bluuebunny/crossref_metadata_2025 huggingface dataset:
Graph-Based Approaches to Placement of Processing Element Networks on FPGAs for Physical Model Simulation
Authors: Miller Bailey , Vahid Frank , Givargis Tony , Brisk Philip
Published: December 2014

Physical models utilize mathematical equations to characterize physical systems like airway mechanics, neuron networks, or chemical reactions. Previous work has shown that field programmable gate arrays (FPGAs) execute physical models efficiently. To improve the implementation of physical models on FPGAs, this article leverages graph theoretic techniques to synthesize physical models onto FPGAs. The first phase maps physical model equations onto a structured virtual processing element (PE) graph using graph theoretic folding techniques. The second phase maps the structured virtual PE graph onto physical PE regions on an FPGA using graph embedding theory. A simulated annealing algorithm is introduced that can map any physical model onto an FPGA regardless of the model's underlying topology. We further extend the simulated annealing approach by leveraging existing graph drawing algorithms to generate the initial placement. Compared to previous work on physical model implementation on FPGAs, embedding increases clock frequency by 25% on average (for applicable topologies), whereas simulated annealing increases frequency by 13% on average. The embedding approach typically produces a circuit whose frequency is limited by the FPGA clock instead of routing. Additionally, complex models that could not previously be routed due to complexity were made routable when using placement constraints.
Plug&Chip
Authors: Diamantopoulos Dionysios , Sotiriou-Xanthopoulos Efstathios , Siozios Kostas , Economakos George , Soudris Dimitrios
Published: December 2014

In the embedded system domain there is a continuous demand towards providing higher flexibility for application development. This trend strives for virtual prototyping solutions capable of performing fast system simulation. Among other benefits, such a solution supports concurrent hardware/software system design by enabling to start developing, testing, and validating the embedded software substantially earlier than has been possible in the past. Towards this direction, throughout this article we introduce a new framework, named Plug&Chip, targeting to support rapid prototyping of 2D and 3D digital systems. In contrast to other relevant approaches, our solution provides higher flexibility by enabling incremental system design, while also handling platforms developed with the usage of 3D integration technology.
Optimal Radius for Connectivity in Duty-Cycled Wireless Sensor Networks
Authors: Bagchi Amitabha , Galhotra Sainyam , Mangla Tarun , Pinotti Cristina M.
Published: December 2014

We investigate the condition on transmission radius needed to achieve connectivity in duty-cycled wireless sensor networks (briefly, DC-WSNs). First, we settle a conjecture of Das et al. [2012] and prove that the connectivity condition on random geometric graphs (RGGs), given by Gupta and Kumar [1989], can be used to derive a weakly sufficient condition to achieve connectivity in DC-WSNs. To find a stronger result, we define a new vertex-based random connection model that is of independent interest. Following a proof technique of Penrose [1991], we prove that when the density of the nodes approaches infinity, then a finite component of size greater than 1 exists with probability 0 in this model. We use this result to obtain an optimal condition on node transmission radius that is both necessary and sufficient to achieve connectivity and is hence
optimal
. The optimality of such a radius is also tested via simulation for two specific duty-cycle schemes, called the
contiguous
and the
random selection
duty-cycle schemes. Finally, we design a minimum-radius duty-cycling scheme that achieves connectivity with a transmission radius arbitrarily close to the one required in random geometric graphs. The overhead in this case is that we have to spend some time computing the schedule.
Provenance Quality Assessment Methodology and Framework
Authors: Cheah You-Wei , Plale Beth
Published: December 2014

Data provenance, a form of metadata describing the life cycle of a data product, is crucial in the sharing of research data. Research data, when shared over decades, requires recipients to make a determination of both use and trust. That is, can they use the data? More importantly, can they trust it? Knowing the data are of high quality is one factor to establishing fitness for use and trust. Provenance can be used to assert the quality of the data, but the quality of the provenance must be known as well. We propose a framework for assessing the quality of data provenance. We identify quality issues in data provenance, establish key quality dimensions, and define a framework of analysis. We apply the analysis framework to synthetic and real-world provenance.
Accurate and Novel Recommendations
Authors: Javari Amin , Jalili Mahdi
Published: December 2014

Recommender systems are in the center of network science, and they are becoming increasingly important in individual businesses for providing efficient, personalized services and products to users. Previous research in the field of recommendation systems focused on improving the precision of the system through designing more accurate recommendation lists. Recently, the community has been paying attention to diversity and novelty of recommendation lists as key characteristics of modern recommender systems. In many cases, novelty and precision do not go hand in hand, and the accuracy--novelty dilemma is one of the challenging problems in recommender systems, which needs efforts in making a trade-off between them.

