bluuebunny/crossref_metadata_2025 huggingface dataset:
Statistical analysis of process parameters in micromachining of Ti-6Al-4V alloy
Authors: Jaffery Syed H Imran , Khan Mushtaq , Ali Liaqat , Mativenga Paul T
Published: January 2015

The demand for miniaturized components is on the rise, especially from the biomedical and aerospace industry. As a result, there is a strong research potential towards the micro-manufacturing of biomedical and aerospace components. Titanium-based alloys are known for their biocompatibility and high strength-to-weight ratio, making them most suitable for such applications. In this research, flank wear progression, surface roughness and side burrs, the basic performance parameters of a typical micromachining operation, are presented and analysed through analysis of variance in order to determine the key process parameters. It was found that micromachining can be classified into two categories: micromachining with undeformed chip thickness below the tool edge radius and micromachining keeping the undeformed chip thickness above the tool edge radius. The results showed that when machining with undeformed chip thickness above edge radius, the feedrate remains the most significant parameter affecting tool wear (41% contribution ratio), surface roughness (83%) and burr width (80%). This result places this type of machining closer to macro-machining where feed contribution was found to be 69%, 92% and 75% as against micromachining below edge radius, where contributions stood at 17%, 53% and 52% on tool wear, surface roughness and burr width, respectively. The results underscored the importance of considering the tool edge radius in micromachining.
Automatic robotic polishing on titanium alloy parts with compliant force/position control
Authors: Du Huapeng , Sun Yuwen , Feng Deyang , Xu Jinting
Published: January 2015

In this article, an automatic robotic polishing technique and system is developed for the polishing of titanium alloy curved parts. By means of a designed compliant end-effector with a force sensor, the robotic polishing system with a position-based explicit force control architecture is first built to perform the polishing operation. Then, a specially designed multi-axis robotic post-processor based on computer-aided design/computer-aided manufacturing is developed to generate the basic position and posture of the polishing tool without any complicated teaching processes. Subsequently, an adaptive Anti-Saturation Integral Separated Fuzzy PI controller, which is able to imitate the manual polishing operation and prevent undesirable vibrations and mechanical collisions, is designed to control the normal contact force. The basic trajectory is changed each time after the current polishing cycle has been finished by online self-learning, and a new basic trajectory is generated for the next polishing cycle. Finally, the effectiveness of the proposed automatic polishing technique is evaluated by actual polishing experiments on titanium alloy (TC11) parts, and the experimental results show that the proposed automatic robotic polishing technique has a perfect control effect on the contact force and thus can achieve a good and uniform surface quality of the part.
An effective numerical control machining process reuse approach by merging feature similarity assessment and data mining for computer-aided manufacturing models
Authors: Huang Rui , Zhang Shusheng , Bai Xiaoliang , Xu Changhong , Huang Bo
Published: January 2015

To effectively reuse existing numerical control machining process of similar feature, a novel numerical control machining process reuse approach by merging feature similarity assessment and data mining for computer-aided manufacturing models is proposed. First, a feature-based numerical control machining process model is proposed to formalize the links between machining feature and its associated machining operations. Based on feature-based numerical control machining process model, the machining know-how database is automatically generated through data mining for existing computer-aided manufacturing models. Then, an effective numerical control machining process reuse–enabled feature similarity assessment approach is presented to locate the similar features. Moreover, two numerical control machining process reuse modes are explored to reuse the associated machining operations of the selected similar feature. Finally, a prototype system based on CATIA has been developed to verify the effectiveness of the proposed approach.
Numerical investigation of influence of inlet guide vanes on unsteady flow in a centrifugal pump
Authors: Yuchuan Wang , Lei Tan , Baoshan Zhu , ShuLiang Cao , Binbin Wang
Published: January 2015

The influence of inlet guide vanes on unsteady flow in a centrifugal pump is numerically investigated. The independences of mesh elements, time steps and turbulence models are studied, and the satisfactory agreement between experimental and numerical results of the centrifugal pump performance validates the reliability and accuracy of the numerical model. The frequency characteristics of pressure fluctuations in impeller and volute are nearly the same for the pump without and with inlet guide vanes in the angle range from −36° to +36°. In the pump impeller, the dominant frequencies are mainly the rotational frequency fi (24.17 Hz) or 2 fi, and in volute they are the blade passing frequency fBPF (145 Hz). For the large inlet guide vanes angles of −60°and +60°, the maximum amplitudes of pressure fluctuations in pump impeller and volute are stronger than that in pump without inlet guide vanes. Therefore, the influence of inlet guide vanes on unsteady flow in the centrifugal pump is slight when the inlet guide vanes angles are regulated in a suitable region.
Critical observations on the modeling of nonreacting and reacting diesel sprays
Authors: Abraham John
Published: January 2015

