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Παρασκευή 23 Φεβρουαρίου 2018

A novel approach in red mud neutralization using cow dung

Abstract

In this study, cow dung was identified as a neutralizing agent for red mud (RM). Present research estimated a significant reduction in pH value of red mud (10 g) from 10.28 to 8.15 and reduction in alkalinity of ~148 mg/L from ~488 mg/L by adding 80 g of cow dung in 40 days of anaerobic condition. XRD results exhibit a high intensity of quartz and found new compound, the calcium carbide. The acid neutralizing capacity (ANC) of NRM reduces to ~0.87 from ~1.506 mol H+/kg. Based on the resultant research, present study proposes cow dung as an efficient neutralizing agent for reducing the pH and alkalinity in the red mud.



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Disparity in breast cancer mortality by age and geography in 10 racially diverse US cities

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Dominique Sighoko, Bijou R. Hunt, Bethliz Irizarry, Karriem Watson, David Ansell, Anne Marie Murphy
ObjectivesAssess geographic variation in breast cancer racial mortality disparity by age cohorts in US and ten cities with large African American populations.MethodsNon-Hispanic Black (NHB) and Non-Hispanic White (NHW) female breast cancer mortality rates and NHB:NHW rate ratio (RR) (disparity) were calculated by four age group categories: <40, 40–49, 50–64 and 65+ with time period 1999–2013.ResultsIn all 10 cities and the US, the most pronounced breast cancer disparities, measured by RR, were seen among younger women. In age group <40, the RR ranges from 1.71 in Houston to 5.37 in Washington, DC. For age group 50–64, the disparity was less pronounced, ranging from 1.24 in New York to 1.72 in Chicago. For 65+ age group, there was wide city to city variation in breast cancer mortality disparity. Three cities had higher mortality for NHW compared to NHB; Baltimore 0.78, Washington DC 0.94 and New York 0.98. One city had no statistically significant racial variation in breast cancer mortality in this age group and six cities had increased NHB: NHW mortality disparities.ConclusionsWhile the mortality rate for breast cancer is lower among younger women, the NHB:NHW disparities, as measured by rate ratios, are most pronounced in these age groups. Given the absence of available data regarding incidence, stage and subtypes, further research is necessary and such research is important, given the possible policy implications of these results with respect to screening guidelines and coverage for mammography and breast cancer treatment in particular for younger NHB women.



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Incidence of malignant lymphoma in adolescents and young adults in the 58 counties of California with varying synthetic turf field density

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Archie Bleyer, Theresa Keegan
BackgroundCase reports of cancer among soccer players raised concerns that the crumb rubber infill in synthetic turf fields may cause malignant lymphoma. One prior epidemiologic study on the topic found no association.MethodsAn ecologic evaluation of county-level incidence of lymphomas by race/ethnicity and socioeconomic status for the state of California with data obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results Program. Synthetic turf field density by county was obtained from the Synthetic Turf Council. During 2000–2013, 7214 14- to 30-year-old Californians were diagnosed with malignant lymphoma.ResultsAnnual lymphoma county incidence trends were not associated with the county-level synthetic turf field density. None of 20 sub-analyses by race/ethnicity, sex and county median household income indicated a correlation of lymphoma incidence with synthetic turf field density. In California, there was no evidence at the county-level that synthetic turf fields are associated with an increased incidence of lymphoma in adolescents and young adults.ConclusionOur findings in the state with the greatest number of such fields and a large, diverse patient population are consistent with those of a prior study observing no association between individual-level exposures to turf fields and cancer incidence. Avoidance of synthetic turf fields for fear of increased cancer risk is not warranted.



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Maintenance proton pump inhibition therapy and risk of oesophageal cancer

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Nele Brusselaers, Lars Engstrand, Jesper Lagergren
BackgroundThe association of long-term use of proton pump inhibitors (PPIs) with oesophageal adenocarcinoma has been poorly defined. Our aim was to assess the risk of oesophageal cancer assessing confounding by indication.MethodsThis population-based cohort study included all 796,492 adults exposed to maintenance therapy with PPIs in Sweden in 2005–2012. Standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated to assess the risk of oesophageal adenocarcinoma (and squamous cell carcinoma as a comparison) among long-term PPI users relative to the corresponding background population. The different indications for maintenance PPI therapy were analysed separately.ResultsAmong all individuals using maintenance PPI therapy, the overall SIR of oesophageal adenocarcinoma was 3.93 (95% CI 3.63–4.24). The SIRs of adenocarcinoma were increased also among individuals without gastro-oesophageal reflux disease who used PPIs for indications not associated with any increased risk of oesophageal adenocarcinoma. For example, the SIRs among participants using maintenance PPI therapy because of maintenance treatment with non-steroidal anti-inflammatory drugs and aspirin were 2.74 (95% CI 1.96–3.71) and 2.06 (95% CI 1.60–2.60), respectively. The SIRs of oesophageal squamous cell carcinoma were increased for most investigated indications, but to a lesser degree than for oesophageal adenocarcinoma.ConclusionIn conclusion, the long term use of PPIs is associated with increased risk of oesophageal adenocarcinoma in the absence of other risk factors. Long term use of PPIs should be addressed with caution.



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Impact of metformin on gastric adenocarcinoma survival: A Belgian population based study

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Olivia Lacroix, Alexandra Couttenier, Evelien Vaes, Chris R. Cardwell, Harlinde De Schutter, Annie Robert
BackgroundPreclinical studies have shown anticancer activities of metformin in gastric cancer and a recent epidemiological study showed a decrease in recurrence and mortality of gastric cancer in metformin users. This study aimed to assess the impact of metformin on gastric cancer survival in diabetic patients at a Belgian population level.MethodsWe conducted an observational, population-based study by linking data of the Belgian Cancer Registry with medical claims data coming from the health insurance companies for patients diagnosed with stage I to III gastric adenocarcinoma between 2006 and 2012. Information on gastric cancer-specific deaths was retrieved from mortality records collected by regional governments. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) and cancer-specific mortality (CSS).ResultsIn our population of 371 patients, a reduction in all-cause mortality was observed in metformin users (adjusted HR = 0.73, 95% CI: [0.52; 1.01], p = 0.06) but not for cancer specific mortality (adjusted HR = 0.86, 95% CI: [0.56; 1.33], p = 0.50). Pre-diagnosis exposure to metformin was associated with a significant improvement in OS (adjusted HR = 0.75, 95% CI: [0.57; 0.98], p = 0.04) that was not significant for CSS (adjusted HR = 0.89, 95% CI: [0.62; 1.28], p = 0.52). Moreover, no dose-response relationship between metformin use and either all-cause or cancer-specific mortality was observed.ConclusionIn the first population based study of metformin use in gastric cancer adenocarcinoma patients with previous diabetes, our findings suggest that metformin use might improve overall mortality. However, no such association was found for cancer-specific survival. Additional studies in other populations are required.



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Evaluation of data quality at the National Cancer Registry of Ukraine

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Anton Ryzhov, Freddie Bray, Jacques Ferlay, Zoya Fedorenko, Liudmyla Goulak, Yevgeniy Gorokh, Olena Soumkina, Ariana Znaor
BackgroundCancer notification has been mandatory in Ukraine since 1953, with the National Cancer Registry of Ukraine (NCRU) established in 1996. The aim of this study was to provide a comprehensive evaluation of the data quality at the NCRU.MethodsQualitative and semi-quantitative methods were used to assess the comparability, completeness, validity and timeliness of cancer incidence data from the NCRU for the period 2002–2012.ResultsCancer registration procedures at the NCRU are in accordance with international standards and recommendations. Semi-quantitative methods suggested the NCRU's data was reasonably complete, although decreases in age-specific incidence and mortality rates in the elderly indicated some missing cases at older ages. The proportion of microscopically-verified cases increased from 73.6% in 2002 to 82.3% in 2012, with death-certificate-only (DCO) proportions stable at around 0.1% and unknown stage recorded in 9.6% of male and 7.5% of female solid tumours. Timeliness was considered acceptable, with reporting >99% complete within a turn-around time of 15 months.ConclusionWhile timely reporting of national data reflects the advantages of a mandatory data collection system, a low DCO% and observed age-specific declines suggest possible underreporting of incidence and mortality data, particularly at older ages. Overall, the evaluation indicates that the data are reasonably comparable and thus may be used to describe the magnitude of the cancer burden in Ukraine. Given its central role in monitoring and evaluation of cancer control activities, ensuring the sustainability of NCRU operations throughout the process of healthcare system reform is of utmost importance.



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Morphological MR features and quantitative ADC evaluation in invasive breast cancer: Correlation with prognostic factors

Publication date: July–August 2018
Source:Clinical Imaging, Volume 50
Author(s): Francesca Boria, Corrado Tagliati, Silvia Baldassarre, Paola Ercolani, Elisabetta Marconi, Barbara Franca Simonetti, Alfredo Santinelli, Gian Marco Giuseppetti
ObjectiveAssess the correlation between MRI characteristics of invasive breast cancer and tumor prognostic features.Materials and methods95 women with invasive breast cancer underwent pre-treatment MR. Morphological findings and quantitative ADC were retrospectively evaluated.ResultsSmaller size, round shape, spiculated margins and homogeneous internal enhancement pattern on dynamic MRI were independently associated with established predictors of good prognosis, while larger size and rim enhancement pattern were related to predictors of poor prognosis. A positive correlation was observed between ADC value and clinical stage.ConclusionsMRI may be a useful tool for breast cancer aggressiveness prediction and for guiding subsequent clinical-therapeutic management.



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Pictorial review: Renal ultrasound

Publication date: September–October 2018
Source:Clinical Imaging, Volume 51
Author(s): Mittul Gulati, Justin Cheng, Jerry T. Loo, Matt Skalski, Harshawn Malhi, Vinay Duddalwar
Ultrasound (US) is the first-line imaging modality for evaluating azotemic patients for urinary obstruction and renal size. US is also valuable for distinguishing congenital variants and simple cystic lesions from renal masses. Doppler US is effective in detection of renal calculi and evaluation of vascular pathology. Unfortunately, renal US is limited in distinguishing causes of medical renal disease. The kidneys have a complex internal architecture with a highly variable appearance on US. This article illustrates non-neoplastic renal conditions, including normal and embryological variants, parenchymal, cystic, and vascular diseases. Renal infections, calcifications, and trauma and fluid collections are also discussed, with an emphasis on distinguishing US features and pathophysiology.



