bluuebunny/crossref_metadata_2025 huggingface dataset:
Controlled trial of propranolol in intermittent claudication
Authors: Shoulson Ira , Chase Thomas N.
Published: January 2016

A double‐blind trial of orally administered fenfluramine was conducted in 7 non‐obese adults with various neurological disorders. Caloric intake and body weight fell significantly after 8 days of treatment although there was no definite change in appetite ratings. Average central turnover of serotonin, as estimated by the cerebrospinal fluid (CSF) accumulation of 5‐hydroxyindoleacetic acid (5‐HIAA) during probenecid loading, decreased by 66%. No significant change in homovanillic acid, the major dopamine product, was apparent. The results support the contention that the effect of fenfluramine on human dietary intake may be mediated by alterations in serotonergic rather than dopaminergic mechanisms.
Lack of effect of rheumatoid arthritis on clonixin metabolism
Authors: Furst Daniel E. , Paulus Harold E.
Published: January 2016

The effect of rheumatoid arthritis on the metabolism of the analgesic, 2‐(3‐chloro‐o‐toluidino) nicotinic acid (clonixin), was evaluated in 12 patients with rheumatoid arthritis and in 12 matched healthy control subjects. Males, age‐matched by decades, had no renal, gastrointestinal, or hepatic disease, and took no drugs during the study. Lower (p < 0.02) serum albumins and higher globulins in the patients (albumin: 3.87 ± 0.18; globulin: 3.14 ‐ 0.28 gm/100 ml) than in the control subjects (albumin: 4.42 ± 0.10; globulin: 2.36 ± 0.08 gm/l00 ml) were considered to be manifestations of rheumatoid arthritis. Fasting subjects were given single oral doses of 750 mg of clonixin. A spectrophotometric method was used to determine drug blood levels. Serum half‐life was 1.45 ± 0.12 hr inpatients and 1.50 ± 0.13 hr in control subjects (p > 0.5). Mean peak concentration developed at 1.7 hr and was 40.0 ± 2.6 μg/ml for patients and 46.1 ± 3.1 μg/ml for control subjects. Thus a single oral dose of clonixin results in comparable blood levels in male patients suffering from rheumatoid arthritis and in healthy control subjects.
Eco‐friendly Energy Storage System: Seawater and Ionic Liquid Electrolyte
Authors: Kim Jae‐Kwang , Mueller Franziska , Kim Hyojin , Jeong Sangsik , Park Jeong‐Sun , Passerini Stefano , Kim Youngsik
Published: January 2016

Invited for this month′s cover are the groups of Youngsik Kim at the Ulsan National Institute of Science and Technology (UNIST) and Stefano Passerini at the Helmholtz Institute Ulm (KIT‐HIU). The image illustrates a novel energy storage system based on an open seawater cathode and a sealed Sn–C anode in contact with an ionic liquid‐based electrolyte and a NASICON solid electrolyte. The Full Paper itself is available at 10.1002/cssc.201501328.
Impact of deprivation on breast cancer survival among women eligible for mammographic screening in the West Midlands (UK) and New South Wales (Australia): Women diagnosed 1997–2006
Authors: Woods Laura M. , Rachet Bernard , O'Connell Dianne , Lawrence Gill , Coleman Michel P.
Published: January 2016

Women diagnosed with breast cancer in the UK display marked differences in survival between categories defined by socio‐economic deprivation. Timeliness of diagnosis is one of the possible explanations for these patterns. Women whose cancer is screen‐detected are more likely to be diagnosed at an earlier stage. We examined deprivation and screening‐specific survival in order to evaluate the role of early diagnosis upon deprivation‐specific survival differences in the West Midlands (UK) and New South Wales (Australia). We estimated net survival for women aged 50–65 years at diagnosis and whom had been continuously eligible for screening from the age of 50. Records for 5,628 women in West Midlands (98.5% of those eligible, mean age at diagnosis 53.7 years) and 6,396 women in New South Wales (99.9% of those eligible, mean age at diagnosis 53.8 years). In New South Wales, survival was similar amongst affluent and deprived women, regardless of whether their cancer was screen‐detected or not. In the West Midlands, there were large and persistent differences in survival between affluent and deprived women. Deprivation differences were similar between the screen‐detected and non‐screen detected groups. These differences are unlikely to be solely explained by artefact, or by patient or tumour factors. Further investigations into the timeliness and appropriateness of the treatments received by women with breast cancer across the social spectrum in the UK are warranted.
Lysyl oxidase like‐4 monoclonal antibody demonstrates therapeutic effect against head and neck squamous cell carcinoma cells and xenografts
Authors: Görögh Tibor , Quabius Elgar S. , Heidebrecht Hans , Nagy Andreas , Muffels Till , Haag Jochen , Ambrosch Petra , Hoffmann Markus
Published: January 2016