This paper begins by discussing the structure of nonreacting and reacting diesel sprays. After a general discussion of approaches to model nonreacting diesel sprays, results from some recent work employing the Reynolds-averaged Navier–Stokes equations to model the nonreacting spray are presented. It is shown through detailed comparison with measured results that, under conventional high-pressure, high-temperature chamber and high-pressure injection conditions, the vaporizing diesel spray behaves like a gas jet and can be modeled as such without noticeable loss of accuracy in reproducing the structure of the spray. Moving on to consider a reacting diesel spray, turbulence–chemistry interaction models for the reacting spray are reviewed. Challenges in determining the suitability of one model over another, based on information available in the literature, are highlighted. The Reynolds-averaged Navier–Stokes simulation results of reacting diesel sprays in which an unsteady-flamelet-generated manifold model is employed for turbulence–chemistry interactions are discussed in detail. It is shown that the model, like others reported in the literature, can predict the ignition delay and the flame lift-off heights with reasonable accuracy. The model has also been extended to compute the concentrations of soot and nitrogen oxides in reacting diesel sprays. Nitrogen oxides are modeled using the mechanism from GRI-Mech 3.0 and soot is modeled using a kinetic mechanism coupled with a tracer particle approach to estimate the residence times within the jet. As part of this review, other recent studies on modeling pollutants in the reacting diesel spray are also reviewed in this work. Finally, recent studies employing large-eddy simulations of diesel sprays are reviewed. Initial simulations of the reacting diesel spray using a large-eddy simulation approach coupled with an unsteady-flamelet-generated manifold model are presented. The paper closes with a summary and suggestions for further work in modeling diesel sprays.
Using cuckoo optimization algorithm and imperialist competitive algorithm to solve inverse kinematics problem for numerical control of robotic manipulators
Authors: Bayati Mostafa
Published: January 2015

Inverse kinematics is one of the most important and complicated problems in robotics, and there is almost no exact analytical solution for this problem. Alternatively, with significant growth in machine learning techniques in recent decades, numerical methods are widely being used to solve this problem. This article aims to present a novel application of two powerful meta-heuristic optimization algorithms including cuckoo optimization algorithm and imperialist competitive algorithm to solve robotic manipulators’ inverse kinematics problem for the first time. Recently, these two algorithms have been used to solve several problems in different majors more efficiently in comparison with other well-known algorithms. To validate the efficiency of proposed approaches and suggest them as the preferred numerical methods to solve this problem, a comprehensive study has been done on performance of almost all recently used numerical methods to solve the same problem including genetic algorithm, particle swarm optimization, harmony search and differential evolution algorithms as well as adaptive neuro-fuzzy inference system and two artificial neural networks (multilayer perceptron and radial basis function). Simulations have been performed on an anthropomorphic arm with spherical wrist manipulator case study because of its complex model and degree of freedom. Proposed approach can be included in computer-aided manufacturing packages to increase robotic manipulators’ efficiencies.
An Empirical Test of the Theory of Gamified Learning
Authors: Landers Richard N. , Landers Amy K.
Published: January 2015

Background

The theory of gamified learning provides a theoretical framework to test the impact of gamification efforts upon learner behaviors and attitudes, as well as the effect of these behavioral and attitudinal changes on learning. It does so by providing mediating and moderating processes linking specific game elements to learning outcomes.

Aim

This article links specific game elements common to leaderboards (conflict/challenge, rules/goals, and assessment) with a focal learner behavior, time-on-task, by exploring educational research on competition and psychological research on goal-setting theory.

Method

The mediating process of the theory of gamified learning is tested experimentally by assigning learners completing an online wiki-based project to a gamified version with a leaderboard or to a control version without a leaderboard. Leaderboard achievement was not tied to course grades.

Results

Random assignment to leaderboards supported a causal effect. Students with leaderboards interacted with their project 29.61 more times, on average, than those in a control condition. Bootstrapping was used to support the mediation of the effect of gamification on academic achievement by this amount of time.

Conclusion

The mediating process of the theory of gamified instruction is supported. Leaderboards can be used to improve course performance under certain circumstances.
Joint Associations of Residential Density and Neighborhood Involvement With Physical Activity Among a Multiethnic Sample of Urban Adults
Authors: Johnson-Lawrence Vicki , Schulz Amy J. , Zenk Shannon N. , Israel Barbara A. , Wineman Jean , Marans Robert W. , Rowe Zachary
Published: January 2015

Regular physical activity is associated with improvements in overall health. Although resident involvement in neighborhood social activities is positively associated with physical activity, neighborhood design features, including residential density, have varied associations with physical activity. Using data from a multiethnic sample of 696 adults in Detroit, Michigan, multilevel models were used to examine joint effects of residential density and resident involvement in neighborhood activities in relation to physical activity. We found a marginally significant negative interaction of higher residential density and resident neighborhood involvement. Higher residential density was negatively associated with physical activity, and resident neighborhood involvement was positively associated with physical activity. Our findings suggest that future work incorporate additional neighborhood and individual-level characteristics to understand the complexity of the association between the neighborhood environment, resident social engagement in the neighborhood, and physical activity.
Deciding Whether to Offer “Early-Bird” or “Night-Owl” Specials in Restaurants
Authors: Thompson Gary M.
Published: January 2015