In this work, we propose an algorithm for providing novel and accurate recommendation to users. We consider the standard definition of accuracy and an effective self-information--based measure to assess novelty of the recommendation list. The proposed algorithm is based on item popularity, which is defined as the number of votes received in a certain time interval. Wavelet transform is used for analyzing popularity time series and forecasting their trend in future timesteps. We introduce two filtering algorithms based on the information extracted from analyzing popularity time series of the items. The popularity-based filtering algorithm gives a higher chance to items that are predicted to be popular in future timesteps. The other algorithm, denoted as a novelty and population-based filtering algorithm, is to move toward items with low popularity in past timesteps that are predicted to become popular in the future. The introduced filters can be applied as adds-on to any recommendation algorithm. In this article, we use the proposed algorithms to improve the performance of classic recommenders, including item-based collaborative filtering and Markov-based recommender systems. The experiments show that the algorithms could significantly improve both the accuracy and effective novelty of the classic recommenders.
A Sensor System for High-Fidelity Temperature Distribution Forecasting in Data Centers
Authors: Chen Jinzhu , Tan Rui , Wang Yu , Xing Guoliang , Wang Xiaorui , Wang Xiaodong , Punch Bill , Colbry Dirk
Published: December 2014

Data centers have become a critical computing infrastructure in the era of cloud computing. Temperature monitoring and forecasting are essential for preventing server shutdowns because of overheating and improving a data center’s energy efficiency. This article presents a novel cyber-physical approach for temperature forecasting in data centers, one that integrates Computational Fluid Dynamics (CFD) modeling,
in situ
wireless sensing, and real-time data-driven prediction. To ensure forecasting fidelity, we leverage the realistic physical thermodynamic models of CFD to generate transient temperature distribution and calibrate it using sensor feedback. Both simulated temperature distribution and sensor measurements are then used to train a real-time prediction algorithm. As a result, our approach reduces not only the computational complexity of online temperature modeling and prediction, but also the number of deployed sensors, which enables a portable, noninvasive thermal monitoring solution that does not rely on the infrastructure of a monitored data center. We extensively evaluated the proposed system on a rack of 15 servers and a testbed of five racks and 229 servers in a small-scale production data center. Our results show that our system can predict the temperature evolution of servers with highly dynamic workloads at an average error of 0.52○C, within a duration up to 10 minutes. Moreover, our approach can reduce the required number of sensors by 67% while maintaining desirable prediction fidelity.
A Qualitative Study of Students' Computational Thinking Skills in a Data-Driven Computing Class
Authors: Yuen Timothy T. , Robbins Kay A.
Published: December 2014

Critical thinking, problem solving, the use of tools, and the ability to consume and analyze information are important skills for the 21st century workforce. This article presents a qualitative case study that follows five undergraduate biology majors in a computer science course (CS0). This CS0 course teaches programming within a data-driven context and is part of a university-wide initiative to improve students' quantitative scholarship. In this course, students learn computing concepts and computational thinking by writing programs in MATLAB that compute with data, by performing meaningful analyses, and by writing about the results. The goal of the study reported here is to better understand the thought processes students use in such a data-driven approach. Findings show that students engage in an ongoing organizational process to understand the structure of the data. The computational and visualization tasks appear to be closely linked, and the visualization component appears to provide valuable feedback for students in accomplishing the programming tasks.
Severe/Extreme Hypertriglyceridemia and LDL Apheretic Treatment: Review of the Literature, Original Findings
Authors: Diakoumakou Olga , Hatzigeorgiou Georgios , Gontoras Nikos , Boutsikou Maria , Kolovou Vana , Mavrogeni Sophie , Giannakopoulou Vassiliki , Kolovou Genovefa D.
Published: December 2014

Hypertriglyceridemia (HTG) is a feature of numerous metabolic disorders including dyslipidemias, metabolic syndrome, and diabetes mellitus type 2 and can increase the risk of premature coronary artery disease. HTG may also be due to genetic factors (called primary HTG) and particularly the severe/extreme HTG (SEHTG), which is a usually rare genetic disorder. Even rarer are secondary cases of SEHTG caused by autoimmune disease. This review considers the causes of SEHTG, and their management including treatment with low density lipoprotein apheresis and analyzes the original findings.
Complications of Inflatable Penile Prostheses Implantation Classified according to the Modified Clavien System
Authors: Vakalopoulos Ioannis , Kampantais Spyridon , Gkagkalidis Konstantinos , Ioannidis Stavros , Dimitriadis Georgios , Patsialas Christos , Toutziaris Chrysovalantis , Anagnostou Ioannis , Pavlakis Dimitrios , Henry Gerard D.
Published: December 2014

Introduction. In patients with erectile dysfunction (ED), inflatable penile prosthesis (IPP) surgery is regarded as the gold standard treatment in medically refractory cases or where its conservative treatment options are contraindicated. Despite improvements in surgical technique and implanted materials, IPP surgery retains a substantial complication rate. The aim of the study was to record and grade the postoperative complications of IPP implantation according to a modified Clavien system. Methods. A total of 60 three-piece IPP implantations were performed between 2007 and 2013 by a single surgeon. The primary outcome was to stratify the early (first 30 days) complications into five categories using the modified Clavien-Dindo classification system. A secondary aim was to record the long-term adverse events and to identify possible factors related to complication occurrence. Results. Overall, there were 21 (35%) postoperative complications in 17 of 60 men (28.3%), with 15 adverse events occurring early after surgery. In terms of late complications, there were six (10%) major complications managed by either revision surgery or removal of the prosthesis. Conclusion. This study utilizes a validated morbidity scale thus overcoming problems of previous studies reporting IPP surgery complications. The modified Clavien classification system easily aids in assessing and comparing accurately patients’ postoperative complications, thus improving management and prevention.
Corneal Bee Sting Controlled with Early Surgical Intervention and Systemic High-Dose Steroid Therapy
Authors: Kim Jung-Hoon , Kim Moosang , Lee Seung-Jun , Han Sang Beom , Hyon Joon Young
Published: December 2014