A new member of the lysyl oxidase (LOX) family, lysyl oxidase‐like 4 (LOXL4), is overexpressed in head and neck squamous cell carcinoma (HNSCC) compared to normal squamous epithelium. A monoclonal antibody (mAb) derived from fusion of Balb/c mouse splenocytes immunized with LOXL4 specific peptide was used to evaluate its therapeutic efficacy in 15 HNSCC cell lines associated with LOXL4 overexpression. For xenograft experiments 41 severe combined immunodeficient (SCID) mice were used to analyze LOXL4‐mAb mediated tumor regression. Cell viability was analyzed using cytotoxicity‐, and clonogenic‐assays. Significant suppression of tumor cell growth was observed in 12 out of 15 (80%) tumor cell lines after 48 hr exposure to the mAb (LD50 of 15 µg/ml to 45 µg/ml). The effect induced by the antibody could be blocked by pre‐incubation of the antibody with the peptide used for immunization of the mice and antibody generation, indicating that the effect of the antibody is specific. In mice inoculated with HNSCC cells, i.v. injections of the LOXL4‐mAb resulted within 70 days in extensive tumor destruction in all treated animals whereas no tumor regression occurred in control animals. In mice pre‐immunized i.v. with LOXL4‐mAb and subsequently injected with HNSCC cells, tumor development was considerably delayed in contrast to non LOXL4‐mAb pre‐immunized animals. These results demonstrate that the LOXL4‐mAb has potent antitumor activity and suggest its suitability as a therapeutic immune agent applicable to HNSCC exhibiting tumor specific upregulation of LOXL4.
Treatment to sustain a Th17‐type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer
Authors: Young M. Rita I. , Levingston Corinne A. , Johnson Sara D.
Published: January 2016

While immune suppression is a hallmark of head and neck squamous cell carcinoma (HSNCC), the immunological impact of premalignant oral lesions, which often precedes development of HNSCC, is unknown. The present study assessed the changes in splenic and draining lymph node CD4+ cell populations and their production of select cytokines that occur in mice with carcinogen‐induced premalignant oral lesions and the changes that occur as lesions progress to oral cancer. These studies found skewing toward Th1 and Th17‐type phenotypes in the spleen and lymph nodes of mice with premalignant oral lesions and a shift to Treg as lesions progress to cancer. Since the role of Th17 cells in the progression from premalignant lesions to cancer is not clear, studies determined the immunological and clinical effect of treating mice bearing premalignant oral lesions with a TGF‐β type 1 receptor inhibitor plus IL‐23 as an approach to sustain the Th17 phenotype. These studies showed that the treatment approach not only sustained the Th17 phenotype, but also increased distal spleen cell and regional lymph node cell production of other stimulatory/inflammatory mediators and slowed premalignant lesion progression to cancer.
Serum haptoglobin as a novel molecular biomarker predicting colorectal cancer hepatic metastasis
Authors: Sun Lichao , Hu Shusheng , Yu Long , Guo Chunguang , Sun Lixin , Yang Zhihua , Qi Jun , Ran Yuliang
Published: January 2016

Early detection of liver metastasis is important for improving colorectal cancer (CRC) patient survival. Our previous studies showed haptoglobin was highly expressed in primary CRC tissues, especially in heterochronous metastatic cases. Here, we assessed the potential of serum haptoglobin (sHP) as a biomarker for early detection of CRC liver metastasis by evaluating the sHP in 475 CRC patients and 152 healthy volunteers. In the training set (250 cases), sHP level in CRC‐M1 (1773.18 ± 690.25 ng/mL) were significantly increased as compared to in CRC‐M0 (1544.37 ± 1497.65 ng/mL) or healthy (917.76 ± 571.59 ng/mL). And the high sHP level was correlated with poor survival. Logistic regression analysis revealed that sHP, serum carcinoembryonic antigen (sCEA) and serum carbohydrate antigen 19.9 (sCA19.9) level were the significant parameters for detecting liver metastasis. In leave‐one‐out‐cross‐validation, these three markers resulted in 89.1% sensitivity and 85.8% specificity for hepatic metastasis detection. In an independent test set (225 cases), receiver operating characteristic curve analysis of sHP in CRC liver metastasis showed an area under the curve of 0.735, with a sensitivity of 87.2% and a specificity of 59.9%. Combination of sHP, sCEA and sCA19.9 improved diagnostic accuracy to 0.880, with a sensitivity of 88.5% and a specificity of 87.8%. Silencing of HP by specific shRNA significantly inhibited the LOVO and SW620 cell invasion, and suppressed xenograft tumor invasive growth. In summary, these results demonstrate that sHP is associated with poor prognosis of CRC patients and that HP promotes colorectal cancer cell invasion. sHP combining with sCA19.9 and sCEA may be used as accurate predictors of CRC liver metastasis.
Cancer incidence among alcoholic liver disease patients in Finland: A retrospective registry study during years 1996–2013
Authors: Sahlman Perttu , Nissinen Markku , Pukkala Eero , Färkkilä Martti
Published: January 2016

Both alcohol abuse and liver cirrhosis are known risk factors for various cancers. This article was aimed to assess the long‐term risk of malignancies among patients with severe alcoholic liver disease (ALD), i.e., alcoholic liver cirrhosis and alcoholic hepatitis. A cohort of 8,796 male and 3,077 female ALD patients from 1996 to 2012 was identified from the Finnish National Hospital Discharge Register. This nationwide cohort was combined with the data from the Finnish Cancer Registry for incidence of malignancies during the years 1996–2013. The cancer cases diagnosed were compared with the number of cancers in the general population. The number of malignancies in our cohort was 1,052 vs. 368 expected. There was statistically significant excess of cancers of the liver, (standardized incidence ratio [SIR] 59.20; 95% CI 53.11–65.61), pancreas (SIR 3.71; 95% CI 2.72–4.94), pharynx (SIR 9.25; 95% CI 6.05–13.56), mouth (SIR 8.31; 95% CI 4.84–13,29), oesophagus (SIR 7.92; 95% CI 5.49–11.07), tongue (SIR 7,21; 95% CI 3.60–12.89), larynx (SIR 5.20; 95% CI 2.77–8.89), lung (SIR 2.77; 95% CI 2.27–3.32), stomach (SIR 2.76; 95% CI 1.79–4.07), kidney (SIR 2.69; 95% CI 1.84–3.79) and colon (SIR 2.33; 95% CI 1.70–3.11). There was no decreased risk of any cancer among ALD patients. Severe ALD is associated with markedly increased risk of malignancies. The risk is especially high for hepatocellular carcinoma, but also significantly increased for cancers of the upper aerodigestive tract, pancreas and kidneys, and warrants cancer surveillance in selected cases.
Investigating the role of tumour cell derived iNOS on tumour growth and vasculature in vivo using a tetracycline regulated expression system
Authors: Papaevangelou Efthymia , Whitley Guy S. , Johnstone Alan P. , Robinson Simon P. , Howe Franklyn A.
Published: January 2016