In a long history of capacity and demand management research in services, it has often been suggested that pricing discounts and specials can increase demand in off-peak periods. We examine this issue in the contexts of restaurants, where the practices of offering discounts to restaurant patrons for dining early or dining late—commonly known as “early-bird” and “night-owl” specials, respectively—exist throughout the world. These specials bridge marketing and operations—marketing from the goal of increasing customer demand in the off-peak periods and operations from the perspective of having to serve those customers. The effectiveness of these specials has yet to be examined. While simulation would be an ideal tool for predicting the specials’ net revenue benefits, it might be impractical for many restaurateurs, so we develop three simple “back-of-the-envelope” type calculations. Restaurateurs could use these calculations when deciding whether to offer a special. In the eight large simulation-based experiments we conducted, we find that it is important to estimate revenue cannibalization from full-fare customers. The calculations prove to be far more accurate for night-owl specials than for early-bird specials. This has important implications for decisions about offering the specials and raises a flag regarding a potential marketing-operations conflict.
The Complex Role of Complexity
Authors: Mikolon Sven , Kolberg Anika , Haumann Till , Wieseke Jan
Published: January 2015

During professional service encounters, integrating customers into the process of service provision is both important and challenging, as the complexity of professional services can impair value creation at the service provider–customer interface. This study addresses this problem by examining how service complexity impacts customer cognitive capacity and finally important marketing outcomes. Through an examination of 310 interactions between service providers and customers of a retail bank, this study shows that customers’ cognitive capacity is drastically reduced at moderate levels of perceived complexity. Subsequently, a lack of cognitive capacity decreases customer satisfaction with the encounter and loyalty intentions toward the company, two important drivers of company profitability. Results further show that service providers’ ability to adapt to the specific nature of the encounter helps customers to conserve cognitive capacity. This study hence contributes to service literature by emphasizing the central role of perceived service complexity and establishing the importance of customers’ cognitive capacity in professional service encounters. From a managerial perspective, this study underlines the importance of decreasing service complexity to avoid the negative consequences of mentally overtaxing customers and shows how service providers can effectively use adaptive selling to manage customers’ cognitive capacity at the service provider–customer interface.
Representations of women on Australian breast cancer websites: Cultural ‘inclusivity’ and marginalisation
Authors: Gibson Alexandra , Lee Christina , Crabb Shona
Published: January 2015

Despite ‘cultural competence’ rhetoric within health care, women’s varied breast cancer experiences are often overlooked within the ‘pink ribbon culture’ of breast cancer, which focuses on white, heterosexual, middle-class women’s accounts. We present a multimodal critical discourse analysis of four Australian breast cancer organisations’ websites, which provide information and support to women. We examine how they represent the needs and experiences of women from minority groups, specifically lesbians, women from ‘culturally and linguistically diverse’ backgrounds, and women from Indigenous backgrounds. Through the two discursive themes: ‘boys do cry’ and ‘being breast aware’, we illustrate how women from these groups are sometimes included and at times marginalised on websites. We also identify a discourse of ‘diversity’, which seemingly supports ‘cultural competence’ but actually obscures the assumptions that underpin cancer care. We suggest that women who are not white, heterosexual or middle class could find available resources inappropriate, or experience barriers to access.
Assessment of a bicycle helmet liner with semispherical cones
Authors: Teng Tso-Liang , Liang Cho-Chung , Nguyen Van-Hai
Published: January 2015

Helmets reduce the frequency and severity of head and brain injuries resulting from bicycle crashes. Generally, a bike helmet consists of the outer shell, liner, vents and straps. The liner is the major helmet component reducing head injury in an accident. Using superior energy absorbing structures and materials as helmet liners to meet the higher safety standards should thus be considered. In this study, a shock absorption test was performed in accordance with the EN1078 standard to evaluate the energy absorption capability of a helmet on the market. Then, the finite element analyses of helmet impact tests modelled using LS-DYNA software. To verify the accuracy of the model, the simulation results were compared with experimental data. Finally, an innovative design of helmet model with semispherical cone liner was considered in this study. To assess the dynamic energy absorption of this helmet, a simulation was performed in accordance with the EN1087 standard for shock absorption tests. The resultant simulation revealed that the helmet with the semispherical cone liner has the potential to protect the human head. This innovative design for a helmet liner can serve as a valuable idea to assist future development of safety-helmet technologies.
“Deal of the day”: An analysis of subscriber purchase behavior
Authors: Boon Edward , Pitt Leyland , Ofek Nir
Published: January 2015

Deal of the day is a form of sales promotion that offers merchants the possibility to promote their product at a discount to a mailing list of subscribers that is managed by an intermediary. The objective of the study presented in this paper is to learn more about the development of deal of the day and to assess its attractiveness for merchants. For this purpose, the study examines the purchase history database of a small Swiss deal website. The key findings are: the deal of the day industry is still growing steadily, and late subscribers are as attractive as early adopters; most subscribers buy only one deal or none at all; and only a minority of subscribers buys deals frequently enough to be labeled as high-frequency purchasers. The findings offer insight into the past and future development of deal of the day and show that there are segments within the subscriber base that intermediaries need to treat differently.
Retinal ganglion cell neuroprotection by an angiotensin II blocker in an ex vivo retinal explant model
Authors: White Andrew JR , Heller Janosch P , Leung Johahn , Tassoni Alessia , Martin Keith R
Published: January 2015

Purpose:

An ex vivo organotypic retinal explant model was developed to examine retinal survival mechanisms relevant to glaucoma mediated by the renin angiotensin system in the rodent eye.

