bluuebunny/crossref_metadata_2025 huggingface dataset:
Accelerating radiation dose calculation
Authors: Zhou Bo , Hu Xiaobo Sharon , Chen Danny Z. , Yu Cedric X.
Published: December 2013

Remarkable progress has been made in the past few decades in various aspects of radiation therapy (RT). However, some of these promising technologies, such as image-guided online replanning and arc therapy, rely heavily on the availability of fast dose calculation. In this article, based on a popular dose calculation algorithm, the Collapsed-Cone Convolution/Superposition (CCCS) algorithm, we present a multi-FPGA accelerator to speed up radiation dose calculation. Our performance-driven design strategy yields a fully pipelined architecture, which includes a resource-economic raytracing engine and high-performance energy deposition pipeline. An evaluation based on a set of clinical treatment planning cases confirms that our FPGA design almost fully utilizes the available external memory bandwidth and achieves close to the best possible performance for the CCCS algorithm while using less resource. Compared with an existing FPGA design which aimed to accelerate the identical algorithm, the proposed design achieved 1.9X speedup by providing better memory bandwidth utilization (81.7% v.s. 43% of the available external memory bandwidth), higher working frequency (90MHz v.s. 70MHz) and less logic resource usage (25K v.s. 55K logic cells). Furthermore, it obtains a speedup of 20X over a commercial multithreaded software on a quad-core system and 15X performance improvement over closely related results. In terms of accuracy, the measured less than 1% statistical fluctuation indicates that our solution is practical in real medical scenarios.
Configuration and operation of networked control systems over heterogeneous WSANs
Authors: Furtado Pedro , Cecílio José
Published: December 2013

There have been both research and commercial advances on applying Wireless Sensor and Actuator Networks (WSN) in industrial premises. These have cost advantages related to avoiding some cabled deployments. A possible architecture involves a Networked Control System (NCS) with many small WSN subnetworks, cabled nodes and computer servers (e.g., servers, control stations). In those systems individual sensor nodes can be programmed, as opposed to cabled analog systems. We investigate approaches for networked-wide configuration, where all nodes—cabled or WSN sensors—can be configured with simplicity from a single interface, instead of hand-coding or complex configurations of individual nodes. We propose an architecture and approach for configuration and operation. Previous related proposals on middleware involving WSNs suffer from two major limitations: they either program within an individual WSN or configure operation outside WSNs, wrapping data coming from WSN. They do not allow configuring WSN and non-WSN nodes for operation from a single interface. We discuss the architecture and propose the NCSWSN configuration and operation approach. We are applying this system in an industrial testbed, therefore we test the approach and also show user interfaces and results from the deployment.
Automatic generation of high-speed accurate TLM models for out-of-order pipelined bus
Authors: Lo Chen-Kang , Li Mao-Lin , Chen Li-Chun , Lu Yi-Shan , Tsay Ren-Song , Huang Hsu-Yao , Yeh Jen-Chieh
Published: December 2013

Although pipelined/out-of-order (PL/OO) execution features are commonly supported by the state-of-the-art bus designs, no existing manual Transaction-Level-Modeling (TLM) approaches can effectively construct fast and accurate simulation models for PL/OO buses. Mainly, the inherent high design complexity of concurrent PL/OO behaviors makes the manual approaches tedious and error-prone. To tackle the complicated modeling task, this article presents an automatic approach that performs systematic abstraction and generation of fast-and-accurate simulation models. The experimental results show that our approach reduces 21 times modeling efforts, while our generated models perform simulation an order of magnitude faster than Cycle-Accurate models with the same PL/OO transaction execution cycle counts preserved.
Models for characterizing noise based PCMOS circuits
Authors: Singh Anshul , Basu Arindam , Ling Keck-Voon , Mooney III Vincent J.
Published: December 2013

Quick and accurate error-rate prediction of Probabilistic CMOS (PCMOS) circuits is crucial for their systematic design and performance evaluation. While still in the early stage of research, PCMOS has shown potential to drastically reduce energy consumption at a cost of increased errors. Recently, a methodology has been proposed which could predict the error rates of cascade structures of blocks in PCMOS. This methodology requires error rates of unique blocks to predict the error rates of multiblock cascade structures composed of these unique blocks. In this article we present a new model for characterization of probabilistic circuits/blocks and present a procedure to find and characterize unique circuits/blocks. Unlike prior approaches, our new model distinguishes distinct filtering effects per output, thereby improving prediction accuracy by an average of 95% over the prior art by Palem and coauthors. Furthermore, we show two models where our new model with three stages is 18% more accurate, on average, than our simpler two-stage model. We apply our proposed models to Ripple Carry Adders and Wallace Tree Multipliers and show that using our models, the methodology of cascade structures can predict error rates of PCMOS circuits with reasonable accuracy (within 9%) in PCMOS for uniform voltages as well as multiple voltages. Finally, our approach takes seconds of simulation time whereas using HSPICE would take days of simulation time.
XLynx
—An FPGA-based XML filter for hybrid XQuery processing
Authors: Teubner Jens , Woods Louis , Nie Chongling
Published: December 2013

While offering unique performance and energy-saving advantages, the use of
Field-Programmable Gate Arrays
(FPGAs) for database acceleration has demanded major concessions from system designers. Either the programmable chips have been used for very basic application tasks (such as implementing a rigid class of selection predicates) or their circuit definition had to be completely recompiled at runtime—a very CPU-intensive and time-consuming effort.

