomposition via elimination of CF(3) to give FC(O)OCHF(2) and is unaffected by the method used to generate the CF(3)C(O)FOCHF(2) radicals. CF(3)CHFOCF(2) radicals add O(2) and are converted by subsequent reactions into CF(3)CHFOCF(2)O alkoxy radicals, which decompose to give COF(2) and CF(3)CHFO radicals. In 700 Torr of air 82% of CF(3)CHFO radicals undergo C-C scission to yield HC(O)F and CF(3) radicals with the remaining 18% reacting with O(2) to give CF(3)C(O)F. Atmospheric oxidation of (CF(3))(2)CHOCH(2)F gives (CF(3))(2)CHOC(O)F in a molar yield of 93 ± 6% with CF(3)C(O)CF(3) and HCOF as minor products. The IR spectra of (CF(3))(2)CHOC(O)F and FC(O)OCHF(2) are reported for the first time. The atmospheric lifetimes of CF(3)CHClOCHF(2), CF(3)CHFOCHF(2), and (CF(3))(2)CHOCH(2)F (sevoflurane) are estimated at 3.2, 14, and 1.1 years, respectively. The 100 year time horizon global warming potentials of isoflurane, desflurane, and sevoflurane are 510, 2540, and 130, respectively. The atmospheric degradation products of these anesthetics are not of environmental concern.

The Role Of Contact Force In Atrial Fibrillation Ablation.

PubMed

Nakagawa, Hiroshi; Jackman, Warren M

2014-01-01

During radiofrequency (RF) ablation, low electrode-tissue contact force (CF) is associated with ineffective RF lesion formation, whereas excessive CF may increase the risk of steam pop and perforation. Recently, ablation catheters using two technologies have been developed to measure real-time catheter-tissue CF. One catheter uses three optical fibers to measure microdeformation of a deformable body in the catheter tip. The other catheter uses a small spring connecting the ablation tip electrode to the catheter shaft with a magnetic transmitter and sensors to measure microdeflection of the spring. Pre-clinical experimental studies have shown that 1) at constant RF power and application time, RF lesion size significantly increases with increasing CF; 2) the incidence of steam pop and thrombus also increase with increasing CF; 3) modulating RF power based on CF (i.e, high RF power at low CF and lower RF power at high CF) results in a similar and predictable RF lesion size. In clinical studies in patients undergoing pulmonary vein (PV) isolation, CF during mapping in the left atrium and PVs showed a wide range of CF and transient high CF. The most common high CF site was located at the anterior/rightward left atrial roof, directly beneath the ascending aorta. There was a poor relationship between CF and previously used surrogate parameters for CF (unipolar or bipolar atrial potential amplitude and impedance). Patients who underwent PV isolation with an average CF of <10 g experienced higher AF recurrence, whereas patients with ablation using an average CF of > 20g had lower AF recurrence. AF recurred within 12 months in 6 of 8 patients (75%) who had a mean Force-Time Integral (FTI, area under the curve for contact force vs. time) < 500 gs. In contrast, AF recurred in only 4 of 13 patients (21%) with ablation using a mean FTI >1000 gs. In another study, controlling RF power based on CF prevented steam pop and impedance rise without loss of lesion effectiveness. These studies confirm that CF is a major determinant of RF lesion size and future systems combining CF, RF power and application time may provide real-time assessment of lesion formation.

A data model of the Climate and Forecast metadata conventions (CF-1.6) with a software implementation (cf-python v2.1)

NASA Astrophysics Data System (ADS)

Hassell, David; Gregory, Jonathan; Blower, Jon; Lawrence, Bryan N.; Taylor, Karl E.

2017-12-01

The CF (Climate and Forecast) metadata conventions are designed to promote the creation, processing, and sharing of climate and forecasting data using Network Common Data Form (netCDF) files and libraries. The CF conventions provide a description of the physical meaning of data and of their spatial and temporal properties, but they depend on the netCDF file encoding which can currently only be fully understood and interpreted by someone familiar with the rules and relationships specified in the conventions documentation. To aid in development of CF-compliant software and to capture with a minimal set of elements all of the information contained in the CF conventions, we propose a formal data model for CF which is independent of netCDF and describes all possible CF-compliant data. Because such data will often be analysed and visualised using software based on other data models, we compare our CF data model with the ISO 19123 coverage model, the Open Geospatial Consortium CF netCDF standard, and the Unidata Common Data Model. To demonstrate that this CF data model can in fact be implemented, we present cf-python, a Python software library that conforms to the model and can manipulate any CF-compliant dataset.

Carbon nanotubes/carbon fiber hybrid material: a super support material for sludge biofilms.

PubMed

Liu, Qijie; Dai, Guangze; Bao, Yanling

2017-07-16

Carbon fiber (CF) is widely used as a sludge biofilm support material for wastewater treatment. Carbon nanotubes/carbon fiber (CNTs/CF) hybrid material was prepared by ultrasonically assisted electrophoretic deposition (EPD). CF supports (CF without handling, CF oxidized by nitric acid, CNTs/CF hybrid material) were evaluated by sludge immobilization tests, bacterial cell adsorption tests and Derjaguin -Landau -Verwey -Overbeek (DLVO) theory. We found that the CNTs/CF hybrid material has a high capacity for adsorbing activated sludge, nitrifying bacterial sludge and pure strains (Escherichia coli and Staphylococcus aureus). CNTs deposited on CF surface easily wound around the curved surface of bacterial cell which resulted in capturing more bacterial cells. DLVO theory indicated the lowest total interaction energy of CNTs/CF hybrid material, which resulted in the highest bacteria cell adsorption velocity. Experiments and DLVO theory results proved that CNTs/CF hybrid material is a super support material for sludge biofilms.