A 34-year-old Asian woman presented with painful corneal bee sting. Examinations revealed severe corneal swelling with stinger stuck in deep stroma and endothelial cell loss. She was treated with early surgery including stinger removal and anterior chamber irrigation combined with systemic high-dose steroid therapy. Vision and corneal clarity was recovered in 5 days and no additional corneal endothelial damage was observed. This report suggests that early surgical intervention and high-dose steroid therapy appear to be a useful option in the treatment of corneal bee sting.
Mathematical Analysis of the Reduction of Wüstite at Different Basicity Using Factorial Design
Authors: Mousa E. A.
Published: December 2014

Numerical prediction is performed on the reduction of wüstite under simulated blast furnace conditions using factorial design approach. Wüstite sinter samples with different basicity (0.5, 1.0, and 2.0) are reduced with a gas mixture consisting of 30% CO, 10% H2, 5% CO2, and 55% N2 at 950–1100°C. In all cases, the reduction degree of wüstite increased with basicity and temperature. A 23 factorial design is applied to derive a regression model based on the experimental data of acidic (CaO/SiO2 = 0.5) and basic (CaO/SiO2 = 2.0) wüstite which is reduced at 950°C and 1100°C for 5 and 35 min. The developed mathematical model is applied to predict the reduction degree of wüstite at different basicity (0.5, 1.0, and 2.0), interval of time (5–35 min), and temperatures (950, 1000, 1050°C, and 1100°C). In general, the results of the driven models are found to be in good agreement with the experimental data of reduction of wüstite in many cases. The MATLAB program is used to carry out the required calculations.
On Certain Subclasses of Analytic Functions Involving Carlson-Shaffer Operator and Related to Lemniscate of Bernoulli
Authors: Patel Jagannath , Sahoo Ashok Kumar
Published: December 2014

The object of the present investigation is to solve the Fekete-Szegö problem and determine the sharp upper bound to the second Hankel determinant for a new class R(a,c) of analytic functions involving the Carlson-Shaffer operator in the unit disk. We also obtain a sufficient condition for normalized analytic functions in the unit disk to be in this class.
Analysis of Unweighted Amino Acids Network
Authors: Akhtar Adil , Ali Tazid
Published: December 2014

The analysis of amino acids network is very important to studying the various physicochemical properties of amino acids. In this paper we consider the amino acid network based on mutation of the codons. To analyze the relative importance of the amino acids we have discussed different measures of centrality. The measure of centrality is a powerful tool of graph theory for ranking the vertices and analysis of biological network. We have also investigated the correlation coefficients between various measures of centrality. Also we have discussed clustering coefficient as well as average clustering coefficient of the network. Finally we have discussed the degree of distribution as well as skewness.
The Effectiveness of Self-Expandable Metallic Stent Insertion in Treating Right-Sided Colonic Obstruction: A Comparison between SEMS and Decompression Tube Placement and an Investigation of the Safety and Difficulties of SEMS Insertion in Right Colons
Authors: Moroi Rintaro , Endo Katsuya , Ichikawa Ryo , Nagai Hiroshi , Shinkai Hirohiko , Kimura Tomoya , Ishiyama Fumitake , Yaguchi Kei , Kayaba Shoichi , Shimosegawa Tooru
Published: December 2014

Objectives.Self-expandable metallic stent (SEMS) is widely used to treat malignant colonic obstruction. However, most reports about SEMS insertion have concentrated on the left colon. This study aimed to (1) investigate the effectiveness of SEMS insertion compared with conventional decompression tube for right-sided colonic obstruction and (2) compare the safety and technical success of SEMS insertion between left- and right-sided colonic obstructions.Methods.The data from thirty-seven patients who underwent SEMS or conventional decompression tube placement for malignant colonic obstruction in our hospital were analyzed retrospectively. Technical and clinical success, complications, and technical difficulties were analyzed. We compared the results between SEMS insertion and decompression tube placement in right colons and the outcomes of SEMS insertion between right- and left-sided colonic obstructions.Results.For right colons, the clinical success rate of SEMS insertion (100%) was significantly higher than that of decompression tube placement (55.9%). Concerning SEMS insertion, the technical difficulty and safety of SEMS insertion were similar between right- and left-sided colonic obstructions.Conclusion.SEMS insertion for right-sided colon is significantly more effective than conventional decompression tube placement, and this procedure was safer and less technically challenging than expected. SEMS insertion should be considered for treating right-sided malignant colonic obstruction.
Influence of Plantation Establishment on Discharge Characteristics in a Small Catchment of Tropical Forest
Authors: Shamsuddin Siti Aisah , Yusop Zulkifli , Noguchi Shoji
Published: December 2014

A study was conducted on the impact of forest clearance on discharge from newly established Hopea odorata plantations catchment (14.4 ha). The stands were two years old when this study commenced in year 2006 and the data collection was carried out for two years. The forested catchment (C3) was clear-cut during the preparation of the forest plantation and catchment C1 was left undisturbed. Discharge and rainfall were measured continuously for two years. The discharge measured from years 1997 to 2003 was used also to determine the water yield before and after forest clear-cut. This study showed that the plantation catchment is more responsive to storm with higher total water yield than in the forested catchment. The effect of forest clear cutting to discharge was clearly shown by the increment in the amount following the clear-cut activities and time taken for the recovery of the discharge back to its original state was almost three years. The peak discharge in C3 also was affected in which the biggest change was obtained during the forest clear-cutting period compared with during calibration and after clearing periods. This study is useful as basis for improving the existing guidelines on forest plantation establishment.
A Newly Developed Sublingual Tonometric Method for the Evaluation of Tissue Perfusion and Its ValidationIn Vitroand in Healthy PersonsIn Vivoand the Results of the Measurements in COPD Patients
Authors: Rózsavölgyi Zoltán , Boda Domokos , Hajnal Andrea , Boda Krisztina , Somfay Attila
Published: December 2014