This work eliminates the need for such concessions. As part of our
XLynx
implementation—an FPGA-based XML filter—we present
skeleton automata
, which is a design principle for data-intensive hardware circuits that offers high expressiveness and quick reconfiguration at the same time. Skeleton automata provide a generic implementation for a class of
finite-state automata
. They can be parameterized to any particular automaton instance in a matter of microseconds or less (as opposed to minutes or hours for complete recompilation).

We showcase skeleton automata based on
XML projection
[Marian and Siméon 2003], a filtering technique that illustrates the feasibility of our strategy for a real-world and challenging task. By performing XML projection in hardware and filtering data in the network, we report on performance improvements of several factors while remaining nonintrusive to the back-end XML processor (we evaluate
XLynx
using the Saxon engine).
A bloat-aware design for big data applications
Authors: Bu Yingyi , Borkar Vinayak , Xu Guoqing , Carey Michael J.
Published: December 2013

Over the past decade, the increasing demands on data-driven business intelligence have led to the proliferation of large-scale, data-intensive applications that often have huge amounts of data (often at terabyte or petabyte scale) to process. An object-oriented programming language such as Java is often the developer's choice for implementing such applications, primarily due to its quick development cycle and rich community resource. While the use of such languages makes programming easier, significant performance problems can often be seen --- the combination of the inefficiencies inherent in a managed run-time system and the impact of the huge amount of data to be processed in the limited memory space often leads to memory bloat and performance degradation at a surprisingly early stage.

This paper proposes a bloat-aware design paradigm towards the development of efficient and scalable Big Data applications in object-oriented GC enabled languages. To motivate this work, we first perform a study on the impact of several typical memory bloat patterns. These patterns are summarized from the user complaints on the mailing lists of two widely-used open-source Big Data applications. Next, we discuss our design paradigm to eliminate bloat. Using examples and real-world experience, we demonstrate that programming under this paradigm does not incur significant programming burden. We have implemented a few common data processing tasks both using this design and using the conventional object-oriented design. Our experimental results show that this new design paradigm is extremely effective in improving performance --- even for the moderate-size data sets processed, we have observed 2.5x+ performance gains, and the improvement grows substantially with the size of the data set.
Validating Efficacy of Shea Nut Oil Extract in Knee Osteoarthritis Patients
Authors: Chen San-Pei , Lo Sui-Foon , Wang Yu-Chia , Chou Tzu-Yi , Chang Kang-Ming , Chou Li-Wei
Published: December 2013

Objectives. To examine and investigate the efficacy of shea nut oil extract (SheaFlex75) in relation to knee osteoarthritis (OA).Methods. Thirty-three patients (age63.6±5.8years) with knee OA were recruited. Real-time ultrasound imaging and surface electromyography were used to objectively assess the morphological changes and the activity of vastus medialis oblique (VMO) muscles during a 16-week intervention of SheaFlex75. The intraclass correlation coefficient (ICC) was calculated to examine the reliability of the interscans. A paired-samplet-test was used to compare the findings in different stages. The Spearman’s rank correlation coefficient was used to examine the relationship between the relevant variables of OA and percentage of thickness change of VMO at different contraction levels.Results. The baseline findings showed strong correlation, suggesting that the reliability of interscans at pretest was high. The ability to contract the muscles of the knee to a 30% contraction level showed significant change between the baseline and after 16-week testing, both in terms of morphological changes and muscle activity. Pain scale reported a significant decrease at the 16th week.Conclusion. The results suggest that SheaFlex75 can relieve the symptoms of knee OA and can result in improvement of muscle control of the knee.
Further Refinements of Jensen’s Type Inequalities for the Function Defined on the Rectangle
Authors: Adil Khan M. , Khan G. Ali , Ali T. , Batbold T. , Kiliçman A.
Published: December 2013

We give refinement of Jensen’s type inequalities given by Bakula and Pečarić (2006) for the co-ordinate convex function. Also we establish improvement of Jensen’s inequality for the convex function of two variables.
Suspected Endothelial Pencil Graphite Deposition
Authors: Gül Adem , Can Ertuğrul , Yücel Özlem Eşki , Niyaz Leyla , Akgün Halil İbrahim , Arıtürk Nurşen
Published: December 2013

A 14-year-old male patient had an ocular trauma with a pencil. Biomicroscopic examination revealed a broken part of pencil into the cornea. Foreign body removal and corneal wound closure were performed in the same day. After corneal repair, there was a grade 4+ anterior chamber reaction just like in preoperative examination. Dilated examination showed a very small piece broken tip of pencil on the upper nasal quadrant of the lens. A small and linear deposition was also seen on endothelial surface. Endothelial deposition and foreign body disappeared with intensive topical steroid treatment.
Incorporated W Roles on Microstructure and Properties of W‐C:H Films by a Hybrid Linear Ion Beam Systems
Authors: Guo Peng , Ke Peiling , Wang Aiying
Published: December 2013

W‐incorporated diamond‐like carbon (W‐C:H) films were fabricated by a hybrid beams system consisting of a DC magnetron sputtering and a linear ion source. The W concentration (1.08~31.74 at.%) in the film was controlled by varying the sputtering current. The cross‐sectional topography, composition, and microstructure of the W‐C:H films were investigated by SEM, XPS, TEM, and Raman spectroscopy. The mechanical and tribological properties of the films as a function of W concentration were evaluated by a stress‐tester, nanoindentation, and ball‐on‐disk tribometer, respectively. The results showed that films mainly exhibited the feature of amorphous carbon when W concentration of the films was less than 4.38 at.%, where the incorporated W atoms would be bonded with C atoms and resulted in the formation of WC1−x nanoparticles. The W‐C:H film with 4.38 at.% W concentration showed a minimum value of residual compressive stress, a higher hardness, and better tribological properties. Beyond this W concentration range, both the residual stress and mechanical properties were deteriorated due to the growth of tungsten carbide nanoparticles in the carbon matrix.
Interspecies Communication and Periodontal Disease
Authors: Mahajan Ajay , Singh Baljeet , Kashyap Divya , Kumar Amit , Mahajan Poonam
Published: December 2013

