bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Imaging using PET/CT Applying 68Ga-Labeled Tracers and Targeted Radionuclide Therapy: Theranostics on the Way to Personalized Medicine
Authors: Baum Richard P , Kulkarni Harshad R
Published: February 2013

Theranostics is an acronym, which exemplifies the togetherness of diagnostics and therapeutics in the individualized management of disease. The key to personalized medicine in cancer is to determine the molecular phenotypes of neoplasms, so that specific probes can be selected to target the tumor and its microenvironment. Molecular imaging and radionuclide therapy using a particular probe is based on this premise. Neuroendocrine neoplasms express somatostatin receptors, enabling the use of somatostatin analogs for molecular imaging, when labeled with the positron-emitter 68Ga for receptor positron emission tomography/computed tomography (PET/CT), and targeted radionuclide therapy, when labeled with beta-emitters 90Y and 177Lu.

How to cite this article

Kulkarni HR, Baum RP. Molecular Imaging using PET/CT Applying 68Ga-Labeled Tracers and Targeted Radionuclide Therapy: Theranostics on the Way to Personalized Medicine. J Postgrad Med Edu Res 2013; 47(1):47-53.
Ga-68: A Versatile PET Imaging Radionuclide
Authors: Mittal BR , Shukla Jaya
Published: February 2013

Gallium-68, a positron emitter, is available via 68Ge/68Ga generators. The simple chemistry and easy availability has increased its application from the clinical diagnosis to personalized therapy and has lot more potential in future.

How to cite this article

Shukla J, Mittal BR. Ga-68: A Versatile PET Imaging Radionuclide. J Postgrad Med Edu Res 2013;47(1):74-76.
Global and regional sea surface temperature trends during Marine Isotope Stage 11
Authors: Milker Y. , Rachmayani R. , Weinkauf M. , Prange M. , Raitzsch M. , Schulz M. , Kučera M.
Published: February 2013

Abstract. The Marine Isotope Stage (MIS) 11 (424–374 ka) was characterized by a protracted deglaciation and an unusually long climatic optimum. It remains unclear to what degree the climate development during this interglacial reflects the unusually weak orbital forcing or greenhouse gas trends. Previously, arguments about the duration and timing of the MIS11 climatic optimum and about the pace of the deglacial warming were based on a small number of key records, which appear to show regional differences. In order to obtain a global signal of climate evolution during MIS11, we compiled a database of 78 sea surface temperature (SST) records from 57 sites spanning MIS11, aligned these individually on the basis of benthic (N = 28) or planktonic (N = 31) stable oxygen isotope curves to a common time-frame and subjected 48 of them to an Empirical Orthogonal Function (EOF) analysis. The analysis revealed a high commonality among all records, with the principal SST trend explaining almost 49% of the variability. This trend indicates that on the global scale, the surface ocean underwent rapid deglacial warming during Termination V, in pace with carbon dioxide rise, followed by a broad SST optimum centered at ~ 410 kyr. The second EOF, which explained 19% of the variability, revealed the existence of a different SST trend, characterized by a delayed onset of the temperature optimum during MIS11 at ~ 398 kyr, followed by a prolonged warm period lasting beyond 380 kyr. This trend is most consistently manifested in the mid-latitude North Atlantic and Mediterranean Sea and is here attributed to the strength of the Atlantic meridional overturning circulation. A sensitivity analysis indicates that these results are robust to record selection and to age-model uncertainties of up to 3–6 kyr, but more sensitive to SST seasonal attribution and SST uncertainties > 1 °C. In order to assess the effect of orbital forcing on MIS11 SST trends, the annual and seasonal SST anomalies recorded in a total of 74 proxy records were compared with CCSM3 (Community Climate System Model, version 3) runs for three time slices representing orbital configuration extremes during the peak interglacial of MIS11. The modeled SST anomalies are characterized by a significantly lower variance compared to the reconstructions. Nevertheless, significant correlations between proxy and model data are found in comparisons on the seasonal basis, indicating that the model captures part of the long-term variability induced by astronomical forcing, which appears to have left a detectable signature in SST trends.
CHRONO: a parallel multi-physics library for rigid-body, flexible-body, and fluid dynamics
Authors: Mazhar H. , Heyn T. , Pazouki A. , Melanz D. , Seidl A. , Bartholomew A. , Tasora A. , Negrut D.
Published: February 2013

Abstract. The last decade witnessed a manifest shift in the microprocessor industry towards chip designs that promote parallel computing. Until recently the privilege of a select group of large research centers, Teraflop computing is becoming a commodity owing to inexpensive GPU cards and multi to many-core x86 processors. This paradigm shift towards large scale parallel computing has been leveraged in CHRONO, a freely available C++ multi-physics simulation package. CHRONO is made up of a collection of loosely coupled components that facilitate different aspects of multi-physics modeling, simulation, and visualization. This contribution provides an overview of CHRONO::Engine, CHRONO::Flex, CHRONO::Fluid, and CHRONO::Render, which are modules that can capitalize on the processing power of hundreds of parallel processors. Problems that can be tackled in CHRONO include but are not limited to granular material dynamics, tangled large flexible structures with self contact, particulate flows, and tracked vehicle mobility. The paper presents an overview of each of these modules and illustrates through several examples the potential of this multi-physics library.
A recent tipping point in the Arctic sea-ice cover: abrupt and persistent increase in the seasonal cycle since 2007
Authors: Livina V. N. , Lenton T. M.
Published: February 2013