Introduction. Since its first publication in the medical literature, an extremely large number of references have demonstrated that the tonometric measurement of tissue perfusion is a reliable indicator of the actual condition of critically ill patients. Later a new method was developed by the introduction of sublingual tonometry for the determination of tissue perfusion. In comparison with gastric tonometry, the new method was simpler and could even be used in awake patients. Unfortunately, at present, because of severe failures of manufacturing, the device is withdrawn from commerce.Materials and Methods. In this study, we present a new method using a newly developed tool for the PslCO2measurement in sublingual tonometry as well as the data for its validationin vitroandin vivoand the results of 25 volunteers and 54 COPD patients belonging to different GOLD groups at their hospitalization due to the acute exacerbation of the disease but already in a stable condition at the time of the examination.Results and Conclusion. The results of the performed examinations showed that the method is suitable for monitoring the actual condition of the patients by mucosal perfusion tonometry in the sublingual region.
Optimal Duration of Daily Antituberculosis Therapy before Switching to DOTS Intermittent Therapy to Reduce Mortality in HIV Infected Patients: A Duration-Response Analysis Using Restricted Cubic Splines
Authors: Alvarez-Uria Gerardo , Pakam Raghavakalyan , Midde Manoranjan , Naik Praveen Kumar
Published: December 2014

Compared with thrice-weekly intermittent antituberculosis therapy (ATT), the use of daily ATT during the intensive phase has shown improved survival in HIV infected patients with tuberculosis. However, the optimal duration of daily ATT before initiating intermittent ATT is not well known. In this study, we analysed the mortality of HIV-related tuberculosis according to the duration of daily ATT before switching to thrice-weekly ATT in patients who completed at least two months of treatment in an HIV cohort study. Statistical analysis was performed using Cox proportional hazard models. To relax the linearity assumption in regression models and to allow for a flexible interpretation of the relationship between duration of daily ATT and mortality, continuous variables were modelled using restricted cubic splines. The study included 520 HIV infected patients with tuberculosis and 8,724.3 person-months of follow-up. The multivariable analysis showed that the mortality risk was inversely correlated with the duration of daily ATT before switching to intermittent therapy during the first 30 days of ATT but, after approximately 30 days of treatment, differences were not statistically significant. The results of this study suggest that daily ATT should be given for at least 30 days before switching to intermittent ATT in HIV infected patients with tuberculosis.
Inhibitory Effect on β‐Hexosaminidase Release from RBL‐2H3 Cells of Extracts and Some Pure Constituents of Benchalokawichian, a Thai Herbal Remedy, Used for Allergic Disorders
Authors: Juckmeta Thana , Thongdeeying Pakakrong , Itharat Arunporn
Published: December 2014

Introduction. Benchalokawichian (BCW), a Thai traditional herbal formulation, has long been used as antipyretic and to treat skin disorders. It comprises roots from five herbs: Ficus racemosa, Capparis micracantha, Clerodendrum petasites, Harrisonia perforata, and Tiliacora triandra. This polyherbal remedy has recently been included in the Thailand National List of Essential Medicines (Herbal Products list). Methodology. A Bioassay‐guided fractionation technique was used to evaluate antiallergy activities of crude extracts, and those obtained by the multistep column chromatography isolation of pure compounds. Inhibitory effect on the release of β‐hexosaminidase from RBL‐2H3 cells was used to determine antiallergic activity. Results. Two pure compounds from BCW formulation showed higher antiallergic activity than crude or semipure extracts. Pectolinarigenin showed the highest antiallergic activity, followed by O‐methylalloptaeroxylin, with IC50 values of 6.3 μg/mL and 14.16 μg/mL, respectively. Moreover, the highest activities of pure compounds were significantly higher than chlorpheniramine (16.2 μg/mL). Conclusions. This study provides some support for the use of BCW in reducing itching and treatment of other skin allergic disorders. The two isolated constituents exhibited high antiallergic activity and it is necessary to determine their mechanism of action. Further phytochemical and safety studies of pure compounds are required before development of these as antiallergy commercial remedies.
E. coliInduced Experimental Model of Primary Biliary Cirrhosis: At Last
Authors: Koutsoumpas Andreas L. , Smyk Daniel S. , Bogdanos Dimitrios P.
Published: December 2014

Recurrent urinary tract infections (UTI) have been considered potential triggers of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterised by progressive destruction of intrahepatic bile ducts. Additional support for the link made between PBC and UTI was based on early observations of recurrent episodes of bacteriuria in female patients with PBC. A series of large epidemiological studies demonstrated a strong correlation between recurrent UTI and PBC, initiating a series of studies investigating the role ofEscherichia coli(E. coli, the most prevalent organism isolated in women with UTI) as a trigger of PBC. Immunological evidence of B- and T-cell cross-reactive responses implicating PBC-specific autoantigens andE. colimimics have been clearly demonstrated, adding support to the notion thatE. coliis a potential infectious inducer of PBC in susceptible individuals. One of the major limitations in proving theE. coli/PBC association was the lack of reliableE. coli-infected animal models of PBC. This review provides an overview of the evidence linking this infectious agent with PBC and discusses the pros and cons of a recently developedE. coli-infected animal model of PBC.
Risk Factors for Hospital and Long-Term Mortality of Critically Ill Elderly Patients Admitted to an Intensive Care Unit
Authors: Mukhopadhyay A. , Tai B. C. , See K. C. , Ng W. Y. , Lim T. K. , Onsiong S. , Ee S. , Chua M. J. , Lee P. R. , Loh M. L. , Phua J
Published: December 2014

