bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilevel Probabilistic Morphological Analysis for Facilitating Modeling and Simulation of Notional Scenarios
Authors: Payan Alexia P. , Mavris Dimitri N.
Published: February 2016

Despite advances in computational power, simulation‐based experiments of complex problems remain time‐consuming. Significant efforts are required to define an accurate representation of the problem and draw relevant conclusions about relationships between input parameters and output performance measures. To reduce the computational burden without sacrificing accuracy, it is customary to design a set of relevant scenarios. Doing so necessitates that the problem be decomposed into relevant parameters and that the consistency of these parameters be analyzed. To address this challenge, we propose a multilevel probabilistic morphological analysis. Traditionally, morphological analysis documents the decomposition of a system into its main components, and performs binary compatibility assessments to document relational data between component options. However, this approach leads to a rigid definition of the problem space and a static solution space that does not account for uncertain and dynamic behaviors associated with complex systems‐of‐systems. This research incorporates two important improvements. First, it explicitly incorporates a multilevel approach accommodating any successive decomposition steps that may be required when dealing with a complex system‐of‐systems problem. Second, this research introduces probabilistic cross‐consistency assessments instead of traditional binary assessments to account for uncertain future states of the world. This probabilistic scheme is used to describe degrees of likelihood that two elements may coexist in a given scenario. This way, more complex interactions may also be captured and more realistic scenarios may be defined. Finally, the proposed method is applied to a problem investigating the design of architectures of detection systems for the protection of homeland critical assets.
Implementing Systems Engineering in Civil Engineering Consulting Firm: An Evaluation
Authors: de Graaf Robin , Voordijk Hans , van den Heuvel Len
Published: February 2016

This study explores the challenges that civil engineering consulting firms face in their projects when they apply Systems Engineering (SE). It is also explained were these firms should focus when improving the use of SE. To conduct this study, the methodology of Eisenhardt (Building theories from case study research, Acad Manage Rev 14 [1989], 532–550) for building theory from case study research is used. The extent, to which SE is applied, is assessed in six civil engineering projects, using a newly developed framework containing an extensive list of questions about how and why SE was applied. Based on this assessment, it is shown that there are three major reasons why SE was not applied to the full extent. First, SE procedures and responsibilities were not always clearly established and communicated to team members. Second, team members were in a learning process and did not yet possess all the SE knowledge and skills required. Finally, there was a lack of a demanding client to enforce the use of SE. This paper also presents recommendations for improving the application of SE in projects, related to methods, skills, and the client. Further research should focus on different (kinds of) companies within the civil engineering industry.
How I Became a “Different” English Speaker and Listener
Authors: Hashimoto Ryota
Published: February 2016

The author went to the United States to study applied linguistics. Although he was there for nine months, his English proficiency did not improve as much as he had hoped, considering that he was using English almost exclusively every day. After his time in the United States, he spent 10 months in Australia working and traveling on a working holiday visa. After 5 months he realized that he did not have to concentrate when speaking or listening in English, and he stopped translating from Japanese to English in his mind when producing English. His use of English was different. It was not that his proficiency in English had improved a great deal, but it meant that he was comfortable when speaking and listening in English, and he was able to use English without requiring all of his concentration. He believes this change took place because he was immersed in an environment where he was required to use English all the time. His brain stopped processing English as a foreign or second language and simply viewed English as a language to be processed like he naturally processed Japanese.
Integrated design of downwind land‐based wind turbines using analytic gradients
Authors: Ning Andrew , Petch Derek
Published: February 2016

Wind turbines are complex systems where component‐level changes can have significant system‐level effects. Effective wind turbine optimization generally requires an integrated analysis approach with a large number of design variables. Optimizing across large variable sets is orders of magnitude more efficient with gradient‐based methods as compared with gradient‐free method, particularly when using exact gradients. We have developed a wind turbine analysis set of over 100 components where 90% of the models provide numerically exact gradients through symbolic differentiation, automatic differentiation, and adjoint methods. This framework is applied to a specific design study focused on downwind land‐based wind turbines.

Downwind machines are of potential interest for large wind turbines where the blades are often constrained by the stiffness required to prevent a tower strike. The mass of these rotor blades may be reduced by utilizing a downwind configuration where the constraints on tower strike are less restrictive. The large turbines of this study range in power rating from 5–7MW and in diameter from 105m to 175m. The changes in blade mass and power production have important effects on the rest of the system, and thus the nacelle and tower systems are also optimized. For high‐speed wind sites, downwind configurations do not appear advantageous. The decrease in blade mass (10%) is offset by increases in tower mass caused by the bending moment from the rotor‐nacelle‐assembly. For low‐wind speed sites, the decrease in blade mass is more significant (25–30%) and shows potential for modest decreases in overall cost of energy (around 1–2%). Copyright © 2016 John Wiley & Sons, Ltd.
Adaptive symbiotic organisms search (SOS) algorithm for structural design optimization
Authors: Tejani Ghanshyam G. , Savsani Vimal J. , Patel Vivek K.
Published: February 2016