Abstract. There is ongoing debate over whether Arctic sea ice has already passed a "tipping point", or whether it will do so in the future. Several recent studies argue that the loss of summer sea ice does not involve an irreversible bifurcation, because it is highly reversible in models. However, a broader definition of a "tipping point" also includes other abrupt, non-linear changes that are neither bifurcations nor necessarily irreversible. Examination of satellite data for Arctic sea-ice area reveals an abrupt increase in the amplitude of seasonal variability in 2007 that has persisted since then. We identified this abrupt transition using recently developed methods that can detect multi-modality in time-series data and sometimes forewarn of bifurcations. When removing the mean seasonal cycle (up to 2008) from the satellite data, the residual sea-ice fluctuations switch from uni-modal to multi-modal behaviour around 2007. We originally interpreted this as a bifurcation in which a new lower ice cover attractor appears in deseasonalised fluctuations and is sampled in every summer–autumn from 2007 onwards. However, this interpretation is clearly sensitive to how the seasonal cycle is removed from the raw data, and to the presence of continental land masses restricting winter–spring ice fluctuations. Furthermore, there was no robust early warning signal of critical slowing down prior to the hypothesized bifurcation. Early warning indicators do however show destabilization of the summer–autumn sea-ice cover since 2007. Thus, the bifurcation hypothesis lacks consistent support, but there was an abrupt and persistent increase in the amplitude of the seasonal cycle of Arctic sea-ice cover in 2007, which we describe as a (non-bifurcation) "tipping point". Our statistical methods detect this "tipping point" and its time of onset. We discuss potential geophysical mechanisms behind it, which should be the subject of further work with process-based models.
An inventory of glacier changes between 1973 and 2011 for the Geladandong Mountain area, China
Authors: Zhang J. , Braaten D. , Li X. , She J. , Tao F.
Published: February 2013

Abstract. The snow and ice of the Geladangong Mountain area supply the headwaters of the Yangtze River, and long-term changes to glaciers and ice masses in this region due to a warming climate are of great concern. An inventory of glacier boundaries and changes over decades for the Geladandong Mountain area in China has been conducted using remote sensing imagery from Landsat (MSS, TM, ETM+), CERBES CCD, and GIS techniques. Variations in glacier extent has been measured using a~series of digital images since 1973, including Landsat MSS in 1973, Landsat TM in 1992, Landsat ETM+ in 2004, and CBERS CCD in 2011. All Landsat data are snow-free outside the glacier boundaries, allowing an unsupervised classification method to be used to extract glacier area. For the CBERS CCD data, some areas were covered by clouds and snow, requiring an initial unsupervised classification method to divide glacier, clouds and snow from other land types, followed by a supervised visual interpretation to extract glacier area. The results show a decrease in glacier ice cover in the study area during the past 38 yr. From 1973 to 2011, glacier area decreased from 107 105 hectares to 94 220 hectares, or a change of −12%. The speed at which ice cover is being lost has been decreasing during the past 38 yr. The rate of glacier area loss was 0.47% yr−1 from 1973–1992, 0.19% yr−1 from 1992–2004, and 0.14% yr−1 from 2004–2011. While most of the glaciers are shrinking, some are expanding. For the 1973 to 2004 period, retreating glaciers exposed 14 447 hectares of land, and advancing glaciers spread over 2682 hectares that were not covered by ice in 1973. The net glacier area decrease is 11 765 hectares from 1973–2004. For the 1973 to 2011 period, glaciers expanded over 3791 hectares, and retreated from 16 504 hectares.
Investigating the Relationship between Trust and Intention to Purchase Online
Authors: Jamaludin Azahari , Ahmad Fais
Published: February 2013

Nowadays, the usage of Internet has grown rapidly over the past years and it has become a common medium for delivering and trading of goods, services and information at global marketplace. Even though this method of business transaction or exchange has started to win the hearts of Malaysian buyers, the element influencing the willingness to purchase online is still unknown. Therefore, the objective of the current study is to examine the element that influence buyer’s intention to purchase online (dependent variable). The independent component is trust to visit the website. A total number of 78 (100 percent) returned questionnaires were accepted, coded and were subject to further analysis. The finding support the hypothesis stated in the current study. The results indicates that website trust contributed 16.1 percent (R2 = 0.161) to the variance in intention to purchase online.
Childhood Development after Maternal Metal-on-Metal Hip Resurfacing
Authors: Johnson Alicia J. , Woon Regina P. , Le Duff Michel J. , Amstutz Harlan C.
Published: February 2013

Metal-on-metal (MoM) hip resurfacing has been used in many young, active patients, including women of childbearing age. While ion levels have been measured in mothers with MoM hip resurfacing and their babies, little is known about how these ions affect child development. Out of 1300, MoM hip resurfacing surgeries, we had 48 women of childbearing age (defined as 40 years of age or younger at the time of surgery). These women were contacted to see if they had had pregnancies after their surgery, and those who had were sent surveys asking about their pregnancies and the development of their children. Eleven women reported pregnancies, and eight returned the surveys. There were no significant differences between women with pregnancies and those without pregnancies in any demographic or clinical measures. From the eight women who completed surveys, there were seventeen pregnancies resulting in fourteen births. There were complications in three of the births resulting in two premature births, but no children were born with birth defects. Overall, the children appear to be developing normally. Based on this unique data, we do not feel that MoM hip resurfacing is contraindicated for women of childbearing age, but power analyses show that we cannot draw conclusive results from our sample. We recommend that other groups publish their own data to allow us to generate sufficient sample sizes to draw meaningful conclusions.
Dietary Supplementation of Calendula officinalis Counteracts the Oxidative Stress and Liver Damage Resulted from Aflatoxin
Authors: Hamzawy Mohamed A. , El-Denshary Ezzeldein S. M. , Hassan Nabila S. , Mannaa Fathia A. , Abdel-Wahhab Mosaad A.
Published: February 2013