Background. Data on long-term outcomes of elderly (≥65 years) patients in ICU are sparse.Materials and Methods. Adult patients (n=1563, 45.4% elderly) admitted over 28 months were analyzed by competing risks regression model to determine independent factors related to in-hospital and long-term mortality.Results. 414 (26.5%) and 337 (21.6%) patients died in-hospital and during the 52 months following discharge, respectively; the elderly group had higher mortality during both periods. After discharge, elderly patients had 2.3 times higher mortality compared to the general population of the same age-group. In-hospital mortality was independently associated with mechanical ventilation (subdistribution hazard ratio (SHR) 2.74), vasopressors (SHR 2.56), neurological disease (SHR 1.77), and Mortality Prediction Model II score (SHR 1.01) regardless of age and with malignancy (SHR, hematological 3.65, nonhematological 3.4) and prior renal replacement therapy (RRT, SHR 2.21) only in the elderly. Long-term mortality was associated with low hemoglobin concentration (SHR 0.94), airway disease (SHR 2.23), and malignancy (SHR hematological 1.11, nonhematological 2.31) regardless of age and with comorbidities especially among the nonelderly.Conclusions. Following discharge, elderly ICU patients have higher mortality compared to the nonelderly and general population. In the elderly group, prior RRT and malignancy contribute additionally to in-hospital mortality risk. In the long-term, comorbidities (age-related), anemia, airway disease, and malignancy were significantly associated with mortality.
An Interesting Cause of Hyperandrogenemic Hirsutism
Authors: Atmaca Murat , Seven İsmet , Üçler Rıfkı , Alay Murat , Barut Veysi , Dirik Yaren , Sezgin Yasin
Published: December 2014

Mild clinical signs of hyperandrogenism such as hirsutism may appear during the menopausal transition as part of the normal aging process, but the development of frank virilization suggests a specific source of androgen excess. We report a case of a 68-year-old woman with signs of virilization that had started 6 months before. Clinical analyses revealed high levels of serum testosterone for a postmenopausal woman. Pelvic MRI and abdomen CT showed no evidence of ovarian and adrenal tumor. Postmenopausal hyperandrogenism can be the result of numerous etiologies ranging from normal physiologic changes to ovarian or rarely adrenal tumors. Our patient was found to have iatrogenic hyperandrogenism. This condition is rarely reported cause of virilization.
Role of Chitinase 3–like-1 and Semaphorin 7a in Pulmonary Melanoma Metastasis
Authors: Ma Bing , Herzog Erica L. , Lee Chun Geun , Peng Xueyan , Lee Chang-Min , Chen Xiaosong , Rockwell Sara , Koo Ja Seok , Kluger Harriet , Herbst Roy S. , Sznol Mario , Elias Jack A.
Published: December 2014

The prototypic chitinase-like protein Chi3l1 is induced in cancers and portends a poor prognosis, but whether it contributes to cancer progression is unknown. To address this gap in knowledge, we investigated the production of Chi3l1 in melanoma lung metastases. We found that Chi3l1 was induced during pulmonary melanoma metastasis and that this induction was regulated by the semaphorin Sema7a, interacting in stimulatory or inhibitory ways with its β1 integrin or Plexin C1 receptors, respectively. In mouse strains with genetic deletions of Chi3l1 or Sema7a, there was a significant reduction in pulmonary metastasis. Notably, antiserum raised against Chi3l1 or Sema7a phenocopied the reduction produced by genetic deletions. Melanoma lung metastasis was also decreased in the absence of IL13Rα2, a recently identified receptor for Chi3l1, consistent with a key role for Chi3l1 in melanoma spread. We confirmed roles for Sema7a and Chi3l1 in pulmonary metastasis of EMT6 breast cancer cells. Taken together, our studies establish a novel pathway through which Sem7a and its receptors regulate Chi3l1, revealing a host axis involving IL13Rα2 that plays a critical role in generating a pulmonary microenvironment that is critical to license metastasis. Cancer Res; 75(3); 487–96. ©2014 AACR.
BRCA2-Deficient Sarcomatoid Mammary Tumors Exhibit Multidrug Resistance
Authors: Jaspers Janneke E. , Sol Wendy , Kersbergen Ariena , Schlicker Andreas , Guyader Charlotte , Xu Guotai , Wessels Lodewyk , Borst Piet , Jonkers Jos , Rottenberg Sven
Published: December 2014