Methods:

Eyes from adult Sprague Dawley rats were enucleated immediately post-mortem and used to make four retinal explants per eye. Explants were treated either with irbesartan (10 µM), vehicle or angiotensin II (2 μM) for four days. Retinal ganglion cell density was estimated by βIII tubulin immunohistochemistry. Live imaging of superoxide formation with dihydroethidium (DHE) was performed. Protein expression was determined by Western blotting, and mRNA expression was determined by RT-PCR.

Results:

Irbesartan (10 µM) almost doubled ganglion cell survival after four days. Angiotensin II (2 µM) reduced cell survival by 40%. Sholl analysis suggested that irbesartan improved ganglion cell dendritic arborisation compared to control and angiotensin II reduced it. Angiotensin-treated explants showed an intense DHE fluorescence not seen in irbesartan-treated explants. Analysis of protein and mRNA expression determined that the angiotensin II receptor At1R was implicated in modulation of the NADPH-dependent pathway of superoxide generation.

Conclusion:

Angiotensin II blockers protect retinal ganglion cells in this model and may be worth further investigation as a neuroprotective treatment in models of eye disease.
Crack detection and health monitoring of highway steel-girder bridges
Authors: Schallhorn Charles , Rahmatalla Salam
Published: January 2015

A vibration-based damage-detection methodology is presented in this work to monitor the health condition of a highway steel-girder bridge in Iowa. The contribution of the proposed methodology is to combine the transmissibility function, coherence function, and probabilistic schemes to construct a percent-violation that gives critical information about the health condition of the bridge. The percent-violation creates two alarm severities, watch and warning, depending on how many times the percent-violation successively crosses an objective threshold created from the healthy data. Field results using stochastic operational traffic loading have indicated the capability of the proposed methodology in evaluating the changes in the health condition of a section of the bridge and in consistently detecting cracks of various sizes (30–60 mm) on a sacrificial specimen integrated with the bridge abutment and a floor beam. Fluctuations in environmental and loading conditions have been known to create some uncertainties in most damage-detection processes; however, this work demonstrated that using an objective threshold, these uncertainties will be contained. Additionally, based on the sacrificial specimen’s results, once damage is initiated or propagated on the structure, the effect of these parameters becomes less relevant. The results of additional field testing using controlled impact forces on the sacrificial specimen have reinforced the findings from the operational loading in detecting damage.
To Be a Some Thing
Authors: Wilkinson Alex
Published: January 2015

Drawing on the burgeoning field of affect theory, this article problematizes the possibilities of historical discourse in the slowly collapsing sense of disciplinary efficacy in the social sciences. Not satisfied with any sense of “method,” which reduces the effectiveness of critiques in the suspension of their own becoming, the article insists on a poetic form with which to explore the interstices of memory in the supposedly rational, knowledge producing economy of history’s own becoming. Deflecting the reduction to sign producing systems with which to coral the past in neoliberal political ontologies and regimes of knowing, the article suggests that much greater openness is required to consider the affective force of history as a mode of seeing peculiar to modernist desires to make some thing of the past and its passing. Interweaving personal and public memory in a manner that attempts to deconstruct the boundary between the two, the article argues that perhaps what is most prominent about the desire-to-history is the temporal passing of its forms and their materialization (and striation) across time(s). Written in “parts,” the article evokes the fuzzy boundaries of the fragment and the whole to provoke a poetics of the in-between form.
Prognostic Value of Expression of Cyclin E in Gastrointestinal Cancer
Authors: Huang Lanshan , Ren Fanghui , Tang Ruixue , Feng Zhenbo , Chen Gang
Published: January 2015

Cyclin E is a critical regulator in cell cycle and promotes the initiation of DNA replication and centrosome duplication in late G1. The overexpression of cyclin E is common in cancers of the digestive system. However, whether cyclin E represents a prognostic biomarker in gastrointestinal cancer remains controversial. We reviewed the published literatures to clarify the association between cyclin E determined by immunohistochemistry (IHC) and survival in gastrointestinal cancer. Literatures were searched in PubMed and Cochrane Library published up to December 1, 2014. A total of 282 articles were initially identified, and 14 articles were included in this study. Meta-analysis was performed for 10 studies with a total of 1300 patients. Combined hazard risk (HR) and corresponding 95% confidence interval (CI) were calculated by random-effect model due to the heterogeneity. The quality of included studies was assessed by the Newcastle-Ottawa Scale and the Methodological Index for Non-Randomized Studies (MINORS). We found that high level of cyclin E was a predicator of poor prognosis among patients with gastrointestinal cancer (HR = 1.67, 95% CI = 1.06-2.63, P = .028). In summary, overexpression of cyclin E is associated with poor prognosis in gastrointestinal cancer and expression of cyclin E determined by IHC might be a prognostic marker for gastrointestinal cancer in clinical practice.
Tyrosine phosphorylation of WW proteins
Authors: Reuven Nina , Shanzer Matan , Shaul Yosef
Published: January 2015