Photoionisation study of Xe.CF{sub 4} and Kr.CF{sub 4} van-der-Waals molecules

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

Alekseev, V. A., E-mail: alekseev@va3474.spb.edu; Kevorkyants, R.; Garcia, G. A.

2016-05-14

We report on photoionization studies of Xe.CF{sub 4} and Kr.CF{sub 4} van-der-Waals complexes produced in a supersonic expansion and detected using synchrotron radiation and photoelectron-photoion coincidence techniques. The ionization potential of CF{sub 4} is larger than those of the Xe and Kr atoms and the ground state of the Rg.CF{sub 4}{sup +} ion correlates with Rg{sup +} ({sup 2}P{sub 3/2}) + CF{sub 4}. The onset of the Rg.CF{sub 4}{sup +} signals was found to be only ∼0.2 eV below the Rg ionization potential. In agreement with experiment, complementary ab initio calculations show that vertical transitions originating from the potential minimummore » of the ground state of Rg.CF{sub 4} terminate at a part of the potential energy surfaces of Rg.CF{sub 4}{sup +}, which are approximately 0.05 eV below the Rg{sup +} ({sup 2}P{sub 3/2}) + CF{sub 4} dissociation limit. In contrast to the neutral complexes, which are most stable in the face geometry, for the Rg.CF{sub 4}{sup +} ions, the calculations show that the minimum of the potential energy surface is in the vertex geometry. Experiments which have been performed only with Xe.CF{sub 4} revealed no Xe.CF{sub 4}{sup +} signal above the first ionization threshold of Xe, suggesting that the Rg.CF{sub 4}{sup +} ions are not stable above the first dissociation limit.« less

Size-specific dose estimate (SSDE) provides a simple method to calculate organ dose for pediatric CT examinations

PubMed Central

Moore, Bria M.; Brady, Samuel L.; Mirro, Amy E.; Kaufman, Robert A.

2014-01-01

Purpose: To investigate the correlation of size-specific dose estimate (SSDE) with absorbed organ dose, and to develop a simple methodology for estimating patient organ dose in a pediatric population (5–55 kg). Methods: Four physical anthropomorphic phantoms representing a range of pediatric body habitus were scanned with metal oxide semiconductor field effect transistor (MOSFET) dosimeters placed at 23 organ locations to determine absolute organ dose. Phantom absolute organ dose was divided by phantom SSDE to determine correlation between organ dose and SSDE. Organ dose correlation factors (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ ) were then multiplied by patient-specific SSDE to estimate patient organ dose. The \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ were used to retrospectively estimate individual organ doses from 352 chest and 241 abdominopelvic pediatric CT examinations, where mean patient weight was 22 kg ± 15 (range 5–55 kg), and mean patient age was 6 yrs ± 5 (range 4 months to 23 yrs). Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm; thus, showing appropriate scalability of the phantoms across the entire pediatric population in this study. Individual\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ were determined for a total of 23 organs in the chest and abdominopelvic region across nine weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7–1.4) and abdominopelvic region (average 0.9; range 0.7–1.3) was near unity. For organ/tissue that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1–0.4) for both the chest and abdominopelvic regions, respectively. A means to estimate patient organ dose was demonstrated. Calculated patient organ dose, using patient SSDE and \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ , was compared to previously published pediatric patient doses that accounted for patient size in their dose calculation, and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). Conclusions: For organs fully covered within the scan volume, the average correlation of SSDE and organ absolute dose was found to be better than ±10%. In addition, this study provides a complete list of organ dose correlation factors (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}${\\rm CF}_{{\\rm SSDE}}^{{\\rm organ}}$\\end{document} CF SSDE organ ) for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE. PMID:24989395

Background and Epidemiology

PubMed Central

Sanders, Don B.; Fink, Aliza

2016-01-01

SYNOPSIS Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians. Significant advances in therapies and outcomes have occurred for people with CF over the past 30 years. Many of these improvements have come about through the concerted efforts of the US CF Foundation and international CF societies, networks of CF care centers, and the worldwide community of care providers, researchers, and patients and families. Despite these gains, there are still hurdles to overcome to continue to improve the quality of life, reduce CF complications, prolong survival, and ultimately cure CF. This article reviews the epidemiology of CF, including trends in incidence and prevalence, clinical characteristics, common complications, and survival. PMID:27469176

Atmospheric chemistry of cyc-CF2CF2CF2CH=CH-: Kinetics, products, and mechanism of gas-phase reaction with OH radicals, and atmospheric implications

NASA Astrophysics Data System (ADS)

Guo, Qin; Zhang, Ni; Uchimaru, Tadafumi; Chen, Liang; Quan, Hengdao; Mizukado, Junji

2018-04-01

The rate constants for the gas-phase reactions of cyc-CF2CF2CF2CH=CH- with OH radicals were determined by a relative rate method between 253 and 328 K. The rate constant k1 at 298 K was measured to be (1.08 ± 0.04) × 10-13 cm3 molecule-1 s-1, and the Arrhenius expression was k1 = (3.72 ± 0.14) × 10-13 exp [(-370 ± 12)/T]. The atmospheric lifetime of cyc-CF2CF2CF2CH=CH- was calculated to be 107 d. The products and mechanism for the reaction of cyc-CF2CF2CF2CH=CH- with OH radicals were also investigated. CO, CO2, and COF2 were identified as the main carbon-containing products following the OH-initiated reaction. Moreover, the radiative efficiency (RE) was determined to be 0.143 W m-2 ppb-1, and the global warming potentials (GWPs) for 20, 100, and 500 yr were 54, 15, and 4, respectively. The photochemical ozone creation potential of the title compound was estimated to be 1.3.