Pan- or multidrug resistance is a central problem in clinical oncology. Here, we use a genetically engineered mouse model of BRCA2-associated hereditary breast cancer to study drug resistance to several types of chemotherapy and PARP inhibition. We found that multidrug resistance was strongly associated with an EMT-like sarcomatoid phenotype and high expression of the Abcb1b gene, which encodes the drug efflux transporter P-glycoprotein. Inhibition of P-glycoprotein could partly resensitize sarcomatoid tumors to the PARP inhibitor olaparib, docetaxel, and doxorubicin. We propose that multidrug resistance is a multifactorial process and that mouse models are useful to unravel this. Cancer Res; 75(4); 732–41. ©2014 AACR.
Gain of Glucose-Independent Growth upon Metastasis of Breast Cancer Cells to the Brain
Authors: Chen Jinyu , Lee Ho-Jeong , Wu Xuefeng , Huo Lei , Kim Sun-Jin , Xu Lei , Wang Yan , He Junqing , Bollu Lakshmi R. , Gao Guang , Su Fei , Briggs James , Liu Xiaojing , Melman Tamar , Asara John M. , Fidler Isaiah J. , Cantley Lewis C. , Locasale Jason W. , Weihua Zhang
Published: December 2014

Breast cancer brain metastasis is resistant to therapy and a particularly poor prognostic feature in patient survival. Altered metabolism is a common feature of cancer cells, but little is known as to what metabolic changes benefit breast cancer brain metastases. We found that brain metastatic breast cancer cells evolved the ability to survive and proliferate independent of glucose due to enhanced gluconeogenesis and oxidations of glutamine and branched chain amino acids, which together sustain the nonoxidative pentose pathway for purine synthesis. Silencing expression of fructose-1,6-bisphosphatases (FBP) in brain metastatic cells reduced their viability and improved the survival of metastasis-bearing immunocompetent hosts. Clinically, we showed that brain metastases from human breast cancer patients expressed higher levels of FBP and glycogen than the corresponding primary tumors. Together, our findings identify a critical metabolic condition required to sustain brain metastasis and suggest that targeting gluconeogenesis may help eradicate this deadly feature in advanced breast cancer patients. Cancer Res; 75(3); 554–65. ©2014 AACR.
Characteristics and Long-Term Outcome of Patients with Systemic Immunoglobulin Light-Chain Amyloidosis
Authors: Nelson Lærke Marie , Gustafsson Finn , Gimsing Peter
Published: December 2014

Background/Aims: Immunoglobulin light-chain (AL) amyloidosis is a systemic disorder that causes progressive organ dysfunction. The optimal treatment strategy requires accurate patient stratification with an emphasis on the extent of cardiac involvement. Reports on its prognosis are sparse and predominantly originate from highly selected centers. We aimed to evaluate patient characteristics and outcomes in a cohort treated at a single center. Methods: This is a single-center retrospective study of 63 consecutive patients diagnosed with AL amyloidosis between January 2000 and December 2012. Patients were evaluated by treatment strategy and cardiac involvement. Results: The mean age at diagnosis was 61.4 years (±8.9), and 39 patients (62%) were male. Thirty-two (51%) patients presented with cardiac amyloid involvement (CA) and the remaining 31 (49%) had noncardiac amyloidosis (NCA). The median follow-up time was 12.7 months (0.3-90.8), and 38 (60%) patients died during follow-up. The median overall survival (OS) was 29 months (95% CI 12.1-57.2) and the OS was not significantly lower for patients with CA compared to NCA (log-rank = 0.21). Conclusion: The prognosis in AL amyloidosis is grave, but the outcome with treatment in the current series was comparable to those in series from larger centers. CA did not significantly predict the OS.
Depression: Discrete or Continuous?
Authors: Bowins Brad
Published: December 2014

Elucidating the true structure of depression is necessary if we are to advance our understanding and treatment options. Central to the issue of structure is whether depression represents discrete types or occurs on a continuum. Nature almost universally operates on the basis of continuums, whereas human perception favors discrete categories. This reality might be formalized into a ‘continuum principle': natural phenomena tend to occur on a continuum, and any instance of hypothesized discreteness requires unassailable proof. Research evidence for discrete types falls far short of this standard, with most evidence supporting a continuum. However, quantitative variation can yield qualitative differences as an emergent property, fostering the appearance of discreteness. Depression as a continuum is best characterized by duration and severity dimensions, with the latter understood in terms of depressive inhibition. In the absence of some degree of cognitive, emotional, social, and physical inhibition, depression should not be diagnosed. Combining the dimensions of duration and severity provides an optimal way to characterize the quantitative and related qualitative aspects of depression and to describe the overall degree of dysfunction. The presence of other symptom types occurs when anxiety, hypomanic/manic, psychotic, and personality continuums interface with the depression continuum.
The Role of 123I Imaging in the Evaluation of Infants with Mild Congenital Hypothyroidism
Authors: Graber Evan , Regelmann Molly O. , Annunziato Rachel , Machac Josef , Rapaport Robert
Published: December 2014

Background/Aims: Controversy exists regarding the diagnosis and treatment of mild congenital hypothyroidism (MCH). We studied the value of 123I imaging in patients with MCH. Methods: Retrospective chart review of infants and children <4 years of age who underwent 123I imaging: group 1 = MCH [thyroid-stimulating hormone (TSH) <25 µIU/ml, normal free T4/T3], group 2 = severe congenital hypothyroidism (TSH ≥25 µIU/ml), and group 3 = MCH in infancy imaged after treatment withdrawal at age 3 years. Data collected included 4- and 24-hour 123I uptake, TSH, free T4/total T3 at imaging, age at imaging, and levothyroxine (L-T4) dose at 1 year of. Results: Thirty-six patients underwent 123I imaging. In group 1 (n = 20, median TSH: 8.49 µIU/ml), 85% had abnormal imaging consistent with dyshormonogenesis. Two patients were referred after 1 year of age. The median age at imaging for the remaining 18 patients was 54 days. Median L-T4 dose at 1 year of age for these 18 patients was 2.8 μg/kg, which is consistent with dyshormonogenesis. Ninety-one percent of group 2 (n = 11, median TSH: 428.03 µIU/ml) had abnormal imaging. The median age at imaging was 13 days. Four patients in group 3 had abnormal 123I imaging and restarted treatment. Conclusion:123I imaging is a valuable tool for evaluation, diagnosis, and treatment of MCH.
Dual Renin-Angiotensin System Blockade for Nephroprotection: Still under Scrutiny
Authors: Gentile Giorgio , Remuzzi Giuseppe , Ruggenenti Piero
Published: December 2014