Nitric oxide (NO) is a free radical signalling molecule involved in various physiological and pathological processes, including cancer. Both tumouricidal and tumour promoting effects have been attributed to NO, making its role in cancer biology controversial and unclear. To investigate the specific role of tumour‐derived NO in vascular development, C6 glioma cells were genetically modified to include a doxycycline regulated gene expression system that controls the expression of an antisense RNA to inducible nitric oxide synthase (iNOS) to manipulate endogenous iNOS expression. Xenografts of these cells were propagated in the presence or absence of doxycycline. Susceptibility magnetic resonance imaging (MRI), initially with a carbogen (95% O2/5% CO2) breathing challenge and subsequently an intravascular blood pool contrast agent, was used to assess haemodynamic vasculature (ΔR2*) and fractional blood volume (fBV), and correlated with histopathological assessment of tumour vascular density, maturation and function. Inhibition of NO production in C6 gliomas led to significant growth delay and inhibition of vessel maturation. Parametric fBV maps were used to identify vascularised regions from which the carbogen‐induced ΔR2* was measured and found to be positively correlated with vessel maturation, quantified ex vivo using fluorescence microscopy for endothelial and perivascular cell staining. These data suggest that tumour‐derived iNOS is an important mediator of tumour growth and vessel maturation, hence a promising target for anti‐vascular cancer therapies. The combination of ΔR2* response to carbogen and fBV MRI can provide a marker of tumour vessel maturation that could be applied to non‐invasively monitor treatment response to iNOS inhibitors.
The influence of myeloid‐derived suppressor cells on angiogenesis and tumor growth after cancer surgery
Authors: Wang Jun , Su Xiaosan , Yang Liu , Qiao Fei , Fang Yu , Yu Lu , Yang Qian , Wang Yiyin , Yin Yanfeng , Chen Rui , Hong Zhipeng
Published: January 2016

While myeloid‐derived suppressor cells (MDSCs) have been reported to participate in the promotion of angiogenesis and tumor growth, little is known about their presence and function during perioperative period. Here, we demonstrated that human MDSCs expressing CD11b+, CD33+ and HLA‐DR– significantly increased in lung cancer patients after thoracotomy. CD11b+ CD33+ HLA‐DR– MDSCs isolated 24 hr after surgery from lung cancer patients were more efficient in promoting angiogenesis and tumor growth than MDSCs isolated before surgical operation in allograft tumor model. In addition, CD11b+ CD33+ HLA‐DR– MDSCs produced high levels of MMP‐9. Using an experimental lung metastasis mouse model, we demonstrated that the numbers of metastases on lung surface and Gr‐1+ CD11b+ MDSCs at postoperative period were enhanced in proportion to the degree of surgical manipulation. We also examined that syngeneic bone marrow mesenchymal stem cells (BMSCs) significantly inhibited the induction and proliferation of Gr‐1+ CD11b+ MDSCs and further prevented lung metastasis formation in the mice undergoing laparotomy. Taken together, our results suggest that postoperatively induced MDSCs were qualified with potent proangiogenic and tumor‐promotive ability and this cell population should be considered as a target for preventing postoperative tumor metastasis.
Evidence for electron‐based ion generation in radio‐frequency ionization
Authors: Olaitan Abayomi D. , Zekavat Behrooz , Solouki Touradj
Published: January 2016

Radio‐frequency ionization (RFI) is a novel ionization method coupled to mass spectrometry (MS) for analysis of semi‐volatile and volatile organic compounds (VOCs). Despite the demonstrated capabilities of RFI MS for VOC analysis in both positive‐ and negative‐ion modes, mechanism of RFI is not completely understood. Improved understanding of the ion generation process in RFI should expand its utility in MS. Here, we studied the possibility of electron emission in RFI using both direct charged particle current measurements and indirect electron detection in a 9.4‐T Fourier transform‐ion cyclotron resonance (FT‐ICR) mass spectrometer. We show that RF‐generated electrons can be trapped in the ICR cell and, subsequently, reacted with neutral hexafluorobenzene (C6F6) molecules to generate C6F6●−. Intensity of observed C6F6●− species correlated with the number of trapped electrons and decreased as a function of electron quenching period. We also measured the electron attachment rate constant of hexafluorobenzene using a post‐RF electron trapping experiment. Measured electron attachment rate constant of hexafluorobenzene (1.19 (±0.53) × 10−9 cm3 molecule−1 s−1) for post‐RF FT‐ICR MS agreed with the previously reported value (1.60 (±0.30) × 10−9 cm3 molecule−1 s−1) from low‐pressure ICR MS measurements. Experimental results from direct and indirect electron measurements suggest that RFI process involves RF‐generated electrons under ultrahigh vacuum conditions. Copyright © 2015 John Wiley & Sons, Ltd.
Negative ion electrospray high‐resolution tandem mass spectrometry of polyphenols
Authors: Schmidt Jürgen
Published: January 2016