Assessment of the atmospheric loss processes initiated by OH radicals and sunlight, and the radiative efficiency for a series of hydrofluoroolefins, CF3(CF2)x=1,3,5CHCH2.

PubMed

González, Sergio; Jiménez, Elena; Albaladejo, José

2016-05-01

Hydrofluoroolefins (HFOs) of the type CF3(CF2)x≥0CHCH2, are currently being suggested as substitutes of some hydrofluorocarbons (HFCs). In this work, an assessment of the atmospheric removal of CF3(CF2)x=1,3,5CHCH2, initiated by reaction with hydroxyl (OH) radicals and UV solar radiation is addressed. For that purpose, the rate coefficients for the OH + CF3(CF2)x=1,3,5CHCH2 reaction, kOH(T = 263-358 K), were determined by the pulsed laser photolysis-laser induced fluorescence technique. A slightly negative temperature dependence of kOH was observed, obtaining Ea/R (in K) values of -124 ± 15, -128 ± 6 and -160 ± 10, for CF3CF2CHCH2, CF3(CF2)3CHCH2 and CF3(CF2)5CHCH2, respectively. The estimated atmospheric lifetimes are around 8 days, considering that HFOs are well-mixed in the troposphere. Furthermore, an evaluation of the long-wave and short-wave absorption process of these HFOs have been carried out by determining the UV (191-367 nm) and IR (4000-500 cm(-1)) absorption cross sections at 298 K. Based on the obtained UV absorption cross sections, no photolysis of CF3(CF2)x=1,3,5CHCH2 is expected in the troposphere (λ > 290 nm). These species strongly absorb IR radiation in the atmospheric IR window. Despite the strong absorption in the IR region, the lifetime corrected radiative efficiencies are low (0.033 W m(-2) ppb(-1) for CF3(CF2)3CHCH2 and 0.039 Wm(-2) ppb(-1) for CF3(CF2)5CHCH2). Calculation of GWPs for these species has been performed as a function of the horizon time, providing values higher than unity for a short-period term, decreasing dramatically for longer periods. Therefore, it is concluded that emissions of these species do not affect the radiative forcing of climate, making them suitable replacements of large-GWP HFCs. Copyright © 2016. Published by Elsevier Ltd.

Improvement of mechanical strength of sintered Mo alloyed steel by optimization of sintering and cold-forging processes with densification

NASA Astrophysics Data System (ADS)

Kamakoshi, Y.; Shohji, I.; Inoue, Y.; Fukuda, S.

2017-10-01

Powder metallurgy (P/M) materials have been expected to be spread in automotive industry. Generally, since sintered materials using P/M ones contain many pores and voids, mechanical properties of them are inferior to those of conventional wrought materials. To improve mechanical properties of the sintered materials, densification is effective. The aim of this study is to improve mechanical strength of sintered Mo-alloyed steel by optimizing conditions in sintering and cold-forging processes. Mo-alloyed steel powder was compacted. Then, pre-sintering (PS) using a vacuum sintering furnace was conducted. Subsequently, coldforging (CF) by a backward extrusion method was conducted to the pre-sintered specimen. Moreover, the cold-forged specimen was heat treated by carburizing, tempering and quenching (CQT). Afterwards, mechanical properties were investigated. As a result, it was found that the density of the PS specimen is required to be more than 7.4 Mg/m3 to strengthen the specimen by heat treatment after CF. Furthermore, density and the microstructure of the PS specimen are most important factors to make the high density and strength material by CF. At the CF load of 1200 kN, the maximum density ratio reached approximately 99% by the use of the PS specimen with proper density and microstructure. At the CF load of 900 kN, although density ratio was high like more than 97.8%, transverse rupture strength decreased sharply. Since densification caused high shear stress and stress concentration in the surface layer, microcracks occurred by the damages of inter-particle sintered connection of the surface layer. On the contrary, in case of the CF load of 1200 kN, ultra-densification of the surface layer occurred by a sufficient plastic flow. Such sufficient compressed specimens regenerated the sintered connections by high temperature heat treatment and thus the high strength densified material was obtained. These processes can be applicable to near net shape manufacturing without surface machining.

Pseudomonas aeruginosa AES-1 exhibits increased virulence gene expression during chronic infection of cystic fibrosis lung.