The symbiotic organisms search (SOS) algorithm is an effective metaheuristic developed in 2014, which mimics the symbiotic relationship among the living beings, such as mutualism, commensalism, and parasitism, to survive in the ecosystem. In this study, three modified versions of the SOS algorithm are proposed by introducing adaptive benefit factors in the basic SOS algorithm to improve its efficiency. The basic SOS algorithm only considers benefit factors, whereas the proposed variants of the SOS algorithm, consider effective combinations of adaptive benefit factors and benefit factors to study their competence to lay down a good balance between exploration and exploitation of the search space. The proposed algorithms are tested to suit its applications to the engineering structures subjected to dynamic excitation, which may lead to undesirable vibrations. Structure optimization problems become more challenging if the shape and size variables are taken into account along with the frequency. To check the feasibility and effectiveness of the proposed algorithms, six different planar and space trusses are subjected to experimental analysis. The results obtained using the proposed methods are compared with those obtained using other optimization methods well established in the literature. The results reveal that the adaptive SOS algorithm is more reliable and efficient than the basic SOS algorithm and other state-of-the-art algorithms.

Highlights Correlation between organisms, optimization and engineering. Adaptive symbiotic organisms search (SOS) algorithm is proposed. Implementation on structural design problems. Effective over other methods.
Knockdown of TMEM14A expression by RNAi inhibits the proliferation and invasion of human ovarian cancer cells
Authors: Zhang Qingmei , Chen Xiufeng , Zhang Xuan , Zhan Jingfen , Chen Jie
Published: February 2016

Transmembrane protein 14A (TMEM14A) is a member of TMEMs. Alterations in TMEMs expression have been identified in several types of cancer, but the expression and function of TMEM14A in ovarian cancer is still unclear. Here, analysis on the expression data of the Cancer Genome Atlas (TCGA) ovarian serous cystadenocarcinoma (OV) dataset demonstrated the overexpression of TMEM14A in ovarian cancer tissues compared with normal tissues, which was consistent with our real-time PCR analysis on ovarian cancer and normal tissues collected from 30 patients. In addition, TMEM14A knockdown in two ovarian cancer cell lines, A2780 and HO-8910, reduced cell proliferation, causes cell cycle arrest and suppressed cell invasion. Moreover, silencing of TMEM14A notably repressed G1/S cell cycle transition and cell invasion via down-regulating the expression of cell cycle related proteins (Cyclin D1, Cyclin E and PCNA) and metastasis-related proteins (MMP-2 and MMP-9), respectively. TMEM14A knockdown significantly reduced the phosphorylation status of Smad2 and Smad3, downstream effectors of TGF-β signalling. In summary, these results indicate that TMEM14A has a pro-tumorigenic effect in ovarian cancer cells, suggesting an important role of this protein in ovarian cancer oncogenesis and metastasis.
Patterns of water stress and temperature for Australian chickpea production
Authors: Lake Lachlan , Chenu Karine , Sadras Victor O.
Published: February 2016

The environment is the largest component of the phenotypic variance of crop yield, hence the importance of its quantitative characterisation. Many studies focussed on the patterns of water deficit for specific crops and regions, but concurrent water and thermal characterisations have not been reported. To quantify the types, spatial patterns, frequency and distribution of both water stress and thermal regimes for chickpea in Australia, we combined trial and modelled data. Data from National Variety Trials including sowing time, yield and weather from 295 production environments were entered into simulations. Associations between actual yield, in a range from 0.2 to 5.2 t/ha, actual temperature and modelled crop water stress were explored. Yield correlated positively with minimum temperature in the 800 degree-days window bracketing flowering and the correlation shifted to negative after flowering. A negative correlation between maximum temperature over 30°C and yield was found from flowering through to 1000 degree-days after flowering. Yield was negatively correlated with simulated water stress from flowering until 800 degree-days after flowering.
Cluster analysis from 3905 environments (71 locations × 55 years between 1958 and 2013) identified three dominant patterns for both maximum and minimum temperature accounting for 77% and 61% of the overall variation, and four dominant patterns for water stress accounting for 87% of total variation. The most frequent environments for minimum and maximum temperature were associated with low actual yield (1.5–1.8 t/ha) whereas the most frequent water-stress environment was associated with the second lowest actual yield (1.75 t/ha). For all temperature and water-stress types, we found significant spatial variation that is relevant to the allocation of effort in breeding programs.
Generation of Ni–Si3N4 nanocomposites by DC, PC and PRC electrodeposition methods
Authors: Reddy R. Mohan , Praveen B. M. , Chandrappa K. G. , Nayana K. O.
Published: February 2016

Ni–Si3N4 nanocomposite thin films were fabricated by direct current (DC), Pulse current (PC) and Pulse reverse current (PRC) electrodeposition methods. The structure and surface morphology of thin films were analysed by XRD, Scanning Electron Microscopy and Atomic Force Microscope. Corrosion protection performance of the Ni–Si3N4 nanocomposite on mild steel in 3.5% NaCl corrosive medium was assessed by electrochemical method. Texture coefficient and microhardness of the thin films were determined and discussed. Comparisons and performance of corrosion resistance of these coatings obtained by DC electrodeposition, PC electrodeposition and with PRC electrodeposition were investigated.
Ventilatory acclimatisation is beneficial for high‐intensity exercise at altitude in elite cyclists
Authors: Townsend Nathan E. , Gore Christopher J. , Ebert Tammie R. , Martin David T. , Hahn Allan G. , Chow Chin‐Moi
Published: February 2016