Representative compounds with a 1,3‐dihydroxybenzene substructure belonging to different important polyphenol classes (stilbenes, flavones, isoflavones, flavonols, flavanones, flavanols, phloroglucinols, anthraquinones and bisanthraquinones) were investigated based on detailed high‐resolution tandem mass spectrometry measurements with an Orbitrap system under negative ion electrospray conditions. The mass spectral behaviour of these compound classes was compared among each other not only with respect to previously described losses of CO, CH2CO and C3O2 but also concerning the loss of CO2 and successive specific fragmentations. Furthermore, some unusual fragmentations such as the loss of a methyl radical during mass spectral decomposition are discussed. The obtained results demonstrate both similarities and differences in their mass spectral fragmentation under MSn conditions, allowing a characterization of the corresponding compound type. Copyright © 2015 John Wiley & Sons, Ltd.
MALDI ionization mechanisms investigated by comparison of isomers of dihydroxybenzoic acid
Authors: Kirmess Kristopher M. , Knochenmuss Richard , Blanchard Gary J. , Kinsel Gary R.
Published: January 2016

Matrix‐assisted laser desorption/ionization (MALDI) ion formation mechanisms were investigated by comparison of isomers of dihydroxybenzoic acid (DHB). These exhibit substantially different MALDI performance, the basis for which was not previously understood. Luminescence decay curves are used here to estimate excited electronic state properties relevant for the coupled chemical and physical dynamics (CPCD) model. With these estimates, the CPCD predictions for relative total ion and analyte ion yields are in good agreement with the data for the DHB isomers. Predictions of a thermal equilibrium model were also compared and found to be incompatible with the data. Copyright © 2015 John Wiley & Sons, Ltd.
The use of matrix coating assisted by an electric field (MCAEF) to enhance mass spectrometric imaging of human prostate cancer biomarkers
Authors: Wang Xiaodong , Han Jun , Hardie Darryl B. , Yang Juncong , Borchers Christoph H.
Published: January 2016

In this work, we combined a newly developed matrix coating technique – matrix coating assisted by an electric field (MCAEF) and matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) to enhance the imaging of peptides and proteins in tissue specimens of human prostate cancer. MCAEF increased the signal‐to‐noise ratios of the detected proteins by a factor of 2 to 5, and 232 signals were detected within the m/z 3500–37500 mass range on a time‐of‐flight mass spectrometer and with the sinapinic acid MALDI matrix. Among these species, three proteins (S100‐A9, S100‐A10, and S100‐A12) were only observed in the cancerous cell region and 14 proteins, including a fragment of mitogen‐activated protein kinase/extracellular signal‐regulated kinase kinase kinase 2, a fragment of cAMP‐regulated phosphoprotein 19, 3 apolipoproteins (C‐I, A‐I, and A‐II), 2 S100 proteins (A6 and A8), β‐microseminoprotein, tumor protein D52, α‐1‐acid glycoprotein 1, heat shock protein β‐1, prostate‐specific antigen, and 2 unidentified large peptides at m/z 5002.2 and 6704.2, showed significantly differential distributions at the p < 0.05 (t‐test) level between the cancerous and the noncancerous regions of the tissue. Among these 17 species, the distributions of apolipoprotein C‐I, S100‐A6, and S100‐A8 were verified by immunohistological staining. In summary, this study resulted in the imaging of the largest group of proteins in prostate cancer tissues by MALDI‐MS reported thus far, and is the first to show a correlation between S100 proteins and prostate cancer in a MS imaging study. The successful imaging of the three proteins only found in the cancerous tissues, as well as those showing differential expressions demonstrated the potential of MCAEF‐MALDI/MS for the in situ detection of potential cancer biomarkers. Copyright © 2015 John Wiley & Sons, Ltd.
Phytoremediation of a Nitrogen‐Contaminated Desert Soil by Native Shrubs and Microbial Processes
Authors: Glenn Edward P. , Jordan Fiona , Waugh W. Joseph
Published: January 2016

We combined phytoremediation and soil microbial nitrification and denitrification cycles to reduce nitrate and ammonium levels at a former uranium mill site near Monument Valley, Arizona. Ammonia used in uraxnium extraction was present throughout the soil profile. Sulfate, applied as sulfuric acid to solubilize uranium, was also present in the soil. These contaminants were leaching from a denuded area where a tailings pile had been removed and were migrating away from the site in groundwater. We planted the source area with two deep‐rooted native shrubs, Atriplex cansescens and Sarcobatus vermiculatus, and irrigated transplants for 11 years at 20% the rate of potential evapotranspiration to stimulate growth, then discontinued irrigation for 4 years. Over 15 years, total nitrogen levels dropped 82%, from 347 to 64 mg kg−1. Analysis of δ15N supported our hypothesis that coupled microbial nitrification and denitrification processes were responsible for the loss of N. Soil sulfate levels changed little; however, evapotranspiration reduced sulfate leaching into the aquifer. For arid sites where traditional pump‐and‐treat methods are problematic, the Monument Valley data suggest that alternatives that incorporate native plants and rely on vadose zone biogeochemistry and hydrology could be a sustainable remediation for nitrogen contaminated soil. Copyright © 2016 John Wiley & Sons, Ltd.
Controllable femtosecond laser‐induced dewetting for plasmonic applications
Authors: Makarov Sergey V. , Milichko Valentin A. , Mukhin Ivan S. , Shishkin Ivan I. , Zuev Dmitry A. , Mozharov Alexey M. , Krasnok Alexander E. , Belov Pavel A.
Published: January 2016

Dewetting of thin metal films is one of the most widespread method for functional plasmonic nanostructures fabrication. However, simple thermal‐induced dewetting does not allow to control degree of nanostructures order without additional lithographic process steps. Here we propose a novel method for lithography‐free and large‐scale fabrication of plasmonic nanostructures via controllable femtosecond laser‐induced dewetting. The method is based on femtosecond laser surface pattering of a thin film followed by a nanoscale hydrodynamical instability, which is found to be very controllable under specific irradiation conditions. We achieve control over degree of nanostructures order by changing laser irradiation parametrs and film thickness. This allowed us to exploit the method for the broad range of applications: resonant light absorbtion and scattering, sensing, and potential improving of thin‐film solar cells.