A number of key regulatory proteins contain one or two copies of the WW domain known to mediate protein–protein interaction via proline-rich motifs, such as PPxY. The Hippo pathway components take advantage of this module to transduce tumor suppressor signaling. It is becoming evident that tyrosine phosphorylation is a critical regulator of the WW proteins. Here, we review the current knowledge on the involved tyrosine kinases and their roles in regulating the WW proteins.
Experimental and theoretical study of the oblique impact of a tennis ball with a racket
Authors: Ghaednia Hamid , Cermik Ozdes , Marghitu Dan B
Published: January 2015

The normal and the oblique impact of a tennis ball with a racket has been studied. An accurate setup has been built in order to provide consistent initial conditions for the impacts. Experiments have been done for a wide range of impact angles and initial velocities. The motion of the ball before, during and after the impact has been recorded using a high-speed camera with 10,000 frames per second. The impact has been divided into two phases, compression and restitution. An expression for the contact force has been provided. The coefficient of restitution and effective coefficient of friction have been analyzed experimentally. For low impact velocities, the coefficient of restitution is constant at different impact angles. The effective coefficient of friction changes as a function of the impact angle. The contact force expression has been determined for the compression and the restitution phases using the experimental data from normal impact experiments. The simulation and experimental results are compared and verified for the normal and the oblique impacts.
Can pictorial images communicate the quality of pain successfully?
Authors: Closs S José , Knapp Peter , Morley Stephen , Stones Catherine
Published: January 2015

Chronic pain is common and difficult for patients to communicate to health professionals. It may include neuropathic elements which require specialised treatment. A little used approach to communicating the quality of pain is through the use of images. This study aimed to test the ability of a set of 12 images depicting different sensory pain qualities to successfully communicate those qualities. Images were presented to 25 student nurses and 38 design students. Students were asked to write down words or phrases describing the quality of pain they felt was being communicated by each image. They were asked to provide as many or as few as occurred to them. The images were extremely heterogeneous in their ability to convey qualities of pain accurately. Only 2 of the 12 images were correctly interpreted by more than 70% of the sample. There was a significant difference between the two student groups, with nurses being significantly better at interpreting the images than the design students. Clearly, attention needs to be given not only to the content of images designed to depict the sensory qualities of pain but also to the differing audiences who may use them. Education, verbal ability, ethnicity and a multiplicity of other factors may influence the understanding and use of such images. Considerable work is needed to develop a set of images which is sufficiently culturally appropriate and effective for general use.
The Dance of Reflexive Monitoring in a Family Co-Mediation Context
Authors: Bowen Don
Published: January 2015

This article describes a qualitative study of the co-mediation process from the perspective of mediation practitioners, and what salient features distinguish it from sole mediation. The study examined the nature and character of the interactive patterns of communication performed by all participants as central features of the process. Forty-seven mediators were surveyed by questionnaire in relation to the co-mediation process. A further seven mediators were subjected to in-depth interviews. Their combined responses revealed co-mediators as “agents of change” tasked in a distinctive way with facilitating fair and just outcomes to family disputes. Exploration of the characteristics unique to co-mediation revealed a dynamic reflexive monitoring interplay with interconnected functions comprising a complex “dance” that involved all participants.
GROUP PROFILE Computer Technique
Authors: Sidorenkov Andrey V. , Pavlenko Roman V.
Published: January 2015

This article contains a description of the structure, the software and functional capabilities, and the scope and purposes of application of the Group Profile (GP) computer technique. This technique rests on a conceptual basis (the microgroup theory), includes 16 new and modified questionnaires, and a unique algorithm, tied to the questionnaires, for identification of informal groups. The GP yields a wide range of data about the group as a whole (47 indices), each informal group (43 indices), and each group member (16 indices). The GP technique can be used to study different types of groups: production (work groups, design teams, military units, etc.), academic (school classes, student groups), and sports.
Evaluation of sulfobutylether-β-cyclodextrin (SBECD) accumulation and voriconazole pharmacokinetics in critically ill patients undergoing continuous renal replacement therapy
Authors: Kiser Tyree H , Fish Douglas N , Aquilante Christina L , Rower Joseph E , Wempe Michael F , MacLaren Robert , Teitelbaum Isaac
Published: January 2015

Introduction

Intravenous (IV) voriconazole is not recommended in patients with creatinine clearance <50 ml/min to avoid potentially toxic accumulation of sulfobutylether-β-cyclodextrin (SBECD). The purpose of this study was to evaluate the pharmacokinetics of SBECD, voriconazole, and voriconazole N-oxide in critically ill patients undergoing continuous renal replacement therapy (CRRT) and to determine if CRRT removes SBECD sufficiently to allow for the use of IV voriconazole without significant risk of SBECD accumulation.