In experimental diabetic and non-diabetic chronic kidney disease (CKD), angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) combination therapy reduces proteinuria and prevents structural lesions more effectively than either drug alone. Consistently, in humans, a multidrug individually tailored antiproteinuric treatment based on combination therapy with maximum tolerated doses of ACEi and ARB (Remission Clinic protocol) reduced proteinuria and prevented end-stage renal disease (ESRD) more effectively than ACEi/ARB monotherapy, in particular in subjects with non-diabetic CKD. Fixed doses of an ACEi or renin inhibitor added to losartan failed to exert any additional renoprotective effect as compared with losartan monotherapy in patients at increased cardiovascular risk (ONTARGET study) or with type 2 diabetes and overt nephropathy (ALTITUDE study). The VA NEPHRON D study found that losartan and lisinopril combination therapy reduced by 34% the risk of predefined reductions in estimated glomerular filtration rate, ESRD or death as compared to losartan in 1,448 type 2 diabetes patients with overt nephropathy. Unfortunately, the treatment effect failed to achieve the nominal significance (p = 0.07) because of premature trial interruption. Thus, the Remission Clinic protocol is the most powerful tool to prevent progression to ESRD in non-diabetic proteinuric CKD. Results of the ongoing VALID trial will show whether this approach can be safely extended to type 2 diabetes patients.
Head-Up Tilt Testing for Detecting Orthostatic Hypotension: How Long Do We Need to Wait?
Authors: Gurevich Tanya , Machmid Hanadi , Klepikov Dina , Ezra Adi , Giladi Nir , Peretz Chava
Published: December 2014

Background: Orthostatic hypotension (OH) is a common underdiagnosed condition characterized by a fall in systolic or diastolic blood pressure (BP). There is some uncertainty about the minimum duration needed to detect OH beyond 3 min (delayed OH). We aimed to define a minimum time range for measurement of delayed OH in subjects referred to as tilt testing. Methods: A repeated measurements study Tel-Aviv Medical Center, on 692 subjects who underwent prolonged (40 min, vertical position) drug-free tilt testing. Survival curves were used to study time to an OH event; logistic regression to study factors associated with delayed OH and mixed models to study the pattern of repeated BP measures. Results: In our sample, 17% had OH within 3 min, 35% within 30 min, and 40% within 40 min. Among the 270 OH patients, 43 and 91% were identified within 3 and 30 min, respectively. Delayed OH was associated with female gender (OR = 1.95, 1.16-3.27) and age <65 years (OR = 2.17, 1.24-3.80). Older patients differed significantly from younger patients in BP pattern changes and had a higher rate of a fall in systolic BP. Conclusion: Tilt testing for 30 min identifies most cases of delayed OH in older patients, while those younger than 65 years need 10 min longer.
Future Time Perspective: Opportunities and Limitations Are Differentially Associated with Subjective Well-Being and Hair Cortisol Concentration
Authors: Kozik Pavel , Hoppmann Christiane A. , Gerstorf Denis
Published: December 2014

Background: Future time perspective has been associated with subjective well-being, though depending on the line of research considered either an open-ended future time perspective or a limited future time perspective has been associated with high well-being. Most of this research however has conceptualized future time perspective as a one-dimensional construct, whereas recent evidence has demonstrated that there are likely at least two different underlying dimensions, a focus on opportunities and a focus on limitations. This project first seeks to replicate the two-dimensional structure of the Future Time Perspective Scale, and then examines the associations these dimensions may have with different measures of subjective well-being and a biological index of chronic stress. Objective: To test if the two dimensions of the Future Time Perspective Scale, a focus on opportunities and a focus on limitations, differentially associate with two measures of subjective well-being and a biological indicator of chronic stress, namely hair cortisol. Method: Sixty-six community-dwelling participants with a mean age of 72 years (SD = 5.83) completed the Future Time Perspective Scale, Center for Epidemiologic Studies Depression Scale, and Philadelphia Geriatric Center Morale Scale. Participants also provided a 3-cm-long hair strand to index cortisol accumulation over the past 3 months. Following the results of a factor analysis, a mediation model was created for each dimension of the Future Time Perspective Scale, and significance testing was done through a bootstrapping approach to harness maximal statistical power. Results: Factor analysis results replicated the two-dimensional structure of the Future Time Perspective Scale. Both dimensions were then found to have unique associations with well-being. Specifically, a high focus on opportunities was associated with fewer depressive symptoms and higher morale, whereas a low focus on limitations was associated with reduced hair cortisol, though this association was mediated by subjective well-being. Conclusion: Results replicate and extend previous research by pointing to the multi-dimensional nature of the Future Time Perspective Scale. While an open future time perspective was overall beneficial for well-being, the exact association each dimension had with well-being differed depending on whether subjective measures of well-being or biological indices of chronic stress were considered.
Trimethoprim and Sulfamethoxazole Transmembrane Clearance during Modeled Continuous Renal Replacement Therapy
Authors: Kesner Jacob M. , Yardman-Frank Joseph Michael , Mercier Renee-Claude , Wong Craig S. , Walker Scott E. , Argyres Dean P. , Vilay Aloun Mary
Published: December 2014