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The relationship between in vivo nasal drug clearance and in vitro nasal mucociliary clearance: Application to the prediction of nasal drug absorption

Publication date: 30 May 2018
Source:European Journal of Pharmaceutical Sciences, Volume 117
Author(s): Daisuke Inoue, Akiko Tanaka, Shunsuke Kimura, Akiko Kiriyama, Hidemasa Katsumi, Akira Yamamoto, Ken-ichi Ogawara, Toshikiro Kimura, Kazutaka Higaki, Reiko Yutani, Toshiyasu Sakane, Tomoyuki Furubayashi
Drug absorption after nasal application is dependent on drug clearance from the nasal cavity, which is determined by nasal mucociliary clearance (MC). We previously developed an in vitro method to evaluate MC via the translocation velocity of fluorescent microspheres (VFMS) applied to excised rat nasal mucosa. In the present study, the relationship between in vivo nasal MC and in vitro VFMS was examined to optimize our PK model for the prediction of nasal drug absorption. Appropriate inhibitors (propranolol and atropine) and enhancers (terbutaline and acetylcholine chloride) of MC were utilized to modify MC. In vivo clearance of drug from the nasal cavity was determined from the disappearance of fluorescent microspheres (FMS) from the nasal cavity following nasal application to rats. The first order elimination rate constant, kmc, was determined from the disappearance profiles of FMS. kmc was decreased to 35.8% by propranolol and 52.6% by atropine, but increased to 117% by terbutaline and 168% by acetylcholine chloride. A significant linear correlation was observed between kmc and VFMS (r2 = 0.9745, p < 0.001). These results indicate that in vivo kmc can be estimated from the in vitro parameter, VFMS. By introducing linear correlation into our PK model, nasal drug absorption may be precisely estimated, even with changes in MC.

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Incidental hepatic lesions detected on breast MRI: Rate of malignancy and implications for utilization

Publication date: September–October 2018
Source:Clinical Imaging, Volume 51
Author(s): Priya K. Shah, Ilana A. Kafer, Gregory M. Grimaldi
ObjectiveThe objective of this study was to determine the rate of malignancy in incidentally detected T2 hyperintense hepatic lesions at breast MRI.MethodsIncidental hepatic lesions identified during breast MRI, for which abdominal imaging was recommended, were retrospectively analyzed.ResultsOf the hepatic lesions, 97.3% were benign, and 2.7% were malignant, with a significant association between indication for the breast MRI and the malignancy status of the hepatic lesion (Fisher's Exact, P < 0.0142).ConclusionOur initial experience suggests the benign nature of incidentally detected T2 hyperintense hepatic lesions at breast MRI in women without a newly diagnosed breast cancer.



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CT-angiography of the aorta in patients with Marfan disease - High-pitch MDCT at different levels of tube voltage combined with Sinogram Affirmed Iterative Reconstruction

Publication date: September–October 2018
Source:Clinical Imaging, Volume 51
Author(s): P. Freyhardt, N. Solowjowa, G. Böning, J. Kahn, B. Aufmesser, P. Haage, F. Streitparth
ObjectivesAim of the study was the comparison of high-pitch dual-source CTA of the aorta acquired with different tube currents and methods of image reconstruction in patients with Marfan Disease (MFS).BackgroundPatients with MFS receive repeatedly CT examinations of the entire aorta what leads to high cumulative lifetime radiation doses. Routine clinical use of low-kV-protocols in combination with iterative reconstruction for imaging of the aorta is still limited although this approach may be of great benefit for patients in need of serial follow-up scans.Methods106 patients with MFS received CTA of the entire aorta in a 2nd generation dual-source Flash-CT at 120, 100 or 80 kV. 120 kV images were reconstructed with FBP, low-kV images with an IR algorithm (SAFIRE) at different noise reduction levels. CTDIvol, DLP and effective dose were analyzed. Quantitative image analysis included comparison of SNR, CNR and Noise levels. For qualitative analysis, two blinded readers assessed noise, contour delineation, contrast, overall image quality and diagnostic confidence.ResultsEffective dose was 9.4 (±1.5) mSv for 120 kV, 4.2 (±1.1) mSv for 100 kV and 1.9 (±0.42) mSv for 80 kV. 100 kV images showed the highest SNR and CNR values, followed by 80 kV and 120 kV. Qualitative image analysis showed the lowest scores for all evaluated aspects at 80 kV. Overall image quality and diagnostic confidence was excellent at all kV strengths.ConclusionsIn MFS patients low-kV CT protocols with IR allow for CTA of the entire aorta in excellent image quality and diagnostic confidence with a dose reduction of up to 80% compared to 120 kV. For baseline CT, we recommend 100 kV, for follow-up CT scans 80 kV as tube voltage.



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Magnetic resonance elastography to estimate brain stiffness: Measurement reproducibility and its estimate in pseudotumor cerebri patients

Publication date: September–October 2018
Source:Clinical Imaging, Volume 51
Author(s): Arunark Kolipaka, Peter A. Wassenaar, Sangmin Cha, Wael M. Marashdeh, Xiaokui Mo, Prateek Kalra, Bradley Gans, Brian Raterman, Eric Bourekas
This study determines the reproducibility of magnetic resonance elastography (MRE) derived brain stiffness in normal volunteers and compares it against pseudotumor patients before and after lumbar puncture (LP).MRE was performed on 10 normal volunteers for reproducibility and 14 pseudotumor patients before and after LP. During LP, opening and closing cerebrospinal fluid (CSF) pressures were recorded before and after removal of CSF and correlated to brain stiffness.Stiffness reproducibility was observed (r > 0.78; p < 0.008). Whole brain opening LP stiffness was significantly (p = 0.04) higher than normals, but no significant difference (p = 0.11) in closing LP measurements. No significant correlation was observed between opening and closing pressure and brain stiffness.

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Topically used corticosteroids: What is the big picture of drug product degradation?

Publication date: 30 May 2018
Source:European Journal of Pharmaceutical Sciences, Volume 117
Author(s): A.J.P. van Heugten, W. de Boer, W.S. de Vries, R.J. Pieters, H. Vromans
Corticosteroids are widely used in topical formulations such as creams (aqueous) and ointments (non-aqueous). The generally used corticosteroids show large molecular resemblance, where especially the 20-keto-21-hydroxyl group bound to the 17 carbon is important for their chemical stability. Oxidation in both aqueous and non-aqueous environment occurs for triamcinolone acetonide (TCA), hydrocortisone (HC) and desoximethasone (DS). Besides the 20-keto-21-hydroxyl group, TCA, HC and DS have different other moieties attached to the same C17. These moieties are shown to influence not only the type of degradation product formed but also the degradation kinetics. Seven degradation products are found in total and a degradation mechanism is proposed. Furthermore the transesterfication of betamethasone-17-valerate to betamethasone-21-valerate is shown to occur both in aqueous and non-aqueous environment. Finally, a comprehensive scheme of degradation pathways is presented that is applicable for both aqueous and non-aqueous formulations.

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Chitosan-based nanosystems and their exploited antimicrobial activity

Publication date: 30 May 2018
Source:European Journal of Pharmaceutical Sciences, Volume 117
Author(s): Diego Romano Perinelli, Laura Fagioli, Raffaella Campana, Jenny K.W. Lam, Wally Baffone, Giovanni Filippo Palmieri, Luca Casettari, Giulia Bonacucina
Chitosan is a biodegradable and biocompatible natural polysaccharide that has a wide range of applications in the field of pharmaceutics, biomedical, chemical, cosmetics, textile and food industry. One of the most interesting characteristics of chitosan is its antibacterial and antifungal activity, and together with its excellent safety profile in human, it has attracted considerable attention in various research disciplines. The antimicrobial activity of chitosan is dependent on a number of factors, including its molecular weight, degree of deacetylation, degree of substitution, physical form, as well as structural properties of the cell wall of the target microorganisms. While the sole use of chitosan may not be sufficient to produce an adequate antimicrobial effect to fulfil different purposes, the incorporation of this biopolymer with other active substances such as drugs, metals and natural compounds in nanosystems is a commonly employed strategy to enhance its antimicrobial potential. In this review, we aim to provide an overview on the different approaches that exploit the antimicrobial activity of chitosan-based nanosystems and their applications, and highlight the latest advances in this field.

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Improving sustained drug delivery from ophthalmic lens materials through the control of temperature and time of loading

Publication date: 30 May 2018
Source:European Journal of Pharmaceutical Sciences, Volume 117
Author(s): Ana Topete, Andreia S. Oliveira, A. Fernandes, T.G. Nunes, A.P. Serro, B. Saramago
Although the possibility of using drug-loaded ophthalmic lens to promote sustained drug release has been thoroughly pursued, there are still problems to be solved associated to the different alternatives. In this work, we went back to the traditional method of drug loading by soaking in the drug solution and tried to optimize the release profiles by changing the temperature and the time of loading. Two materials commercially available under the names of CI26Y and Definitive 50 were chosen. CI26Y is used for intraocular lenses (IOLs) and Definitive 50 for soft contact lenses (SCLs). Three drugs were tested: an antibiotic, moxifloxacin, and two anti-inflammatories, diclofenac and ketorolac. Sustained drug release from CI26Y disks for, at least 15 days, was obtained for moxifloxacin and diclofenac increasing the loading temperature up to 60 °C or extending the loading time till two months. The sustained release of ketorolac was limited to about 8 days. In contrast, drug release from Definitive 50 disks could not be improved by changing the loading conditions. An attempt to interpret the impact of the loading conditions on the drug release behavior was done using solid-state NMR and differential scanning calorimetry. These studies suggested the establishment of reversible, endothermic interactions between CI26Y and the drugs, moxifloxacin and diclofenac. The loading temperature had a slight effect on the mechanical and optical properties of drug loaded CI26Y samples, which still kept adequate properties to be used as IOL materials. The in vivo efficacy of CI26Y samples, drug loaded at 60 °C for two weeks, was predicted using a simplified mathematical model to estimate the drug concentration in the aqueous humor. The estimated concentrations were found to comply with the therapeutic needs, at least, for moxifloxacin and diclofenac.

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Systematic evaluation of common lubricants for optimal use in tablet formulation

Publication date: 30 May 2018
Source:European Journal of Pharmaceutical Sciences, Volume 117
Author(s): Shubhajit Paul, Changquan Calvin Sun
As an essential formulation component for large-scale tablet manufacturing, the lubricant preserves tooling by reducing die-wall friction. Unfortunately, lubrication also often results in adverse effects on tablet characteristics, such as prolonged disintegration, slowed dissolution, and reduced mechanical strength. Therefore, the choice of lubricant and its optimal concentration in a tablet formulation is a critical decision in tablet formulation development to attain low die-wall friction while minimizing negative impact on other tablet properties. Three commercially available tablet lubricants, i.e., magnesium stearate, sodium stearyl fumerate, and stearic acid, were systematically investigated in both plastic and brittle matrices to elucidate their effects on reducing die-wall friction, tablet strength, tablet hardness, tablet friability, and tablet disintegration kinetics. Clear understanding of the lubrication efficiency of commonly used lubricants as well as their impact on tablet characteristics would help future tablet formulation efforts.