PubMed

Naughton, Sharna; Parker, Dane; Seemann, Torsten; Thomas, Torsten; Turnbull, Lynne; Rose, Barbara; Bye, Peter; Cordwell, Stuart; Whitchurch, Cynthia; Manos, Jim

2011-01-01

Pseudomonas aeruginosa, the leading cause of morbidity and mortality in people with cystic fibrosis (CF), adapts for survival in the CF lung through both mutation and gene expression changes. Frequent clonal strains such as the Australian Epidemic Strain-1 (AES-1), have increased ability to establish infection in the CF lung and to superimpose and replace infrequent clonal strains. Little is known about the factors underpinning these properties. Analysis has been hampered by lack of expression array templates containing CF-strain specific genes. We sequenced the genome of an acute infection AES-1 isolate from a CF infant (AES-1R) and constructed a non-redundant micro-array (PANarray) comprising AES-1R and seven other sequenced P. aeruginosa genomes. The unclosed AES-1R genome comprised 6.254Mbp and contained 6957 putative genes, including 338 not found in the other seven genomes. The PANarray contained 12,543 gene probe spots; comprising 12,147 P. aeruginosa gene probes, 326 quality-control probes and 70 probes for non-P. aeruginosa genes, including phage and plant genes. We grew AES-1R and its isogenic pair AES-1M, taken from the same patient 10.5 years later and not eradicated in the intervening period, in our validated artificial sputum medium (ASMDM) and used the PANarray to compare gene expression of both in duplicate. 675 genes were differentially expressed between the isogenic pairs, including upregulation of alginate, biofilm, persistence genes and virulence-related genes such as dihydroorotase, uridylate kinase and cardiolipin synthase, in AES-1M. Non-PAO1 genes upregulated in AES-1M included pathogenesis-related (PAGI-5) genes present in strains PACS2 and PA7, and numerous phage genes. Elucidation of these genes' roles could lead to targeted treatment strategies for chronically infected CF patients.

Influence of contact force on voltage mapping: A combined magnetic resonance imaging and electroanatomic mapping study in patients with tetralogy of Fallot.

PubMed

Teijeira-Fernandez, Elvis; Cochet, Hubert; Bourier, Felix; Takigawa, Masateru; Cheniti, Ghassen; Thompson, Nathaniel; Frontera, Antonio; Camaioni, Claudia; Massouille, Gregoire; Jalal, Zakaria; Derval, Nicolas; Iriart, Xavier; Denis, Arnaud; Hocini, Meleze; Haissaguerre, Michel; Jais, Pierre; Thambo, Jean-Benoit; Sacher, Frederic

2018-03-20

Voltage criteria for ventricular mapping have been obtained from small series of patients and prioritizing high specificity. The purpose of this study was to analyse the potential influence of contact force (CF) on voltage mapping and to define voltage cutoff values for right ventricular (RV) scar using the tetralogy of Fallot as a model of transmural RV scar and magnetic resonance imaging (MRI) as reference. Fourteen patients (age 32.6 ± 14.3 years; 5 female) with repaired tetralogy of Fallot underwent high-resolution cardiac MRI (1.25 × 1.25 × 2.5 mm). Scar, defined as pixels with intensity >50% maximum, was mapped over the RV geometry and merged within the CARTO system to RV endocardial voltage maps acquired using a 3.5-mm ablation catheter with CF technology (SmartTouch, Biosense Webster). In total, 2446 points were analyzed, 915 within scars and 1531 in healthy tissue according to MRI. CF correlated to unipolar (ρ = 0.186; P <.001) and bipolar voltage in healthy tissue (ρ = 0.245; P <.001) and in scar tissue. Receiver operating characteristic curve analysis excluding points with very low CF (<5g) identified optimal voltage cutoffs of 5.19 mV for unipolar voltage and 1.76 mV for bipolar voltage, yielding sensitivity/specificity of 0.89/0.85 and 0.9/0.9, respectively. CF is an important factor to be taken into account for voltage mapping. If good CF is applied, unipolar and bipolar voltage cutoffs of 5.19 mV and 1.76 mV are optimal for identifying RV scar on endocardial mapping with the SmartTouch catheter. Data on the diagnostic accuracy of different voltage cutoff values are provided. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Seasonality of acquisition of respiratory bacterial pathogens in young children with cystic fibrosis.

PubMed

Psoter, Kevin J; De Roos, Anneclaire J; Wakefield, Jon; Mayer, Jonathan D; Rosenfeld, Margaret

2017-06-09

Seasonal variations are often observed for respiratory tract infections; however, limited information is available regarding seasonal patterns of acquisition of common cystic fibrosis (CF)-related respiratory pathogens. We previously reported differential seasonal acquisition of Pseudomonas aeruginosa in young children with CF and no such variation for methicillin-susceptible Staphylococcus aureus acquisition. The purpose of this study was to describe and compare the seasonal incidence of acquisition of other respiratory bacterial pathogens in young children with CF. We conducted a retrospective study to describe and compare the seasonal incidence of methicillin-resistant Staphylococcus aureus (MRSA), Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Haemophilus influenzae acquisition in young CF patients residing in the U.S. using the Cystic Fibrosis Foundation National Patient Registry, 2003-2009. Log-linear overdispersed Poisson regression was used to evaluate seasonal acquisition of each of these pathogens. A total of 4552 children met inclusion criteria. During follow-up 910 (20%), 1161 (26%), 228 (5%), and 2148 (47%) children acquired MRSA, S. maltophilia, A. xylosoxidans and H. influenzae, respectively. Compared to winter season, MRSA was less frequently acquired in spring (Incidence Rate Ratio [IRR]: 0.79; 95% Confidence Interval [CI]: 0.65, 0.96) and summer (IRR: 0.69; 95% CI: 0.57, 0.84) seasons. Similarly, a lower rate of A. xylosoxidans acquisition was observed in spring (IRR: 0.59; 95% CI: 0.39, 0.89). For H. influenzae, summer (IRR: 0.88; 95% CI: 0.78, 0.99) and autumn (IRR: 0.78; 95% CI: 0.69, 0.88) seasons were associated with lower acquisition rates compared to winter. No seasonal variation was observed for S. maltophilia acquisition. Acquisition of CF-related respiratory pathogens displays seasonal variation in young children with CF, with the highest rate of acquisition for most pathogens occurring in the winter. Investigation of factors underlying these observed associations may contribute to our understanding of the aetiology of these infections and guide future infection control strategies.