Aim: The aim of this study was to examine the relationship between ventilatory adaptation and performance during altitude training at 2700 m. Methods: Seven elite cyclists (age: 21.2 ± 1.1 yr, body mass: 69.9 ± 5.6 kg, height 176.3 ± 4.9 cm) participated in this study. A hypoxic ventilatory response (HVR) test and a submaximal exercise test were performed at sea level prior to the training camp and again after 15 d at altitude (ALT15). Ventilation (VE), end‐tidal carbon‐dioxide partial pressure (PETCO2) and oxyhaemoglobin saturation via pulse oximetry (SpO2) were measured at rest and during submaximal cycling at 250 W. A hill climb (HC) performance test was conducted at sea level and after 14 d at altitude (ALT14) using a road of similar length (5.5–6 km) and gradient (4.8–5.3%). Power output was measured using SRM cranks. Average HC power at ALT14 was normalised to sea level power (HC%). Multiple regression was used to identify significant predictors of performance at altitude. Results: At ALT15, there was a significant increase in resting VE (10.3 ± 1.9 vs. 12.2 ± 2.4 L·min−1) and HVR (0.34 ± 0.24 vs. 0.71 ± 0.49 L·min−1·%−1), while PETCO2 (38.4 ± 2.3 vs. 32.1 ± 3.3 mmHg) and SpO2 (97.9 ± 0.7 vs. 94.0 ± 1.7%) were reduced (P < .05). Multiple regression revealed ΔHVR and exercise VE at altitude as significant predictors of HC% (adjusted r2 = 0.913; P = 0.003). Conclusions: Ventilatory acclimatisation occurred during a 2 wk altitude training camp in elite cyclists and a higher HVR was associated with better performance at altitude, relative to sea level. These results suggest that ventilatory acclimatisation is beneficial for cycling performance at altitude.
Multilevel biological characterization of exomic variants at the protein level significantly improves the identification of their deleterious effects
Authors: Raimondi Daniele , Gazzo Andrea M. , Rooman Marianne , Lenaerts Tom , Vranken Wim F.
Published: February 2016

Motivation: There are now many predictors capable of identifying the likely phenotypic effects of single nucleotide variants (SNVs) or short in-frame Insertions or Deletions (INDELs) on the increasing amount of genome sequence data. Most of these predictors focus on SNVs and use a combination of features related to sequence conservation, biophysical, and/or structural properties to link the observed variant to either neutral or disease phenotype. Despite notable successes, the mapping between genetic variants and their phenotypic effects is riddled with levels of complexity that are not yet fully understood and that are often not taken into account in the predictions, despite their promise of significantly improving the prediction of deleterious mutants.

Results: We present DEOGEN, a novel variant effect predictor that can handle both missense SNVs and in-frame INDELs. By integrating information from different biological scales and mimicking the complex mixture of effects that lead from the variant to the phenotype, we obtain significant improvements in the variant-effect prediction results. Next to the typical variant-oriented features based on the evolutionary conservation of the mutated positions, we added a collection of protein-oriented features that are based on functional aspects of the gene affected. We cross-validated DEOGEN on 36 825 polymorphisms, 20 821 deleterious SNVs, and 1038 INDELs from SwissProt. The multilevel contextualization of each (variant, protein) pair in DEOGEN provides a 10% improvement of MCC with respect to current state-of-the-art tools.

Availability and implementation: The software and the data presented here is publicly available at http://ibsquare.be/deogen.

Contact: wvranken@vub.ac.be

Supplementary information: Supplementary data are available at Bioinformatics online.
A Randomized Control Trial: Supplementing Hearing Aid Use with Listening and Communication Enhancement (LACE) Auditory Training
Authors: Saunders Gabrielle H. , Smith Sherri L. , Chisolm Theresa H. , Frederick Melissa T. , McArdle Rachel A. , Wilson Richard H.
Published: February 2016

Objective:

To examine the effectiveness of the Listening and Communication Enhancement (LACE) program as a supplement to standard-of-care hearing aid intervention in a Veteran population.

Design:

A multisite randomized controlled trial was conducted to compare outcomes following standard-of-care hearing aid intervention supplemented with (1) LACE training using the 10-session DVD format, (2) LACE training using the 20-session computer-based format, (3) placebo auditory training (AT) consisting of actively listening to 10 hr of digitized books on a computer, and (4) educational counseling—the control group. The study involved 3 VA sites and enrolled 279 veterans. Both new and experienced hearing aid users participated to determine if outcomes differed as a function of hearing aid user status. Data for five behavioral and two self-report measures were collected during three research visits: baseline, immediately following the intervention period, and at 6 months postintervention. The five behavioral measures were selected to determine whether the perceptual and cognitive skills targeted in LACE training generalized to untrained tasks that required similar underlying skills. The two self-report measures were completed to determine whether the training resulted in a lessening of activity limitations and participation restrictions. Outcomes were obtained from 263 participants immediately following the intervention period and from 243 participants 6 months postintervention. Analyses of covariance comparing performance on each outcome measure separately were conducted using intervention and hearing aid user status as between-subject factors, visit as a within-subject factor, and baseline performance as a covariate.

