bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative risk of serious hypoglycemia with oral antidiabetic monotherapy: A retrospective cohort study
Authors: Leonard Charles E. , Han Xu , Brensinger Colleen M. , Bilker Warren B. , Cardillo Serena , Flory James H. , Hennessy Sean
Published: November 2017

Purpose

To examine and compare risks of serious hypoglycemia among antidiabetic monotherapy‐treated adults receiving metformin, a sulfonylurea, a meglitinide, or a thiazolidinedione.

Methods

We performed a retrospective cohort study of apparently new users of monotherapy with metformin, glimepiride, glipizide, glyburide, pioglitazone, rosiglitazone, nateglinide, or repaglinide within a dataset of Medicaid beneficiaries from California, Florida, New York, Ohio, and Pennsylvania. We did not include users of dipeptidyl peptidase‐4 inhibitors, glucagon‐like peptide‐1 agonists, or sodium‐glucose co‐transporter 2 inhibitors. We identified serious hypoglycemia outcomes within 180 days following new use using a validated, diagnosis‐based algorithm. We calculated age‐ and sex‐standardized outcome occurrence rates for each drug and generated propensity score–adjusted hazard ratios vs metformin using Cox proportional hazards regression.

Results

The ranking of standardized occurrence rates of serious hypoglycemia was glyburide > glimepiride > glipizide > repaglinide > nateglinide > rosiglitazone > pioglitazone > metformin. Rates were increased for all study drugs at higher average daily doses. Adjusted hazard ratios (95% confidence intervals) vs metformin were 3.95 (3.66‐4.26) for glyburide, 3.28 (2.98‐3.62) for glimepiride, 2.57 (2.38‐2.78) for glipizide, 2.03 (1.64‐2.52) for repaglinide, 1.21 (0.89‐1.66) for nateglinide, 0.90 (0.75‐1.07) for rosiglitazone, and 0.80 (0.68‐0.93) for pioglitazone.

Conclusions

Sulfonylureas were associated with the highest rates of serious hypoglycemia. Among all study drugs, the highest rate was seen with glyburide. Pioglitazone was associated with a lower adjusted hazard for serious hypoglycemia vs metformin, while rosiglitazone and nateglinide had hazards similar to that of metformin.
Application and optimisation of the Comparison on Extreme Laboratory Tests (CERT) algorithm for detection of adverse drug reactions: Transferability across national boundaries
Authors: Tham Mun Yee , Ye Qing , Ang Pei San , Fan Liza Y. , Yoon Dukyong , Park Rae Woong , Ling Zheng Jye , Yip James W. , Tai Bee Choo , Evans Stephen JW , Sung Cynthia
Published: November 2017

Purpose

The Singapore regulatory agency for health products (Health Sciences Authority), in performing active surveillance of medicines and their potential harms, is open to new methods to achieve this goal. Laboratory tests are a potential source of data for this purpose. We have examined the performance of the Comparison on Extreme Laboratory Tests (CERT) algorithm, developed by Ajou University, Korea, as a potential tool for adverse drug reaction detection based on the electronic medical records of the Singapore health care system.

Methods

We implemented the original CERT algorithm, comparing extreme laboratory results pre‐ and post‐drug exposure, and 5 variations thereof using 4.5 years of National University Hospital (NUH) electronic medical record data (31 869 588 laboratory tests, 6 699 591 drug dispensings from 272 328 hospitalizations). We investigated 6 drugs from the original CERT paper and an additional 47 drugs. We benchmarked results against a reference standard that we created from UpToDate 2015.

Results

The original CERT algorithm applied to all 53 drugs and 44 laboratory abnormalities yielded a positive predictive value (PPV) and sensitivity of 50.3% and 54.1%, respectively. By raising the minimum number of cases for each drug‐laboratory abnormality pair from 2 to 400, the PPV and sensitivity increased to 53.9% and 67.2%, respectively. This post hoc variation, named CERT400, performed particularly well for drug‐induced hepatic and renal toxicities.

Discussion

We have demonstrated that the CERT algorithm can be applied across national boundaries. One modification (CERT400) was able to identify adverse drug reaction signals from laboratory data with reasonable PPV and sensitivity, which indicates potential utility as a supplementary pharmacovigilance tool.
Global Proteome Analysis Links Lysine Acetylation to Diverse Functions in Oryza Sativa
Authors: Xue Chao , Liu Shuai , Chen Chen , Zhu Jun , Yang Xibin , Zhou Yong , Guo Rui , Liu Xiaoyu , Gong Zhiyun
Published: November 2017

Lysine acetylation (Kac) is an important protein post‐translational modification in both eukaryotes and prokaryotes. Herein, we report the results of a global proteome analysis of Kac and its diverse functions in rice (Oryza sativa). We identified 1353 Kac sites in 866 proteins in rice seedlings. A total of 11 Kac motifs are conserved, and 45% of the identified proteins are localized to the chloroplast. Among all acetylated proteins, 38 Kac sites are combined in core histones. Bioinformatics analysis revealed that Kac occurs on a diverse range of proteins involved in a wide variety of biological processes, especially photosynthesis. Protein–protein interaction networks of the identified proteins provided further evidence that Kac contributes to a wide range of regulatory functions. Furthermore, we demonstrated that the acetylation level of histone H3 (lysine 27 and 36) is increased in response to cold stress. In summary, our approach comprehensively profiles the regulatory roles of Kac in the growth and development of rice.
Substituent effects on gas‐phase homolytic Fe–N bond energies of m‐G‐C6H4NHFe(CO)2(η5‐C5H5) and m‐G‐C6H4N(COMe)Fe(CO)2(η5‐C5H5) studied using density functional theory methods
Authors: Zeng Qing , Li Zucheng , Wang Yi‐Bo
Published: November 2017