Methods

This prospective, open-label pharmacokinetic study enrolled patients >18 years old receiving IV voriconazole for a known or suspected invasive fungal infection while undergoing CRRT. Serial blood and effluent samples were collected on days 1, 3, 5, 7, and every 3 to 5 days thereafter. SBECD, voriconazole, and voriconazole N-oxide plasma and effluent concentrations were measured by liquid chromatography-tandem mass spectrometry. Pharmacokinetic, pharmacodynamic, and pharmacogenetic analyses were conducted.

Results

Ten patients (mean ± standard deviation (SD)) 53 ± 11 years old, 50% male, 81 ± 14 kg, with Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores of 31.5 ± 3.8 were evaluated. All patients underwent continuous venovenous hemofiltration (CVVH) with a median predilution replacement fluid rate of 36 (interquartile range (IQR) 32 to 37) ml/kg/hr and total ultrafiltration rate of 38 (IQR 34 to 39) ml/kg/hr. Mean ± SD voriconazole and SBECD dosages administered were 8.1 ± 2.1 mg/kg/day and 129 ± 33 mg/kg/day, respectively. Voriconazole plasma trough concentrations were >1 mg/L in all patients with CVVH accounting for only 15% of the total body clearance. CVVH accounted for 86% of the total body clearance of SBECD with the majority of the dose being recovered in the effluent. Minimal increases in dose normalized SBECD area under the concentration-time curve from 0 to 12 hours (AUC0-12) (4,484 ± 4,368 to 4,553 ± 2,880 mg*hr/L; P = 0.97) were observed after study day 1.

Conclusions

CVVH effectively removed SBECD at a rate similar to the ultrafiltration rate. Voriconazole clearance by CVVH was not clinically significant. Standard dosages of IV voriconazole can be utilized in patients undergoing CVVH without significant risk of SBECD accumulation.

Trial registration

ClinicalTrials.gov NCT01101386. Registered 6 April 2010.
Simplified lung ultrasound protocol shows excellent prediction of extravascular lung water in ventilated intensive care patients
Authors: Enghard Philipp , Rademacher Sibylle , Nee Jens , Hasper Dietrich , Engert Ulrike , Jörres Achim , Kruse Jan M
Published: January 2015

Introduction

Ultrasound of the lung and quantification of B lines was recently introduced as a novel tool to detect overhydration. In the present study, we aimed to evaluate a four-region protocol of lung ultrasound to determine the pulmonary fluid status in ventilated patients in the intensive care unit.

Methods

Fifty patients underwent both lung ultrasound and transpulmonary thermodilution measurement with the PiCCO system. An ultrasound score based on number of single and confluent B lines per intercostal space was used to quantify pulmonary overhydration. To check for reproducibility, two different intensivists who were blinded as to the ultrasound pictures reassessed and classified them using the same scoring system. The results were compared with those obtained using other methods of evaluating hydration status, including extravascular lung water index (EVLWI) and intrathoracic blood volume index calculated with data from transpulmonary thermodilution measurements. Moreover, chest radiographs were assessed regarding signs of pulmonary overhydration and categorized based on a numeric rating scale.

Results

Lung water assessment by ultrasound using a simplified protocol showed excellent correlation with EVLWI over a broad range of lung hydration grades and ventilator settings. Correlation of chest radiography and EVLWI was less accurate. No correlation whatsoever was found with central venous pressure measurement.

Conclusion

Lung ultrasound is a useful, non-invasive tool in predicting hydration status in mechanically ventilated patients. The four-region protocol that we used is time-saving, correlates well with transpulmonary thermodilution measurements and performs markedly better than chest radiography.
Point accuracy and reliability of an interstitial continuous glucose-monitoring device in critically ill patients: a prospective study
Authors: van Hooijdonk Roosmarijn TM , Leopold Jan Hendrik , Winters Tineke , Binnekade Jan M , Juffermans Nicole P , Horn Janneke , Fischer Johan C , van Dongen-Lases Edmée C , Schultz Marcus J
Published: January 2015

Introduction

There is a need for continuous glucose monitoring in critically ill patients. The objective of this trial was to determine the point accuracy and reliability of a device designed for continuous monitoring of interstitial glucose levels in intensive care unit patients.

Methods

We evaluated point accuracy by comparing device readings with glucose measurements in arterial blood by using blood gas analyzers. Analytical and clinical accuracy was expressed in Bland-Altman plots, glucose prediction errors, and Clarke error grids. We used a linear mixed model to determine which factors affect the point accuracy. In addition, we determined the reliability, including duration of device start-up and calibration, skips in data acquisition, and premature disconnections of sensors.