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Impact of change of matrix crystallinity and polymorphism on ovalbumin release from lipid-based implants

Publication date: 30 May 2018
Source:European Journal of Pharmaceutical Sciences, Volume 117
Author(s): Luisa Duque, Martin Körber, Roland Bodmeier
The objectives of this study were to prepare lipid-based implants by hot melt extrusion (HME) for the prolonged release of ovalbumin (OVA), and to relate protein release to crystallinity and polymorphic changes of the lipid matrix. Two lipids, glycerol tristearate and hydrogenated palm oil, with different composition and degree of crystallinity were studied. Solid OVA was dispersed within the lipid matrixes, which preserved its stability during extrusion. This was partially attributed to a protective effect of the lipidic matrix. The incorporation of OVA decreased the mechanical strength of the implants prepared with the more crystalline matrix, glycerol tristearate, whereas it remained comparable for the hydrogenated palm oil because of stronger physical and non-covalent interactions between the protein and this lipid. This was also the reason for the faster release of OVA from the glycerol tristearate matrix when compared to the hydrogenated palm oil (8 vs. 28 weeks). Curing induced and increased crystallinity, and changes in the release rate, especially for the more crystalline matrix. In this case, both an increase and a decrease in release, were observed depending on the tempering condition. Curing at higher temperatures induced a melt-mediated crystallization and solid state transformation of the glycerol tristearate matrix and led to rearrangements of the inner structure with the formation of larger pores, which accelerated the release. In contrast, changes in the hydrogenated palm oil under the same curing conditions were less noticeable leading to a more robust formulation, because of less polymorphic changes over time. This study helps to understand the effect of lipid matrix composition and crystallinity degree on the performance of protein-loaded implants, and to establish criteria for the selection of a lipid carrier depending on the release profile desired.

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Investigation of supersaturation and in vitro permeation of the poorly water soluble drug ezetimibe

Publication date: 30 May 2018
Source:European Journal of Pharmaceutical Sciences, Volume 117
Author(s): Amani Alhayali, Mohammed Ali Selo, Carsten Ehrhardt, Sitaram Velaga
The interplay between supersaturation, precipitation and permeation characteristics of the poorly water-soluble drug ezetimibe (EZ) was investigated. Supersaturation and precipitation characteristics of EZ in the presence of Caco-2 cells were compared to those in a cell-free environment. The effect of the water-soluble polymer polyvinyl pyrrolidone (PVP-K30) on the supersaturation, precipitation and transport of EZ was also investigated and the amount of drug taken up by Caco-2 cells was quantified.A one-compartment setup without Caco-2 cells (i.e. in the wells of cell-culture plates) was used to mimic a non-sink in vitro dissolution chamber. The two-compartment Caco-2 cell monolayer setup (with apical and basolateral compartments) was used to investigate how the absorption of EZ affects supersaturation. EZ in varying degrees of supersaturation (DS; 10, 20, 30 and 40) was introduced into the one-compartment setup or the apical chamber of the two-compartment setup. Samples were collected at specific times to determine supersaturation, precipitation and permeation. At the end of the study, Caco-2 cells were lysed and the intracellular amount of EZ was quantified.In the one-compartment setup, a high DS was associated with rapid precipitation. Supersaturation was maintained for longer time periods and precipitation was lower in the presence of Caco-2 cells. There were no significant differences in the absorption rate of the drug, even at high concentrations on the apical side. Permeability coefficients for all supersaturated solutions (i.e. DS 10–40) were significantly (p < 0.05) different from those when EZ was present in crystalline form. Both concentrations of PVP-K30 (i.e. 0.05% and 0.1% w/v) improved solubility and supersaturation of EZ when added to the apical side, however, the increase in absorption at the higher concentration was not proportional. The amount of intracellular EZ increased with increasing DS in the apical side, until the saturation limit was reached in the cells (i.e. at DS 30 and higher).This study demonstrated that precipitation of EZ could be overestimated when supersaturation was investigated without the implementation of an absorption compartment in vitro, both in the absence and in the presence of polymer.

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Safety and clinical efficacy of tenvermectin, a novel antiparasitic 16-membered macrocyclic lactone antibiotics

Publication date: 30 May 2018
Source:European Journal of Pharmaceutical Sciences, Volume 117
Author(s): Chenzhong Fei, Rufeng She, Guiyu Li, Lifang Zhang, Wushun Fan, suhan Xia, Feiqun Xue
Tenvermectin (TVM) is a novel 16-membered macrocyclic lactone antibiotics, which contains component TVM A and TVM B. However there is not any report on safety and clinical efficacy of TVM for developing as a potential drug. In order to understand the part of safety and clinical efficacy of TVM, we conducted the acute toxicity test, the standard bacterial reverse mutation (Ames) test and the clinical deworming test. In the acute toxicity studies, TVM, TVM A and ivermectin (IVM) were administrated once by oral gavage to mice and rats. Results showed that the oral LD50 values of TVM, TVM A and IVM in mice were 74.41, 106.95 and 53.06 mg/kg respectively. The oral LD50 values of TVM and TVM A in rats were determined to be 164.22 and 749.34 mg/kg respectively. TVM and IVM are moderately toxic substances, meanwhile the TVM A belongs to low toxic compounds, implying that the acute toxicity is highly related to the length of side chain of TVM at position C25. In the Ames test, results showed that TVM did not induce mutagenicity in Salmonella typhimurium TA97a, TA98, TA100, TA102 and TA1535 with and without metabolic activation system, speculating that the mutagenicity is probably not related to the side chain at position C25 of 16-membered macrocyclic lactone antibiotics. In the efficacy trail of TVM against swine nematodes, growing pigs natural infection of Ascaris suum and Trichuris suis were treated with a single subcutaneous injection 0.3 mg/kg b.w.. Results showed that TVM and IVM had excellent effect in expelling Ascaris suum, and TVM had potential efficacy against Trichuris suis, however IVM had no effect on Trichuris suis. This study suggests that the side chain of TVM at position C25 may have important biological functions, which is one of the key sites of the studies on structure-activity relationship of 16-membered macrocyclic lactone compounds. TVM is a new compound exhibited some advantages worthy of developing.

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Safety evaluation of a human chimeric monoclonal antibody that recognizes the extracellular loop domain of claudin-2

Publication date: 30 May 2018
Source:European Journal of Pharmaceutical Sciences, Volume 117
Author(s): Yosuke Hashimoto, Tomoyuki Hata, Minoru Tada, Manami Iida, Akihiro Watari, Yoshiaki Okada, Takefumi Doi, Hiroki Kuniyasu, Kiyohito Yagi, Masuo Kondoh
Claudin-2 (CLDN-2), a pore-forming tight junction protein with a tetra-transmembrane domain, is involved in carcinogenesis and the metastasis of some cancers. Although CLDN-2 is highly expressed in the tight junctions of the liver and kidney, whether CLDN-2 is a safe target for cancer therapy remains unknown. We recently generated a rat monoclonal antibody (mAb, clone 1A2) that recognizes the extracellular domains of human and mouse CLDN-2. Here, we investigated the safety of CLDN-2-targeted cancer therapy by using 1A2 as a model therapeutic antibody. Because most human therapeutic mAbs are IgG1 subtype that can induce antibody-dependent cellular cytotoxicity, we generated a human–rat chimeric IgG1 form of 1A2 (xi-1A2). xi-1A2 activated Fcγ receptor IIIa in the presence of CLDN-2-expressing cells, indicating that xi-1A2 likely exerts antibody-dependent cellular cytotoxicity. At 24 h after its intravenous injection, xi-1A2 was distributed into the liver, kidney, and tumor tissues of mice bearing CLDN-2-expressing fibrosarcoma cells. Treatment of the xenografted mice with xi-1A2 attenuated tumor growth without apparent adverse effects, such as changes in body weight and biochemical markers of liver and kidney injury. These results support xi-1A2 as the lead candidate mAb for safe CLDN-2-targeted cancer therapy.

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Value of ictal and interictal epileptiform discharges and high frequency oscillations for delineating the epileptogenic zone in patients with focal cortical dysplasia

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Publication date: Available online 22 February 2018
Source:Clinical Neurophysiology
Author(s): C. Cuello-Oderiz, N. von Ellenrieder, R. Sankhe, A. Olivier, J. Hall, F. Dubeau, J. Gotman
ObjectivesThere are different neurophysiological markers of the Epileptogenic Zone (EZ), but their sensitivity and specificity for the EZ is not known in Focal Cortical Dysplasia (FCD) patients.MethodsWe studied patients with FCD who underwent stereoelectroencephalography (SEEG) and surgery. We marked in the SEEG: a) typical and atypical interictal epileptiform patterns, b) ictal onset patterns, and c) rates of ripples (80-250 Hz) and fast ripples (FRs) (>250 Hz). High frequency oscillations were marked automatically during one hour of deep sleep. Surgical outcome was defined as good (Engel I) or poor (Engel II-IV). We computed the sensitivity and, as a measure of specificity, the false positive rate to identify the EZ, and compared them across the different neurophysiological markers.ResultsWe studied 21 patients, 19 with FCD II. Ictal and typical interictal pattern were the markers with highest sensitivity, while the atypical interictal pattern had the lowest. We found no significant difference in specificity among markers. However, there is a tendency that FRs had the lowest false positive rate.ConclusionThe typical interictal pattern has the highest sensitivity. The clinical use of FRs is limited by their low sensitivity.SignificanceWe suggest to analyze the typical interictal pattern first. FRs should be analyzed in a second step. If, for instance, a focus with FRs and no typical interictal pattern is found, this area could be considered for resection.