Results:

No statistically significant main effects or interactions were found for the use of LACE on any outcome measure.

Conclusions:

Findings from this randomized controlled trial show that LACE training does not result in improved outcomes over standard-of-care hearing aid intervention alone. Potential benefits of AT may be different than those assessed by the performance and self-report measures utilized here. Individual differences not assessed in this study should be examined to evaluate whether AT with LACE has any benefits for particular individuals. Clinically, these findings suggest that audiologists may want to temper the expectations of their patients who embark on LACE training.
Nicorandil Infusion during Off-Pump Coronary Artery Bypass Grafting Reduces Incidence of Intra-aortic Balloon Pump Insertion
Authors: Saha Kamales Kumar , Kumar Ajay , Deval Mandar Manohar , Saha Kakalee K. , Jacob Rinu V. , Jagdale Lukash , Kaul Shibban K.
Published: February 2016

Objective

Off-pump coronary artery bypass grafting in patients with left ventricular dysfunction has proven to be advantageous. However, it carries risk of emergency conversion to cardiopulmonary bypass. We have successfully used an intra-aortic balloon pump to prevent such conversion. The objective of the present study was to evaluate if intravenous nicorandil infusion reduces the incidence of intraoperative intra-aortic balloon pump insertion.

Methods

Consecutive cases of isolated off-pump coronary artery bypass surgery performed by a single surgeon were studied. Patients were divided into two groups. The first group did not receive nicorandil, and the second group received intraoperative nicorandil infusion (started in the operating room after central line insertion).

Results

A total of 375 patients were included in the study. Four patients in the non-nicorandil group and the patients in nicorandil group were on preoperative intra-aortic balloon pump and hence excluded from the study. After routine use of nicorandil infusion, incidence of intra-aortic balloon pump insertion during off-pump coronary artery bypass surgery decreased from 12.4% (21/169) to 2.9% (6/206).

Conclusions

Nicorandil infusion significantly (P = 0.007) reduced the incidence of intra-aortic balloon pump insertion in our series. In patients with left ventricular dysfunction (ejection fraction ≤ 30%), this difference (P = 0.008) assumes a special significance as off-pump bypass surgery is considered high risk in this subset. Nicorandil is an inexpensive drug, and the reduction in cost of surgery by avoiding intra-aortic balloon pump insertion is an added advantage. The use of nicorandil infusion during off-pump coronary artery bypass may result in favorable patient outcomes by reducing invasive intra-aortic balloon pump insertion during off-pump coronary artery bypass grafting.
Trends in the Treatment of Metastatic Colon and Rectal Cancer in Elderly Patients
Authors: Bradley Cathy J. , Yabroff K. Robin , Warren Joan L. , Zeruto Christopher , Chawla Neetu , Lamont Elizabeth B.
Published: February 2016

Background:

Little is known about the use and costs of antineoplastic regimens for elderly patients with metastatic colorectal cancer (mCRC). We report population-based trends over a 10-year period in the treatment, survival, and costs in mCRC patients, stratified by ages 65–74 and 75+.

Methods:

We used Surveillance, Epidemiology, and End Results–Medicare data for persons diagnosed with metastatic colon (N=16117) or rectal cancer (N=4008) between 2000 and 2009. We estimated the adjusted percent of patients who received antineoplastic agents, by type, number, and their costs 12 months following diagnosis. We report the percent of patients who received 3 or more of commonly prescribed agents and estimate survival for the 24-month period following diagnosis by age and treatment.

Results:

The percentage that received 3 or more agents increased from 3% to 73% in colon patients aged 65–74 and from 2% to 53% in patients 75+. Similar increases were observed in rectal patients. Average 1-year costs per patient in 2009 were $106,461 and $102,680 for colon and rectal cancers, respectively, reflecting an increase of 32% and 20%, for patients who received antineoplastic agents. Median survival increased by about 6 and 10 months, respectively, for colon and rectal patients aged 65–74 who received antineoplastic agents, but an improvement of only 1 month of median survival was observed for patients 75+.

Conclusions:

Expensive multiple agent regimens are increasingly used in older mCRC patients. For patients aged 64–75 years, these treatments may be associated with several months of additional life, but patients aged 75+ may incur considerable expense without any survival benefit.
High-resolution maps of hunter-gatherer social networks reveal human adaptation for cultural exchange
Authors: Migliano Andrea Bamberg , Page Abigail , Gómez-Gardeñes Jesus , Viguier Sylvain , Dyble Mark , Thompson James , Chaudhary Nikhill , Salali Gul Deniz , Smith Daniel , Strods Janis , Latora Vito , Mace Ruth , Vinicius Lucio
Published: February 2016

Are interactions with unrelated and even unknown individuals a by-product of modern life in megacities? Here we argue instead that social ties among non-kin are a crucial human adaptation. By deploying a new portable wireless sensing technology (motes), we mapped social networks in Agta and BaYaka hunter-gatherers in unprecedented detail. We show that strong friendships with non-kin optimize the global efficiency of their social networks thereby facilitating cultural exchange, and that the adaptation for forming friendship ties appears early in development. The ability to extend networks and form strong non-kin ties may explain some human distinctive characteristics such as hypersociality and cumulative culture, and the tendency to exchange ideas with unrelated and unknown individuals in megacities and online social networks.