More than 500 bacterial strains may be found in dental plaque. In the beginning, the emphasis was laid on the isolation of bacteria in pure culture to define their properties. However, now, it has been well established that in nature the bacteria exist as a member of polymicrobial community or consortium of interacting species. Interactions among human oral bacteria are integral to the development and maturation of the plaque. These interactions occur at several levels including physical contact, metabolic exchange, small‐signal molecule‐mediated communication, and exchange of genetic material. This high level of interspecies interaction benefits the microorganism by providing a broader habitat range, effective metabolism, increasing the resistance to host defence, and enhancing their virulence. This generally has a detrimental effect on the host and is attributed to many chronic infections which poses a therapeutic challenge.
Development of Mobile Social Network Systems Using Real-Time Facial Authentication and Collaborative Recommendations
Authors: Kwon Hyeong-Joon , Kim Dong-Ju , Hong Kwang-Seok
Published: December 2013

We propose a location-based mobile social networking system (SNS) that integrates biometric facial authentication using a modified local directional pattern (MLDP), collaborative content recommendations, and communication among users. The proposed system is an effective fusion of a traditional social networking system, a location-based system, and a provider of intelligent recommendations. The prototype and service scenario in this study show possibilities for technical advancement and the future extension of mobile social networking services. To verify the proposed system, we performed experiments to determine the recognition rate for a user's facial image on a real-world smartphone and the preference prediction accuracy of a collaborative filtering-based recommendation system. Through our implementation and preference prediction experiments, we confirmed that the proposed system is highly effective and applicable to convergence using a location-based service and a content recommender.
Sieve Method for Polynomial Linear Equivalence
Authors: Wang Baocang , Hu Yupu
Published: December 2013

We consider the polynomial linear equivalence (PLE) problem arising from the multivariate public key cryptography, which is defined as to find an invertible linear transformationℒsatisfying𝒫=𝒮∘ℒfor given nonlinear polynomial maps𝒫and𝒮over a finite field𝔽q. Some cryptographic and algebraic properties of PLE are discussed, and from the properties we derive three sieves called multiplicative, differential, and additive sieves. By combining the three sieves, we propose a sieve method for the PLE problem. As an application of our sieve method, we show that it is infeasible to construct public key encryption schemes from the PLE problem.
Recognition of the Script in Serbian Documents Using Frequency Occurrence and Co‐Occurrence Analysis
Authors: Brodić Darko , Milivojević Zoran N. , Maluckov Čedomir A.
Published: December 2013

Any document in Serbian language can be written in two different scripts: Latin or Cyrillic. Although characteristics of these scripts are similar, some of their statistical measures are quite different. The paper proposed a method for the extraction of certain script from document according to the occurrence and co‐occurrence of the script types. First, each letter is modeled with the certain script type according to characteristics concerning its position in baseline area. Then, the frequency analysis of the script types occurrence is performed. Due to diversity of Latin and Cyrillic script, the occurrence of modeled letters shows substantial statistics dissimilarity. Furthermore, the co‐occurrence matrix is computed. The analysis of the co‐occurrence matrix draws a strong margin as a criteria to distinguish and recognize the certain script. The proposed method is analyzed on the case of a database which includes different types of printed and web documents. The experiments gave encouraging results.
Metformin Selectively Targets Tumor-Initiating Cells in ErbB2-Overexpressing Breast Cancer Models
Authors: Zhu Pei , Davis Meghan , Blackwelder Amanda J. , Bachman Nora , Liu Bolin , Edgerton Susan , Williams Leonard L. , Thor Ann D. , Yang Xiaohe
Published: December 2013

Metformin is an oral biguanide used for type II diabetes. Epidemiologic studies suggest a link between metformin use and reduced risk of breast and other types of cancers. ErbB2-expressing breast cancer is a subgroup of tumors with poor prognosis. Previous studies demonstrated that metformin is a potent inhibitor of ErbB2–overexpressing breast cancer cells; metformin treatment extends the life span and impedes mammary tumor development in ErbB2 transgenic mice in vivo. However, the mechanisms of metformin associated antitumor activity, especially in prevention models, remain unclear. We report here for the first time that systemic administration of metformin selectively inhibits CD61high/CD49fhigh subpopulation, a group of tumor-initiating cells (TIC) of mouse mammary tumor virus (MMTV)-ErbB2 mammary tumors, in preneoplastic mammary glands. Metformin also inhibited CD61high/CD49fhigh subpopulation in MMTV-ErbB2 tumor-derived cells, which was correlated with their compromised tumor initiation/development in a syngeneic tumor graft model. Molecular analysis indicated that metformin induced downregulation of ErbB2 and EGFR expression and inhibited the phosphorylation of ErbB family members, insulin-like growth factor-1R, AKT, mTOR, and STAT3 in vivo. In vitro data indicate that low doses of metformin inhibited the self-renewal/proliferation of cancer stem cells (CSC)/TICs in ErbB2–overexpressing breast cancer cells. We further demonstrated that the expression and activation of ErbB2 were preferentially increased in CSC/TIC-enriched tumorsphere cells, which promoted their self-renewal/proliferation and rendered them more sensitive to metformin. Our results, especially the in vivo data, provide fundamental support for developing metformin-mediated preventive strategies targeting ErbB2–associated carcinogenesis. Cancer Prev Res; 7(2); 199–210. ©2013 AACR.
Penetration Studies of an Extremely Lipophilic Active Model Substance from an Oil-in-Water Emulsion: Influence of the Lipophilicity of the Formulation in Human Skin - Part 2
Authors: Naumann S. , Lange S. , Polak G. , Kalhoelfer V. , Motlagh L. , Goebel A. , Wohlrab J. , Neubert R.H.H.
Published: December 2013