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A novel, fast and efficient single-sensor automatic sleep-stage classification based on complementary cross-frequency coupling estimates

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Publication date: April 2018
Source:Clinical Neurophysiology, Volume 129, Issue 4
Author(s): Stavros I. Dimitriadis, Christos Salis, David Linden
ObjectiveLimitations of the manual scoring of polysomnograms, which include data from electroencephalogram (EEG), electro-oculogram (EOG), electrocardiogram (ECG) and electromyogram (EMG) channels have long been recognized. Manual staging is resource intensive and time consuming, and thus considerable effort must be spent to ensure inter-rater reliability. As a result, there is a great interest in techniques based on signal processing and machine learning for a completely Automatic Sleep Stage Classification (ASSC).MethodsIn this paper, we present a single-EEG-sensor ASSC technique based on the dynamic reconfiguration of different aspects of cross-frequency coupling (CFC) estimated between predefined frequency pairs over 5 s epoch lengths. The proposed analytic scheme is demonstrated using the PhysioNet Sleep European Data Format (EDF) Database with repeat recordings from 20 healthy young adults. We validate our methodology in a second sleep dataset.ResultsWe achieved very high classification sensitivity, specificity and accuracy of 96.2 ± 2.2%, 94.2 ± 2.3%, and 94.4 ± 2.2% across 20 folds, respectively, and also a high mean F1 score (92%, range 90–94%) when a multi-class Naive Bayes classifier was applied. High classification performance has been achieved also in the second sleep dataset.ConclusionsOur method outperformed the accuracy of previous studies not only on different datasets but also on the same database.SignificanceSingle-sensor ASSC makes the entire methodology appropriate for longitudinal monitoring using wearable EEG in real-world and laboratory-oriented environments.



http://ift.tt/2FoMtwh

Sodium-potassium pump assessment by submaximal electrical nerve stimulation

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Publication date: April 2018
Source:Clinical Neurophysiology, Volume 129, Issue 4
Author(s): Steven Hageman, Maria O. Kovalchuk, Boudewijn T.H.M. Sleutjes, Leonard J. van Schelven, Leonard H. van den Berg, Hessel Franssen
ObjectiveSodium-potassium pump dysfunction in peripheral nerve is usually assessed by determining axonal hyperpolarization following maximal voluntary contraction (MVC) or maximal electrical nerve stimulation. As MVC may be unreliable and maximal electrical stimulation too painful, we assessed if hyperpolarization can also be induced by submaximal electrical nerve stimulation.MethodsIn 8 healthy volunteers different submaximal electrical stimulus trains were given to the median nerve at the wrist, followed by 5 min assessment of thresholds for compound muscle action potentials of 20%, 40% or 60% of maximal.ResultsThreshold increase after submaximal electrical nerve stimulation was most prominent after an 8 Hz train of at least 5 min duration evoking submaximal CMAPs of 60%. It induced minimal discomfort and was not painful. Threshold increase after MVC was not significantly higher than this stimulus train.ConclusionsSubmaximal electrical stimulation evokes activity dependent hyperpolarization in healthy test subjects without causing significant discomfort.SignificanceSodium-potassium pump function may be assessed using submaximal electrical stimulation.



http://ift.tt/2ELDswg

BAG3 Overexpression and Cytoprotective Autophagy Mediate Apoptosis Resistance in Chemoresistant Breast Cancer Cells

Publication date: March 2018
Source:Neoplasia, Volume 20, Issue 3
Author(s): Chandan Kanta Das, Benedikt Linder, Florian Bonn, Florian Rothweiler, Ivan Dikic, Martin Michaelis, Jindrich Cinatl, Mahitosh Mandal, Donat Kögel
Target-specific treatment modalities are currently not available for triple-negative breast cancer (TNBC), and acquired chemotherapy resistance is a primary obstacle for the treatment of these tumors. Here we employed derivatives of BT-549 and MDA-MB-468 TNBC cell lines that were adapted to grow in the presence of either 5-Fluorouracil, Doxorubicin or Docetaxel in an aim to identify molecular pathways involved in the adaptation to drug-induced cell killing. All six drug-adapted BT-549 and MDA-MB-468 cell lines displayed cross resistance to chemotherapy and decreased apoptosis sensitivity. Expression of the anti-apoptotic co-chaperone BAG3 was notably enhanced in two thirds (4/6) of the six resistant lines simultaneously with higher expression of HSP70 in comparison to parental controls. Doxorubicin-resistant BT-549 (BT-549rDOX20) and 5-Fluorouracil-resistant MDA-MB-468 (MDA-MB-468r5-FU2000) cells were chosen for further analysis with the autophagy inhibitor Bafilomycin A1 and lentiviral depletion of ATG5, indicating that enhanced cytoprotective autophagy partially contributes to increased drug resistance and cell survival. Stable lentiviral BAG3 depletion was associated with a robust down-regulation of Mcl-1, Bcl-2 and Bcl-xL, restoration of drug-induced apoptosis and reduced cell adhesion in these cells, and these death-sensitizing effects could be mimicked with the BAG3/Hsp70 interaction inhibitor YM-1 and by KRIBB11, a selective transcriptional inhibitor of HSF-1. Furthermore, BAG3 depletion was able to revert the EMT-like transcriptional changes observed in BT-549rDOX20 and MDA-MB-468r5-FU2000 cells. In summary, genetic and pharmacological interference with BAG3 is capable to resensitize TNBC cells to treatment, underscoring its relevance for cell death resistance and as a target to overcome therapy resistance of breast cancer.



http://ift.tt/2CcHujH

Dynamics of the Intratumoral Immune Response during Progression of High-Grade Serous Ovarian Cancer

Publication date: March 2018
Source:Neoplasia, Volume 20, Issue 3
Author(s): Mandy Stanske, Stephan Wienert, Dan Cacsire Castillo-Tong, Caroline Kreuzinger, Ignace Vergote, Sandrijne Lambrechts, Hani Gabra, Charlie Gourley, Ram N. Ganapathi, Ivonne Kolaschinski, Jan Budczies, Jalid Sehouli, Ilary Ruscito, Carsten Denkert, Hagen Kulbe, Wolfgang Schmitt, Korinna Jöhrens, Ioana Braicu, Silvia Darb-Esfahani
PURPOSE: Tumor-infiltrating lymphocytes (TILs) have an established impact on the prognosis of high-grade serous ovarian carcinoma (HGSOC), however, their role in recurrent ovarian cancer is largely unknown. We therefore systematically investigated TIL densities and MHC class I and II (MHC1, 2) expression in the progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2 expression were evaluated by immunohistochemistry on tissue microarrays in 113 paired primary and recurrent HGSOC. TILs were quantified by image analysis. All patients had been included to the EU-funded OCTIPS FP7 project. RESULTS: CD3+, CD4+, CD8+ TILs and MHC1 and MHC2 expression showed significant correlations between primary and recurrent tumor levels (Spearman rho 0.427, 0.533, 0.361, 0.456, 0.526 respectively; P<.0001 each). Paired testing revealed higher CD4+ densities and MHC1 expression in recurrent tumors (Wilcoxon P=.034 and P=.018). There was also a shift towards higher CD3+ TILs levels in recurrent carcinomas when analyzing platinum-sensitive tumors only (Wilcoxon P=.026) and in pairs with recurrent tumor tissue from first relapse only (Wilcoxon P=.031). High MHC2 expression was the only parameter to be significantly linked to prolonged progression-free survival after first relapse (PFS2, log-rank P=.012). CONCLUSIONS: This is the first study that analyzed the development of TILs density and MHC expression in paired primary and recurrent HGSOC. The level of the antitumoral immune response in recurrent tumors was clearly dependent on the one in the primary tumor. Our data contribute to the understanding of temporal heterogeneity of HGSOC immune microenvironment and have implications for selection of samples for biomarker testing in the setting of immune-targeting therapeutics.



http://ift.tt/2BM56KT

Apoptosis Reversal Promotes Cancer Stem Cell-Like Cell Formation

Publication date: March 2018
Source:Neoplasia, Volume 20, Issue 3
Author(s): Yiyue Xu, Chun So, Hon-Ming Lam, Ming-Chiu Fung, Suk-Ying Tsang
It has long been a puzzle in cancer treatment that despite the initial appearance of apoptosis, the process could be reversed in some cancer cells and often results in more aggressive tumors and metastasis. The mechanism for this recurrence is yet unknown. Here we report that human mammary carcinoma cells induced to undergo apoptosis could recover with increased tumorigenicity in vitro and in vivo, and induced lymph node metastasis. Specifically, the reversed cells underwent epithelial-to-mesenchymal transitions in the primary tumors in situ, and mesenchymal-to-epithelial transitions in the metastatic cells. Flow cytometry confirmed an elevated percentage of cells carrying cancer stem cells (CSCs) markers (CD44+/CD24-) in the reversed breast cancer cell population, with hypomethylated CD44 promoters and hypermethylated CD24 promoters. More importantly, CSCs were generated anew from non-stem cancer cells after apoptosis reversal possibly through epigenetic modifications. The results from this study can open doors to discovering more effective cancer treatments by suppressing apoptosis reversal.



http://ift.tt/2Cg8v5B

Effect of platelets-rich plasma on scalp hair diameter

Summary

Objectives

To measure the effects of platelet-rich plasma (PRP) on hair diameter in Pakistani population.

Materials and methods

The study was conducted in a private setup in the adult patients undergoing PRP treatment. Baseline platelets count was noted for each patient. PRP was prepared using a commercial kit. Three PRP injections were administered in the scalp at 0, 1, and 3 months of interval. The hair caliber was measured in the mid-scalp area using a separate stencil for each patient. The diameter of 10 hair (1 cm sq) was measured randomly using the caliper (2 hair on each side of the square and 4 in the center). After 6 months of 3rd injection, the hair caliber was measured and the results were analyzed statistically using Mann-Whitney's test.

Results

Seven men and 3 women were included in the study. The mean age of the patients was 24.2 years (26.3 years in males and 19.3 in females). The average platelets count was found to be 283,580/μL. The mean hair caliber was 37.3 μm (39.1 μm in men and 33.0 μm in women). At the end of the study, the mean hair caliber was found to be 52.3 μm (P < .01). The mean hair caliber was 53.9 μm in men and 48.7 μm in women (P < .01). The increase in the hair caliber was noted to be 27.5% more in men and 31.3% more in women (P < .01).