One Sentence Summary

Social networks of two hunter-gatherer groups in Congo and the Philippines reveal that friendships are an ancestral adaptation for the exchange of information and culture.
MetaCycle: an integrated R package to evaluate periodicity in large scale data
Authors: Wu Gang , Anafi Ron C. , Hughes Michael E. , Kornacker Karl , Hogenesch John B.
Published: February 2016

Detecting periodicity in large scale data remains a challenge. Different algorithms offer strengths and weaknesses in statistical power, sensitivity to outliers, ease of use, and sampling requirements. While efforts have been made to identify best of breed algorithms, relatively little research has gone into integrating these methods in a generalizable method. Here we present MetaCycle, an R package that incorporates ARSER, JTK_CYCLE, and Lomb-Scargle to conveniently evaluate periodicity in time-series data.

Availability and implementation:

MetaCycle package is available on the CRAN repository (https://cran.r-project.org/web/packages/MetaCycle/index.html) and GitHub (https://github.com/gangwug/MetaCycle).

Contact:

hogenesch@gmail.com

Supplementary information:

Supplementary data are available at Bioinformatics online.
Distinct stages in the recognition, sorting and packaging of proTGFα into COPII coated transport vesicles
Authors: Zhang Pengcheng , Schekman Randy
Published: February 2016

In addition to its role in forming vesicles from the endoplasmic reticulum (ER), the coat protein complex II (COPII) is also responsible for selecting specific cargo proteins to be packaged into COPII transport vesicles. Comparison of COPII vesicle formation in mammalian systems and in yeast suggested that the former employs more elaborate mechanisms for cargo recognition, presumably to cope with a significantly expanded repertoire of cargo that transits the secretory pathway. Using proTGFα, the transmembrane precursor of transforming growth factor alpha (TGFα), as a model cargo protein, we demonstrate in cell-free assays that at least one auxiliary cytosolic factor is specifically required for the efficient packaging of proTGFα into COPII vesicles. Using a knockout HeLa cell line generated by CRISPR/Cas9, we provide functional evidence showing that a transmembrane protein, Cornichon-1 (CNIH), acts as a cargo receptor of proTGFα. We show that both CNIH and the auxiliary cytosolic factor(s) are required for efficient recruitment of proTGFα to the COPII coatin vitro. Moreover, we provide evidence that the recruitment of cargo protein by the COPII coat precedes and may be distinct from subsequent cargo packaging into COPII vesicles.

Abbreviations

CNIH

Cornichon
Long‐term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia
Authors: Tsunemi Yuichiro , Irisawa Ryokichi , Yoshiie Hiromu , Brotherton Betsy , Ito Hisahiro , Tsuboi Ryoji , Kawashima Makoto , Manyak Michael ,   the ARI114264 Study Group
Published: February 2016

Androgenetic alopecia is an androgen‐induced pattern of progressive hair loss, which occurs in genetically predisposed people. This study aimed to determine long‐term safety, tolerability and efficacy of dutasteride 0.5 mg, an inhibitor of 5‐α‐reductase, in Japanese male patients with androgenetic alopecia. This was a multicenter, open‐label, prospective outpatient study (clinicaltrials.gov NCT01831791, GSK identifier ARI114264) in which patients took dutasteride 0.5 mg p.o. once daily for 52 weeks. Primary end‐points included adverse event assessment, incidence of drug‐related adverse event and premature discontinuations. Secondary end‐points included hair growth, hair restoration and global improvement in hair. A total of 120 patients were enrolled, of whom 110 completed 52 weeks of treatment. Nasopharyngitis, erectile dysfunction and decreased libido were the most frequently reported adverse events and most adverse events were mild. Drug‐related adverse events were reported with an incidence of 17%, none of which led to study withdrawal. Hair growth (mean target area hair count at week 52), hair restoration (mean target area hair width at week 52) and global appearance of hair (mean of the median score at week 52) improved from baseline during the study. As a potential future treatment option for male androgenetic alopecia, dutasteride 0.5 mg exhibited long‐term safety, tolerability and efficacy within this study population.
Long‐term efficacy of endoscopic ligation plus cyanoacrylate injection with or without sclerotherapy for variceal bleeding
Authors: Chen Jie , Zeng Xiao Qing , Ma Li Li , Huang Xiao Quan , Tseng Yu Jen , Wang Jian , Luo Tian Cheng , Chen Shi Yao
Published: February 2016

Objective

This study aimed to evaluate the long‐term outcomes and efficacy of continued ligation plus cyanoacrylate injection compared with those of combined ligation and sclerotherapy plus cyanoacrylate injection for secondary prophylaxis of variceal bleeding in cirrhotic patients with concomitant esophageal and gastric varices.

Methods

Medical records of the patients who were admitted for variceal bleeding due to liver cirrhosis were retrospectively reviewed and their related data was collected. The patients were divided into two groups, including the continued ligation plus cyanoacrylate injection group [the sclerotherapy (‐) group] and the combined ligation and sclerotherapy plus cyanoacrylate injection group [the sclerotherapy (+) group]. The Kaplan–Meier survival analysis was conducted and log–rank test was used to compare the differences between the two groups.