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What Do We Really Need? Goals and Values, Security, and the Perception of Consumer Necessity
Authors: Norris J. Ian , Williams Chloe E.
Published: January 2016

There is a general trend for consumer goods considered luxuries to become thought of as necessities. Although the luxury/necessity distinction is central to the fields of marketing and economics, little research has examined the perception of necessity as a psychological phenomenon. Three studies examined the relationship of the perceived necessity of a variety of consumer goods to goals, values, and insecurity. In Study 1, the number of goods considered necessities as opposed to luxuries correlated negatively with intrinsic and positively with extrinsic goal pursuit. In Study 2, this pattern generalized to the distinction between needs and wants, the extent to which participants reported needing their possessions, and to materialistic values. In Study 3, the perception of necessity mediated the relationship between anxious attachment and materialism, suggesting that needing consumer products has in part a basis in interpersonal insecurity. In turn, it may facilitate materialistic consumption.
A review on the determination of isotope ratios of boron with mass spectrometry
Authors: Aggarwal Suresh Kumar , You Chen‐Feng
Published: January 2016

The present review discusses different mass spectrometric techniques—viz, thermal ionization mass spectrometry (TIMS), inductively coupled plasma mass spectrometry (ICPMS), and secondary ion mass spectrometry (SIMS)—used to determine 11B/10B isotope ratio, and concentration of boron required for various applications in earth sciences, marine geochemistry, nuclear technology, environmental, and agriculture sciences, etc. The details of the techniques‐P‐TIMS, which uses Cs2BO2+, N‐TIMS, which uses BO2−, and MC‐ICPMS, which uses B+ ions for bulk analysis or B− and B+ ions for in situ micro‐analysis with SIMS—are highlighted. The capabilities, advantages, limitations, and problems in each mass spectrometric technique are summarized. The results of international interlaboratory comparison experiments conducted at different times are summarized. The certified isotopic reference materials available for boron are also listed. Recent developments in laser ablation (LA) ICPMS and QQQ‐ICPMS for solids analysis and MS/MS analysis, respectively, are included. The different aspects of sample preparation and analytical chemistry of boron are summarized. Finally, the future requirements of boron isotope ratios for future applications are also given. Presently, MC‐ICPMS provides the best precision and accuracy (0.2–0.4‰) on isotope ratio measurements, whereas N‐TIMS holds the potential to analyze smallest amount of boron, but has the issue of bias (+2‰ to 4‰) which needs further investigations. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 36:499–519, 2017
Identification and antimicrobial resistance prevalence of pathogenic Escherichia coli strains from treated wastewater effluents in Eastern Cape, South Africa
Authors: Adefisoye Martins A. , Okoh Anthony I.
Published: January 2016

Antimicrobial resistance (AMR) is a global problem impeding the effective prevention/treatment of an ever‐growing array of infections caused by pathogens; a huge challenge threatening the achievements of modern medicine. In this paper, we report the occurrence of multidrug resistance (MDR) in Escherichia coli strains isolated from discharged final effluents of two wastewater treatment facilities in the Eastern Cape Province of South Africa. Standard disk diffusion method was employed to determine the antibiotic susceptibility profile of 223 polymerase chain reaction (PCR)‐confirmed E. coli isolates against 17 common antibiotics in human therapy and veterinary medicine. Seven virulence associated and fourteen antibiotic resistance genes were also evaluated by molecular methods. Molecular characterization revealed five pathotypes of E. coli in the following proportions: enterotoxigenic ETEC (1.4%), enteropathogenic EPEC (7.6%), enteroaggregative EAEC (7.6%), neonatal meningitis (NMEC) (14.8%), uropathogenic (41.7%), and others (26.9%). Isolates showed varying (1.7–70.6%) degrees of resistance to 15 of the test antibiotics. Multidrug resistance was exhibited by 32.7% of the isolates, with the commonest multiple antibiotic‐resistant phenotype (MARP) being AP‐T‐CFX (12 isolates), while multiple antibiotic‐resistant indices (MARI) estimated are 0.23 (Site 1) and 0.24 (Site 2). Associated antibiotic resistance genes detected in the isolates include: strA (88.2%), aadA (52.9%), cat I (15%), cmlA1 (4.6%), blaTEM (56.4%), tetA (30.4%), tetB (28.4%), tetC (42.2%), tetD (50%), tetK (11.8%), and tetM (68.6%). We conclude that municipal wastewater effluents are important reservoirs for the dissemination of potentially pathogenic E. coli (and possibly other pathogens) and antibiotic resistance genes in the aquatic milieu of the Eastern Cape and a risk to public health.
A framework for creating low‐order shell elements free of membrane locking
Authors: Quaglino A.
Published: January 2016