The effect of the lipophilicity of a carrier on human skin penetration of an extremely lipophilic active model substance was evaluated by using Franz type diffusion cells. Oil-in-water model emulsions containing different amounts of the oily phase were prepared, and Myritol® PC (M-PC) was selected as lipophilic marker component of the oily phase. The penetrated amounts of the lipophilic model substance salicyloyl phytosphingosine (SP) were determined by high-performance liquid chromatography with ultraviolet detection, while M-PC was detected using gas chromatography coupled with mass spectrometry. It has been ascertained that the amount of the lipid phase within the emulsion influenced the penetration profile of the active ingredient SP. The emulsion containing the lowest proportion of the lipid phase provides the best conditions for SP penetration. Surprisingly, the penetration behavior of M-PC was influenced by the oily phase in the same way. Regarding the M-PC and the SP penetration profiles from each emulsion, a solvent drag mechanism can be assumed whereby M-PC acts as penetration enhancer. In conclusion, the penetration rate of the active ingredient SP and the marker component M-PC are in reverse proportion to the oil content of the formulations. The lipophilicity of SP and M-PC, their solubility and their thermodynamic activity within the vehicle could have an effect on their penetration behavior. Additionally, M-PC has the property to enhance the penetration rates of extremely lipophilic substances even at low concentrations.
The Risk of Toxicities from Trastuzumab, Alone or in Combination, in an Elderly Breast Cancer Population
Authors: Adamo Vincenzo , Ricciardi Giuseppina Rosaria Rita , Adamo Barbara , Ferraro Giuseppa , Franchina Tindara , Rossello Rosalba , Zanghì Mariangela , Cicero Giuseppe , Rizzo Sergio , Caristi Nicola , Russo Antonio
Published: December 2013

Background: Breast cancer in the elderly is associated with high recurrence and death rates, due mostly to undertreatment. Human epidermal growth factor receptor type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab-based chemotherapy is often withheld from elderly patients because of its cardiotoxicity. Patients and Methods: Medical records of consecutive HER2-positive breast cancer patients aged ≥70 years old treated between 2005 and 2010 in the participating centers were retrospectively reviewed. All patients underwent multidimensional geriatric assessment (MGA). Results: Among 59 patients identified, 51 patients were evaluable (median age 76 years). The rate of any adverse event was 20% (10/51). The most relevant cardiac adverse event consisted of symptomatic congestive heart failure (CHF; n = 1, 2%) followed by asymptomatic decreases of left ventricular ejection fraction (LVEF; n = 6, 12%). Other toxicities included moderate hypersensitivity reactions during trastuzumab infusions (n = 3, 6%). Hypertension, obesity, prior anthracyclines exposure and concurrent chemotherapy were associated with a higher incidence of toxic events. Previous radiotherapy, concurrent endocrine therapy and different trastuzumab-based regimens did not seem to influence toxicity. Conclusions: Our data suggest that trastuzumab has a good safety profile in nonfrail women aged 70 years and older. These favorable findings may be related to a limited number of anthracycline pretreatments, patient selection and a close cardiologic monitoring.
Clinical Features in Association with Neurodegenerative Diseases and Malignancies
Authors: Nozaki Ichiro , Kato-Motozaki Yuko , Ikeda Tokuhei , Tagami Atsuro , Takahashi Kazuya , Ishida Chiho , Komai Kiyonobu
Published: December 2013

Objective: To examine whether there are clinical features in Japanese patients with both neurodegenerative diseases and cancers. Methods: We analyzed the clinical characteristics of consecutive Japanese patients with neurodegenerative diseases during the past 5 years, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), dementia with Lewy bodies, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA). Results: Out of 292 patients, 39 patients had cancers, including a past history, as follows: ALS, n = 16; PD, n = 8; PSP, n = 7; CBD, n = 1, and MSA, n = 7. About 10% of patients with neurodegenerative diseases developed cancer after onset of the disease; about 30% of patients with ALS, PD, or PSP occurring with cancers died of cancer. Gastric cancer was most common before the onset of ALS (62.5%) but did not develop after the onset of ALS. Conversely, PD patients frequently developed gastric cancers after the onset of neurological signs (60.0%) in spite of no cancer before the onset of PD. The proportion of breast cancer in MSA (45.5%) was significantly higher than in other neurodegenerative diseases. Conclusion: ALS, PD, or MSA patients with cancer showed clinical characteristics unique to each neurodegenerative disease in Japan compared to other countries.
Well-Leg Compartment Syndrome after Fracture Fixation in Hemilithotomy Position: Case Report of a Preventable Condition
Authors: Meena Sanjay , Trikha Vivek , Saini Pramod , Kumar Nishikant , KR Subhash
Published: December 2013