One of the most fundamental properties in chemistry is the bond dissociation energy, the energy required to break a specific bond of a molecule. In this paper, the Fe–N homolytic bond dissociation energies [ΔHhomo(Fe–N)'s] of 2 series of (meta‐substituted anilinyl)dicarbonyl(η5‐cyclopentadienyl) iron [m‐G‐C6H4NHFp (1)] and (meta‐substituted α‐acetylanilinyl)dicarbonyl(η5‐cyclopentadienyl) iron [m‐G‐C6H4N(COMe)Fp (2)] were studied using density functional theory methods with large basis sets. In this study, Fp is (η5‐C5H5)Fe(CO)2, and G is NO2, CN, COMe, CO2Me, CF3, Br, Cl, F, H, Me, MeO, and NMe2. The results show that Tao‐Perdew‐Staroverov‐Scuseria, Minnesota 2006, and Becke's power‐series ansatz from 1997 with dispersion corrections functionals can provide the best price/performance ratio and accurate predictions of ΔHhomo(Fe–N)'s. The ΔΔHhomo(Fe–N)'s (1 and 2) conform to the captodative principle. The polar effects of the meta‐substituents show the dominant role to the magnitudes of ΔΔHhomo(Fe–N)'s. σα· and σc· values for meta‐substituents are all related to polar effects. Spin‐delocalization effects of the meta‐substituents in ΔΔHhomo(Fe–N)'s are small but not necessarily zero. RE plays an important role in determining the net substituent effects on ΔHhomo(Fe–N)'s. Insight from this work may help the design of more effective catalytic processes.
Strategy for rational control of stereosequence in free radical polymerization of acrylates
Authors: Tanaka Hitoshi , Maki Kazuyoshi , Matsubara Yoshitaka
Published: November 2017

Radical polymerization of cyclic analogs of acrylates, (S)‐ and (R)‐2‐isopropyl‐5‐methylene‐1,3‐dioxolan‐4‐ones (1S and 1R), successfully afforded a functional polymer having the tacticity continuously controlled from 29% to ∼100% of meso triad (mm) over a wide range of temperature only by changing the molar ratio of 1S/1R in feed. Plot of the number fractions of the triad versus diad of poly(1) was in good agreement with the Bernoulli statistics. In the polymerization in chiral solvents having analogs structure of the monomers, the tacticity and specific rotation of the resulting polymer were specifically varied depending on the structure and concentration of the solvents. Model propagation reaction at dimeric radical calculated with density functional theory reproduced a methodical induction of the chirality to the main chain from the branched chiral monomeric unit, which supports the experimental expectations. It is remarkable that the ceiling temperature of 1 is tremendously high, for example, 193 °C in [1 (ee = 72.6%)] = 0.05 mol/L, and the isospecific polymerization is maintained even at such a high temperature, which enabled the control of polymer tacticity over a wide range of temperature. The mechanism of the stereosequence in radical polymerization was discussed experimentally and theoretically. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 184–193
Effect of chloride on bacterial inactivation by discharge plasma at the gas‐solution interface: Potentiation or attenuation?
Authors: Ke Zhigang , Chen Zhu , Huang Qing
Published: November 2017

Bacterial inactivation by discharge plasma at the gas‐solution interface is affected by many factors. Chloride is essential for all life, but whether chloride can modulate the compositions and levels of plasma‐produced reactive species and consequently influence the bactericidal efficiency is still undefined. In this work, the plasma‐induced inactivation behavior of Gram‐negative Escherichia coli and Gram‐positive Bacillus subtilis without or with the presence of chloride were investigated. Potentiation effect of chloride on bacterial inactivation was observed for O2 plasma, but attenuation effect was discovered for N2 and air plasmas. For unveiling the underlying mechanisms, the influence of chloride on the production of reactive species including chlorine, hydroxyl radical, hydrogen peroxide and nitrite was examined.
99mTc‐MIP‐1404‐SPECT/CT for the detection of PSMA‐positive lesions in 225 patients with biochemical recurrence of prostate cancer
Authors: Schmidkonz Christian , Hollweg Claudia , Beck Michael , Reinfelder Julia , Goetz Theresa I. , Sanders James C. , Schmidt Daniela , Prante Olaf , Bäuerle Tobias , Cavallaro Alexander , Uder Michael , Wullich Bernd , Goebell Peter , Kuwert Torsten , Ritt Philipp
Published: November 2017

Background

99mTc‐MIP‐1404 (Progenics Pharmaceuticals, Inc., New York, NY) is a novel, SPECT‐compatible 99mTc‐labeled PSMA inhibitor for the detection of prostate cancer. We present results of its clinical use in a cohort of 225 men with histologically confirmed prostate cancer referred for workup of biochemical relapse.

Methods

From April 2013 to April 2017, 99mTc‐MIP1404‐scintigraphy was performed in 225 patients for workup of PSA biochemical relapse of prostate cancer. Whole‐body planar and SPECT/CT images of the lower abdomen and thorax were obtained 3‐4 h p.i. of 710 ± 64 MBq 99mTc‐MIP‐1404. Images were visually analyzed for presence and location of abnormal uptake. In addition, quantitative analysis of the SPECT/CT data was carried out on a subset of 125 patients. Follow‐up reports of subsequent therapeutic interventions were available for 59% (139) of all patients.