This study was conducted to evaluate the total phenolic compounds, the antioxidant properties, and the hepatorenoprotective potential of Calendula officinalis extract against aflatoxins (AFs-) induced liver damage. Six groups of male Sprague-Dawley rats were treated for 6 weeks included the control; the group fed AFs-contaminated diet (2.5 mg/kg diet); the groups treated orally with Calendula extract at low (CA1) and high (CA2) doses (500 and 1000 mg/kg b.w); the groups treated orally with CA1 and CA2 one week before and during AFs treatment for other five weeks. The results showed that the ethanol extract contained higher phenolic compounds and posses higher 1,1-diphenyl 1-2-picryl hydrazyl (DPPH) radical scavenging activity than the aqueous extract. Animals fed AFs-contaminated diet showed significant disturbances in serum biochemical parameters, inflammatory cytokines, and the histological and histochemical pictures of the liver accompanied by a significant increase in malondialdehyde (MDA) and a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) in liver. Calendula extract succeeded to improve the biochemical parameters, inflammatory cytokines, decreased the oxidative stress, and improved the histological pictures in the liver of rats fed AFs-contaminated diet in a dose-dependent manner. It could be concluded that Calendula extract has potential hepatoprotective effects against AFs due to its antioxidant properties and radical scavenging activity.
Ten Years Later, Experienced Teacher Reflections on "Beginning Music Teacher Perceptions of District-Sponsored Induction Programs" (2001)
Authors: Conway Colleen
Published: February 2013

The purpose of this inquiry was to examine the 2010 reflections of experienced teachers (N = 7) on their past perceptions of induction as documented in Conway (2001). Research questions included: (a) How do participants describe their reactions to a present-day examination of 1999/2000 data (journals, individual and focus group interviews, and two questionnaires) and findings? and (b) What can this reflective examination from experienced teachers reveal about current trends in beginning teacher induction and professional development? New data collected in 2010 included participant email survey responses and individual interviews. Findings suggest: (a) Induction and professional development are still inconsistent in the field; (b) Participants now focus more on students in their teaching; (c) Participants feel as if they "understand schools" better now than they did as beginning teachers; and (d) the notion that music content is necessary in induction and professional development was an inconsistent issue between participants.
A Comparison of Contracted and Ideal Music Education Faculty Workload
Authors: Chandler Kyle W. , Russell Joshua A.
Published: February 2013

The purpose of this study was to compare contractual and ideal teaching, research, and service workload data for tenured and tenure-track music education faculty working at National Association of Schools of Music (NASM)-accredited institutions that offered undergraduate and/or graduate degrees in music education. More specifically, two research questions informed this study: (1) What are the contracted and ideal teaching, research, and service workloads for tenured and tenure-track music education faculty according to institution: type (private/public); enrollment; mission (liberal arts, research or teaching/comprehensive); and community (rural, suburban or urban)? And (2), how do these compare? The researchers developed a two-page, 14-item questionnaire, the Music Education Workload Questionnaire (MEWQ) to explore these questions. The 88 completed questionnaires (32.6% return rate) highlighted that contractual teaching, research, and service responsibilities differ little between tenured and tenure-track music education faculty, and that workloads generally involve about 74% teaching, 14% research, and 12% service. In addition, respondents felt that the ideal workload would involve 63% teaching, 22% research, and 15% service. The ideal workload trend of less teaching and more research and service held true regardless of school type, enrollment, mission, or community.
Impact of the Quality of Spatial 3D City Models on Sensor Networks Placement Optimization
Authors: Argany Meysam , Mostafavi Mir Abolfazl , Akbarzadeh Vahab , Gagné Christian , Yaagoubi Reda
Published: February 2013

Sensor networks are increasingly used for tracking, monitoring, and observing spatial dynamic phenomena in the real world (e.g. urban area). In order to ensure an efficient deployment of a sensor network, several optimization algorithms have been proposed in recent years. Most of these algorithms often rely on oversimplified sensor models. In addition, they do not consider information on the terrain topography, city models, and the presence of diverse obstacles in the sensing area (e.g. buildings, trees, poles). Only some of those optimization algorithms attempt to consider the terrain information in the optimization of a sensor network deployment. However, most of these algorithms consider that the spatial models used for this purpose are perfect representations of the reality and are not sensitive to the quality of the information. However, spatial models are simplified representations of a complex reality, and hence are inherently uncertain. In this paper we will investigate the impact of the spatial data quality on the optimization of a sensor network and its spatial coverage in an urban area. For this purpose, we will investigate specific implications of spatial data quality criteria for a 3D city model that will be used in sensor network optimization algorithms. Then, we will analyze the impact of some of those criteria on the estimation of sensor network coverage.!Afterwards, a case study for sensor network deployment in an urban area will be presented. This case study will demonstrate the impact of 3D city models quality on the estimation of coverage using global and local optimization algorithms. Finally, the results obtained from this experimentation will be presented and discussed.
An Assessment of Nonlinear Optimization and Speeded up Robust Features (SURF) Algorithm for Estimating Object Space Transformation Parameters for UAV Pose Estimation
Authors: Sheta Bassem , Elhabiby Mohamed , El-Sheimy Naser
Published: February 2013