Results

Altogether 125 patients were enrolled between 1 April 2004 and 31 December 2012. After a median follow‐up of 23.4 months, no significant difference was observed between the two groups in regard to variceal rebleeding (29.7% vs 47.5%, P = 0.097) and mortality (12.5% vs 14.8%, P = 0.879). Among patients with ascites the cumulative rebleeding rate was significantly lower in the sclerotherapy (‐) group (26.3% vs 59.4%, P = 0.020). A relapse of bleeding after the initial endoscopic therapy was an independent prognostic factor of rebleeding (P = 0.004). Portal thrombosis was an independent prognostic factor for mortality (P = 0.044).

Conclusion

No superiority of combined ligation and sclerotherapy compared with continued ligation and cyanoacrylate injection for secondary prophylaxis of variceal bleeding is observed.
Hydrologic Landscape Characterization for the Pacific Northwest, USA
Authors: Leibowitz Scott G. , Comeleo Randy L. , Wigington Parker J. , Weber Marc H. , Sproles Eric A. , Sawicz Keith A.
Published: February 2016

We update the Wigington et al. (2013) hydrologic landscape (HL) approach to make it more broadly applicable and apply the revised approach to the Pacific Northwest (PNW; i.e., Oregon, Washington, and Idaho). Specific changes incorporated are the use of assessment units based on National Hydrography Dataset Plus V2 catchments, a modified snowmelt model validated over a broader area, an aquifer permeability index that does not require preexisting aquifer permeability maps, and aquifer and soil permeability classes based on uniform criteria. Comparison of Oregon results for the revised and original approaches found fewer and larger assessment units, loss of summer seasonality, and changes in rankings and proportions of aquifer and soil permeability classes. Differences could be explained by three factors: an increased assessment unit size, a reduced number of permeability classes, and use of smaller cutoff values for the permeability classes. The distributions of the revised HLs in five groups of Oregon rivers were similar to the original HLs but less variable. The improvements reported here should allow the revised HL approach to be applied more often in situations requiring hydrologic classification and allow greater confidence in results. We also apply the map results to the development of hydrologic landscape regions.
Geochemistry and Sr‐Nd‐Pb Isotopes of the Granites from the Hashitu Mo Deposit of Inner Mongolia, China: Constraints on Their Origin and Tectonic Setting
Authors: Chengwu DING , Pan DAI , Leon BAGAS , Fengjun NIE , Sihong JIANG , Junhao WEI , Chengzhen DING , Pengfei ZUO , Ke ZHANG
Published: February 2016

The Hashitu molybdenum deposit is located in the southern part of the Great Hinggan Range, NE China. Molybdenum mineralization is hosted by and genetically associated with monzogranite and porphyritic syenogranite. Sr‐Nd‐Pb isotopes of the intrusions show that the porphyritic syenogranite has initial87Sr/86Sr ratios of 0.70418–0.70952,εNd(t) values of 1.3 to 2.1 (t=143 Ma),206Pb/204Pb ratios of 19.191–19.573,207Pb/204Pb ratios of 15.551–15.572, and208Pb/204Pb ratios of 38.826–39.143. The monzogranite has initial87Sr/86Sr ratios of 0.70293–0.71305,εNd(t) values of 1.1 to 2.0 (t=147 Ma),206Pb/204Pb ratios of 19.507–20.075,207Pb/204Pb ratios of 15.564–15.596, and208Pb/204Pb ratios of 39.012–39.599. The calculated Nd model ages (TDM) for monzogranite and porphyritic syenogranite range from 866 to 1121 Ma and 795 to 1020 Ma, respectively. The granitic rocks in the Hashitu area have the same isotope range as granites in the southern parts of the Great Hinggan Range. The isotope composition indicates that these granites are derived from the partial melting of a juvenile lower crust originating from a depleted mantle with minor contamination by ancient continental crust. The integrating our results with published data and the Late Mesozoic regional tectonic setting of the region suggest that the granites in the Hashitu area formed in an intra‐continent extensional setting, and they are related to the thinning of the thickened lithosphere and upwelling of the asthenosphere.
Geochemistry of Thermal Waters of Continental Margin of Far East of Russia
Authors: BRAGIN Ivan V. , CHELNOKOV Georgy A. , CHUDAEV Oleg V. , KHARITONOVA Natalia A. , VYSOTSKIY Sergey V.
Published: February 2016