Results

Tracer‐positive lesions were detected in 77% (174/225) of all patients. Detections occurred at the area of local recurrence in the prostate in 25% of patients (or a total of 56), with metastases in lymph nodes in 47% (105), bone in 27% (60), lung in 5% (12), and other locations in 2% (4) of patients. Detection rates were 90% at PSA levels ≥2 ng/mL and 54% below that threshold. Lesional SUVmax values were, on average, 32.2 ± 29.6 (0.8–142.2), and tumor‐to‐normal ratios 146.6 ± 160.5 (1.9–1482.4). The PSA level correlated significantly with total uptake of MIP‐1404 in tumors (P < 0.001). Furthermore, total tumor uptake was significantly higher in patients with Gleason scores ≥8 compared to those with Gleason scores ≤7 (P < 0.05). In patients with androgen deprivation therapy, the detection rate was significantly higher compared to patients without androgen deprivation therapy (86% vs 71%, P < 0.001). Based on 99mTc‐MIP‐1404‐imaging and other information, an interdisciplinary tumor board review recommended changes to treatment plans in 74% (104/139) of those patients for whom the necessary documentation was available.

Conclusion

SPECT/CT with 99mTc‐labeled MIP‐1404 has a high probability in detecting PSMA‐positive lesions in patients with elevated PSA. Statistical analysis disclosed significant relationship between quantitative 99mTc‐MIP‐1404 uptake, PSA level, and Gleason score.
Circulating microRNAs and treatment response in the Phase II SWOG S0925 study for patients with new metastatic hormone‐sensitive prostate cancer
Authors: Cheng Heather H. , Plets Melissa , Li Hongli , Higano Celestia S. , Tangen Catherine M. , Agarwal Neeraj , Vogelzang Nicholas J. , Hussain Maha , Thompson Ian M. , Tewari Muneesh , Yu Evan Y.
Published: November 2017

Background

Previous studies suggest circulating, blood‐based microRNAs (miRNAs) may serve as minimally invasive prostate cancer biomarkers, however there is limited data from prospective clinical trials. Here, we explore the role of candidate plasma miRNAs as potential biomarkers in the SWOG 0925 randomized phase II study of androgen deprivation combined with cixutumumab versus androgen deprivation alone in patients with new metastatic hormone‐sensitive prostate cancer.

Methods

Correlative biospecimens, including circulating tumor cells (CTCs) and plasma for miRNA analysis, were collected at baseline and after 12 weeks on treatment from 50 patients enrolled on SWOG 0925. Circulating microRNAs were quantified using real‐time RT‐PCR microRNA array that allowed specific analysis of previously identified candidate miRNAs (miR‐141, miR‐200a, miR‐200b, miR‐210, and miR‐375) as well as discovery analysis to identify new candidate miRNAs. MiRNA levels were correlated to previously reported CTC counts using CellSearch® (Veridex) and with the primary study outcome of 28‐week PSA response (≤0.2, 0.2 to ≤4.0, or >4.0 ng/mL), previously shown to correlate with overall survival.

Results

We observed a correlation between baseline circulating miR‐141, miR‐200a, and miR‐375 levels with baseline CTCs. Baseline miR‐375 levels were associated with 28‐week PSA response (≤0.2, 0.2 to ≤4.0, or >4.0 ng/mL, P = 0.007). Using ROC curve analysis, there was no significant difference between baseline miR‐375 and baseline CTC in predicting 28‐week PSA response (≤0.2 vs >0.2 ng/mL). To discover novel candidate miRNAs, we analyzed 365 miRNAs for association with the 28‐week PSA response endpoint and identified new candidate miRNAs along with the existing candidates miR‐375 and miR‐200b (P = 0.0012, P = 0.0046, respectively.

Conclusions

Baseline plasma miR‐141, miR‐200a, and miR‐375 levels are associated with baseline CTC count. Baseline miR‐375 was also associated with the trial endpoint of 28‐week PSA response. Our results provide evidence that circulating miRNA biomarkers may have value as prognostic biomarkers and warrant further study in larger prospective clinical trials.
The orally active pterocarpanquinone LQB‐118 exhibits cytotoxicity in prostate cancer cell and tumor models through cellular redox stress
Authors: Martino Thiago , Kudrolli Tarana A. , Kumar Binod , Salviano Isis , Mencalha André , Coelho Marsen Garcia P. , Justo Graça , Costa Paulo R. Ribeiro , Sabino Kátia C. Carvalho , Lupold Shawn E.
Published: November 2017

Background

The targeted induction of reactive oxygen species (ROS) is a developing mechanism for cancer therapy. LQB‐118 is a pterocarpanquinone and ROS‐inducing agent with proven antineoplastic activity. Here, LQB‐118 efficacy and mechanism of activity, were examined in Prostate Cancer (PCa) cell and tumor models.

Methods

PC3, LNCaP, and LAPC4 PCa cells were applied. Dicoumarol treatment was used to inhibit quinone reductase activity. N‐acetylcysteine (NAC) was applied as a ROS scavenger. ROS production was quantified by H2DCFDA flow cytometry. LQB‐118 treated cells were evaluated for changes in lipid peroxidation, viability, and apoptosis. Treatment‐induced gene expression was measured by RT‐qPCR and Western Blot. SOD1 knockdown was achieved with siRNA or miRNA mimic transfection. MicroRNA specificity was determined by 3′UTR reporter assay. Oral LQB‐118 treatment (10 mg/kg/day) efficacy was determined in athymic male nude mice bearing subcutaneous PC3 xenograft tumors.

Results

LQB‐118 treatment triggered PCa cell death and apoptosis. Therapeutic activity was at least partially dependent upon quinone reduction and ROS generation. LQB‐118 treatment caused an increase in cellular ROS and lipid peroxidation. Treated cells exhibited elevated levels of NQO1, Nrf2, and SOD1. The miRNAs miR‐206, miR‐1, and miR‐101 targeted and reduced SOD1 expression. The knockdown of SOD1, by siRNA or miRNA, enhanced LQB‐118 cytotoxicity. Orally administered LQB‐118 treatment significantly reduced the growth of established PCa xenograft tumors.