Localizing set of features (with known coordinates) on the ground and finding their matches in the image taken by imaging sensor on the aerial vehicle is the basic concept behind Vision Based Navigation (VBN). The number of matching points necessary for solving the collinearity equation is a critical factor to be investigated while using the VBN approach for navigation. Although a robust scale and rotation invariant image matching algorithm is important for VBN of aerial vehicles, the proper estimation of the collinearity equation object space transformation parameters improves the efficiency of the navigation process through the real-time estimation of transformation parameters. These parameters can then be used in aiding the inertial measurements data in the navigation estimation filter. The main objective of this paper is to investigate the estimation of the object space transformation parameters necessary for VBN of aerial vehicles with the assumption that the aerial vehicle experiences large values of the rotational angles, which will lead to non-linearity of the estimation model. In this case, traditional least squares approaches will fail or will take longer to estimate the object space transformation parameters, because of the expected non-linearity of the mathematical model. Five different nonlinear optimization methods are presented for estimating the transformation parameters – these include four gradient based nonlinear optimization methods; Trust region, Trust region dogleg algorithm, Levenberg-Marquardt, and Quasi-Newton line search method and one non-gradient method; Nelder-Mead simplex direct search is employed for the six transformation parameters estimation process. Assessments of the proposed nonlinear optimization approaches on the image matching algorithm necessary for the VBN approach are investigated.
S Corporation Valuations—An Analysis in Search of a Solution
Authors: Kasper Larry J.
Published: February 2013

Until now, the approaches to valuing S corporations have focused on two main aspects: differences in tax rates for subchapter S and C corporations and the appropriate discount rates to use in valuing them. The problem lies with the fact that traditional earnings methods of valuation, including discounted cash flow, are faced with the dilemma of having a “pretax,” that is, untaxed, cash flow passed through to the S corporation shareholder that should be discounted at the post-corporate, but preshareholder, tax discount rate. Empirical evidence is critically reviewed herein.
Relationship between Variability of Past Returns and Levels of Future Returns for Common Stocks, 1926–1960
Authors: Pratt Shannon P.
Published: February 2013

The relationship of risk and expected returns of common stocks has been an integral part of the study of valuation theory even before Graham and Dodd authored their classic Security Analysis in 1934. In 1959, Harry Markowitz established a quantitative framework to the discussion. He adopted variance (or the square root of variance, the standard deviation) of annual returns as a usable measure of risk. The empirical study of the standard deviation of annual returns as a measure of total risk to ex post annual returns is the subject of this essay.

This essay reports on one of the first empirical studies using the data bases of the center for Research in Security Prices at the Graduate School of Business of the University of Chicago.
Incaprettamento: An Unusual Homicide by Ligature Strangulation
Authors: Grattagliano Ignazio , Troccoli Giuseppe , Zelano Carmen , Catanesi Roberto
Published: February 2013

This case study regards the murder of a Tunisian national residing in a small town in southern Italy who was murdered by fellow Tunisian citizen, also living in Italy. The victim was found hogtied and hanged by a cord that was suspended from an iron staff situated between two concrete electrical poles. This method of killing is known as "incaprettemento". It is an unusual type of strangulation whereby a rope is passed around the victim’s wrists, ankles, and throat causing suffocation. This results in a very slow and painful death. Typically, it is a method employed by Italian organized crime groups, but it has also been used in the execution of war crimes. This means of killing is meant to impart a particularly degrading and humiliating revenge on the victim. It may also serve as sign of intimidation and a warning to others. There is very little written about incaprettamento in the literature, but it has, nonetheless, important psychological, anthropological, and cultural implications in the field of criminology. The perpetrator underwent psychodiagnostic evaluations, and was ultimately deemed fit to stand trial.
Independent Influences of Current and Childhood Socioeconomic Status on Health Outcomes in a North Carolina Family Practice Sample of Arthritis Patients
Authors: Baldassari Antoine R. , Cleveland Rebecca J. , Callahan Leigh F.
Published: February 2013

Objective

Compelling evidence suggests that socioeconomic status (SES) is a determinant of health outcomes among persons with arthritis. SES in early life has likewise been associated with various aspects of health, but the connection between childhood SES and health among people with arthritis remains to be investigated. The purpose of this study was to determine the influences of current and childhood SES on self‐reported disability, depression, and physical and mental health among people with self‐reported doctor‐diagnosed arthritis.

Methods

Data originated from a North Carolina network of primary care centers. Participants with self‐reported arthritis with complete sociodemographic and relevant health information were retained in our sample (n = 782). We created summary measures for current and childhood SES from indicators of education, occupation, and homeownership, using parental SES as a proxy for participants' childhood SES. Linear regression models were used to assess the associations between health outcomes and SES variables separately and together, adjusting for key covariates.