Conclusion

The PRP injections can increase the hair diameter.



http://ift.tt/2BLs2tu

The Effort Paradox: Effort Is Both Costly and Valued

Publication date: Available online 21 February 2018
Source:Trends in Cognitive Sciences
Author(s): Michael Inzlicht, Amitai Shenhav, Christopher Y. Olivola
According to prominent models in cognitive psychology, neuroscience, and economics, effort (be it physical or mental) is costly: when given a choice, humans and non-human animals alike tend to avoid effort. Here, we suggest that the opposite is also true and review extensive evidence that effort can also add value. Not only can the same outcomes be more rewarding if we apply more (not less) effort, sometimes we select options precisely because they require effort. Given the increasing recognition of effort's role in motivation, cognitive control, and value-based decision-making, considering this neglected side of effort will not only improve formal computational models, but also provide clues about how to promote sustained mental effort across time.



http://ift.tt/2GEfymC

Hierarchical Active Inference: A Theory of Motivated Control

Publication date: Available online 20 February 2018
Source:Trends in Cognitive Sciences
Author(s): Giovanni Pezzulo, Francesco Rigoli, Karl J. Friston
Motivated control refers to the coordination of behaviour to achieve affectively valenced outcomes or goals. The study of motivated control traditionally assumes a distinction between control and motivational processes, which map to distinct (dorsolateral versus ventromedial) brain systems. However, the respective roles and interactions between these processes remain controversial. We offer a novel perspective that casts control and motivational processes as complementary aspects − goal propagation and prioritization, respectively − of active inference and hierarchical goal processing under deep generative models. We propose that the control hierarchy propagates prior preferences or goals, but their precision is informed by the motivational context, inferred at different levels of the motivational hierarchy. The ensuing integration of control and motivational processes underwrites action and policy selection and, ultimately, motivated behaviour, by enabling deep inference to prioritize goals in a context-sensitive way.



http://ift.tt/2HFe4dx

Reaffirming the Sensory Recruitment Account of Working Memory

Publication date: Available online 20 February 2018
Source:Trends in Cognitive Sciences
Author(s): Jason M. Scimeca, Anastasia Kiyonaga, Mark D'Esposito




http://ift.tt/2EO49EJ

The Partisan Brain: An Identity-Based Model of Political Belief

Publication date: Available online 20 February 2018
Source:Trends in Cognitive Sciences
Author(s): Jay J. Van Bavel, Andrea Pereira
Democracies assume accurate knowledge by the populace, but the human attraction to fake and untrustworthy news poses a serious problem for healthy democratic functioning. We articulate why and how identification with political parties – known as partisanship – can bias information processing in the human brain. There is extensive evidence that people engage in motivated political reasoning, but recent research suggests that partisanship can alter memory, implicit evaluation, and even perceptual judgments. We propose an identity-based model of belief for understanding the influence of partisanship on these cognitive processes. This framework helps to explain why people place party loyalty over policy, and even over truth. Finally, we discuss strategies for de-biasing information processing to help to create a shared reality across partisan divides.



http://ift.tt/2CEfLDW

The Myth of Optimality in Clinical Neuroscience

Publication date: Available online 20 February 2018
Source:Trends in Cognitive Sciences
Author(s): Avram J. Holmes, Lauren M. Patrick
Clear evidence supports a dimensional view of psychiatric illness. Within this framework the expression of disorder-relevant phenotypes is often interpreted as a breakdown or departure from normal brain function. Conversely, health is reified, conceptualized as possessing a single ideal state. We challenge this concept here, arguing that there is no universally optimal profile of brain functioning. The evolutionary forces that shape our species select for a staggering diversity of human behaviors. To support our position we highlight pervasive population-level variability within large-scale functional networks and discrete circuits. We propose that, instead of examining behaviors in isolation, psychiatric illnesses can be best understood through the study of domains of functioning and associated multivariate patterns of variation across distributed brain systems.



http://ift.tt/2ELyraR

Clarifying the Conceptualization, Dimensionality, and Structure of Emotion: Response to Barrett and Colleagues

Publication date: Available online 21 February 2018
Source:Trends in Cognitive Sciences
Author(s): Alan S. Cowen, Dacher Keltner
We present a mathematically based framework distinguishing the dimensionality, structure, and conceptualization of emotion-related responses. Our recent findings indicate that reported emotional experience is high-dimensional, involves gradients between categories traditionally thought of as discrete (e.g., 'fear', 'disgust'), and cannot be reduced to widely used domain-general scales (valence, arousal, etc.). In light of our conceptual framework and findings, we address potential methodological and conceptual confusions in Barrett and colleagues' commentary on our work.



http://ift.tt/2CGVsGk

Level of agreement between laboratory and point-of-care prothrombin time in patients after stopping or continuation of acenocoumarol anticoagulation: A comparison of diagnostic accuracy

BACKGROUND Procedures requiring optimisation of the coagulation status of patients using vitamin K antagonists are frequently postponed due to the late availability of laboratory international normalised ratio (INR) test results. A point-of-care (POC) alternative may facilitate early decision-making in peri-operative patients. OBJECTIVES To assess the level of agreement between the POC-INR and the laboratory INR in patients who continue or stop vitamin K antagonists to determine whether the POC test may be a good alternative to the laboratory INR. DESIGN Study of diagnostic accuracy. SETTING Single-centre study at Zaans Medical Centre, The Netherlands. PATIENTS Included patients were scheduled for cardioversion (these continued taking vitamin K antagonists), or a surgical procedure (these stopped taking vitamin K antagonists). MAIN OUTCOME MEASURES The level of agreement and clinical acceptability of the laboratory and POC-INR results, evaluated by Bland–Altman analysis and error grid analysis. RESULTS The surgical and cardioversion groups consisted of 47 and 46 patients, respectively. The bias in the INR in the surgical group was −0.12 ± 0.09 with limits of agreement of −0.29 to 0.05, whereas the cardioversion group showed a bias in the INR of −0.22 ± 0.36 with limits of agreement from −0.93 to 0.48. The percentage errors between methods in the surgical and cardioversion groups were 16 and 21%, respectively. Error grid analysis showed that the diagnostic accuracy of the POC prothrombin time is clinically acceptable as the difference did not lead to a different clinical decision in the surgical group with INR values less than 1.8. CONCLUSION The current study shows a good level of agreement and clinical accuracy between the laboratory and POC-INR in patients who stopped anticoagulation intake for surgery. However, in patients who continued their anticoagulation therapy, the agreement between the two methods was less accurate. Correspondence to Elisabeth A.J. de Vos, MD, Department of Anesthesiology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands Tel: +31 20 4443830; e-mail: e.devos@vumc.nl © 2018 European Society of Anaesthesiology

http://ift.tt/2Fm6dk1

Improving detection of patient deterioration in the general hospital ward environment

Patient monitoring on low acuity general hospital wards is currently based largely on intermittent observations and measurements of simple variables, such as blood pressure and temperature, by nursing staff. Often several hours can pass between such measurements and patient deterioration can go unnoticed. Moreover, the integration and interpretation of the information gleaned through these measurements remains highly dependent on clinical judgement. More intensive monitoring, which is commonly used in peri-operative and intensive care settings, is more likely to lead to the early identification of patients who are developing complications than is intermittent monitoring. Early identification can trigger appropriate management, thereby reducing the need for higher acuity care, reducing hospital lengths of stay and admission costs and even, at times, improving survival. However, this degree of monitoring has thus far been considered largely inappropriate for general hospital ward settings due to device costs and the need for staff expertise in data interpretation. In this review, we discuss some developing options to improve patient monitoring and thus detection of deterioration in low acuity general hospital wards. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/OBJ4xP Correspondence to Dr Jean-Louis Vincent, Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik 808, 1070 Brussels, Belgium E-mail: jlvincent@intensive.org © 2018 European Society of Anaesthesiology

http://ift.tt/2EMdvwh

Opioid-related genetic polymorphisms do not influence postoperative opioid requirement: A prospective observational study

BACKGROUND Among the various factors that may influence the pharmacological response to opioids, genetic polymorphisms [single nucleotide polymorphisms (SNP)] have generated some interest. OBJECTIVES To examine the influence on morphine dose requirements and adverse events in the postoperative period of four SNP [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member 1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine pharmacodynamics and pharmacokinetics. DESIGN A single centre prospective study. SETTING University Hospital, Paris, France, from 2 January 2007 to 15 November 2011. PATIENTS A total of 438 white adults scheduled for major orthopaedic surgery (spine, hip and knee) under general anaesthesia. The main exclusion criteria were receiving opioids for chronic pain, nonopioid drugs within 2 days prior to surgery, pregnancy, renal insufficiency, sleep apnoea obstruction syndrome, morbid obesity, severe hepatic impairment, cognitive dysfunction. INTERVENTIONS Assays of plasma concentrations of morphine and metabolites (morphine 3-glucuronide and morphine 6-glucuronide) were performed and common polymorphisms in four candidate genes [OPRM1 A118G rs1799971; P-glycoprotein (ABCB1) T3435C (rs1045642) and G2677T/A (rs2032582); COMT Val 158 Met (rs4680)] were analysed. Morphine was titrated by staff in the postanaesthesia care unit (PACU) and in the ward patient-controlled intravenous analgesia was used for 24 h. MAIN OUTCOME MEASURES The dose of morphine required to achieve pain relief and the influence of SNP in genes involved in morphine pharmacodynamics and kinetics on morphine dose requirements. Secondary endpoints were the concentrations of morphine, morphine 6-glucuronide and morphine 3-gluguronide, the proportion of patients requiring a rescue analgesic and the proportion of morphine-related adverse events. RESULTS A total of 404 patients completed the study to final analysis. The mean ± SD morphine dose to achieve pain relief was 15.8 ± 8.8 mg in the PACU and 22.7 ± 18.6 mg during patient-controlled intravenous administration. Morphine-related adverse events were observed in 37%. There was no relationship between any genetic polymorphisms and morphine dose, morphine 3-gluguronide and morphine 6-glucuronide concentration, morphine-related adverse events or pain level. In the PACU only, P-glycoprotein polymorphisms (ex-21; ex-26) were significantly associated with morphine concentration but the prediction of the model was poor (R2 = 0.04) CONCLUSION No major relationship has been demonstrated between SNP of OPRM1, ABCB1, COMT and morphine requirement, pain level or adverse effects in the postoperative period. TRIAL REGISTRATION NCT00822549 (www.clinicaltrials.gov). Correspondence to Frédéric Aubrun, Département d'Anesthésie-Réanimation, Hôpital de la Croix-Rousse, 103 Boulevard de La Croix Rousse, 69004 Lyon, France E-mail: frederic.aubrun@chu-lyon.fr Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

http://ift.tt/2ENaOuJ

Arbuscular mycorrhizal fungi in two vertical-flow wetlands constructed for heavy metal-contaminated wastewater bioremediation