Objective: To report a case of subtrochanteric femur fracture that led to intraoperative compartment syndrome in the well leg. Clinical Presentation and Intervention: A 28-year-old obese male who presented with a comminuted subtrochanteric fracture underwent a prolonged open reduction and internal fixation using dynamic condylar screw. In the postoperative period, after the effect of epidural analgesia had worn off, the patient complained of severe pain and swelling of the well leg. A diagnosis of well-leg compartment syndrome was made and urgent two-incision fasciotomy was performed. Conclusion: Obesity and prolonged surgery could have caused the acute compartment syndrome of the well leg in this patient.
Influence of Mesenchymal Stem Cells on the Response of Endothelial Cells to Laminar Flow and Shear Stress
Authors: Hong Minsung , Jo Hansu , Ankeny Randell F. , Holliday-Ankeny Casey J. , Kim Hyengseok , Khang Gilson , Nerem Robert M.
Published: December 2013

The interactions between endothelial cells (ECs) and smooth muscle cells (SMCs) in a complex hemodynamic environment play an important role in the control of blood vessel function. Since autologous SMCs are not readily available for the tissue engineering of a blood vessel substitute, a substitute for SMCs, such as human adult bone marrow-derived mesenchymal stem cells (MSCs), is needed. The objective of this study was to use a three-dimensional coculture model of the blood vessel wall, comprised of ECs and MSCs, to determine how the presence of MSCs affects EC function. Two vascular coculture models with an EC monolayer were created using type I collagen. All models were exposed to steady laminar flow with a shear stress of 15 dyn/cm2 for up to 48 h. ECs in both the MSC and SMC coculture models expressed up-regulated EC-specific markers compared to the EC-only control model. The most dramatic difference observed between the two coculture models was in the experiments assessing monocyte adhesion. Here, fewer monocytes bound after laminar shear compared to static conditions; however, the number of bound monocytes was much lower for the EC-MSC coculture model than the EC-SMC coculture model for both static and shear conditions. These results suggest the feasibility of developing a tissue-engineered blood vessel substitute using MSCs as a substitute for SMCs.
Pharmacokinetics of a New Fentanyl Tape with a Novel Delivery System of Transdermal Matrix Patches in Patients with Cancer Pain
Authors: Saito Takefumi , Fujii Masato , Saito Shiro , Shimada Ken , Fujiwara Keiichi , Kobayashi Kunihiko
Published: December 2013

Objectives: A novel delivery system for transdermal matrix patches of fentanyl has been developed. The new fentanyl tape consists of a backing layer, a drug-containing layer and a release liner that is originally made of rubber adhesive. This open-label prospective study investigated the pharmacokinetics and safety of the fentanyl tape in patients with cancer pain. Methods: The tape was applied to the patient's chest for 72 h, and serum samples were collected from 0 to 72 h. Fentanyl concentrations were determined using liquid chromatography with mass spectrometry. Pharmacokinetic parameters were calculated, and adverse events were evaluated according to the Common Terminology Criteria for Adverse Events (version 3.0). Results: Since 1 patient treated with 2.1 mg fentanyl was found to represent unique pharmacokinetic parameters by Shapiro-Wilk test, only 15 of the 16 study patients were investigated. Maximum serum concentrations (Cmax) and area under the curve (AUC)0-72 at 2.1 and 4.2 mg were 0.26 and 0.35 ng/ml, and 11.58 and 15.95 ng·h/ml, respectively. The Cmax and AUC0-72 tended to increase with dosage from 2.1 to 4.2 mg. There were no grade 3 toxicities, and only grade 1 ALT and AST elevations were observed. Conclusion: The novel delivery system of fentanyl may be a very promising approach to manage cancer pain clinically.
Minimalinvasive Chirurgie bei Malignomen des Gastrointestinaltrakts: Magen - Kontra-Position
Authors: Ott Katja , Blank Susanne , Büchler Markus
Published: December 2013

Hintergrund: Bedingt durch Änderungen im Lebensstil gewinnen laparoskopische Verfahren zunehmend an Bedeutung. Zur laparoskopischen Magenchirugie existieren vor allem Studien aus Asien, wo die Inzidenz des Magenkarzinoms und besonders des Frühkarzinoms hoch ist und wo Tumoren häufig im unteren Magendrittel lokalisiert sind. Konträr verhält es sich in Deutschland mit einer rückläufigen Inzidenz des Magenkarzinoms und mit meist lokal fortgeschrittenen Tumoren proximaler Lokalisation. Methode und Ergebnisse: Die Metaanalysen enthalten überwiegend Daten zur laparoskopisch assistierten distalen Gastrektomie mit einer Inzision von 5-6 cm zum Bergen bzw. für schwierige Operationsschritte wie Schließen der Anastomose bzw. Komplettierung der Lymphadenektomie. Für das laparoskopische Vorgehen sprechen übereinstimmend der geringere intraoperative Blutverlust, die kürzere Hospitalisierungsdauer, der geringere postoperative Schmerzmittelverbrauch und das frühere Einsetzen der Darmtätigkeit - allesamt Parameter, die theoretisch auch durch den Einsatz von entsprechendem Instrumentarium und die Etablierung von standardisierten «FastTrack»-Abläufen in der offenen Chirurgie erreicht werden könnten. Bezüglich der Kosten sowie der Morbidität sind die Studien nicht eindeutig. Mit etwa 300 min bleibt die Operationsdauer signifikant länger, auch nach abgeschlossener Lernkurve von etwa 20-60 laparoskopischen Operationen pro Operateur. Dies sind Operationszahlen, die im Westen nur an wenigen Zentren realistisch erreicht werden können. Schlussfolgerungen: Onkologische Gleichwertigkeit konnte bisher nur durch eine ähnliche Anzahl entfernter Lymphknoten, nicht durch ein Langzeit-Follow-up gezeigt werden. Somit ist die laparoskopische Magenchirurgie derzeit in Deutschland kein Standard.
Minimalinvasive Chirurgie bei Malignomen des Gastrointestinaltrakts: Ösophagus - Kontra-Position
Authors: Gertler Ralf , Feith Marcus
Published: December 2013