Results

Lower childhood and current SES scores were associated with worse disability and physical health. Current SES was furthermore associated with mental health and depressive symptoms. Associations of low current and childhood SES with health outcomes remained significant when concurrently included in a linear model.

Conclusion

Childhood and current SES are both determinants of health among persons with arthritis. This underscores the importance of childhood SES as a determinant of adult health among individuals with arthritis. Further studies should focus on these associations in different populations and across different types of arthritis.
Patient‐Reported Quality of Care for Osteoarthritis: Development and Testing of the OsteoArthritis Quality Indicator Questionnaire
Authors: Østerås Nina , Garratt Andrew , Grotle Margreth , Natvig Bård , Kjeken Ingvild , Kvien Tore K. , Hagen Kåre B.
Published: February 2013

Objective

To develop and test a new instrument for patient self‐reported quality of osteoarthritis (OA) care, and to provide quality indicator (QI) pass rates in a Norwegian OA cohort.

Methods

The OsteoArthritis Quality Indicator (OA‐QI) questionnaire was developed using published QIs, expert panels, and patient interviews. Self‐reported data were collected from 359 persons in a Norwegian OA cohort, and test–retest reliability and validity were assessed. Separate QI pass rates and summary QI pass rates were calculated.

Results

The 17‐item questionnaire includes QIs related to patient education and information, regular provider assessments, referrals, and pharmacologic treatment. The patient self‐reported questionnaire was completed with minimal respondent burden. Support for content validity was confirmed by 2 patient research partners and 2 expert panels. All 10 predefined hypotheses relating to construct validity were confirmed. Test–retest kappa coefficients ranged from 0.20–0.80 and the percentage of exact agreement ranged from 62–90%. The mean pass rate for individual QIs was 31% (range 5–49%). The median summary QI pass rate was 27% (interquartile range 12–50%), with lower summary pass rates for nonpharmacologic compared to pharmacologic treatments.

Conclusion

To our knowledge, this is the first instrument developed to measure patient‐reported QI pass rates for OA care. This study indicates that the OA‐QI questionnaire is acceptable to persons with OA, and its short format makes it suitable for population surveys. The low patient self‐reported QI pass rates in this study suggest a potential for quality improvement in OA care.
Synthesis, Characterization, and Application of Antibody Functionalized Fluorescent Silica Nanoparticles
Authors: Hurley Matthew T. , Wang Zifan , Mahle Amanda , Rabin Daniel , Liu Qing , English Douglas S. , Zachariah Michael R. , Stein Daniel , DeShong Philip
Published: February 2013

Fluorescent silica nanoparticles (FSNs) are prepared by incorporating dye into a mesoporous silica nanoparticle (MSN) synthesis procedure. FSNs containing sulforhodamine B, hydrophobically modified sulforhodamine B, and Cascade Blue hydrazide are made. The MSN‐based FSNs do not leach dye under simulated physiological conditions and have strong, stable fluorescence. FSNs prepared with sulforhodamine B are compared to FSNs prepared with hydrophobically modified sulforhodamine B. The data indicate that FSNs prepared with sulforhodamine B are equally as stable but twice as fluorescent as particles made with hydrophobically modified sulforhodamine B. The fluorescence of a FSN prepared with sulforhodamine B is 10 times more intense than the fluorescence of a 4.5 nm core–shell CdSe/ZnS quantum dot. For diagnostic applications, a method to selectively and covalently bind antibodies to the surface of the FSNs is devised. FSNs that are functionalized with antibodies specific for Neisseria gonorrhoeae specifically bind to Neisseria gonorrhoeae in flow cytometry experiments, thus demonstrating the functionality of the attached antibodies and the potential of MSN‐based FSNs to be used in diagnostic applications.
A computer‐aided methodology to design safe food packaging and related systems
Authors: Nguyen Phuong‐Mai , Goujon Audrey , Sauvegrain Patrick , Vitrac Olivier
Published: February 2013

A specific “Failure Mode, Effects, and Criticality Analysis” (FMECA) methodology has been developed to detect substances, materials, and steps that are critical for the safety of packaging systems used in food contact and related applications. Contamination levels in the finished product beyond acceptable thresholds are screened via a systematic analysis of crossed mass transfer between components and a serialization of mass‐transfer instances during product lifetime. The whole framework, including physical modeling and expert systems, has been integrated within the open‐source simulation software FMECAengine. The whole approach is illustrated on three case studies representative of applications along the food packaging supply chain: (1) identification of critical routes of the contamination by printing ink constituents, (2) concurrent engineering of multipurpose packaging, and (3) application to surveys or control plans. The implementation of this framework within industrial commitments such as compliance with EU regulations and ISO 22000 type food safety management systems is discussed. © 2013 American Institute of Chemical Engineers AIChE J, 59: 1183–1212, 2013
Interaction analysis and geometric interconnection decoupling for networks of process systems
Authors: Hioe Denny , Bao Jie , Hudon Nicolas
Published: February 2013

The effects of interactions between nonlinear subprocesses on the stabilizability of plantwide systems via the concept of dissipative systems are studied. Conditions for which controlled variables of each interconnected subprocess can be driven to and maintained at their desired values are established through the application of interconnection decoupling techniques. The resulting decoupling feedback law encodes the interaction effects between subprocesses and determines the required information structure for achieving desired control performance using distributed control laws. The proposed constructive approach leads to new criteria for the selection of manipulated and controlled variables that guarantee plantwide stability. © 2013 American Institute of Chemical Engineers AIChE J, 59: 2795–2809, 2013
Beyond classical theory: Predicting the free energy barrier of bubble nucleation in polymer foaming
Authors: Kusaka Isamu , Talreja Manish , Tomasko David L.
Published: February 2013