Studied waters belong to warm (T=30–50°C), alkaline (pH=8.9–9.3), low mineralized (TDS<235 mg/l) Na–HCO3 or Na–SO4–HCO3 thermal waters with high content of SiO2 (up to 81 mg/l) and F (up to 3.9 mg/l), occur on modern volcano–tectonic rejuvenated areas of Eastern Sikhote–Alin orogenic belt. Low 3He concentration as well as N2/O2 and N2/Ar ratios exclude influence of deep mantle fluid. New rare earth element data constrain our understanding of water–rock interaction occurring in the water source region. Meteoric origin of waters is proved by stable isotope values varying from −71‰ to −136.1‰ and from −10.8‰ to −18.8‰ for δ2H and δ18O respectively. REE patterns reflect high pH, resultfing from water–rock interaction and oxidative conditions. Calculations of deep aquifer temperature using Na–K and quartz geothermometers show 116.8–131.1° C and 82.2–125.8°C respectively. Presence of deep faults both with abnormal thermal gradient (∼45–50 K/km) define unique geochemical shape of thermal waters of Sikhote–Alin, area, where no present volcanic activity is registered.
Should compulsive sexual behavior be considered an addiction?
Authors: Kraus Shane W. , Voon Valerie , Potenza Marc N.
Published: February 2016

Aims

To review the evidence base for classifying compulsive sexual behavior (CSB) as a non‐substance or ‘behavioral’ addiction.

Methods

Data from multiple domains (e.g. epidemiological, phenomenological, clinical, biological) are reviewed and considered with respect to data from substance and gambling addictions.

Results

Overlapping features exist between CSB and substance use disorders. Common neurotransmitter systems may contribute to CSB and substance use disorders, and recent neuroimaging studies highlight similarities relating to craving and attentional biases. Similar pharmacological and psychotherapeutic treatments may be applicable to CSB and substance addictions, although considerable gaps in knowledge currently exist.

Conclusions

Despite the growing body of research linking compulsive sexual behavior (CSB) to substance addictions, significant gaps in understanding continue to complicate classification of CSB as an addiction.
An alternative interpretation of cellular ‘selfish spermatogonial selection’‐ clusters in the human testis indicates the need for 3‐D‐analyses
Authors: Pohl E. , Gromoll J. , Kliesch S. , Wistuba J.
Published: February 2016

The ‘selfish spermatogonial selection’‐ model was proposed to explain the paternal age effect (PAE) of some congenital disorders associated with point mutations in male germ cells. According to this, spermatogonia carrying pathogenic mutations gain a selection advantage over non‐mutated spermatogonia which leads to an increased number of mutated spermatogonia and consequently spermatozoa over time. Recently, an immunohistochemical approach using the premeiotic marker melanoma antigen family A4 (MAGE A4) was undertaken by the Wilkie group to confirm the presence of microclones of putatively mutated spermatogonia in testes of elderly men. The objective of our study was the age‐dependent assessment of testes from men with normal spermatogenesis using MAGE A4 immunohistochemistry to identify and corroborate cellular clusters indicative for ‘selfish spermatogonial selection’ in our cohort. We analyzed testicular tissues obtained from men with normal spermatogenesis assigned to three age groups [(1) 28.8 ± 2.7 years; (2) 48.1 ± 1 years; (3) 71.9 ± 6.8 years, n/group = 8]. We could detect very similar distribution patterns of MAGE A4‐positive cells and the presence of several types of microclusters as reported previously. However, these cellular clusters, indicative for clonal expansion, were not only present in testes from elderly men but also in those from age group 1 and 2. Using graphical three‐dimensional modelling, we identified that cross‐section directions e.g. longitudinal sections might provoke misleading interpretation of spermatogonial clusters, in particular when the tissue processing is limited. Thus, appropriate fixation and embedding is needed for reliable analysis of testicular sections. We therefore propose a more careful interpretation of such spermatogonial clusters and recommend a 3‐D analysis to unequivocally determine ‘selfish spermatogonial selection’‐manifestations.
Ganglion cell layer measurements correlate with disease severity in patients with Alzheimer's disease
Authors: Garcia‐Martin Elena , Bambo Maria P. , Marques Marcia L. , Satue Maria , Otin Sofia , Larrosa Jose M. , Polo Vicente , Pablo Luis E.
Published: February 2016

Purpose

To evaluate the thickness of the 10 retinal layers of patients with Alzheimer's disease (AD) using a new segmentation technology of the Spectralis optical coherence tomography (OCT) and to determine whether the thickness of specific layers predicts neurodegeneration or AD severity.

Methods

Patients with AD (n = 150) and age‐matched healthy controls (n = 75) were analysed using the segmentation application prototype to automatically segment all retinal layers in a macular scan. Thicknesses of each layer were compared between patients with AD and controls, and between patients with disease durations of less than or at least 3 years. Associations between retinal layer thicknesses, disease duration and AD severity were evaluated.

Results

Patients with AD had reduced thickness in the retinal nerve fibre, ganglion cell, inner plexiform and outer nuclear layers (p < 0.05). The inner retinal layers were more affected in patients with long disease duration. Ganglion cell and retinal nerve fibre layer thicknesses were inversely correlated with AD duration and severity. Ganglion cell and inner plexiform layers thicknesses were predictive of axonal damage.

Conclusions

The segmentation application revealed ganglion cell and retinal layer atrophy in patients with AD compared with controls, especially in the inner layers of patients with long disease duration. Ganglion cell layer reduction was associated with increased axonal damage and may predict greater disease severity.
Toxic effects of melphalan, topotecan and carboplatin on retinal pigment epithelial cells
Authors: Süsskind Daniela , Hagemann Ulrike , Schrader Merle , Januschowski Kai , Schnichels Sven , Aisenbrey Sabine
Published: February 2016

Purpose

Clinical evidence of retinal pigment epithelium (RPE) alterations after intra‐arterial (IAC) and intravitreal chemotherapy (IViC) of retinoblastoma has been reported. We, therefore, investigated the cellular toxic effects of melphalan, topotecan and carboplatin on the RPE in a cell culture model.