Influence of water chemistry on the acute toxicity of copper and zinc to the cladoceran Ceriodaphnia cf dubia.

PubMed

Hyne, Ross V; Pablo, Fleur; Julli, Moreno; Markich, Scott J

2005-07-01

This study determined the influence of key water chemistry parameters (pH, alkalinity, dissolved organic carbon [DOC], and hardness) on the aqueous speciation of copper and zinc and its relationship to the acute toxicity of these metals to the cladoceran Ceriodaphnia cf dubia. Immobilization tests were performed for 48-h in synthetic or natural waters buffered at various pH values from 5.5 to 8.4 (other chemical parameters held constant). The toxicity of copper to C. cf dubia decreased fivefold with increasing pH, whereas the toxicity of zinc increased fivefold with increasing pH. The effect of DOC on copper and zinc toxicity to C. cf dubia was determined using natural fulvic acid in the synthetic water. Increasing DOC was found to decrease linearly the toxicity of copper, with the mean effect concentration of copper that immobilized 50% of the cladocerans (EC50) value 45 times higher at 10 mg/L, relative to 0.1 mg/L DOC at pH 6.5. In contrast, the addition of 10 mg/L DOC only resulted in a very small (1.3-fold) reduction in the toxicity of zinc to C. cf dubia. Copper toxicity to C. cf dubia generally did not vary as a function of hardness, whereas zinc toxicity was reduced by a factor of only two, with an increase in water hardness from 44 to 374 mg CaCO3/L. Increasing bicarbonate alkalinity of synthetic waters (30-125 mg/L as CaCO3) decreased the toxicity of copper up to fivefold, which mainly could be attributed to the formation of copper-carbonate complexes, in addition to a pH effect. The toxicity of copper added to a range of natural waters with varying DOC content, pH, and hardness was consistent with the toxicity predicted using the data obtained from the synthetic waters.

Osteogenesis and cytotoxicity of a new Carbon Fiber/Flax/Epoxy composite material for bone fracture plate applications.

PubMed

Bagheri, Zahra S; Giles, Erica; El Sawi, Ihab; Amleh, Asma; Schemitsch, Emil H; Zdero, Radovan; Bougherara, Habiba

2015-01-01

This study is part of an ongoing program to develop a new CF/Flax/Epoxy bone fracture plate to be used in orthopedic trauma applications. The purpose was to determine this new plate's in-vitro effects on the level of bone formation genes, as well as cell viability in comparison with a medical grade metal (i.e. stainless steel) commonly employed for fabrication of bone plates (positive control). Cytotoxicity and osteogenesis induced by wear debris of the material were assessed using Methyl Tetrazolium (MTT) assay and reverse transcription polymerase chain reaction (RT-PCR) for 3 osteogenesis specific gene markers, including bone morphogenetic proteins (BMP2), runt-related transcription factor 2 (Runx2) and Osterix. Moreover, the Flax/Epoxy and CF/Epoxy composites were examined separately for their wettability properties by water absorption and contact angle (CA) tests using the sessile drop technique. The MTT results for indirect and direct assays indicated that the CF/Flax/Epoxy composite material showed comparable cell viability with no cytotoxicity at all incubation times to that of the metal group (p≥0.05). Osteogenesis test results showed that the expression level of Runx2 marker induced by CF/Flax/Epoxy were significantly higher than those induced by metal after 48 h (p=0.57). Also, the Flax/Epoxy composite revealed a hydrophilic character (CA=68.07°±2.05°) and absorbed more water up to 17.2% compared to CF/Epoxy, which reached 1.25% due to its hydrophobic character (CA=93.22°±1.95°) (p<0.001). Therefore, the new CF/Flax/Epoxy may be a potential candidate for medical applications as a bone fracture plate, as it showed similar cell viability with no negative effect on gene expression levels responsible for bone formation compared to medical grade stainless steel. Copyright © 2014 Elsevier B.V. All rights reserved.

Pseudomonas aeruginosa AES-1 Exhibits Increased Virulence Gene Expression during Chronic Infection of Cystic Fibrosis Lung

PubMed Central

Naughton, Sharna; Parker, Dane; Seemann, Torsten; Thomas, Torsten; Turnbull, Lynne; Rose, Barbara; Bye, Peter; Cordwell, Stuart; Whitchurch, Cynthia; Manos, Jim