Abstract

Over the last three decades, the presence of arbuscular mycorrhizal fungi (AMF) in wetland habitats had been proven, and their roles played in wetland ecosystems and potential functions in wastewater bioremediation technical installations are interesting issues. To increase knowledge on the functions of AMF in the plant-based bioremediation of wastewater, we constructed two vertical-flow wetlands planting with Phragmites australis and investigated AMF distribution in plant roots and their roles played in purification of wastewater polluted by heavy metals (HMs), utilizing the Illumina sequencing technique. A total of 17 operational taxonomic units (OTUs) from 33,031 AMF sequences were obtained, with Glomus being the most dominant. P. australis living in the two vertical-flow constructed wetlands (CWs) harbored diverse AMF comparable with the AM fungal communities in upland habitats. The AMF composition profiles of CW1 (vegetated with non-inoculated plants) and CW2 (vegetated with mycorrhizal plants inoculated with Rhizophagus intraradices) were significantly different. CW1 (15 OTUs) harbored more diverse AMF than CW2 (7 OTUs); however, CW2 harbored much more OTU13 than CW1. In addition, a zipf species abundance distribution (SAD), which might due to the heavy overdominance of OTU13, was observed across AM fugal taxa in P. australis roots of the two CWs. CW1 and CW2 showed high (> 70%) removal capacity of HMs. CW2 exhibited significant higher Cd and Zn removal efficiencies than CW1 (CK) (p = 0.005 and p = 0.008, respectively). It was considered that AMF might play a role in HM removal in CWs.



http://ift.tt/2EKNSAa

In vivo toxicity evaluation of pristine graphene in developing zebrafish ( Danio rerio ) embryos

Abstract

Graphene has been used in several fields covering from electronics to biomedicine, especially exhibiting a widespread variety of promising biological and biomedical applications. In the past decade, the biomedical applications of graphene have attracted much interest. However, the effect of pristine graphene (pG) toxicity in aquatic vertebrates has not been fully studied. Thus, in this study, the toxicity of pG was experimentally evaluated using developing zebrafish embryos as in vivo model system. To determine this, 4-hpf embryos were exposed to different concentrations of pG (1, 5, 10, 15, 20, 25, 30, 35, 40, 45, and 50 μg/L) and different early life-stage parameters were observed at 24, 48, 72, and 96 hpf. Through embryogenesis, pG was observed to induce significant embryonic mortality, delayed hatching, heartbeat, several morphological defects, pericardial toxicity, and bradycardia. Yolk sac edema and pericardial edema were induced by pG in developing embryos. These outcomes would provide new insights into the adverse effects of pG on the developing embryonic cardiac defects in vertebrates and highlight the probable natural environment and health hazards of pG flakes.



http://ift.tt/2CCQOZO

Heat insulating, fire retardant and flexible inorganic nanocomposite paper

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Fa Chen, Jixiang Zhang, Nian Li, Cheng Zhang, Bo Ji, Lihe Hu, Tingting Zhao, Zhenyang Wang, Shudong Zhang
Organic heat insulating materials with low density and low thermal conductivity have been widely used in building and domestic appliances. However, their highly flammable and poorly flexible characteristics hamper the application under certain circumstances. In this work, novel nanocomposite paper with low thermal conductivity, flame retardancy and good mechanical property was prepared by employing ultralong hydroxyapatite (HAP) nanowires as scaffolds for silica aerogels. The conductivity of the HAP/silica aerogel nanocomposite paper at room temperature decreased from 0.056 to 0.045Wm−1K−1 as the amounts of silica aerogels increased from 0 to 50wt%, indicating the excellent heat insulating performance. Meanwhile, the prepared paper showed remarkable flame retardancy with the peak heat release rate (HRR) of only 33.1W/g when silica aerogel content was 50wt%. Thermal stability analysis showed that the weight losses of all the nanocomposite papers with different contents of silica aerogels were <10wt% even at 800°C, which showed that the nanocomposite paper possessed prominent thermal stability. Besides, the nanocomposite paper exhibited good mechanical property. Therefore, the as-prepared HAP/silica aerogel nanocomposite paper is promising for applications in the protection layer of insulation materials, fire-retardant wallpaper, specialty fire clothing, and so on.

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Acoustic band gaps and elastic stiffness of PMMA cellular solids based on triply periodic minimal surfaces

Publication date: 5 May 2018
Source:Materials & Design, Volume 145
Author(s): Diab W. Abueidda, Iwona Jasiuk, Nahil A. Sobh
In this paper, the acoustic band structure, sound attenuation, and uniaxial elastic modulus of three cellular solids are studied computationally. The cellular solids are generated based on mathematical surfaces, called triply periodic minimal surfaces (TPMS), which include Schwarz Primitive, Schoen IWP, and Neovius surfaces. Finite element method is used to find the acoustic band gaps and sound attenuation of the TPMS structures. The numerical investigation revealed the existence of acoustic bandgaps at low frequencies and low relative densities compared to other cellular structures reported in the literature. The band gap analysis is numerically validated using structures with finite dimensions subjected to varying pressure with multiple frequencies. The influence of the porosity of TPMS on the width of the band gaps is also reported. In the considered porosity range, it is found that lower porosities result in wider acoustic band gaps. Furthermore, the uniaxial moduli of these TPMS are numerically determined using periodic boundary conditions. When the uniaxial modulus of the TPMS-structures is studied against their porosities, it is found that the response of the TPMS-structures lies between stretching- and bending-dominating.

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Low-temperature synthesis of large-area graphene-based carbon films on Ni

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Liqiang Lu, Jeff T.M. De Hosson, Yutao Pei
In this work, large-area graphene-based carbon films were synthesized through a fast and low-temperature method. The processing route is illustrated on a free surface of Ni catalyst film by vacuum thermal processing of amorphous carbon. Key in the novel approach is that the synthesis is done at low temperatures, i.e. below 350°C, and within a time as short as 1min. The nucleation and growth of graphene on the free surface of nickel and along the interface between Ni film and SiO2 substrate are investigated by using a thin film Ni-C-Ni sandwiched structure on a SiO2/Si substrate. Raman spectroscopy demonstrates that the graphene-based carbon films consist of graphitic carbon rich of defects. HR-TEM observations reveal that the graphene-based carbon film grown on the top free surface is composed of thin multilayer graphene segments (3–6 atomic layers) and thick multilayer graphene segments (more than atomic 10 layers), covering the entire surface of Ni film over a large area. Growth parameters such as growth time, growth temperature and carbon/Ni ratio are reported in detail for a control of graphene growth kinetics. The results point at several attractive strategies for the facile synthesis of graphene-based carbon films for industrial applications.

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On the fatigue strength enhancement of additive manufactured AlSi10Mg parts by mechanical and thermal post-processing

Publication date: 5 May 2018
Source:Materials & Design, Volume 145
Author(s): Sara Bagherifard, Niccolò Beretta, Stefano Monti, Martina Riccio, Michele Bandini, Mario Guagliano
Selective laser melting fabricated materials regularly exhibit excellent static strength, thanks to the very high thermal gradient that characterizes the process; however, their performance under dynamic loading is somehow restricted due to the limited ductility, tensile residual stresses, the defect density and the inadequate surface morphology in the as built configuration. Currently mechanical or electrochemical surface polishing steps combined with various heat treatments are integrated into the production lines to respectively address these issues. However, these methods are reported to occasionally lead to inconsistent results apart from the burden of additional costs. Herein, we applied various post treatments including shot peening, sand blasting and heat treatment to evaluate their individual and synergetic effect to tackle the aforementioned challenges. Physical, microstructural and mechanical properties of SLM fabricated AlSi10Mg specimens were investigated with special focus on fatigue strength. The results highlight that appropriate post treatments can significantly enhance the fatigue performance of SLM specimens resulting in characteristics that are comparable and even better than conventionally manufactured material. Surface treatments, in particular, were found to be efficient in significantly enhancing the fatigue strength, while eliminating the necessity of polishing steps that are currently applied on as built material.

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Compacting CNT sponge to achieve larger electromagnetic interference shielding performance

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Hui Mei, Xing Zhao, Junchao Xia, Fei Wei, Daoyang Han, Shanshan Xiao, Laifei Cheng
The present study reports a simple route for the synthesis of 3D carbon nanotube (CNT) sponges by vacuum assisted filtration of CNT bundles of variable compaction ratios and its epoxy (EP) composites with superior electromagnetic interference (EMI) shielding performance. The electrical and mechanical properties of CNT sponge/EP composites were investigated and findings enabled identification of a sponge compaction ratio of 70% as optimum for the improvement of the electrical conductivity and EMI shielding effectiveness of the material, by 138 and 41%, respectively, compared to uncompacted samples. Mechanical properties of the composites were also enhanced with the yield strength and elastic modulus of the composite of a compaction ratio of 70% improved by 17 and 25%, respectively compared to pure epoxy. These results indicate that CNT sponge with a higher compaction ratio is a potential filler for mechanically strong and high-performance EMI shielding nanocomposites.

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Predictive models for fatigue property of laser powder bed fusion stainless steel 316L

Publication date: 5 May 2018
Source:Materials & Design, Volume 145
Author(s): Meng Zhang, Chen-Nan Sun, Xiang Zhang, Jun Wei, David Hardacre, Hua Li
The selection of appropriate processing parameters is crucial for producing parts with target properties via the laser powder bed fusion (L-PBF) process. In this work, the fatigue properties of L-PBF stainless steel 316L under controlled changes in laser power and scan speed were studied by employing the statistical response surface method. Processing regions corresponding to different fatigue failure mechanisms were identified. The optimum fatigue properties are associated with crack initiation from microstructure defect, which, by acting as the weakest link, creates enhanced porosity-tolerance at applied stress approaching the fatigue limit. Deviations from the optimum processing condition lead to strength degradation and porosity-driven cracking. Based on the observed relations between microstructural features and failure behaviour, a processing-independent fatigue prediction model was proposed. The microstructure-driven failure was modelled by a reference S-N curve where the intrinsic effect of microstructure inhomogeneity was accounted for by applying a reduction factor on fatigue life. For the porosity-driven failure, high cycle fatigue life follows an inverse-square-root relation with porosity fraction. This relation was incorporated into the Basquin equation for predicting the fatigue strength parameters.