Hintergrund: Die chirurgische Therapie des Ösophaguskarzinoms besteht in der Ösophagektomie mit Lymphadenektomie. Diese wird traditionell offen, in den letzten Jahren jedoch auch zunehmend minimalinvasiv durchgeführt. Methoden: Ziel dieser Übersichtsarbeit ist es, die Kontra-Position zur minimalinvasiven Chirurgie darzulegen. Hierfür führten wir eine Literaturrecherche bei PubMed durch. Es wurden eine randomisiert kontrollierte Studie, vier Metaanalysen sowie 18 retrospektive Kohortenstudien einbezogen. Ergebnisse: Insgesamt zeigt sich bei den vorliegenden Publikationen ein niedriger Evidenzlevel mit anzunehmendem Selektionsbias in den retrospektiven Kohortenstudien. Trotzdem kann davon ausgegangen werden, dass die minimalinvasive Ösophagektomie heutzutage zumindest mit vergleichbarer Morbidität und Mortalität wie die offene Ösophagektomie durchgeführt werden kann und mit weniger Schmerzen, kürzerem Krankenhausaufenthalt und höherer früh-postoperativer Lebensqualität einhergeht. Unterschiedliche Ergebnisse zeigen sich bezüglich einer möglichen Reduktion von postoperativen pulmonalen Komplikationen nach der minimalinvasiven Operation, nicht zuletzt, weil hier neben dem reinen operativen Zugangsweg auch andere Faktoren wie die Ein-Seiten-Lungenbeatmung und eine längere Lungenkompression Einfluss nehmen. Schlussfolgerungen: Der onkologische Stellenwert der minimalinvasiven Ösophagektomie ist auf der Grundlage der vorliegenden Literatur nicht ausreichend zu beurteilen, auch wenn vergleichbare R0-Resektionsraten und Lymphknotenzahlen berichtet werden. Zu wenig standardisiert sind hier die durchgeführten Operationen, während die Patientenkollektive bezüglich Tumortyp, Stadienverteilung und Nachsorge zu heterogen ausfallen.
AKAP150 Contributes to Enhanced Vascular Tone by Facilitating Large-Conductance Ca
2+
-Activated K
+
Channel Remodeling in Hyperglycemia and Diabetes Mellitus
Authors: Nystoriak Matthew A. , Nieves-Cintrón Madeline , Nygren Patrick J. , Hinke Simon A. , Nichols C. Blake , Chen Chao-Yin , Puglisi Jose L. , Izu Leighton T. , Bers Donald M. , Dell’Acqua Mark L. , Scott John D. , Santana Luis F. , Navedo Manuel F.
Published: December 2013

Rationale
:

Increased contractility of arterial myocytes and enhanced vascular tone during hyperglycemia and diabetes mellitus may arise from impaired large-conductance Ca
2+
-activated K
+
(BK
Ca
) channel function. The scaffolding protein A-kinase anchoring protein 150 (AKAP150) is a key regulator of calcineurin (CaN), a phosphatase known to modulate the expression of the regulatory BK
Ca
β1 subunit. Whether AKAP150 mediates BK
Ca
channel suppression during hyperglycemia and diabetes mellitus is unknown.

Objective
:

To test the hypothesis that AKAP150-dependent CaN signaling mediates BK
Ca
β1 downregulation and impaired vascular BK
Ca
channel function during hyperglycemia and diabetes mellitus.

Methods and Results
:

We found that AKAP150 is an important determinant of BK
Ca
channel remodeling, CaN/nuclear factor of activated T-cells c3 (NFATc3) activation, and resistance artery constriction in hyperglycemic animals on high-fat diet. Genetic ablation of AKAP150 protected against these alterations, including augmented vasoconstriction.
d
-glucose–dependent suppression of BK
Ca
channel β1 subunits required Ca
2+
influx via voltage-gated L-type Ca
2+
channels and mobilization of a CaN/NFATc3 signaling pathway. Remarkably, high-fat diet mice expressing a mutant AKAP150 unable to anchor CaN resisted activation of NFATc3 and downregulation of BK
Ca
β1 subunits and attenuated high-fat diet–induced elevation in arterial blood pressure.

Conclusions
:

Our results support a model whereby subcellular anchoring of CaN by AKAP150 is a key molecular determinant of vascular BK
Ca
channel remodeling, which contributes to vasoconstriction during diabetes mellitus.
Cervical Ganglion Block Attenuates the Progression of Pulmonary Hypertension via Nitric Oxide and Arginase Pathways
Authors: Na Sungwon , Kim Ok Soo , Ryoo Sungwoo , Kweon Tae Dong , Choi Yong Seon , Shim Hyo Sup , Oh Young Jun
Published: December 2013