Conclusion

LQB‐118 is a developing and orally active pterocarpanquinone agent that effectively kills PCa cells through quinone reduction and ROS generation. The inhibition SOD1 expression enhances LQB‐118 activity, presumably by impairing the cellular antioxidant response.
Comparative potency of obeticholic acid and natural bile acids on FXR in hepatic and intestinal in vitro cell models
Authors: Zhang Yuanyuan , LaCerte Carl , Kansra Sanjay , Jackson Jonathan P. , Brouwer Kenneth R. , Edwards Jeffrey E.
Published: November 2017

Obeticholic acid (OCA) is a semisynthetic farnesoid X receptor (FXR) agonist, an analogue of chenodeoxycholic acid (CDCA) which is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA). OCA efficiently inhibits bile acid synthesis and promotes bile acid efflux via activating FXR‐mediated mechanisms in a physiologically relevant in vitro cell system, Sandwich‐cultured Transporter Certified ™ human primary hepatocytes (SCHH). The study herein evaluated the effects of UDCA alone or in combination with OCA in SCHH. UDCA (≤100 μmol/L) alone did not inhibit CYP7A1 mRNA, and thus, no reduction in the endogenous bile acid pool observed. UDCA ≤100 μmol/L concomitantly administered with 0.1 μmol/L OCA had no effect on bile acid synthesis beyond what was observed with OCA alone. Furthermore, this study evaluated human Caco‐2 cells (clone C2BBe1) as in vitro intestinal models. Glycine conjugate of OCA increased mRNA levels of FXR target genes in Caco‐2 cells, FGF‐19, SHP, OSTα/β, and IBABP, but not ASBT, in a concentration‐dependent manner, while glycine conjugate of UDCA had no effect on the expression of these genes. The results suggested that UDCA ≤100 μmol/L did not activate FXR in human primary hepatocytes or intestinal cell line Caco‐2. Thus, co‐administration of UDCA with OCA did not affect OCA‐dependent pharmacological effects.
Examining the life course sequence of intending to move and moving
Authors: Clark William A.V. , Lisowski William
Published: November 2017

There is now a substantial body of research that examines the process of making decisions about moving. The questions of interest in that work and in this study using U.S. data are, first, how do life course changes get translated into intentions to move and, second, to what extent are intentions realised or unrealised. This study extends previous work by considering a longer interval in the planning process and by examining how life cycle changes create intentions, which in turn are translated, or not, into actual moves. We study the antecedents of the expressed intention to move and the outcomes that follow the expressed intention to move. We test the process of forming intentions and moving in the context of life course events and changes. We find that the subset of variables that create the intention to move vary subtly from the variables that create moves, though the triggering effects of family composition change are critical dimensions of both creating intentions and fulfilling those intentions by moving.
And then came Brexit: Experiences and future plans of young EU migrants in the London region
Authors: Lulle Aija , Moroşanu Laura , King Russell
Published: November 2017

This paper investigates the potential rupture that the United Kingdom's “Brexit” referendum of June 23, 2016, might bring about in intra‐European Union youth mobilities, with a specific focus on the London region. In many respects, and counter‐intuitively given the Brexit result, London has already become a “Eurocity”: a magnet for young people, both highly educated and less educated, from all over Europe who, especially since the turn of the millennium, have flocked to the city and its wider region to work, study, and play. Now, these erstwhile open‐ended migration trajectories have been potentially disrupted by a referendum result that few anticipated, and whose consequential results are still unclear. The main theoretical props for our analysis are the notions of “liquid migration,” “tactics of belonging,” “whiteness,” “privilege,” and “affect.” Data are drawn from 60 in‐depth interviews with Irish, Italian, and Romanian young‐adult students and higher and lower skilled workers, carried out in late 2015 and early 2016, plus 27 reinterviews carried out in late 2016, post‐Brexit. Results indicate participants' profound and generally negative reaction to Brexit and, as a consequence, a diversity of uncertainties and of plans over their future mobility: either to stay put using “tactics of belonging,” or to return home earlier than planned, or to move on to another country. Finally, we find evidence that new hierarchies and boundaries are drawn between intra‐European Union migrants as a result of Brexit.
Optimized Dielectric Film for Maximum Sensitivity of Nearly Guided‐Wave Surface Plasmon Resonance Sensor
Authors: Lin Chengyou , Chen Shujing
Published: November 2017

In this paper, the dielectric film of the nearly guided‐wave surface plasmon resonance (NGWSPR) sensor is optimized to achieve the maximum sensitivity. By optimizing the thickness of dielectric (Si, AlAs, TiO2, and Si3N4) film in a NGWSPR sensor, the optimized sensitivity of the NGWSPR sensor can be obtained. The optimized sensitivity of the NGWSPR sensor with AlAs film is 5.43, 8.47, and 24.41% higher than that of the NGWSPR sensor with Si, TiO2, or Si3N4 film respectively. In addition, by analyzing the electric field intensity of NGWSPR sensors, the origin of highest sensitivity achieved by the NGWSPR sensor with AlAs film is investigated. Furthermore, by comparing the optimized sensitivity of the NGWSPR sensor with different refractive index of dielectric film, the existence of optimal refractive index of dielectric film for the maximum sensitivity is confirmed. Besides, the effects of refractive index of prism on the optimal dielectric refractive index and the maximum sensitivity are also studied.
Direct Conductive Patterning on 3D Printed Structure Using Laser
Authors: Shin In Joo , Park Min Soo
Published: November 2017