Methods

The effects of melphalan, carboplatin and topotecan on ARPE19 cell morphology were examined by phase contrast microscopy. Cell proliferation was quantified by BrdU incorporation, cell viability studied via MTS assays, and cell densities were estimated by Crystal Violet staining, and apoptosis induction studied via caspase 3/7‐activity assays after a 24‐hr incubation period. Staurosporine, media without fetal bovine serum, diluents of melphalan, carboplatin and topotecan were applied as positive and negative controls, respectively.

Results

We observed a concentration‐dependent increase in the number and size of gaps in the ARPE19 cell layer with each drug. There was a significant decrease in proliferative activity and cell viability of RPE cells as well as an increase in apoptosis after 24 hrs culture in media supplemented with melphalan and topotecan. Carboplatin had comparable effects on cell proliferation and cell viability; however, no significant apoptotic impacts were observed. The three cytostatic drugs had insignificant effects on cell density measurements.

Conclusions

Morphological monitoring and toxicity assays indicate a direct toxic effect of melphalan and the other two cytostatic drugs on ARPE19 cells. Thus, a direct toxic effect of melphalan in vivo after IAC or IViC on the RPE seems probable and may explain the clinical and angiographic RPE alterations observed in some retinoblastoma patients.
Higher burnout scores in paediatric residents are associated with increased brain activity during attentional functional magnetic resonance imaging task
Authors: de Andrade Anarella Penha Meirelles , Amaro Edson , Farhat Sylvia Costa Lima , Schvartsman Claudio
Published: February 2016

Aim

Burnout syndrome is common in healthcare workers. We evaluated its prevalence in paediatric residents and investigated its influence on cerebral function correlations, using functional magnetic resonance imaging (MRI), when they carried out an attentional paradigm.

Methods

This cross‐sectional descriptive study involved 28 residents from the Department of Paediatrics at the University of São Paulo. The functional MRI was carried out while the residents completed the Stroop colour word task paradigm to investigate their attentional task performance. The Maslach Burnout Inventory (MBI) was applied, and stress was assessed using the Lipp Inventory of Stress Symptoms for Adults and by a visual analogue mood scale.

Results

The MBI subscales of depersonalisation and emotional exhaustion indicated that 53.1% of the residents had moderate or high burnout syndrome. The whole‐brain multivariate analysis showed positive correlations between the blood oxygenation level dependent effect and the MBI depersonalisation and emotional exhaustion indices in the dorsolateral prefrontal cortex, which controls for anxiety.

Conclusion

Increased brain activation during an attention task, measured using functional MRI, was associated with higher burnout scores in paediatric residents. This study provides a biological basis for the implementation of measures to reduce burnout syndrome at the start of residency training programmes.
Population pharmacokinetic and pharmacodynamic analysis of BIIB023, an anti‐TNF‐like weak inducer of apoptosis (anti‐TWEAK) monoclonal antibody
Authors: Galluppi Gerald R. , Wisniacki Nicolas , Stebbins Chris
Published: February 2016

Aims

Tumour necrosis factor‐like weak inducer of apoptosis (TWEAK) is implicated in the pathogenesis of lupus nephritis. This study evaluated the pharmacokinetics, using the population approach, and pharmacodynamics of BIIB023, an anti‐TWEAK monoclonal antibody, in healthy Chinese, Japanese and Caucasian volunteers.

Methods

In this single‐dose, randomized, double‐blind, phase 1 study of BIIB023 in healthy volunteers, BIIB023 was administered by intravenous infusion (3 or 20 mg kg−1) on Day 1; follow‐up occurred through Day 71. BIIB023 serum concentration was measured using a validated enzyme‐linked immunosorbent assay; BIIB023 concentration‐time data were subjected to noncompartmental analysis. Population pharmacokinetic analysis was performed using data from this study and a prior phase 1 study of BIIB023 in subjects with rheumatoid arthritis. Soluble TWEAK and TWEAK:BIIB023 complex were evaluated.

Results

There were no differences in BIIB023 pharmacokinetics requiring dose adjustment among the three ethnic groups or between healthy volunteers and arthritis patients. BIIB023 central compartment volume (3050 ml) and clearance (7.42 ml h−1) were comparable to those observed for other monoclonal antibody drugs. BIIB023 serum exposure increased in a dose‐dependent manner in all groups, but not in direct proportion to dose level; at concentrations below ~10 μg ml−1, nonlinear clearance was observed. Soluble TWEAK levels decreased to below the level of quantitation after BIIB023 treatment, with concomitant changes in TWEAK:BIIB023 complex levels.

Conclusions

No clinically meaningful differences were observed in BIIB023 pharmacokinetic and pharmacodynamic properties in healthy Chinese, Japanese and Caucasian volunteers; pharmacodynamic measures suggested target engagement. TWEAK may be an attractive therapeutic target for lupus nephritis treatment.