It has been recognized that the sympathetic nervous system is activated in pulmonary arterial hypertension (PAH), and abnormal sympathetic hyperactivity leads to worsening of PAH via endothelial dysfunction. The purpose of this study was to examine whether sympathetic ganglion block (SGB) can treat PAH by increasing the availability of nitric oxide (NO). PAH was induced in rats by 50 mg/kg of subcutaneous monocrotaline. After 2 weeks, daily injections of ropivacaine into the left superior cervical ganglion were repeated for 14 days (monocrotaline-SGB group). Monocrotaline group received sham SGB with saline, whereas control group received saline instead of monocrotaline. PAH was evident in monocrotaline group, with right ventricular systolic pressures (47±4 mm Hg) that were higher than those of controls (17±2 mm Hg), whereas SGB significantly attenuated monocrotaline-induced PAH (35±4 mm Hg). The right/left ventricular mass ratios exhibited similar changes to those seen with right ventricular pressures. Heart rate variability showed significantly higher sympathetic activity in the monocrotaline group. Microscopy revealed a higher proportion of muscular arteries with thicker medial walls in the monocrotaline group, which was attenuated by SGB. Monocrotaline induced arginase hyperactivity, which was in turn decreased by SGB-induced endothelial NO synthase activation. SGB restored monocrotaline-induced hypoactivity of superoxide dismutase. In conclusion, SGB could suppress PAH and the remodeling of pulmonary arteries via inactivation of arginase and reciprocal elevation of NO bioavailability, thus attenuating disproportionate hyperactivation of the sympathetic nervous system.
Effects of Combination of Perindopril, Indapamide, and Calcium Channel Blockers in Patients With Type 2 Diabetes Mellitus
Authors: Chalmers John , Arima Hisatomi , Woodward Mark , Mancia Giuseppe , Poulter Neil , Hirakawa Yoichiro , Zoungas Sophia , Patel Anushka , Williams Bryan , Harrap Stephen
Published: December 2013

The objective of the present analysis was to determine the effects of a fixed combination of perindopril and indapamide in combination with calcium channel blockers (CCBs) in patients with type 2 diabetes mellitus. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) trial was a factorial randomized controlled trial. A total of 11 140 patients with type 2 diabetes mellitus were randomly assigned to fixed combination of perindopril–indapamide (4/1.25 mg) or placebo. Effects of randomized treatment on mortality and major cardiovascular outcomes were examined in subgroups defined by baseline use of CCBs. Patients on CCB at baseline (n=3427) constituted a higher risk group compared with those not on CCB (n=7713), with more extensive use of antihypertensive and other protective therapies. Active treatment reduced the relative risk of death by 28% (95% confidence interval, 10%–43%) among patients with CCB at baseline compared with 5% (−12% to 20%) among those without CCB (
P
homogeneity=0.02) and 14% (2%–25%) for the whole population. Similarly, the relative risk reduction for major cardiovascular events was 12% (−8% to 28%) versus 6% (−10% to 19%) for those with and without CCB at baseline although the difference was not statistically significant (
P
homogeneity=0.38). There was no detectable increase in adverse effects in those receiving CCB. The combination of perindopril and indapamide with CCBs seems to provide further protection against mortality in patients with type 2 diabetes mellitus.
Ang II–Salt Hypertension Depends on Neuronal Activity in the Hypothalamic Paraventricular Nucleus but Not on Local Actions of Tumor Necrosis Factor-α
Authors: Bardgett Megan E. , Holbein Walter W. , Herrera-Rosales Myrna , Toney Glenn M.
Published: December 2013

Development of angiotensin II (Ang II)–dependent hypertension involves microglial activation and proinflammatory cytokine actions in the hypothalamic paraventricular nucleus (PVN). Cytokines activate receptor signaling pathways that can both acutely grade neuronal discharge and trigger long-term adaptive changes that modulate neuronal excitability through gene transcription. Here, we investigated contributions of PVN cytokines to maintenance of hypertension induced by subcutaneous infusion of Ang II (150 ng/kg per min) for 14 days in rats consuming a 2% NaCl diet. Results indicate that bilateral PVN inhibition with the GABA-A receptor agonist muscimol (100 pmol/50 nL) caused significantly greater reductions of renal and splanchnic sympathetic nerve activity (SNA) and mean arterial pressure in hypertensive than in normotensive rats (
P
<0.01). Thus, ongoing PVN neuronal activity seems required for support of hypertension. Next, the role of the prototypical cytokine tumor necrosis factor-α was investigated. Whereas PVN injection of tumor necrosis factor-α (0.3 pmol/50 nL) acutely increased lumbar and splanchnic SNA and mean arterial pressure, interfering with endogenous tumor necrosis factor-α by injection of etanercept (10 μg/50 nL) was without effect in hypertensive and normotensive rats. Next, we determined that although microglial activation in PVN was increased in hypertensive rats, bilateral injections of minocycline (0.5 μg/50 nL), an inhibitor of microglial activation, failed to reduce lumbar or splanchnic SNA or mean arterial pressure in hypertensive or in normotensive rats. Collectively, these findings indicate that established Ang II–salt hypertension is supported by PVN neuronal activity, but short term maintenance of SNA and arterial blood pressure does not depend on ongoing local actions of tumor necrosis factor-α.
Office Blood Pressure, Ambulatory Blood Pressure Monitoring, and Echocardiographic Abnormalities in Women With Polycystic Ovary Syndrome
Authors: Luque-Ramírez Manuel , Martí David , Fernández-Durán Elena , Alpañés Macarena , Álvarez-Blasco Francisco , Escobar-Morreale Héctor F.
Published: December 2013