Recently, several investigations have been reported on hybrid technology that embeds circuits on 3D printed models during processing. A new direct fabrication method of conductive patterns on 3D printed structure with laser is suggested for process simplicity. In order to fabricate conductive patterns, a conventional 1064 nm fiber laser is utilized to selectively remove the polymer and connect the copper particles to each other. The fabricated patterns achieve high conductivity with a resistance of 0.15 Ω cm−1 when the length of the pattern is 50 mm. In this study, the surface property changes of the 3D printed structure through laser irradiation are presented and the influences of the laser parameters, including average power, scanning mode (repetition rate), scanning speed, and scan line spacing, on the process efficiency are investigated. Finally, a prototype of an electronic circuit is made and demonstrated for powering up LEDs. The proposed method allows to easily and rapidly fabricate high conductive patterns on complex 3D structures by combining the additive manufacturing technology with laser irradiation.
Preparation and Characterization of Curcumin Loaded Chitosan Nanoparticles for Photodynamic Therapy
Authors: Duse Lili , Baghdan Elias , Pinnapireddy Shashank R. , Engelhardt Konrad H. , Jedelská Jarmila , Schaefer Jens , Quendt Peer , Bakowsky Udo
Published: November 2017

Photodynamic therapy (PDT) is a minimally invasive tumor targeting strategy, in which tumor tissues can be selectively destroyed. Upon excitation with light of a specific wavelength, a photosensitizer can produce reactive oxygen species (ROS) in the presence of molecular oxygen, thereby exhibiting a cytotoxic effect toward the surrounding tissues, giving a total control on the onset of therapy. In this research work, curcumin as a natural photosensitizer has been investigated against cancer cells. To enhance the solubility of curcumin, a nanoformulation is developed using chitosan as biodegradable and biocompatible polymer that has the ability to encapsulate curcumin and improve its therapeutic effect. Physicochemical characterizations revealed that the prepared formulations were in the nanoscale range and had a positive ζ‐potential. Upon irradiation using a novel LED device (λex = 457 nm), curcumin nanoparticles were able to generate ROS and destroy tumor cells. Moreover, unloaded nanoparticles exhibited nonsignificant phototoxicity. These outcomes confirm the importance of curcumin nanoparticles in enhancing the efficacy of curcumin and offer new insights in the field of PDT against cancer.
Finite Element Analysis of the Influence of the Covering Auxetic Layer of Plate on the Contact Pressure
Authors: Strek Tomasz , Matuszewska Agata , Jopek Hubert
Published: November 2017

The contact problem between two bodies: plate and semi‐cylindrical bar is studied in this paper. The analysis concerns the contact pressure distribution along the contact region, as well as the deflection of the plate. Furthermore, the case of a composite plate covered with the auxetic layer is also considered. The influence of the Poisson's ratio of the layer on the behavior of the plate is studied. The contact pressure distribution along the contact area is analyzed using finite element analysis.
Effectiveness of phase I applications for identifying randomly scattered out‐of‐control observations and estimating control chart parameters
Authors: Testik Murat Caner , Weiß Christian H. , Koca Yesim , Testik Ozlem Muge
Published: November 2017

Estimation of unknown process parameters with fixed‐size samples are studied in the following. The standard textbook approach for phase I control chart implementation with a Shewhart control chart is evaluated for the case of normally distributed independent observations with random sampling. The
charts are simultaneously implemented by generating observations that have a given percentage of randomly scattered out‐of‐control observations. Simulating the phase I steps, where out‐of‐control samples are detected iteratively by determining trial control limits, identifying samples exceeding these limits, and revising the control limits, the standard practice is evaluated in terms of both detection performance and quality of parameter estimates. It is shown that standard phase I control chart implementations with 3‐σ‐limits may perform very poorly in identifying true out‐of‐control observations and providing a reference set of in‐control observations for estimation in some practical settings. A chart design with 2‐σ‐limits is recommended for a successful phase I analysis.
Bayesian design of life testing plans under hybrid censoring scheme
Authors: Bhattacharya Ritwik , Pradhan Biswabrata
Published: November 2017

This article describes Bayes design of hybrid‐censored life testing plans. A design criterion based on posterior variance of quantile of suitable order is proposed. The Weibull lifetime model with gamma prior distribution on model parameters is considered for illustration. Instead of using Markov chain Monte Carlo technique to compute the posterior quantities of interest, a large sample approximation is considered, which is easy to apply. Some life testing plans are presented. The effect of different prior information on the posterior quantity of interest is studied.
Improving negative liquid chromatography/electrospray ionization mass spectrometry lipidomic analysis of human plasma using acetic acid as a mobile‐phase additive
Authors: Monnin Cian , Ramrup Parsram , Daigle‐Young Carolann , Vuckovic Dajana
Published: November 2017

Rationale

Mobile‐phase additives in liquid chromatography/mass spectrometry (LC/MS) are used to improve peak shape, analyte ionization efficiency and method coverage. Both basic and acidic mobile phases have been used successfully for negative electrospray ionization (ESI), but very few systematic investigations exist to date to justify the choice of mobile phase. Acetic acid was previously shown to improve ionization in untargeted metabolomics of urine, but has not been investigated in lipidomics. The goal of this study was to systematically compare the performance of acetic acid to that of other commonly employed additives in negative LC/ESI‐MS lipidomics.

Methods

The performance of acetic acid was compared to that of commonly used mobile‐phase additives in lipidomics, namely ammonium acetate, ammonium acetate with acetic acid and ammonium hydroxide, using lipid standard solutions containing representatives of major mammalian lipid subclasses and isopropanol‐precipitated human plasma. This design allowed comparison of the influence of additive and additive concentration on lipid signal intensity, lipid peak shape and lipid coverage in both simple and complex biological matrices using both Orbitrap and quadrupole time‐of‐flight MS platforms with different ESI source designs.