This paper proposes a first step towards a framework to develop shell elements applicable to any deformation regime. Here, we apply it to the large and moderate deformations of, respectively, plates and shells, showing with standard benchmarks that the resulting low‐order discretization is competitive against the best elements for either membrane‐dominated or bending‐dominated scenarios. Additionally, we propose a new test for measuring membrane locking, which highlights the mesh‐independence properties of our element. Our strategy is based on building a discrete model that mimics the smooth behavior by construction, rather than discretizing a smooth energy. The proposed framework consists of two steps: (i) defining a discrete kinematics by means of constraints and (ii) formulating an energy that vanishes on such a constraint manifold. We achieve (i) by considering each triangle as a tensegrity structure, constructed to be unstretchable but bendable isometrically (in a discrete sense). We then present a choice for (ii) based on assuming a linear strain field on each triangle, using tools from differential geometry for coupling the discrete membrane energy with our locking‐free kinematic description. We argue that such a locking‐free element is only a member of a new family that can be created using our framework (i) and (ii). Copyright © 2016 John Wiley & Sons, Ltd.
Robust optimal Robin boundary control for the transient heat equation with random input data
Authors: Martínez‐Frutos J. , Kessler M. , Münch A. , Periago F.
Published: January 2016

The problem of robust optimal Robin boundary control for a parabolic partial differential equation with uncertain input data is considered. As a measure of robustness, the variance of the random system response is included in two different cost functionals. Uncertainties in both the underlying state equation and the control variable are quantified through random fields. The paper is mainly concerned with the numerical resolution of the problem. To this end, a gradient‐based method is proposed considering different functional costs to achieve the robustness of the system. An adaptive anisotropic sparse grid stochastic collocation method is used for the numerical resolution of the associated state and adjoint state equations. The different functional costs are analysed in terms of computational efficiency and its capability to provide robust solutions. Two numerical experiments illustrate the performance of the algorithm. Copyright © 2016 John Wiley & Sons, Ltd.
Optimal Bayesian Experimental Design for Priors of Compact Support with Application to Shock‐Tube Experiments for Combustion Kinetics
Authors: Bisetti Fabrizio , Kim Daesang , Knio Omar , Long Quan , Tempone Raul
Published: January 2016

The analysis of reactive systems in combustion science and technology relies on detailed models comprising many chemical reactions that describe the conversion of fuel and oxidizer into products and the formation of pollutants. Shock‐tube experiments are a convenient setting for measuring the rate parameters of individual reactions. The temperature, pressure, and concentration of reactants are chosen to maximize the sensitivity of the measured quantities to the rate parameter of the target reaction. In this study, we optimize the experimental setup computationally by optimal experimental design in a Bayesian framework. We approximate the posterior probability density functions (pdf) using truncated Gaussian distributions in order to account for the bounded domain of the uniform prior pdf of the parameters. The underlying Gaussian distribution is obtained in the spirit of the Laplace method, more precisely, the mode is chosen as the maximum a posteriori (MAP) estimate, and the covariance is chosen as the negative inverse of the Hessian of the misfit function at the MAP estimate. The model related entities are obtained from a polynomial surrogate. The optimality, quantified by the information gain measures, can be estimated efficiently by a rejection sampling algorithm against the underlying Gaussian probability distribution, rather than against the true posterior. This approach offers a significant error reduction when the magnitude of the invariants of the posterior covariance are comparable with the size of the bounded domain of the prior. We demonstrate the accuracy and superior computational efficiency of our method for shock‐tube experiments aiming to measure the model parameters of a key reaction, which is part of the complex kinetic network describing the hydrocarbon oxidation. In the experiments, the initial temperature and fuel concentration are optimized with respect to the expected information gain in the estimation of the parameters of the target reaction rate. We show that the expected information gain surface can change its “shape” dramatically according to the level of noise introduced into the synthetic data. The information that can be extracted from the data saturates as a logarithmic function of the number of experiments, and few experiments are needed when they are conducted at the optimal experimental design conditions. Furthermore, inversion of the legacy data indicates the validity and robustness of our designs. Copyright © 2016 John Wiley & Sons, Ltd.
Modeling the pharmacokinetic‐pharmacodynamic relationship of the monoclonal anti‐macaque‐IL‐15 antibody Hu714MuXHu in cynomolgus monkeys
Authors: Pan Wei. J. , Li Hong , Xiao Jim J. , Horner Michelle J. , Lebrec Herve N. , Butz Eric A. , Kaliyaperumal Arunan , Cheah Tsui C. , Ortiz Robert C. , Prokop Samantha P. , Buntich Sabina A. , Boren Babette M. , Wolford Suzanne T. , Tsuji Wayne H. , Wienkers Larry C. , Köck Kathleen
Published: January 2016

Hu714MuXHu is a recombinant chimeric murine‐human monoclonal antibody directed against interleukin‐15 (IL‐15), a proinflammatory cytokine associated with memory CD8+ and natural killer (NK) T‐cell activation and implicated in the pathogenesis of inflammatory diseases. A pharmacokinetic‐pharmacodynamic (PK/PD) model was developed to describe the NK cell count reduction in cynomolgus monkeys after treatment with Hu714MuXHu. Cynomolgus monkeys were dosed with Hu714MuXHu in three studies: as a single dose at 0.1 or 1 mg·kg−1 i.v.; weekly for 5 weeks at 0, 30, 60, or 150 mg·kg−1 i.v. or 150 mg·kg−1 s.c.; weekly for 13 weeks at 0, 5, 30, or 150 mg·kg−1 s.c. Serum Hu714MuXHu concentration‐time data were analyzed using noncompartmental analysis and the PK/NK cell count relationship was assessed via simultaneous PK/PD modeling. Hu714MuXHu PK was approximately dose‐proportional between 0.1–150 mg·kg−1 for i.v. and 5–150 mg·kg−1 for s.c. administration with an elimination half‐life of 12.7–18 days. Hu714MuXHu administration resulted in rapid and marked reductions in NK cell counts after the first dose which recovered fully after the serum Hu714MuXHu concentrations approached 0.1 μg·mL−1 (assay limit of quantification). PK/PD modeled Hu714MuXHu effects on NK cells had an EC50 of 0.09 μg·mL−1. In summary, weekly i.v. or s.c. doses with Hu714MuXHu for up to 3 months in cynomolgus monkeys demonstrated linear PK and significant NK cell count reduction, which was described using PK/PD modeling. This approach may be used to guide investigative product dose selections for inflammatory diseases where NK cell count alterations are quantifiable.
Stable isotopes reveal spatial variability in the trophic structure of a macro‐benthic invertebrate community in a tropical coral reef
Authors: Kolasinski Joanna , Nahon Sarah , Rogers Karyne , Chauvin Anne , Bigot Lionel , Frouin Patrick
Published: January 2016