Results

We included 50 patients in whom we used 105 sensors. Five patients from whom we could not collect the predefined minimum number of four consecutive comparative blood draws were excluded from the point accuracy analysis. Therefore, we had 929 comparative samples from 100 sensors in 45 patients (11 (7 to 28) samples per patient) during 4,639 hours (46 (27 to 134) hours per patient and 46 (21 to 69) hours per sensor) for the accuracy analysis. Point accuracy did not meet the International Organization for Standardization (ISO) 14971 standard for insulin dosing accuracy but did improve with increasing numbers of calibrations and was better in patients who did not have a history of diabetes. Out of 105 sensors, 60 were removed prematurely for a variety of reasons. The device start-up time was 49 (43 to 58) minutes. The number of skips in data acquisition was low, resulting in availability of real-time data during 95% (89% to 98%) of the connection time per sensor.

Conclusions

The point accuracy of a device designed for continuous real-time monitoring of interstitial glucose levels was relatively low in critically ill patients. The device had few downtimes, but one third of the sensors were removed prematurely because of unresolved sensor- or device-related problems.

Trial registration

Netherlands Trial Registry number: NTR3827. Registered 30 January 2013.
Comprehensive miRNA sequence analysis reveals survival differences in diffuse large B-cell lymphoma patients
Authors: Lim Emilia L , Trinh Diane L , Scott David W , Chu Andy , Krzywinski Martin , Zhao Yongjun , Robertson A Gordon , Mungall Andrew J , Schein Jacqueline , Boyle Merrill , Mottok Anja , Ennishi Daisuke , Johnson Nathalie A , Steidl Christian , Connors Joseph M , Morin Ryan D , Gascoyne Randy D , Marra Marco A
Published: January 2015

Background

Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease, with 30% to 40% of patients failing to be cured with available primary therapy. microRNAs (miRNAs) are RNA molecules that attenuate expression of their mRNA targets. To characterize the DLBCL miRNome, we sequenced miRNAs from 92 DLBCL and 15 benign centroblast fresh frozen samples and from 140 DLBCL formalin-fixed, paraffin-embedded tissue samples for validation.

Results

We identify known and candidate novel miRNAs, 25 of which are associated with survival independently of cell-of-origin and International Prognostic Index scores, which are established indicators of outcome. Of these 25 miRNAs, six miRNAs are significantly associated with survival in our validation cohort. Abundant expression of miR-28-5p, miR-214-5p, miR-339-3p, and miR-5586-5p is associated with superior outcome, while abundant expression of miR-324-5p and NOVELM00203M is associated with inferior outcome. Comparison of DLBCL miRNA-seq expression profiles with those from other cancer types identifies miRNAs that were more abundant in B-cell contexts. Unsupervised clustering of miRNAs identifies two clusters of patients that have distinct differences in their outcomes. Our integrative miRNA and mRNA expression analyses reveal that miRNAs increased in abundance in DLBCL appear to regulate the expression of genes involved in metabolism, cell cycle, and protein modification. Additionally, these miRNAs, including one candidate novel miRNA, miR-10393-3p, appear to target chromatin modification genes that are frequent targets of somatic mutation in non-Hodgkin lymphomas.

Conclusions

Our comprehensive sequence analysis of the DLBCL miRNome identifies candidate novel miRNAs and miRNAs associated with survival, reinforces results from previous mutational analyses, and reveals regulatory networks of significance for lymphomagenesis.
Pancancer analysis of DNA methylation-driven genes using MethylMix
Authors: Gevaert Olivier , Tibshirani Robert , Plevritis Sylvia K
Published: January 2015

Aberrant DNA methylation is an important mechanism that contributes to oncogenesis. Yet, few algorithms exist that exploit this vast dataset to identify hypo- and hypermethylated genes in cancer. We developed a novel computational algorithm called MethylMix to identify differentially methylated genes that are also predictive of transcription. We apply MethylMix to 12 individual cancer sites, and additionally combine all cancer sites in a pancancer analysis. We discover pancancer hypo- and hypermethylated genes and identify novel methylation-driven subgroups with clinical implications. MethylMix analysis on combined cancer sites reveals 10 pancancer clusters reflecting new similarities across malignantly transformed tissues.
TET proteins and the control of cytosine demethylation in cancer
Authors: Scourzic Laurianne , Mouly Enguerran , Bernard Olivier A
Published: January 2015

The discovery that ten-eleven translocation (TET) proteins are α-ketoglutarate-dependent dioxygenases involved in the conversion of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine and 5-carboxycytosine has revealed new pathways in the cytosine methylation and demethylation process. The description of inactivating mutations in TET2 suggests that cellular transformation is in part caused by the deregulation of this 5-mC conversion. The direct and indirect deregulation of methylation control through mutations in DNA methyltransferase and isocitrate dehydrogenase (IDH) genes, respectively, along with the importance of cytosine methylation in the control of normal and malignant cellular differentiation have provided a conceptual framework for understanding the early steps in cancer development. Here, we review recent advances in our understanding of the cytosine methylation cycle and its implication in cellular transformation, with an emphasis on TET enzymes and 5-hmC. Ongoing clinical trials targeting the activity of mutated IDH enzymes provide a proof of principle that DNA methylation is targetable, and will trigger further therapeutic applications aimed at controlling both early and late stages of cancer development.
Principles and management of neuropsychiatric symptoms in Alzheimer’s dementia
Authors: Nowrangi Milap A , Lyketsos Constantine G , Rosenberg Paul B
Published: January 2015