Results

Ammonium hydroxide caused 2‐ to 1000‐fold signal suppression of all lipid classes in comparison to acetic acid. In comparison to ammonium acetate, acetic acid increased lipid signal intensity from 2‐ to 19‐fold for 11 lipid subclasses, and decreased ionization efficiency only for ceramide and phosphatidylcholine lipid classes which can be effectively ionized in positive ESI mode. The improved ionization efficiency using acetic acid also increased lipid coverage by 21–50% versus ammonium acetate additive.

Conclusions

Acetic acid at a concentration of 0.02% (v/v) is the suggested choice as a mobile‐phase additive for lipidomics and targeted lipid profiling with negative LC/ESI‐MS based on signal enhancement and improved lipid coverage compared to ammonium acetate, ammonium acetate with acetic acid and ammonium hydroxide mobile phases.
Investigation of metabolic profile of pimavanserin in rats by ultrahigh‐performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry
Authors: Wu Wenying , Chu Yanjie , Wang Shixiao , Sun Xiaoyang , Zhang Jingjing , Wang Yannian , Chen Xiaohui
Published: November 2017

Rationale

Pimavanserin, a selective serotonin 2A receptor inverse agonist, is a promising candidate for treating Parkinson's disease psychosis. Our previous study revealed that there might be the presence of extensive metabolites of pimavanserin in rats. However, the metabolic fate of pimavanserin in vivo remains unknown. Thus, it is essential to develop an efficient method to investigate the metabolic profile of pimavanserin in rats. Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR‐MS) to date has the highest mass measurement accuracy and resolution of any mass spectrometry platform.

Methods

After a single intragastric administration of pimavanserin at a dose of 50 mg kg−1, plasma, bile, urine and feces were collected from rats. A novel and efficient strategy was developed to analyze the metabolic profile of pimavanserin in vivo based on ultrahigh‐performance liquid chromatography (UHPLC) coupled with FT‐ICR‐MS.

Results

A total of 23 metabolites were detected and tentatively identified through comparing their mass spectrometry profiles with those of pimavanserin. These metabolites were found in feces (22), bile (21), rat urine (16) and plasma (15). Results demonstrated that metabolic pathways of pimavanserin in rats included dehydrogenation, demethylation, deethylation, depropylation, debutylation, hydroxylation, dihydroxylation and trihydroxylation.

Conclusions

A total of 22 phase I metabolites of pimavanserin were detected and tentatively identified. This report presents the first study of screening and identification of the metabolites of pimavanserin. The UHPLC/FT‐ICR‐MS method is a powerful tool for exploring and identifying metabolites in complex biological samples.
Pictures or pellets? Comparing camera trapping and dung counts as methods for estimating population densities of ungulates
Authors: Pfeffer Sabine E. , Spitzer Robert , Allen Andrew M. , Hofmeester Tim R. , Ericsson Göran , Widemo Fredrik , Singh Navinder J. , Cromsigt Joris P.G.M.
Published: November 2017

Across the northern hemisphere, land use changes and, possibly, warmer winters are leading to more abundant and diverse ungulate communities causing increased socioeconomic and ecological consequences. Reliable population estimates are crucial for sustainable management, but it is currently unclear which monitoring method is most suitable to track changes in multi‐species assemblages. We compared dung counts and camera trapping as two non‐invasive census methods to estimate population densities of moose Alces alces and roe deer Capreolus capreolus in Northern Sweden. For camera trapping, we tested the random encounter model (REM) which can estimate densities without the need to recognize individual animals. We evaluated different simplification options of the REM in terms of estimates of detection distance and angle (raw data vs. modelled) and of daily movement rate (camera trap based vs. telemetry based). In comparison to density estimates from camera traps, we found that, dung counts appeared to underestimate population density for roe deer, but not for moose. Estimates of detection distance and angle from modelled versus raw camera data resulted in nearly identical outcomes. The telemetry‐derived daily movement rate for moose and roe deer resulted in much higher density estimates than the camera trap‐derived estimates. We suggest that camera trapping may be a robust complement to dung counts when monitoring ungulate communities, particularly when similarities between dung pellets from sympatric deer species make unambiguous assignment difficult. Moreover, we show that a simplified use of the REM method holds great potential for large‐scale citizen science‐based programmes (e.g. involving hunters) that can track the rapidly changing European wildlife landscape. We suggest to include camera trapping in management programmes, where the analysis can be verified via web‐based applications.
Robust fit of Bayesian mixed effects regression models with application to colony forming unit count in tuberculosis research
Authors: Burger Divan Aristo , Schall Robert
Published: November 2017

Early bactericidal activity of tuberculosis drugs is conventionally assessed using statistical regression modeling of colony forming unit (CFU) counts over time. Typically, most CFU counts deviate little from the regression curve, but gross outliers due to erroneous sputum sampling are occasionally present and can markedly influence estimates of the rate of change in CFU count, which is the parameter of interest. A recently introduced Bayesian nonlinear mixed effects regression model was adapted to offer a robust approach that accommodates both outliers and potential skewness in the data. At its most general, the proposed regression model fits the skew Studenttdistribution to residuals and random coefficients. Deviance information criterion statistics and compound Laplace‐Metropolis marginal likelihoods were used to discriminate between alternative Bayesian nonlinear mixed effects regression models. We present a relatively easy method to calculate the marginal likelihoods required to determine compound Laplace‐Metropolis marginal likelihoods, by adapting methods available in currently available statistical software. The robust methodology proposed in this paper was applied to data from 6 clinical trials. The results provide strong evidence that the distribution of CFU count is often heavy tailed and negatively skewed (suggesting the presence of outliers). Therefore, we recommend that robust regression models, such as those proposed here, should be fitted to CFU count.
A Bayesian approach for analyzing zero‐inflated clustered count data with dispersion
Authors: Choo‐Wosoba Hyoyoung , Gaskins Jeremy , Levy Steven , Datta Somnath
Published: November 2017