Based on the Gibbs‐Tolman‐Koenig formalism, we considered the Tolman correction to the free energy barrier of bubble nucleation in polymer‐gas binary mixtures. For this class of systems, the correction may be estimated with a reasonable accuracy using experimentally accessible macroscopic thermodynamic quantities only. Although the Tolman correction is applicable only in the low supersaturation regime, a simple ansatz regarding the supersaturation dependence of the Tolman length can be made to extend the usefulness of this approach and to yield the free energy barrier that vanishes at the mean‐field spinodal as demanded by thermodynamic considerations. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3042–3053, 2013
Data‐driven model predictive quality control of batch processes
Authors: Aumi Siam , Corbett Brandon , Clarke‐Pringle Tracy , Mhaskar Prashant
Published: February 2013

The problem of driving a batch process to a specified product quality using data‐driven model predictive control (MPC) is described. To address the problem of unavailability of online quality measurements, an inferential quality model, which relates the process conditions over the entire batch duration to the final quality, is required. The accuracy of this type of quality model, however, is sensitive to the prediction of the future batch behavior until batch termination. In this work, we handle this “missing data” problem by integrating a previously developed data‐driven modeling methodology, which combines multiple local linear models with an appropriate weighting function to describe nonlinearities, with the inferential model in a MPC framework. The key feature of this approach is that the causality and nonlinear relationships between the future inputs and outputs are accounted for in predicting the final quality and computing the manipulated input trajectory. The efficacy of the proposed predictive control design is illustrated via closed‐loop simulations of a nylon‐6,6 batch polymerization process with limited measurements. © 2013 American Institute of Chemical EngineersAIChE J, 59: 2852–2861, 2013
The simplest stirred tank for laminar mixing: Mixing in a vessel agitated by an off‐centered angled disc
Authors: Bulnes‐Abundis D. , Alvarez M. M.
Published: February 2013

We study the mixing structure, mixing performance, and short term dynamics in round bottomed laminar tanks agitated by an eccentrically located angled disc. We define eccentricity (E = e/R) as the ratio of the distance of the axis of rotation from the center line of the tank (e) and the tank radius (R). The structural and dynamic features observed at different eccentricity values were compared using planar laser‐induced fluorescence techniques and computational fluid dynamics calculations. A Poincaré analysis demonstrates the chaotic nature of the flow induced by eccentricity. Practically globally chaotic conditions are observed for E = 0.42 and E = 0.50, with mixing times of 5–8 min at Re = 416. We study the effect of different injection points on the short‐term mixing dynamics and we calculate axial flow rates and Power numbers. Stirred tanks agitated by an eccentrically located angled disc are a simple and cost effective system for laminar mixing applications. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3092–3108, 2013
Catalytic Asymmetric Construction of Stereogenic Carbon Centers that Feature a gem‐Difluoroalkyl Group
Authors: Liu Yun‐Lin , Yu Jin‐Sheng , Zhou Jian
Published: February 2013

gem‐Difluoroalkyl groups, characterized as a gem‐difluoromethylene group substituted by a hydrogen atom or an alkyl or other functional group, are not only valuable for the modulation of the properties of organic compounds, but are also useful for the synthesis of various fluorine‐containing compounds. Currently, the catalytic asymmetric construction of stereogenic carbon centers that feature a gem‐difluoroalkyl group is in its infancy. This Focus Review summarizes the latest achievements and discusses the difficulties and challenges in this field.
Direct Arylation of Porphyrins with π‐Extended Aryl Bromides under Ligand‐free Fagnou–Hartwig Conditions
Authors: Yamamoto Yutaro , Tokuji Sumito , Tanaka Takayuki , Yorimitsu Hideki , Osuka Atsuhiro
Published: February 2013

Palladium‐catalyzed direct β‐diarylation of the nickel complexes of 5,10,15‐triarylporphyrins with π‐extended aryl bromides, such as 9‐bromoanthracene, is described. The reaction proceeded in N,N‐dimethylacetamide in the presence of potassium carbonate, pivalic acid, and a catalytic amount of palladium acetate without any additional ligands. The absorption and emission properties as well as X‐ray crystallographic analysis of the arylated porphyrins are also discussed.
Synthesis of 1 Z,4 E,6 E‐Triene Derivatives by Chemo‐ and Regioselective Iridium‐Catalyzed Dienylation of ortho‐Aminostyrenes with Dienyl Carbonates
Authors: Ye Ke‐Yin , Dai Li‐Xin , You Shu‐Li
Published: February 2013

A chemo‐ and regioselective iridium‐catalyzed dienylation of ortho‐aminostyrene derivatives with dienyl carbonates was realized. With a catalyst generated from [Ir(cod)Cl]2 (2 mol %) and a racemic phosphoramidite ligand (4 mol %), 1Z,4E,6E‐trienes were obtained in moderate to good yields with exclusive formation of a cis double bond.
Choosing Wisely: Highest‐cost tests in outpatient neurology
Authors: Burke James F. , Skolarus Lesli E. , Callaghan Brian C. , Kerber Kevin A.
Published: February 2013