Neuropsychiatric symptoms of Alzheimer’s disease (NPS-AD) are highly prevalent and lead to poor medical and functional outcomes. In spite of the burdensome nature of NPS-AD, we are continuing to refine the nosology and only beginning to understand the underlying pathophysiology. Cluster analyses have frequently identified three to five subsyndromes of NPS-AD: behavioral dysfunction (for example, agitation/aggressiveness), psychosis (for example, delusions and hallucinations), and mood disturbance (for example, depression or apathy). Recent neurobiological studies have used new neuroimaging techniques to elucidate behaviorally relevant circuits and networks associated with these subsyndromes. Several fronto-subcortical circuits, cortico-cortical networks, and neurotransmitter systems have been proposed as regions and mechanisms underlying NPS-AD. Common to most of these subsyndromes is the broad overlap of regions associated with the salience network (anterior cingulate and insula), mood regulation (amygdala), and motivated behavior (frontal cortex). Treatment strategies for dysregulated mood syndromes (depression and apathy) have primarily targeted serotonergic mechanisms with antidepressants or dopaminergic mechanisms with psychostimulants. Psychotic symptoms have largely been targeted with anti-psychotic medications despite controversial risk/benefit tradeoffs. Management of behavioral dyscontrol, including agitation and aggression in AD, has encompassed a wide range of psychoactive medications as well as non-pharmacological approaches. Developing rational therapeutic approaches for NPS-AD will require a firmer understanding of the underlying etiology in order to improve nosology as well as provide the empirical evidence necessary to overcome regulatory and funding challenges to further study these debilitating symptoms.
Hop-by-hop traffic-aware routing to congestion control in wireless sensor networks
Authors: Gholipour Majid , Haghighat Abolfazl Toroghi , Meybodi Mohammad Reza
Published: January 2015

One of the major challenges in wireless sensor networks (WSNs) research is to prevent traffic congestion without compromising with the energy of the sensor nodes. Network congestion leads to packet loss, throughput impairment, and energy waste. To address this issue in this paper, a distributed traffic-aware routing scheme with a capacity of adjusting the data transmission rate of nodes is proposed for multi-sink wireless sensor networks that effectively distribute traffic from the source to sink nodes. Our algorithm is designed through constructing a hybrid virtual gradient field using depth and normalized traffic loading to routing and providing a balance between optimal paths and possible congestion on routes toward those sinks. The simulation results indicate that the proposed solution can improve the utilization of network resources, reduce unnecessary packet retransmission, and significantly improve the performance of WSNs.
AGA: Interactive pipeline for reproducible genomics analyses
Authors: Considine Michael , Parker Hilary , Wei Yingying , Xia Xaio , Cope Leslie , Ochs Michael , Fertig Elana
Published: January 2015

Automated Genomics Analysis (AGA) is an interactive program to analyze high-throughput genomic data sets on a variety of platforms. An easy to use, point and click, guided pipeline is implemented to combine, define, and compare datasets, and customize their outputs. In contrast to other automated programs, AGA enables flexible selection of sample groups for comparison from complex sample annotations. Batch correction techniques are also included to further enable the combination of datasets from diverse studies in this comparison. AGA also allows users to save plots, tables and data, and log files containing key portions of the R script run for reproducible analyses. The link between the interface and R supports collaborative research, enabling advanced R users to extend preliminary analyses generated from bioinformatics novices.
Product and Pricing Decisions in Crowdfunding
Authors: Hu Ming , Li Xi , Shi Mengze
Published: January 2015

This paper studies the optimal product and pricing decisions in a crowdfunding mechanism by which a project between a creator and many buyers will be realized only if the total funds committed by the buyers reach a specified goal. When the buyers are sufficiently heterogeneous in their product valuations, the creator should offer a line of products with different levels of product quality. Compared to the traditional situation where orders are placed and fulfilled individually, with the crowdfunding mechanism, a product line is more likely than a single product to be optimal and the quality gap between products is smaller. This paper also shows the effect of the crowdfunding mechanism on pricing dynamics over time. Together, these results underscore the substantial influence of the emerging crowdfunding mechanisms on common marketing decisions.
Renal transplantation: defining the ‘high-risk donor’
Authors: Notay Manisha , Dupont Peter
Published: January 2015

Although transplantation is associated with an overall reduction in mortality compared with dialysis, it is not without risk. However, the risk of transmission of donor-derived infection or malignancy is low and needs to be balanced against the possibility of death associated with continued dialysis.
‘Donating a kidney to my brother is one of the best things I have done’
Authors: Samson Peter
Published: January 2015

After 18 years with a transplanted kidney, Christopher Adams received the terrible news that his organ was starting to fail and reject. Knowing his brother was struggling with renal failure, Steven Adams was found to be a match and donated a kidney to him. Both brothers are now living well.