Rationale

Studies of organic matter fluxes in coral reefs are historically based on physical and biogeochemical approaches. It is important to link these approaches to community analysis as the abundance and behaviour of species, populations or trophic groups can have a profound effect on nutrient budgets.

Methods

We determined the carbon and nitrogen isotopic compositions of coral reef organic matter sources and macro‐benthic invertebrate communities using a Europa Geo 20/20 isotope ratio mass spectrometer interfaced to an ANCA‐SL elemental analyzer in continuous flow mode. Isotopic ecology metrics and a mixing model were used to analyze and interpret the data.

Results

The coral reef macro‐invertebrate community principally relies on detrital or recycled food sources. An increased reliance on reef nitrogen‐derived sources was observed in the cold‐dry season. The community food‐web lengths differ noticeably across the coral reef and reflect the characteristics and origin of organic matter reservoirs.

Conclusions

Anthropogenic and terrestrial inputs lead to a loss of biological diversity. Exclusive dominance of suspension‐feeding species is observed in areas receiving direct surface riverine particulate organic matter. The accumulation of sediment organic matter in eutrophic areas leads to dominance of deposit‐feeding species. Copyright © 2016 John Wiley & Sons, Ltd.
Repairing the efficiency loss due to varying cluster sizes in two‐level two‐armed randomized trials with heterogeneous clustering
Authors: Candel Math J. J. M. , Van Breukelen Gerard J. P.
Published: January 2016

In two‐armed trials with clustered observations the arms may differ in terms of (i) the intraclass correlation, (ii) the outcome variance, (iii) the average cluster size, and (iv) the number of clusters. For a linear mixed model analysis of the treatment effect, this paper examines the expected efficiency loss due to varying cluster sizes based upon the asymptotic relative efficiency of varying versus constant cluster sizes. Simple, but nearly cost‐optimal, correction factors are derived for the numbers of clusters to repair this efficiency loss. In an extensive Monte Carlo simulation, the accuracy of the asymptotic relative efficiency and its Taylor approximation are examined for small sample sizes. Practical guidelines are derived to correct the numbers of clusters calculated under constant cluster sizes (within each treatment) when planning a study. Because of the variety of simulation conditions, these guidelines can be considered conservative but safe in many realistic situations. Copyright © 2016 John Wiley & Sons, Ltd.
Nanoscale Plasmon‐Enhanced Spectroscopy in Memristive Switches
Authors: Di Martino Giuliana , Tappertzhofen Stefan , Hofmann Stephan , Baumberg Jeremy
Published: January 2016

Resistive switching memories are nonvolatile memory cells based on nano‐ionic redox processes and offer prospects for high scalability, ultrafast write and read access, and low power consumption. In two‐terminal cation based devices a nanoscale filament is formed in a switching material by metal ion migration from the anode to the cathode. However, the filament growth and dissolution mechanisms and the dynamics involved are still open questions, restricting device optimization. Here, a spectroscopic technique to optically characterize in situ the resistive switching effect is presented. Resistive switches arranged in a nanoparticle‐on‐mirror geometry are developed, exploiting the high sensitivity to morphological changes occurring in the tightly confined plasmonic hotspot within the switching material. The focus is on electrochemical metallization and the optical signatures detected over many cycles indicate incomplete removal of metal particles from the filament upon RESET and suggest that the filament can nucleate from different positions from cycle to cycle. The technique here is nondestructive and the measurements can be easily performed in tunable ambient conditions and with realistic cell geometries.
Estimation, filtering and smoothing in the stochastic conditional duration model: an estimating function approach
Authors: Thekke Ramanathan , Mishra Anuj , Abraham Bovas
Published: January 2016

Stochastic conditional duration models are widely used in the financial econometrics literature to model the duration between transactions in a financial market. Even though there are developments in terms of modelling aspects, estimation, filtering and smoothing are still being investigated by researchers in this area. Almost all the existing procedures are highly computational intensive because of the complexity of the likelihood function. In this paper, we suggest a new procedure for estimation, filtering and smoothing in stochastic conditional duration models, based on estimating functions. Simulation studies indicate that the suggested procedure performs well and also fast in terms of computation. Copyright © 2016 John Wiley & Sons, Ltd.
Prior Abdominal Surgery Jeopardizes Quality of Resection in Colorectal Cancer
Authors: Stommel Martijn W. J. , de Wilt Johannes H. W. , ten Broek Richard P. G. , Strik Chema , Rovers Maroeska M. , van Goor Harry
Published: January 2016

Background

Prior abdominal surgery increases complexity of abdominal operations. Effort to prevent injury during adhesiolysis might result in less extensive bowel resection in colorectal cancer surgery. The aim of this study was to evaluate the effect of prior abdominal surgery on the outcome of colorectal cancer surgery.