Identifying the tests/procedures ordered by neurologists that contribute most to health care expenditures is a critical step in the process of creating the neurology top 5 list for the Choosing Wisely initiative. Using data from the 2007–2010 National Ambulatory Care Medical Survey, we found that $13.3 billion (95% confidence interval = $10.1–$16.5 billion) was spent on tests ordered at neurologist visits. The tests/procedures with the highest expenditures were magnetic resonance imaging (MRI; 51% of total expenditures; $7.5 billion), electromyography (EMG; 20% of expenditures; $2.6 billion), and electroencephalography (EEG; 8% of expenditures; $1.1 billion). MRI, EMG, and EEG should receive close scrutiny in the development of the neurology top 5 list. Ann Neurol 2013;73:679–683
Mischungen mit niedriger Übergangstemperatur (LTTMs) – eine neue Generation von Designer‐Lösungsmitteln
Authors: Francisco María , van den Bruinhorst Adriaan , Kroon Maaike C.
Published: February 2013

Im Laufe der letzten zehn Jahre trat eine neue Generation von Designer‐Lösungsmitteln als vielversprechendes grünes Medium für viele Anwendungen, einschließlich Trennverfahren, in Erscheinung: Mischungen mit niedriger Übergangstemperatur (LTTMs, low‐transition‐temperature mixtures). Hergestellt werden sie durch Vermischen natürlicher, hochschmelzender Ausgangsmaterialien, die infolge von H‐Brücken‐Bindungen eine Flüssigkeit bilden. Die zu ihnen zählenden tiefeutektischen Lösungsmittel (DESs) werden als aussichtsreiche Alternative zu konventionellen ionischen Flüssigkeiten (ILs) vorgestellt. LTTMs können einige Grenzen der ILs überwinden und zeichnen sich zudem durch eine günstige und einfache Herstellung aus natürlichen und leicht verfügbaren Ausgangsmaterialien, Bioabbaubarkeit sowie Nachhaltigkeit aus.
Low‐Transition‐Temperature Mixtures (LTTMs): A New Generation of Designer Solvents
Authors: Francisco María , van den Bruinhorst Adriaan , Kroon Maaike C.
Published: February 2013

A new generation of designer solvents emerged in the last decade as promising green media for multiple applications, including separation processes: the low‐transition‐temperature mixtures (LTTMs). They can be prepared by mixing natural high‐melting‐point starting materials, which form a liquid by hydrogen‐bond interactions. Among them, deep‐eutectic solvents (DESs) were presented as promising alternatives to conventional ionic liquids (ILs). Some limitations of ILs are overcome by LTTMs, which are cheap and easy to prepare from natural and readily available starting materials, biodegradable, and renewable.
Sifalimumab, a Human Anti–Interferon‐α Monoclonal Antibody, in Systemic Lupus Erythematosus: A Phase I Randomized, Controlled, Dose‐Escalation Study
Authors: Petri Michelle , Wallace Daniel J. , Spindler Alberto , Chindalore Vishala , Kalunian Kenneth , Mysler Eduardo , Neuwelt C. Michael , Robbie Gabriel , White Wendy I. , Higgs Brandon W. , Yao Yihong , Wang Liangwei , Ethgen Dominique , Greth Warren
Published: February 2013

Objective

To evaluate the safety and tolerability of multiple intravenous (IV) doses of sifalimumab in adults with moderate‐to‐severe systemic lupus erythematosus (SLE).

Methods

In this multicenter, double‐blind, placebo‐controlled, sequential dose‐escalation study, patients were randomized 3:1 to receive IV sifalimumab (0.3, 1.0, 3.0, or 10.0 mg/kg) or placebo every 2 weeks to week 26, then followed up for 24 weeks. Safety assessment included recording of treatment‐emergent adverse events (AEs) and serious AEs. Pharmacokinetics, immunogenicity, and pharmacodynamics were evaluated, and disease activity was assessed.

Results

Of 161 patients, 121 received sifalimumab (26 received 0.3 mg/kg; 25, 1.0 mg/kg; 27, 3.0 mg/kg; and 43, 10 mg/kg) and 40 received placebo. Patients were predominantly female (95.7%). At baseline, patients had moderate‐to‐severe disease activity (mean SLE Disease Activity Index score 11.0), and most (75.2%) had a high type I interferon (IFN) gene signature. In the sifalimumab group versus the placebo group, the incidence of ≥1 treatment‐emergent AE was 92.6% versus 95.0%, ≥1 serious AE was 22.3% versus 27.5%, and ≥1 infection was 67.8% versus 62.5%; discontinuations due to AEs occurred in 9.1% versus 7.5%, and death occurred in 3.3% (n = 4) versus 2.5% (n = 1). Serum sifalimumab concentrations increased in a linear and dose‐proportional manner. Inhibition of the type I IFN gene signature was sustained during treatment in patients with a high baseline signature. No statistically significant differences in clinical activity (SLEDAI and British Isles Lupus Assessment Group score) between sifalimumab and placebo were observed. However, when adjusted for excess burst steroids, SLEDAI change from baseline showed a positive trend over time. A trend toward normal complement C3 or C4 level at week 26 was seen in the sifalimumab groups compared with baseline.