In practice, count data may exhibit varying dispersion patterns and excessive zero values; additionally, they may appear in groups or clusters sharing a common source of variation. We present a novel Bayesian approach for analyzing such data. To model these features, we combine the Conway‐Maxwell‐Poisson distribution, which allows both overdispersion and underdispersion, with a hurdle component for the zeros and random effects for clustering. We propose an efficient Markov chain Monte Carlo sampling scheme to obtain posterior inference from our model. Through simulation studies, we compare our hurdle Conway‐Maxwell‐Poisson model with a hurdle Poisson model to demonstrate the effectiveness of our Conway‐Maxwell‐Poisson approach. Furthermore, we apply our model to analyze an illustrative dataset containing information on the number and types of carious lesions on each tooth in a population of 9‐year‐olds from the Iowa Fluoride Study, which is an ongoing longitudinal study on a cohort of Iowa children that began in 1991.
Influence of TiO2 on the Viscosity of a High Alumina Slag and on Carbon Brick Corrosion
Authors: Xu Ren Ze , Zhang Jian Liang , Ma Ru Ye , Jiao Ke Xin , Zhao Yong An
Published: November 2017

The influence of TiO2 on viscosities of CaO–SiO2–MgO–Al2O3–Cr2O3‐based slags and the corrosion mechanism of carbon brick used in blast furnace hearth by slags was investigated in this work. From the viscosity experimental results, it was found that the viscosity decreased with the addition of TiO2. Furthermore, the critical temperature and activation energy for the viscous flow of slags also decreased with increasing content of TiO2. The corrosion of carbon brick depended on the component of the brick surface in contact to the molten slags. In the region consisting mainly of carbon, the corrosion of carbon brick may be caused by the oxidation of carbon and in lower carbon content area, the corrosion of brick was mainly caused by the dissolution and slag penetration. The corrosion of carbon brick by slags could be a consequence of carbon oxidation, brick dissolution and slag infiltration, and the degradation of carbon brick was accelerated with the addition of TiO2.
Trag‐ und Verformungsverhalten von Verbundfugen mit elastischem Verbund
Authors: Kostadinova Natali , Kurz Wolfgang
Published: November 2017

Die Leistungsfähigkeit moderner Verbundkonstruktionen aus Stahl und Beton wird maßgeblich durch das Trag‐ und Verformungsverhalten sowie das Verformungsvermögen der Verbundfuge mitbestimmt. Die weitere Entwicklung hinsichtlich der Sicherheit und Wirtschaftlichkeit verlangt ein tieferes Verständnis der Tragmechanismen, um auch die Verformungen und Verformbarkeiten der Tragelemente besser berücksichtigen zu können. Dabei haben die Verbundmittel und ihre Nachgiebigkeit eine enorme Rolle für das Trag‐ und Verformungsverhalten der Verbundkonstruktionen. Neben den Verschiebungen parallel zur Verbundfuge, die in den bestehenden Untersuchungen zur Theorie des verschieblichen Verbundes berücksichtigt werden, sollen auch die Abhebungen zwischen den Fügepartnern in die Untersuchungen eingehen. Das neuartige Berechnungsmodell von Verbundträgern wird zunächst auf die elastische Verformbarkeit von Kopfbolzendübeln aufgebaut. Das Bemessungsmodell mit seinen relevanten Parametern wird erläutert. Die Lösungsergebnisse werden mit Versuchsergebnissen und Simulationsberechnungen verglichen.
Zum Kleben stückverzinkter Bauteile
Authors: Abeln Björn , Richter Carl , Feldmann Markus
Published: November 2017

Es soll ein Konzept für ein verlässliches klebtechnisches Fügen verzinkter Halbzeuge erarbeitet werden. Im Fokus stehen neben der Festigkeit der Zinkschicht selbst die Haftfestigkeit der Klebung auf der Zinkschicht stückverzinkter Bauteile sowie die sich daraus ergebende Definition geeigneter Oberflächenvorbehandlungsverfahren. Dazu werden drei höherfeste und hochmodulige Klebstoffe für die speziellen Anforderungen des Bauwesens ausgewählt. Als Oberflächenvorbehandlung kommen neben dem üblichen „Sweepen” zwei Beizmedien im Tauch‐ und Sprühverfahren zur Anwendung, womit ein selektiver Schichtabtrag im Bereich der Reinzinkphase der Zinkschicht eingestellt werden konnte. Die Untersuchung ungealterter und vorbewitterter Zinkschichten zeigt einen deutlichen Einfluss der Oberflächenvorbehandlung auf die Alterungsbeständigkeit der Klebverbunde. Die Ergebnisse von standardisierten Prüfkörpern können auf Kleinteilproben übertragen werden, mit deren Hilfe die Lastübertragung im Stahl‐Zinkschicht‐Klebstoff‐Verbund an praxisnahen Geometrien untersucht und die Beizanleitung im Herstellungsprozess auf ihre Anwendbarkeit bestätigt werden können. Mit den Untersuchungen konnte geklärt werden, wie Klebungen auf stückverzinkten Oberflächen konzeptioniert werden müssen, um gleiche Festig‐ und Zuverlässigkeiten wie auf unverzinkten Baustahloberflächen zu erhalten.
Querschnittsgestaltung von Stahlverbundbrücken
Authors: Wehnert‐Brigdar Alexandra , Sprinke Peter , Höfler Thomas
Published: November 2017