2011-01-01

Pseudomonas aeruginosa, the leading cause of morbidity and mortality in people with cystic fibrosis (CF), adapts for survival in the CF lung through both mutation and gene expression changes. Frequent clonal strains such as the Australian Epidemic Strain-1 (AES-1), have increased ability to establish infection in the CF lung and to superimpose and replace infrequent clonal strains. Little is known about the factors underpinning these properties. Analysis has been hampered by lack of expression array templates containing CF-strain specific genes. We sequenced the genome of an acute infection AES-1 isolate from a CF infant (AES-1R) and constructed a non-redundant micro-array (PANarray) comprising AES-1R and seven other sequenced P. aeruginosa genomes. The unclosed AES-1R genome comprised 6.254Mbp and contained 6957 putative genes, including 338 not found in the other seven genomes. The PANarray contained 12,543 gene probe spots; comprising 12,147 P. aeruginosa gene probes, 326 quality-control probes and 70 probes for non-P. aeruginosa genes, including phage and plant genes. We grew AES-1R and its isogenic pair AES-1M, taken from the same patient 10.5 years later and not eradicated in the intervening period, in our validated artificial sputum medium (ASMDM) and used the PANarray to compare gene expression of both in duplicate. 675 genes were differentially expressed between the isogenic pairs, including upregulation of alginate, biofilm, persistence genes and virulence-related genes such as dihydroorotase, uridylate kinase and cardiolipin synthase, in AES-1M. Non-PAO1 genes upregulated in AES-1M included pathogenesis-related (PAGI-5) genes present in strains PACS2 and PA7, and numerous phage genes. Elucidation of these genes' roles could lead to targeted treatment strategies for chronically infected CF patients. PMID:21935417

Implementing groundwater extraction in life cycle impact assessment: characterization factors based on plant species richness for The Netherlands.

PubMed

van Zelm, Rosalie; Schipper, Aafke M; Rombouts, Michiel; Snepvangers, Judith; Huijbregts, Mark A J

2011-01-15

An operational method to evaluate the environmental impacts associated with groundwater use is currently lacking in life cycle assessment (LCA). This paper outlines a method to calculate characterization factors that address the effects of groundwater extraction on the species richness of terrestrial vegetation. Characterization factors (CF) were derived for The Netherlands and consist of a fate and an effect part. The fate factor equals the change in drawdown due to a change in groundwater extraction and expresses the amount of time required for groundwater replenishment. It was obtained with a grid-specific steady-state groundwater flow model. Effect factors were obtained from groundwater level response curves of potential plant species richness, which was constructed based on the soil moisture requirements of 625 plant species. Depending on the initial groundwater level, effect factors range up to 9.2% loss of species per 10 cm of groundwater level decrease. The total Dutch CF for groundwater extraction depended on the value choices taken and ranged from 0.09 to 0.61 m(2)·yr/m(3). For tap water production, we showed that groundwater extraction can be responsible for up to 32% of the total terrestrial ecosystem damage. With the proposed approach, effects of groundwater extraction on terrestrial ecosystems can be systematically included in LCA.

Perceived needs for different components in a rehabilitation program among cancer survivors with chronic fatigue compared to survivors without chronic fatigue.

PubMed

Gjerset, Gunhild M; Loge, Jon H; Kiserud, Cecilie E; Fosså, Sophie D; Gudbergsson, Sævar B; Oldervoll, Line M; Wisløff, Torbjørn; Thorsen, Lene

2017-02-01

Knowledge about the user' needs is important to develop targeted rehabilitation for cancer patients with chronic fatigue (CF). The aims of the study were to examine prevalence of CF in cancer survivors attending an one-week inpatient educational program (IEP) and to identify characteristics of those with CF. Further to examine the perceived needs for different components in a rehabilitation program, need of complex rehabilitation (at least two components) and aspects of health-related quality of life (HRQoL) among survivors with CF versus those without CF. Cancer survivors ≥18 years, diagnosed with different types of cancer within the last 10 years and attending a one-week IEP were invited to this cross-sectional study. CF was assessed by the Fatigue Questionnaire, perceived needs by asking a question about needs for different components in a rehabilitation program and HRQoL was assessed by The Medical Outcomes Study Short Form 36. Of 564 participants, 45% reported CF. Breast cancer, mixed cancer types (including small groups with different cancer types) and comorbidities increased the risk for having CF. Compared to participants without CF, the participants with CF reported more frequently need for physical training (86% vs. 65%, p < 0.001), physiotherapy (71% vs. 55%, p < 0.001) and nutrition counseling (68% vs. 53%, p = 0.001). Among participants with CF, 75% reported need for three or more components whereas 54% reported need for the same number of components among those without CF (p < 0.001). Almost half of the cancer survivors attending the IEP had CF. Physical training, physiotherapy and nutrition counseling were the most frequently reported needs and significantly more often observed in participants with CF than without CF. A higher percentage of those with CF reported need for a complex rehabilitation compared to those without CF. More research is necessary to obtain more knowledge to further make targeted programs to better match cancer survivors' needs.

Postnatal airway growth in cystic fibrosis piglets.

PubMed

Adam, Ryan J; Abou Alaiwa, Mahmoud H; Bouzek, Drake C; Cook, Daniel P; Gansemer, Nicholas D; Taft, Peter J; Powers, Linda S; Stroik, Mallory R; Hoegger, Mark J; McMenimen, James D; Hoffman, Eric A; Zabner, Joseph; Welsh, Michael J; Meyerholz, David K; Stoltz, David A

2017-09-01

Mutations in the gene encoding the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) anion channel cause CF. The leading cause of death in the CF population is lung disease. Increasing evidence suggests that in utero airway development is CFTR-dependent and that developmental abnormalities may contribute to CF lung disease. However, relatively little is known about postnatal CF airway growth, largely because such studies are limited in humans. Therefore, we examined airway growth and lung volume in a porcine model of CF. We hypothesized that CF pigs would have abnormal postnatal airway growth. To test this hypothesis, we performed CT-based airway and lung volume measurements in 3-wk-old non-CF and CF pigs. We found that 3-wk-old CF pigs had tracheas of reduced caliber and irregular shape. Their bronchial lumens were reduced in size proximally but not distally, were irregularly shaped, and had reduced distensibility. Our data suggest that lack of CFTR results in aberrant postnatal airway growth and development, which could contribute to CF lung disease pathogenesis. NEW & NOTEWORTHY This CT scan-based study of airway morphometry in the cystic fibrosis (CF) postnatal period is unique, as analogous studies in humans are greatly limited for ethical and technical reasons. Findings such as reduced airway lumen area and irregular caliber suggest that airway growth and development are CF transmembrane conductance regulator-dependent and that airway growth defects may contribute to CF lung disease pathogenesis. Copyright © 2017 the American Physiological Society.