Conclusion

The observed safety/tolerability and clinical activity profile of sifalimumab support its continued clinical development for SLE.
Circulating MicroRNA Expression Profiles Associated With Systemic Lupus Erythematosus
Authors: Carlsen Anting Liu , Schetter Aaron J. , Nielsen Christoffer T. , Lood Christian , Knudsen Steen , Voss Anne , Harris Curtis C. , Hellmark Thomas , Segelmark Mårten , Jacobsen Søren , Bengtsson Anders A. , Heegaard Niels H. H.
Published: February 2013

Objective

To evaluate the specificity of expression patterns of cell‐free circulating microRNAs (miRNAs) in systemic lupus erythematosus (SLE).

Methods

Total RNA was purified from plasma, and 45 different specific, mature miRNAs were determined using quantitative reverse transcription–polymerase chain reaction assays. A total of 409 plasma samples were obtained from 364 different patients with SLE, healthy control subjects, and control subjects with other autoimmune diseases. The results in the primary cohort of 62 patients with SLE and 29 healthy control subjects were validated in 2 independent cohorts: a validation cohort comprising 68 patients with SLE and 68 healthy control subjects, and a disease control cohort comprising 20 patients with SLE (19 of whom were from the other validation cohort), 46 healthy control subjects, 38 patients with vasculitis, 18 patients with rheumatoid arthritis, and 20 immunosuppressed patients.

Results

Seven miRNAs were statistically significantly differentially expressed in plasma from patients with SLE. The expression of miRNA‐142‐3p (miR‐142‐3p) and miR‐181a was increased, and the expression of miR‐106a, miR‐17, miR‐20a, miR‐203, and miR‐92a was decreased. In addition, the expression of miR‐342‐3p, miR‐223, and miR‐20a was significantly decreased in SLE patients with active nephritis. A predictive model for SLE based on 2 or 4 miRNAs differentiated patients with SLE from control subjects (76% accuracy) when validated independently (P < 2 × 10−9). Use of the 4‐miRNA model provided highly significant differentiation between the SLE group and disease controls, except for those with vasculitis.

Conclusion

Circulating miRNAs are systematically altered in SLE. A 4‐miRNA signature was diagnostic of SLE, and a specific subset of miRNA profiles was associated with nephritis. All of the signature miRNAs target genes in the transforming growth factor β signaling pathways. Other targets include regulation of apoptosis, cytokine–cytokine receptors, T cell development, and cytoskeletal organization. These findings highlight possible dysregulated pathways in SLE and suggest that circulating miRNA patterns distinguish SLE from other immunoinflammatory phenotypes.
A Hot Spot for Systemic Lupus Erythematosus, but Not for Psoriatic Arthritis, Identified by Spatial Analysis Suggests an Interaction Between Ethnicity and Place of Residence
Authors: Al‐Maini Mustafa , Jeyalingam Thurarshen , Brown Patrick , Lee Jennifer J. Y. , Li Lennon , Su Jiandong , Gladman Dafna D. , Fortin Paul R.
Published: February 2013

Objective

To describe the spatial distribution of incident cases of systemic lupus erythematosus (SLE) using geographic information systems (GIS).

Methods

Spatial analyses were carried out on 890 SLE patients and 541 psoriatic arthritis (PsA) patients (controls). Age‐ and sex‐adjusted rates for SLE/PsA for each census tract were calculated using denominator population values from the Canadian census. Spatial variations in relative risk were estimated by modeling risk as the product of a time effect, an age effect, and a spatially autocorrelated risk surface to identify hot spots. Patients within the detected hot spot were compared to those outside the hot spot to identify explanatory factors.

Results

SLE patients were predominantly female (87.75%) and the incidence rate was highest among those 15–19 years of age (2.4 cases/100,000 person‐years). In an SLE hot spot containing 59 patients, 100% of the patients were female and 49.1% (n = 29) were Caucasian, while outside of the hot spot, 86.9% (n = 722) of the patients were female and 68.4% (n = 568) were Caucasian. The proportion of cases of Chinese ethnicity was significantly greater within the hot spot. An interaction was found between Chinese ethnicity and residence within the hot spot, with the risk of SLE to the Chinese population found to be twice the risk to the non‐Chinese population.

Conclusion

GIS was used to map SLE cases and a hot spot was identified after adjustment for age and sex. Ethnicity by itself did not confer an increased risk of SLE, but the interaction of ethnicity with location of residence significantly increased the risk of SLE.
Alginate‐Based Microcapsules with a Molecule Recognition Linker and Photosensitizer for the Combined Cancer Treatment
Authors: Du Cuiling , Zhao Jie , Fei Jinbo , Gao Liang , Cui Wei , Yang Yang , Li Junbai
Published: February 2013

A reactive template method was used to fabricate alginate‐based hydrogel microcapsules. The uniform and well‐dispersed hydrogel capsules have a high drug loading capacity. After they are coated by a folate‐linked lipid mixture on the surface, the capsules possess higher cell uptake efficiency by the molecule recognition between folate and the folate‐receptor overexpressed by the cancer cells. Moreover, in this bioconjugate, the lipid could remarkably reduce the release rate of hydrophilic doxorubicin from the hydrogel microcapsules and encapsulate the hydrophobic photosensitizer hypocrellin B. The biointerfaced capsules could be used as drug carriers for combined treatment against cancer cell proliferation in vitro; this was much more effective than chemotherapy or photodynamic therapy alone.