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Improvement of out-of-plane thermal conductivity of composite laminate by electrostatic flocking

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Yafei Sun, Shaokai Wang, Min Li, Yizhuo Gu, Zuoguang Zhang
Increasing the out-of-plane thermal conductivity of polymer composite laminate is a challenge for applications that require heat dissipation. This paper adopted the electrostatic flocking method to embed different fillers in thin carbon fiber mat to produce a high thermal conductive ply, which was named fuzzy mat. The fuzzy mat was laminated alternatively with two-dimensional fabric to bridge the adjacent fabric plies. The effects of microstructure and structural parameters of fuzzy mat, as well as the filler type, on out-of-plane thermal conductivity were investigated. The results showed that the fuzzy mat effectively filled the resin rich area in the carbon fabric composite and greatly improved thermal conductivity. Pre-cured and double surface implanted fuzzy mat was beneficial for the construction of thermal conduction path. The out-of-plane thermal conductivities of the composite laminates increased as the content and length of pitch-based carbon fiber fillers increased. The thermal conductivity of composite laminate by introducing 10wt% fuzzy mat with 300- to 400-μm-long pitch-based carbon fiber filler was up to 1.2W/(m·K), which was 216% higher than the thermal conductivity of the control sample, which was 0.38W/(m·K). Moreover, the vapor-grown carbon fiber effectively improved both the out-of-plane thermal conductivity and the interlaminar shear strength.

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Direct-writing of 3D periodic TiO2 bio-ceramic scaffolds with a sol-gel ink for in vitro cell growth

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Rong Wang, Pengfei Zhu, Weiyi Yang, Shuang Gao, Bo Li, Qi Li
In this work, three-dimensional (3D) periodic TiO2 bio-ceramic scaffolds were created by continuous filament writing with TiO2 sol-gel ink followed by sintering. The TiO2 sol-gel ink has the advantage of creating 3D bio-ceramic scaffolds with finer feature size than commonly used ceramic powder based ink systems. The structure, pore sizes, and interconnectivity could be controlled through 3D structure design and printing parameter adjustment. To evaluate the potential of these 3D TiO2 bio-ceramic scaffolds for bone tissue engineering, the mouse osteoblastic cell line MC3T3-E1 was cultured on them. The observed good viability demonstrated that 3D TiO2 bio-ceramic scaffolds created by direct-writing technique provide a biocompatible environment that favors cell growth and attachment.

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Microalloyed Zn-Mn alloys: From extremely brittle to extraordinarily ductile at room temperature

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Zhang-Zhi Shi, Jing Yu, Xue-Feng Liu
Zn-0.34Mn and Zn-0.76Mn alloys transit from extremely brittle in as-cast status to extraordinarily ductile with elongations ranging from 88.8% to 94.0% at room temperature through 83.3% hot-rolling, annealing at 200 °C for 2 h and then air cooling, and finally 84% cold-rolling. Both the hot-rolling and the cold-rolling greatly refine Zn grains, while the annealing changes rolled textures into annealed textures. Grains in the as-cold-rolled alloys are smaller than 3 μm. After tensile testing, Zn grains close to the fracture are predominantly equiaxed rather than elongated. An aggregation or a long band of very fine Zn grains smaller than 1 μm is revealed in regions close to the fracture. The extraordinary ductilities of the alloys owe to fine grains before tensile testing and dynamic recrystallization during tensile testing, which helps to relieve accumulated stress.

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Investigations on actuation characteristics and life cycle behaviour of CuAlNiMn shape memory alloy bimorph towards flappers for aerial robots

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): K. Akash, Akash K. Jain, Gaurav Karmarkar, Aniket Jadhav, Dhiraj C. Narayane, Nandini Patra, I.A. Palani
In this work, life cycle and thermomechanical behaviour for quaternary CuAlNiMn alloy, developed through thermal evaporation technique on flexible Kapton polyimide substrate were investigated. Scanning electron microscopic images displayed grains less than 150nm without any porosity and crack. The thickness of the film was found to be around 6.6μm, and the XRD profile revealed the presence of β′ (128) martensite peak. The austenite transformation temperature was As: 221°C and Af: 226°C as obtained from differential scanning calorimetry plots. Further, thermal images were recorded to analyse the heat transfer profile of the film during actuation at various points on the bimorph. The thermomechanical behaviour was studied by actuating the composite film through Joule heating under different loads of 30mg, 45mg and 60mg. Parameters such as voltage and frequency were varied to analyse the actuation properties. The composite bimorph required less than 2V to displace 4mm under 60mg load. The life of eight samples was recorded for more than 20,000cycles, and the reliability of the film was investigated. The bimorph was further actuated by batteries to replicate the actuation and their suitability towards developing flappers for aerial robots.

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An analysis of high-temperature microstructural stability and mechanical performance of the Hastelloy N-Hastelloy N Superalloy joint bonded with pure Ti

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Yanming He, Wenjian Zheng, Jianguo Yang, Dongdong Zhu, Xueshun Yang, Zengliang Gao
The Hastelloy N superalloys were transient liquid phase bonded to themselves using pure Ti foil at 1223–1373K for 1h. The microstructure was examined using SEM, TEM and HRTEM analysis, and mechanical performance was evaluated by a shear test. Prolonged thermal exposure at 873–1173K was also performed for the joints, to examine their microstructural sensitivity to elevated temperatures. Efforts were made to reveal the relationship between the temperature-dependent microstructure and mechanical properties. Results indicate that two reaction zones (Zones 1 and 2) occur in the joint, with Zone 1 close to the Hastelloy N. The microstructure of Zone 1, produced through the eutectic melting of Cr9Mo21Ni20 and Ni3Ti intermetallics, is less sensitive to the joining temperature, while the microstructure of Zone 2 is strongly dependent on the joining temperature. The joint strength, as revealed, is closely related with the microstructure of Zone 2. The maximum joint strength obtained is 320.3MPa. The results of thermal exposure show that the joint can maintain microstructural stability below 973K. The microstructural evolution of joint during thermal exposure and its influence on mechanical performance were revealed. The performed work will provide basic data to join the Hastelloy series superalloys.

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Crashworthiness behavior of Koch fractal structures

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Jin Wang, Yong Zhang, Ning He, Chun H. Wang
Thin-walled structures are currently used in automotive and aerospace fields due to their excellent lightweight and crashworthiness properties. This paper describes a new crush absorber design based on the Koch fractal (KF) geometry to improve energy absorption performance. The crash performance of three Koch fractal designs, one single-wall and two hybrid (double-wall), with different Koch fractal orders and wall thicknesses are investigated by experimental testing and computational modelling. Computational models of 1st order basic Koch and hybrid Koch structures are developed, with the predictions being compared with the experimental data. The computational simulations reveal a significant synergistic effect in the hybrid Koch structure, stemming from the interaction between the inner Koch wall and the external wall. Among the three designs of Koch structures, the 2nd order hybrid Koch absorbers give the highest specific energy absorption performance. Furthermore, these 2nd order hybrid Koch absorbers outperform a wide range of multi-cell structures of the same mass. The findings of this research open up a new route of designing novel lightweight energy absorbers with improved crash characteristics.

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Novel ferrocene-containing organosilicon polymers and uniform microspheres prepared by free radical copolymerization: Precursors for magnetic Si-C-Fe-(O) nanomaterials

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Xiaofei Zhang, Lixin Chen, Jin Yun, Jie Kong
Ferrocene-containing organosilicon polymers demonstrate wide applications in catalysts, redox sensors, ceramic nanomaterials and nanolithography fields. However, most synthesis methods for ferrocene-containing organosilicon polymers require either strict water-free and oxygen-free conditions or the presence of platinum complex catalysts. In this contribution, the free radical copolymerization of 1, 1′‑bis(dimethylvinylsilyl)ferrocene (DVFc) and trimethylolpropane trimethacrylate (TMPTMA) was achieved to construct either soluble branched ferrocene-containing organosilicon polymers or uniform cross-linked microspheres only through the feed ratio tuning of the two monomers. The structures of copolymer and cross-linked microspheres have been characterized by one-dimensional nuclear magnetic resonance (1D NMR) and two-dimensional (2D) NMR measurements. Furthermore, the novel organosilicon polymers could be employed as preceramic precursors to prepare magnetic Si-C-Fe-(O) ceramics with favorable ceramic yield at high temperature. The nanocrystals-containing ceramics magnetism could be tuned through copolymer nature or pyrolysis condition variations.

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Improved optical properties of switchable mirrors based on Pd/Mg-TiO2 films fabricated by magnetron sputtering

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Yue Liu, Juan Chen, Liming Peng, Jingyu Han, Nanxiang Deng, Wenjiang Ding, Weifan Chen
For the past two decades, the reported magnesium-based gasochromic switchable mirrors have been limited to magnesium alloys. Herein, inspired by the excellent catalytic property of TiO2 for the magnesium‑hydrogen reaction, the novel gasochromic switchable mirrors based on Pd/Mg-TiO2 films were fabricated by magnetron sputtering and their optical properties, microstructures and structure-function relationship were investigated in this study. The results show that the mirror based on Pd/0.9Mg-0.1TiO2 film exhibits larger optical dynamic range at visible wavelengths and excellent structural recovery even after 100cycles of hydrogenation and dehydrogenation compared with Pd/Mg film. The brookite TiO2, crystalline Mg and some amorphous phases coexist in the Mg-TiO2 layer of Pd/0.9Mg-0.1TiO2 film with no trace of Pd. Interestingly, the TiO2 nanocrystal clusters are distributed in stripe among Mg matrix. In contrast, the Pd/0.63Mg-0.37TiO2 film consists of crystalline Mg and MgTi2O5 phase, where MgTi2O5 phase is derived from the reaction of superfluous TiO2 with a part of Mg and deteriorates the optical properties of the mirror dramatically. In summary, this work offers a novel strategy for improving optical performance of Mg-based switchable mirrors by introducing metal oxides into switchable layer and uncovers a broad field to be explored.

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A critical review of powder-based additive manufacturing of ferrous alloys: Process parameters, microstructure and mechanical properties

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Haniyeh Fayazfar, Mehrnaz Salarian, Allan Rogalsky, Dyuti Sarker, Paola Russo, Vlad Paserin, Ehsan Toyserkani
Additive manufacturing (AM) is an advanced manufacturing technology, enabling production of complex shapes by adding material layer-upon-layer, as distinct from conventional subtractive, forming and other manufacturing approaches. Thus far, several metallic materials including different types of ferrous alloys have been additively manufactured to full density with better or equivalent properties compared to counterparts made by conventional methods. In this perspective, this review article presents different powder-based additive manufacturing processes deployed to ferrous alloys, their key process parameters, phase transformation and microstructure development during solidification, all of which impact on mechanical behavior. The article enlightens the basics of Laser Powder-Bed (LPB, also known as selective laser melting), Laser Powder-Fed (LPF) and Binder Jetting (BJ) AM processes. These processes involve a sequence of complex/rapid thermal cycle and solidification behavior that influence the development of microstructure and eventually control the mechanical properties. A thorough discussion on mechanical behaviors, i.e., hardness, tensile, and cyclic/fatigue properties of AM manufactured steels is also presented based on several combined process parameters.