Herrn Univ.‐Prof. Dr.‐Ing. Rolf Kindmann zur Vollendung seines 70. Lebensjahres gewidmet

Das Verkehrsaufkommen insbesondere im Fernverkehrsnetz der Autobahnen hat sich in den letzten Jahrzehnten vervielfacht. Zur Engpassbeseitigung wird auf besonders beanspruchten Streckenabschnitten ein Ausbau der Verkehrsanlagen erforderlich. Der marode Brückenbestand wird in diesem Zusammenhang erneuert. Die Ausführung erfolgt in der Regel mit getrennten Richtungsfahrbahnen. Die zu erneuernden Teilbauwerke müssen dabei immer mehr Fahrstreifen mit Auswirkungen auf die Querschnittsgestaltung aufnehmen. In Abhängigkeit von Spannweiten und Überbaubreiten werden anhand von Beispielen mögliche Querschnittsformen bei Wahl eines Stahlverbundüberbaus vorgestellt. Die Vor‐ und Nachteile einzelner Querschnittsformen werden diskutiert.
Why does the orientation change mess up my Android application? From GUI failures to code faults
Authors: Amalfitano Domenico , Riccio Vincenzo , Paiva Ana C. R. , Fasolino Anna Rita
Published: November 2017

This paper investigates the failures exposed in mobile apps by the mobile‐specific event of changing the screen orientation. We focus on GUI failures resulting in unexpected GUI states that should be avoided to improve the apps quality and to ensure better user experience. We propose a classification framework that distinguishes 3 main classes of GUI failures due to orientation changes and exploit it in 2 studies that investigate the impact of such failures in Android apps. The studies involved both open‐source and apps from Google Play that were specifically tested exposing them to orientation change events. The results showed that more than 88% of these apps were affected by GUI failures, some classes of GUI failures were more common than others, and some GUI objects were more frequently involved. The app source code analysis allowed us to identify 6 classes of common faults causing specific GUI failures.
Factors Predicting Ethiopian Anesthetists’ Intention to Leave Their Job
Authors: Kols Adrienne , Kibwana Sharon , Molla Yohannes , Ayalew Firew , Teshome Mihereteab , van Roosmalen Jos , Stekelenburg Jelle
Published: November 2017

Background

Ethiopia has rapidly expanded training programs for associate clinician anesthetists in order to address shortages of anesthesia providers. However, retaining them in the public health sector has proven challenging. This study aimed to determine anesthetists’ intentions to leave their jobs and identify factors that predict turnover intentions.

Methods

A nationally representative, cross‐sectional survey of 251 anesthetists working in public‐sector hospitals in Ethiopia was conducted in 2014. Respondents were asked whether they planned to leave the job in the next year and what factors they considered important when making decisions to quit. Bivariate and multivariable logistic regressions were conducted to investigate 16 potential predictors of turnover intentions, including personal and facility characteristics as well as decision‐making factors.

Results

Almost half (n = 120; 47.8%) of anesthetists planned to leave their jobs in the next year, and turnover intentions peaked among those with 2–5 years of experience. Turnover intentions were not associated with the compulsory service obligation. Anesthetists rated salary and opportunities for professional development as the most important factors in decisions to quit. Five predictors of turnover intentions were significant in the multivariable model: younger age, working at a district rather than regional or referral hospital, the perceived importance of living conditions, opportunities for professional development, and conditions at the workplace.

Conclusions

Human resources strategies focused on improving living conditions for anesthetists and expanding professional development opportunities may increase retention. Special attention should be focused on younger anesthetists and those posted at district hospitals.
Measuring Decision‐Making During Thyroidectomy: Validity Evidence for a Web‐Based Assessment Tool
Authors: Madani Amin , Gornitsky Jordan , Watanabe Yusuke , Benay Cassandre , Altieri Maria S. , Pucher Philip H. , Tabah Roger , Mitmaker Elliot J.
Published: November 2017

Background

Errors in judgment during thyroidectomy can lead to recurrent laryngeal nerve injury and other complications. Despite the strong link between patient outcomes and intraoperative decision‐making, methods to evaluate these complex skills are lacking. The purpose of this study was to develop objective metrics to evaluate advanced cognitive skills during thyroidectomy and to obtain validity evidence for them.

Methods

An interactive online learning platform was developed (www.thinklikeasurgeon.com). Trainees and surgeons from four institutions completed a 33‐item assessment, developed based on a cognitive task analysis and expert Delphi consensus. Sixteen items required subjects to make annotations on still frames of thyroidectomy videos, and accuracy scores were calculated based on an algorithm derived from experts’ responses (“visual concordance test,” VCT). Seven items were short answer (SA), requiring users to type their answers, and scores were automatically calculated based on their similarity to a pre‐populated repertoire of correct responses. Test–retest reliability, internal consistency, and correlation of scores with self‐reported experience and training level (novice, intermediate, expert) were calculated.

Results

Twenty‐eight subjects (10 endocrine surgeons and otolaryngologists, 18 trainees) participated. There was high test–retest reliability (intraclass correlation coefficient = 0.96; n = 10) and internal consistency (Cronbach’s α = 0.93). The assessment demonstrated significant differences between novices, intermediates, and experts in total score (p < 0.01), VCT score (p < 0.01) and SA score (p < 0.01). There was high correlation between total case number and total score (ρ = 0.95, p < 0.01), between total case number and VCT score (ρ = 0.93, p < 0.01), and between total case number and SA score (ρ = 0.83, p < 0.01).

Conclusion

This study describes the development of novel metrics and provides validity evidence for an interactive Web‐based platform to objectively assess decision‐making during thyroidectomy.