Reactivation of the chloroplast CF1-ATPase beta subunit by trace amounts of the CF1 alpha subunit suggests a chaperonin-like activity for CF1 alpha.

PubMed

Avni, A; Avital, S; Gromet-Elhanan, Z

1991-04-25

Incubation of tobacco and lettuce thylakoids with 2 M LiCl in the presence of MgATP removes the beta subunit from their CF1-ATPase (CF1 beta) together with varying amounts of the CF1 alpha subunit (CF1 alpha). These 2 M LiCl extracts, as with the one obtained from spinach thylakoids (Avital, S., and Gromet-Elhanan, Z. (1991) J. Biol. Chem. 266, 7067-7072), could form active hybrid ATPases when reconstituted into inactive beta-less Rhodospirillum rubrum chromatophores. Pure CF1 beta fractions that have been isolated from these extracts could not form such active hybrids by themselves, but could do so when supplemented with trace amounts (less than 5%) of CF1 alpha. A mitochondrial F1-ATPase alpha subunit was recently reported to be a heat-shock protein, having two amino acid sequences that show a highly conserved identity with sequences found in molecular chaperones (Luis, A. M., Alconada, A., and Cuezva, J. M. (1990) J. Biol. Chem. 265, 7713-7716). These sequences are also conserved in CF1 alpha isolated from various plants, but not in F1 beta subunits. The above described reactivation of CF1 beta by trace amounts of CF1 alpha could thus be due to a chaperonin-like function of CF1 alpha, which involves the correct, active folding of isolated pure CF1 beta.

Factors affecting ozone sensitivity of tobacco Bel-W3 seedlings.

PubMed

Cheng, Ji-Fang; Sun, En-Jang

2013-12-01

Since 1962, the tobacco variety Nicotiana tabacum cv. Bel-W3 has been used worldwide as an ozone (O3) bio-indicator. The use of indicator plants to monitor O3 pollution has proven problematic when trying to correlate the severity of injury to ambient O3 concentration. The aim of the present study was to study factors affecting the O3 sensitivity of Nicotiana tabacum cv. Bel-W3 seedlings. In chronic O3 pre-exposure tests, tobacco plants were cultured from seeds in charcoal-filtered air (CF) and noncharcoal-filtered ambient air (NF) for 21 days. During these periods, the mean O3 concentrations of the CF and NF treatments were 5.5 ± 0.2 and 14.7 ± 0.4 ppb h -1 , respectively (p < 0.001). At the end of the culturing period, no O3-induced foliar injury was observed in any of the plants. The O3 sensitivity of the tobacco plants was determined by exposing the plants to 150 ppb O3 for 8 hours in a fumigation chamber. The leaf injury index percentages (LII%) of indicator plants via the CF and NF treatments were 58.0 ± 3.2% and 43.1 ± 4.0%, respectively (p < 0.01). Twenty-one-day-old tobacco seedlings grown in NF air were used to test the effects of exposed leaves on O3 sensitivity. After removing the cotyledons and all true leaves, the NF seedlings with their apical buds intact were transferred to CF air. After another 7 days of culturing, the newly developed leaves were approximately 1 cm in length. After O3 treatment, the LII% values of the newly developed leaves from the untreated and defoliated seedlings were 2.5 ± 1.7% and 27.6 ± 1.3%, respectively (p < 0.001). In acute O3 exposure tests, 21-day-old seedlings grown in CF air were fumigated with 150 ppb O3 for 8 hours in one day or for 4 hours/day in two consecutive days. The LII% values for the two groups were 63.5 ± 7.4% and 20.1 ± 4.3%, respectively (p < 0.001). The present findings suggest that plant pre-exposure to O3 is a critical factor influencing O3 sensitivity and that exposed leaves obtain acquired tolerance against O3 injury later on.

A Conceptual Framework for Barriers to the Recruitment and Retention of Rural CVD Participants in Behavior Intervention Trials.

PubMed

Young, Lufei; Montgomery, Melody; Barnason, Sue; Schmidt, Cindy; Do, Van

2015-08-01

Rural residents diagnosed with cardiovascular disease (CVD) or with CVD-related risks are underrepresented in behavioral intervention trials based on an extensive review of published studies. The low participation rate of rural residents weakens both the internal and external validity of published studies. Moreover, compared to urban residents, limited research exists to describe the unique barriers that limit the participation of rural residents in behavioral intervention trials. The purpose of this review is to identify a conceptual framework (CF) underpinning common barriers faced by rural CVD patients to enroll in behavioral intervention trials. We conducted a literature review using several electronic databases to obtain a representative sample of research articles, synthesized the evidence, and developed a CF to explain the barriers that may affect the research participation rate of rural residents with CVD or related risks. We found our evidence-based CF well explained the barriers for rural CVD patients to take part in behavioral intervention trials. Besides contextual factors (i.e. patient, community and research levels), other common factors impacting rural patients' intent to enroll are lack of awareness and understanding about behavioral trials, limited support from their healthcare providers and social circles, unfavorable attitudes, and the lack of opportunity to participating research. The findings demonstrate the evidence-based model consisting of interlinked multi-level factors may help our understanding of the barriers encountered by rural CVD patients participating interventions to promote behavioral change. The implication for researchers is that identifying and developing strategies to overcome the barriers precedes conducting studies in rural communities.