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Modification of Ti-6Al-4V plates with Schiff base complex and adhesive performance of Ti-6Al-4V/PEEK

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Lei Pan, Jingling Hu, Yunfei Lv, Wenliang Ma, Wenye Ding, Yifan Wang, Aiai Zhang, Fei Wang, Xiaofei Pang, Jie Tao
The adhesion between a metal alloy and a polymer is the problem focus of fiber metal laminates (FMLs) utilization. In this study, the Schiff base complex was firstly tentatively utilized for the surface modification of Ti-6Al-4V (TC4), in order for a bridge between TC4 and PEEK to be built. In addition, the TC4 plates were anodized for the synergistic effects between roughness and complex to be explored. Differently modified TC4 plate surfaces were analyzed through Fourier Transform Infrared Spectroscopy (FT-IR), Thermogravimetry/Differential Scanning Calorimetry (TG/DSC), Contact angle measurements (CA), Scanning Electron Microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and Atomic force microscopy (AFM). Moreover, the adhesive strength was studied through single lap shear testing. It was evidenced that the Schiff base and the corresponding complex were successfully synthesized; furthermore, the complex was loaded on the TC4 plate surface through self-assembly. When the TC4 plates were anodized and loaded the Schiff base complex, single lap shear strength significantly increased, reaching to 47.49MPa. This was a 53.89% growth compared to the anodized TC4 plate strengths. It was demonstrated that the Schiff base complex highly contributed to the adhesive strength through the multiple effects of coordination, hydrogen bonding interactions, mechanical interlocking and molecular entanglement.

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Interface design of graphene/copper composites by matrix alloying with titanium

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Ke Chu, Fan Wang, Xiao-hu Wang, Yu-biao Li, Zhong-rong Geng, Da-jian Huang, Hu Zhang
The attainment of intimate and strong interface is critical for promoting the load transfer ability and strength of graphene/metal composites. Herein, we reported an interface design strategy by matrix-alloying with Ti for in-situ interfacial carbide formation in reduced graphene oxide (RGO)/CuTi composites. It was demonstrated that both Ti8C5 nanolayers and Ti8C5 nanoparticles were in-situ formed at the local interface of RGO/CuTi composite, which played a "rivet" role in enhancing the interfacial bonding between the RGO and CuTi matrix. At 1.5vol% RGO loading, compared to RGO/Cu composite without alloying, the RGO/CuTi composite exhibited a higher enhancement in tensile strength (57.7% vs. 37.5%) and a lower reduction in coefficient of thermal expansion (−10.9% vs. −3.9%). The formed interfacial Ti8C5 nanolayers and Ti8C5 nanoparticles were proposed to originate from the amorphous carbon nanolayers and amorphous carbon nanoparticles on the surface of RGO, respectively. This study provides new insights into the interface design and carbide formation mechanism of advanced graphene/Cu composites with enhanced mechanical/thermal properties.

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Thickness-dependent iridescence of one-dimensional photonic crystals based on anodic alumina

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Sergey E. Kushnir, Kirill S. Napolskii
One-dimensional photonic crystals based on anodic alumina are of high practical importance in modern materials science and photonics owing to wide variety of their applications: from optoelectronics to decorative coatings. Although the variety of anodizing regimes allows one to design the periodic modulation of the porosity of oxide film, the information about the optimal number of layers needed for the appearance of intense photonic band gaps is absent. Here the variation in the spectral properties of one-dimensional photonic crystals on the thickness of porous anodic alumina is examined. The samples consisted of up to 300 periods are obtained by anodizing of aluminium under square-wave current profile in sulfuric acid electrolyte. Fabry–Pérot optical interference of the porous film at different incident angles is used for the calculation of the wavelength dispersion of the effective refractive index of anodic alumina. The influence of the number of layers in anodic alumina photonic crystals on the intensity of photonic band gap and colour of oxide coating is discussed.

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Stability and elasticity of metastable solid solutions and superlattices in the MoN–TaN system: First-principles calculations

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Nikola Koutná, David Holec, Martin Friák, Paul H. Mayrhofer, Mojmír Šob
In order to develop design rules for novel nitride-based coatings, we investigate trends in thermodynamic, structural, elastic, and electronic properties of Mo1−xTaxN single-phase alloys together with (MoN)1−x/(TaN)x superlattices. Our calculations predict that hexagonal Mo1−xTaxN are the overall most stable ones, followed by the disordered cubic solid solutions and superlattices. The disordered cubic systems are energetically clearly favoured over their ordered counterparts. To explain this unexpected phenomenon, we perform an in-depth structural analysis of bond-lengths and angles, revealing that the disordered phase is structurally between the NaCl-type and the hexagonal NiAs-type modifications. Similarly, the bi-axial coherency stresses in MoN/TaN break the cubic symmetry beyond simple tetragonal distortions, leading to a new tetragonal ζ-phase (P4/nmm, #129). Both ζ-MoN and ζ-TaN have lower formation energy than their cubic counterparts. Unlike the cubic TaN, the ζ-TaN is also dynamically stable. The hexagonal alloys are predicted to be extremely hard, though, much less ductile than the cubic polymorphs and superlattices.

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Electroless nickel plating onto Plexiglas® through simple covalent grafting of vinylpyridine seed layer

Publication date: 15 April 2018
Source:Materials & Design, Volume 144
Author(s): Ngoc Pi Vu, Xuan Truong Duong, Viet Anh Ly, Duy Cuong Nguyen, Minh Duc Tran, Quang The Phan, Marek Balazinski, Le Thanh Son, Gul Zeb, Xuan Tuan Le
The development of facile and environment friendly strategies to metallize the surface of insulating polymeric substrates is of paramount important. An acceptable film adhesion with the polymeric substrate usually requires a chemical pretreatment of the polymer surfaces. Here we report a one-step process of covalent grafting of vinylpyridine groups on the surface of commercial Plexiglas® (polymethylmethacrylate) employing diazonium-based aqueous chemistry, without requiring any surface pretreatment step. Prior to the electroless nickel plating, these grafted vinylpyridine groups can be easily activated by simply immersing the substrate into an acidic palladium chloride solution. This results in stable electrostatic interaction between the protonated pyridine functionalities and the palladium complexes. Thanks to the strong attachment to the substrate, this vinylpyridine seed layer also offers excellent adhesion between the Plexiglas® substrate and the electrolessly deposited nickel‑boron film. A sizable patterned Plexiglas® sample has been taken as a model considering its commercial potential and metallized. X-ray photoelectron spectroscopy is carried out to elucidate the mechanism of surface functionalization with pyridine groups as well as the activation of the grafted vinylpyridine seed layer. Comprehensive characterization of the electrolessly deposited metallic film is then performed by means of SEM, AFM, EDX and XPS techniques.

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Imaging pathological activities of human brain tissue in organotypic culture

Publication date: 15 March 2018
Source:Journal of Neuroscience Methods, Volume 298
Author(s): Caroline Le Duigou, Etienne Savary, Mélanie Morin-Brureau, Daniel Gomez-Dominguez, André Sobczyk, Farah Chali, Giampaolo Milior, Larissa Kraus, Jochen C. Meier, Dimitri M. Kullmann, Bertrand Mathon, Liset Menendez de la Prida, Georg Dorfmuller, Johan Pallud, Emmanuel Eugène, Stéphane Clemenceau, Richard Miles
BackgroundInsights into human brain diseases may emerge from tissue obtained after operations on patients. However techniques requiring transduction of transgenes carried by viral vectors cannot be applied to acute human tissue.New methodWe show that organotypic culture techniques can be used to maintain tissue from patients with three different neurological syndromes for several weeks in vitro. Optimized viral vector techniques and promoters for transgene expression are described.ResultsRegion-specific differences in neuronal form, firing pattern and organization as well as pathological activities were maintained over 40–50 days in culture. Both adeno-associated virus and lentivirus based vectors were persistently expressed from ∼10 days after application, providing 30–40 days to exploit genetically expressed constructs. Different promoters, including hSyn, e/hSyn, CMV and CaMKII, provided cell-type specific transgene expression. The Ca probe GCaMP let us explore epileptogenic synchrony and a FRET-based probe was used to follow activity of the kinase mTORC1.Comparison with existing methodsThe use of a defined culture medium, with low concentrations of amino acids and no growth factors, permitted organotypic culture of tissue from humans aged 3–62 years. Epileptic activity was maintained and excitability changed relatively little until ∼6 weeks in culture.ConclusionsCharacteristic morphology and region-specific neuronal activities are maintained in organotypic culture of tissue from patients diagnosed with mesial temporal lobe epilepsy, cortical dysplasia and cortical glioblastoma. Viral vector techniques permit expression of probes for long-term measurements of multi-cellular activity and intra-cellular signaling.

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Evaluation of adequacy of levo-thyroxine dosage in patients with differentiated thyroid carcinoma: correlation between morning and afternoon TSH determination

Abstract

Purpose

The aim of this study was to judge the reliability of evaluating thyroid-stimulating hormone (TSH) and free thyroxine (f-T4) in the morning and afternoon in differentiated thyroid carcinoma (DTC) patients.

Methods

We evaluated 153 DTC patients, aged 61 ± 13 years, in active follow-up in our center after primary treatments and under stabilized levo-thyroxine (L-T4) posology. In each patient, morning and afternoon examinations were performed 1-3 months apart. Blood samples were collected at 08:00–09:00 h and 15:00–16:00 h. TSH and f-T4 were evaluated in both samples. Thyroglobulin (Tg), Tg-antibodies and neck ultrasonography were also evaluated.

Results

According to clinical and laboratory examinations, 92% of patients were disease-free, 6% had biochemical disease, and 2% structural disease. L-T4 dosages (1.64 ± 0.38 µg/kg b.w.) proved the same on both occasions, despite slight changes in body weight or L-T4 posology in 15% of patients. Free-T4 values were significantly higher in the afternoon (21.5 ± 0.3 pmol/L) than in the morning (18.8 ± 0.4 pmol/L; P < 0.0001), whereas TSH values were statistically unchanged (morning 0.85 ± 0.25 mIU/L; afternoon 0.72 ± 0.20 mIU/L). There was a significant correlation (P < 0.0001) between the two TSH determinations in the same patients.

Conclusions

In DTC patients, follow-up examination consists of clinical and laboratory evaluations. The majority of patients have good disease control. Our study suggests that the adequacy of L-T4 therapy can be monitored equally well either in the morning or in the afternoon. Afternoon examinations can alleviate crowding in hospital ambulatories in the morning.



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