Background/Aims: There is limited data regarding trimethoprim (TMP)/sulfamethoxazole (SMX) continuous renal replacement therapy (CRRT) dosing. We aimed to estimate TMP/SMX transmembrane clearance (CLtm) during continuous hemofiltration (CH) and continuous hemodialysis (CD) to guide dosing. Methods: Using an in vitro model, TMP/SMX sieving coefficients (SC) and saturation coefficients (SA) were determined with high-flux polyarylethersulfone and polyacrylonitrile-sodium methallyl sulfonate copolymer hemodiafilters at ultrafiltration/dialysate rates of 1, 2, 3, and 6 l/h. TMP/SMX CLtm was calculated using measured SC and SA. TMP/SMX CRRT doses were modeled using CLtm and published TMP/SMX pharmacokinetic parameters. Results: TMP SC/SA during CH/CD were significantly higher than SMX SC/SA. During modeling, TMP 10 mg/kg/day and its corresponding SMX dose, 50 mg/kg/day, resulted in steady state TMP/SMX peak concentrations associated with efficacy against Pneumocystis jirovecii. Conclusions: CRRT resulted in greater TMP CLtm than SMX. TMP 10 mg/kg/day divided q12h may be an appropriate initial dose to consider in patients undergoing CRRT.
Effects of Ultrapure Hemodialysis and Low Molecular Weight Heparin on the Endothelial Surface Layer
Authors: Cornelis Tom , Broers Natascha J.H. , Titulaer Denise C.L.M. , Henskens Yvonne M. , van Oerle Rene , van der Sande Frank M. , Spronk Henri M. , Vink Hans , Leunissen Karel M. , ten Cate Hugo , Kooman Jeroen P.
Published: December 2014

Background: Chronic kidney disease patients show changes in the endothelial surface layer (ESL). Whether hemodialysis (HD) itself or low molecular weight heparins (LMWH) induce ESL alterations is unknown. Methods: We studied the ESL in 20 HD patients with Sidestream Dark Field Imaging [measuring perfused boundary region (PBR)] and measurement of ESL constituents in plasma during HD in 2 studies. LMWH was administered at the start of HD in study A, and 120 min after the start of HD in study B. Mean platelet volume (MPV) and platelet large cell ratio (P-LCR) were also measured. Results: Syndecan-1 increased significantly 30 min after LMWH administration. sP-Selectin increased 120 min after HD start, and MPV and P-LCR decreased significantly during HD. No significant changes of PBR, sE-Selectin, sICAM-1, or sVCAM-1 were perceived. Conclusions: HD caused a significant increase in Syndecan-1 without a change in PBR. The administration of LMWH appeared to precede the rise in Syndecan-1.
Vitamin E Intake Is Not Associated with Glioma Risk: Evidence from a Meta-Analysis
Authors: Qin Shiyong , Wang Minghai , Zhang Tao , Zhang Shuguang
Published: December 2014

Background: Epidemiological studies evaluating the association between vitamin E intake and glioma risk have produced inconsistent results. Thus, we conducted a meta-analysis to summarize the evidence from epidemiological studies of vitamin E intake with the risk of glioma. Methods: Pertinent studies were identified by a search in pubmed and web of knowledge up to August 2014. The random-effect model was used to combine the results. Publication bias was estimated using the Egger's regression asymmetry test. Results: Twelve studies including 3180 glioma cases about vitamin E intake with the risk of glioma were included in this meta-analysis. The combined relative risk (RR) of glioma associated with vitamin E intake was 0.88 (95% CI = 0.69-1.12). The association was significant neither in the case-control studies nor in the cohort studies. No publication biases were found. Conclusions: Our analysis indicated that vitamin E intake is not associated with the risk of glioma.
High-Flow Carotid Cavernous Fistula and the Use of a Microvascular Plug System: Initial Experience
Authors: Shwe Yamin , Paramasivam Srinivasan , Ortega-Gutierrez Santiago , Altschul David , Berenstein Alejandro , Fifi Johanna T.
Published: December 2014

Purpose: We report our initial experience using a detachable microvascular plug system to occlude the internal carotid artery during endovascular treatment of high-flow carotid cavernous fistula. Case and Technique: An 87-year-old patient was admitted for acute-onset double vision with associated right-eye ptosis. Exam revealed a pupil-sparing, partial right third cranial nerve palsy. MRI showed a carotid cavernous fistula with high-flow drainage. Digital subtraction angiography showed a high-flow, right-sided, direct carotid cavernous fistula with flow from the proximal right internal carotid artery. The ophthalmic artery, posterior communicating artery and anterior communicating arteries supplied retrograde flow to the fistula through the internal carotid artery. Obliteration of the fistula was achieved through coil embolization in combination with proximal and distal microvascular plugs (Reverse Medical, Irvine, Calif., USA). Conclusion: The microvascular plug is a new addition to current endovascular embolization devices for the treatment of high-flow, direct carotid cavernous fistulas. This technique offers easy navigability through tortuous arteries, precise localization and immediate occlusion, which may allow shorter procedure and fluoroscopy times and increased cost-effectiveness. Larger case series are needed to support our observation.