Methods

A nationwide prospective database of patients with primary colorectal cancer resection in The Netherlands between 2010 and 2012 was reviewed for histopathology, morbidity and mortality in patients with compared to patients without prior abdominal surgery.

Results

9042 patients with and 17,679 without prior abdominal surgery were analyzed. After prior abdominal surgery 20.7 % had less than 10 lymph nodes in the histopathological specimen compared to 17.8 % without prior abdominal surgery (adjusted OR 1.17, 95 % CI 1.09–1.26). Adjusted ORs for less than 10 and 12 lymph nodes were significant in colon cancer resection and not in rectal cancer resection. Subgroups of patients who had previous hepatobiliary surgery or other abdominal surgery had a higher incidence of inadequate number of harvested lymph nodes. Prior colorectal surgery increased the percentage of positive circumferential rectal resection margin by 64 % (12.5 and 7.6 %; adjusted OR 1.70, 95 % CI 1.21–2.39). For colon cancer morbidity was significantly higher in patients with prior surgery (33.2 and 29.7 %; adjusted OR 1.18, 95 % CI 1.10–1.26), 30‐day mortality was comparable (4.7 % prior surgery and 3.8 % without prior surgery; adjusted OR 1.01, 95 % CI 0.88–1.17).

Conclusions

Prior abdominal surgery compromises the quality of resection and increases postoperative morbidity in patients with primary colorectal cancer.
Hypolipidemic Effects of Phospholipids (PL) Containing n‐3 Polyunsaturated Fatty Acids (PUFA) Are Not Dependent on Esterification of n‐3 PUFA to PL
Authors: Fukunaga Kenji , Hosomi Ryota , Fukao Midori , Miyauchi Kazumasa , Kanda Seiji , Nishiyama Toshimasa , Yoshida Munehiro
Published: January 2016

Phospholipids (PL) containing n‐3 polyunsaturated fatty acids (PUFA) have beneficial effects of maintaining and promoting health compared with triacylglycerols (TAG) containing n‐3 PUFA or general PL. This study evaluated the effects of dietary PL containing n‐3 PUFA and elucidated the effects of the glycerophosphate structure and n‐3 PUFA on fatty acid (FA) metabolism in rats. Rats were fed a basal diet containing soybean oil alone, TAG containing n‐3 PUFA (1.8 %), soybean PL (2.7 %), PL containing n‐3 PUFA (2.7 %), or TAG containing n‐3 PUFA (1.8 %) + soybean PL (2.7 %). The present n‐3 PUFA‐supplemented diets had similar FA compositions, and the PL diets had similar PL compositions. TAG containing n‐3 PUFA reduced serum TAG contents, but did not affect serum cholesterol contents compared with soybean oil alone. PL diets containing n‐3 PUFA and the combination of TAG containing n‐3 PUFA and soybean PL resulted in decreased serum and liver TAG contents compared with the diet containing soybean oil alone, reflecting enhanced liver FA β‐oxidation. The results of this study show that TAG containing n‐3 PUFA with added soybean PL affects serum and liver TAG and cholesterol contents to a similar degree as PL containing n‐3 PUFA. TAG containing n‐3 PUFA and soybean PL are widely used as functional food ingredients and pharmaceutical constituents and are inexpensive compared with PL containing n‐3 PUFA. Therefore, the combination of TAG containing n‐3 PUFA and soybean PL has potential as a useful and inexpensive component of functional foods.
L'obésité : réflexions anthropologiques autour des pratiques alimentaires dans la région de Tlemcen (Algérie)
Authors: Bessenouci C.
Published: January 2016

Le défi actuel de l'anthropologie de l'alimentation est de contribuer à la compréhension de certains aspects de problématiques nutritionnelles. En tant que science holistique, son approche entreprend de décrire, analyser et comparer les interactions existant entre nature et culture. Elle se représente le système alimentaire dans toute sa complexité sociale et culturelle. En fait, le présent article aborde l'alimentation humaine selon un angle systémique permettant de discuter, d'ores et déjà, de l'interaction des différents facteurs qui la régissent et leur impact sur la persistance de certains déséquilibres nutritionnels.

L'étude a été réalisée à Tlemcen (Algérie). Elle s'est donnée pour objectif d'identifier la culture alimentaire et sa relation avec le problème de l'obésité. Pour ce faire, un choix a été fait d'un échantillon de 100 personnes obèses (relevant des services de médecine interne du Centre Hospitalier Universitaire de Tlemcen) qui ont été sélectionnées sur la base de leurs caractéristiques physiques (taille et poids) et sur la considération que l'obésité est réelle lorsque l'indice de masse corporelle est égal à 30 kg/m2ou plus. Un formulaire spécial leur a été ainsi distribué, qui comprenait des informations sur leurs méthodes de choix alimentaires et leurs modes de nutrition.

Il en ressort que l'alimentation représente un moyen privilégié d'affirmation identitaire chez l'obèse, par conservatisme de culture culinaire algérienne. De plus, avec la modernité et la venue de l'alimentation industrielle ce même obèse se retrouve devant une situation ambivalente, dans laquelle un espace de liberté décisionnelle se serait dégagé en même temps qu'il aurait perdu la sécurité qu'apporte un système normatif socialement défini.

Tout ceci générant une anxiété constante dès lors qu'il s'agit de choix alimentaire. Aussi, le patient justifie un décalage entre représentations et pratiques exclusivement par manque de moyens économiques ou sous l'effet d'une éventuelle stigmatisation.