Preparation & characterization of SiO2 interface layer by dip coating technique on carbon fibre for Cf/SiC composites

NASA Astrophysics Data System (ADS)

Kumar, Kundan; Jariwala, C.; Pillai, R.; Chauhan, N.; Raole, P. M.

2015-08-01

Carbon fibres (Cf) are one of the most important reinforced materials for ceramic matrix composites such as Cf - SiC composites and they are generally sought for high temperature applications in as space application, nuclear reactor and automobile industries. But the major problem arise when Cf reinforced composites exposed to high temperature in an oxidizing environment, Cf react with oxygen and burnt away. In present work, we have studied the effect of silica (SiO2) coating as a protective coating on Cf for the Cf / SiC composites. The silica solution prepared by the sol-gel process and coating on Cf is done by dip coating technique with varying the withdrawing speed i.e. 2, 5, 8 mm/s with fixed dipping cycle (3 Nos.). The uniform silica coating on the Cf is shown by the Scanning Electron Microscope (SEM) analysis. The tensile test shows the increase in tensile strength with respect to increase in withdrawing speed. The isothermal oxidation analysis confirmed enhancement of oxidation resistance of silica coated Cf as compared tothe uncoated Cf.

76 FR 14796 - Airworthiness Directives; General Electric Company CF6-45 and CF6-50 Series Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

... Airworthiness Directives; General Electric Company CF6-45 and CF6-50 Series Turbofan Engines AGENCY: Federal... airworthiness directive (AD) for General Electric Company (GE) CF6-45 and CF6-50 series turbofan engines. That..., and MD-10- 30F. The commenter stated that the proposed AD only listed these airplanes as a series. We...

Direct Carbon Conversion: Review of Production and Electrochemical Conversion of Reactive Carbons, Economics and Potential Impact on the Carbon Cycle

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

Cooper, J F; Cherepy, N; Upadhye, R

Concerns over global warning have motivated the search for more efficient technologies for electric power generation from fossil fuels. Today, 90% of electric power is produced from coal, petroleum or natural gas. Higher efficiency reduces the carbon dioxide emissions per unit of electric energy. Exercising an option of deep geologic or ocean sequestration for the CO{sub 2} byproduct would reduce emissions further and partially forestall global warming. We introduce an innovative concept for conversion of fossil fuels to electricity at efficiencies in the range of 70-85% (based on standard enthalpy of the combustion reaction). These levels exceed the performance ofmore » common utility plants by up to a factor of two. These levels are also in excess of the efficiencies of combined cycle plants and of advanced fuel cells now operated on the pilot scale. The core of the concept is direct carbon conversion a process that is similar to that a fuel cell but differs in that synthesized forms of carbon, not hydrogen, are used as fuel. The cell sustains the reaction, C + O{sub 2} = CO{sub 2} (E {approx} 1.0 V, T = 800 C). The fuel is in the form of fine particulates ({approx}100 nm) distributed by entrainment in a flow of CO{sub 2} to the cells to form a slurry of carbon in the melt. The byproduct stream of CO{sub 2} is pure. It affords the option of sequestration without additional separation costs, or can be reused in secondary oil or gas recovery. Our experimental program has discovered carbon materials with orders of magnitude spreads in anode reactivity reflected in cell power density. One class of materials yields energy at about 1 kW/m{sup 2} sufficiently high to make practical the use of the cell in electric utility applications. The carbons used in such cells are highly disordered on the nanometer scale (2-30 nm), relative to graphite. Such disordered or turbostratic carbons can be produced by controlled pyrolysis (thermal decomposition) of hydrocarbons extracted from coal, petroleum or natural gas. For coal and lignite, such hydrocarbons may be produced by cyclic hydrogenation (hydropyrolysis), with the recycle of the hydrogen intermediate following pyrolysis. Starting with common CH{sub x} feedstock for carbon black manufacture, the ash entrained into the carbon (<0.03%) does not jeopardize cell life or enter into the economic estimates for power generation. The value of carbon (relative to hydrogen) as an electrochemical fuel derives from thermodynamic aspects of the C/O{sub 2} reaction. First, the entropy change of the C/O{sub 2} reaction is nearly zero, allowing theoretical efficiencies ({Delta}G(T)/{Delta}H{sub i298}) of 100% (cf. H{sub 2}/O{sub 2} theoretical efficiency of 70%). Second, the thermodynamic activity of the carbon fuel and the CO{sub 2} product are spatially and temporally invariant. This allows 100% utilization of the carbon fuel in single pass (cf. hydrogen utilizations of 75-85%). The carbodmelt slurry is non-explosive at operating temperatures. The total energy efficiency for the C/O{sub 2} is roughly 80% for cell operation at practical rates. In summary, what gives this route its fundamental advantage in energy conversion is that it derives the greatest possible fraction of energy of the fossil resource from an electrochemical reaction (C+O{sub 2} = CO{sub 2}) that is comparatively simple to operate at efficiencies of 80%, in a single-pass cell configuration without bottoming turbine cycles.« less