Whether or not blood pressure (BP) and heart function of women with polycystic ovary syndrome (PCOS) are altered remains unclear, albeit subtle abnormalities in the regulation of BP observed in these women might suggest a mild masculinization of their cardiovascular system. To study the influence of obesity and androgen excess on BP and echocardiographic profiles of women with the syndrome, we conducted a cross-sectional case–control study comparing office and ambulatory BP monitoring, as well as echocardiographic assessments, in 63 premenopausal women with the classic phenotype, 33 nonhyperandrogenic women with regular menses, and 25 young men. Forty-nine subjects were lean and 72 had weight excess (body mass index ≥25 kg/m
2
). Participants had no previous history of hypertension and were nonsmokers. Men showed the highest BP readings, and the lowest readings were observed in control women, whereas women with PCOS had intermediate values. Undiagnosed hypertension was more common in subjects with weight excess irrespective of sex and hyperandrogenism. Women with PCOS and weight excess showed frequencies of previously undiagnosed hypertension that were similar to those of men with weight excess and higher than those observed in nonhyperandrogenic women. Lastly, male sex, weight excess and hypertension, the latter in men as well as in women with PCOS, increased left ventricular wall thickness. In summary, our results show that patients with classic PCOS and weight excess frequently have undiagnosed BP abnormalities, leading to target organ damage.
Supraglottoplasty in Premature Infants with Laryngomalacia: Does Gestation Age at Birth Influence Outcomes?
Authors: Durvasula Venkata S. P. B. , Lawson Bradley R. , Bower Charles M. , Richter Gresham T.
Published: December 2013

Purpose

Prematurity is thought to be to be an independent risk factor for supraglottoplasty (SGP) failure. The purpose of this study was to compare the outcomes of supraglottoplasty in premature infants with congenital laryngomalacia (LM) with that of term infants.

Study Design

Case series with chart review.

Setting

Tertiary‐care pediatric institution.

Methods

Analysis was performed on 325 consecutive patients undergoing SGP between 2004 and 2012. Patients older than 12 months age or with syndrome, neurologic, or cardiac comorbidities were excluded. Resolution of airway symptoms after SGP was considered successful while revision SGP and tracheostomy were considered failures. The rates of secondary airway lesions (SAL), dysphagia, and gastrostomy tube (GT) placement were also compared.

Results

A total of 176 infants (136 term, 40 preterm) were identified. SGP was successful in 92.7% term and 90% preterm infants with no significant difference (P =. 5865). Incidence of revision SGP and tracheostomy was similar among the groups. The outcomes of SGP were the same in all groups stratified by age. Incidence of SAL was significantly higher in preterm (72.5%) compared to term infants (34.6%, P =. 0002). Dysphagia rates in the follow‐up were higher in preterm (32.5%) versus term infants (6.6%, P <. 001). The rate of GT insertion was significantly greater (P =. 003) in preterm (27.5%) than term infants (6.6%). The preoperative dysphagia, persistent dysphagia, and GT in follow‐up was significantly higher when gestation age <32 weeks (25%, P =. 0168).

Conclusion

Supraglottoplasty outcomes in term and preterm infants were similar irrespective of gestation age. Higher rates of dysphagia in follow‐up are seen when gestation age <32 weeks.
Nonspecific Hyper‐reactivity and Localized Allergy: Cause of Discrepancy Between Skin Prick and Nasal Provocation Test
Authors: Chang Geun Uck , Jang Tae Young , Kim Kyu‐Sung , Choi Hyuk , Kim Young Hyo
Published: December 2013

Objective

Disagreement between results of skin prick test (SPT) and nasal provocation tests (NPT) causes difficulty in differential diagnosis of allergic rhinitis (AR) and nonallergic rhinitis (NAR). We hypothesized this discrepancy could be due to the nonspecific hyper‐reactivity (NHR) and localized allergy of the nasal cavity.

Study Design

Prospective pilot.

Setting

Academic tertiary rhinologic practice.

Subjects and Methods

Sixty patients with AR and 62 with NAR were enrolled. We categorized patients according to results of SPT and NPT. We compared: (1) the clinical characteristics and severity of the disease, (2) change of minimal cross‐sectional area (MCA) and total nasal volume (TNV) after normal saline (NS) challenge, and (3) change of nasal symptoms and acoustic parameters after intranasal house dust mite (HDM) challenge between groups.

Results

Patients in groups A (SPT[+]/NPT[+]) and C (SPT[–]/NPT[+]) complained of more persistent discomfort than those in groups B (SPT[+]/NPT[–]) and D (SPT[–]/NPT[–]). The proportion of moderate to severe symptoms was significantly higher in groups A, B, and C compared to group D. After NS challenge, MCA/TNV showed a significantly greater decrease in groups A (MCA: 27.6% ± 21.3%, TNV: 24.6% ± 16.4%) and C (MCA: 31.2% ± 24.0%, TNV: 24.1% ± 23.4%) compared to groups B (MCA: 0.1% ± 13.2%, TNV: 3.9% ± 13.5%) and D (MCA: 2.1% ± 12.1%, TNV: 2.0% ± 17.2%) (P <. 05). After HDM challenge, groups A/B showed a greater decrease in MCA (Group A: 62.4% ± 16.1%, Group B: 6.4% ± 11.3%) compared to groups C/D (Group C: 45.5% ± 14.4%, Group D: –3.0% ± 9.5%).

Conclusion

NHR and/or localized allergy should be considered in patients with rhinitis whose SPT and NPT results are not in agreement.
Global analysis of cis-natural antisense transcripts and their heat-responsive nat-siRNAs in Brassica rapa
Authors: Yu Xiang , Yang Jun , Li Xiaorong , Liu Xuxin , Sun Chuanbao , Wu Feijie , He Yuke
Published: December 2013

Background

Brassica rapaincludes several important leaf vegetable crops whose production is often damaged by high temperature. Cis-natural antisense transcripts (cis-NATs) andcis-NATs-derived small interfering RNAs (nat-siRNAs) play important roles in plant development and stress responses. However, genome-wide cis-NATs inB. rapaare not known. The NATs and nat-siRNAs that respond to heat stress have never been well studied inB. rapa. Here, we took advantage of RNA-seq and small RNA (sRNA) deep sequencing technology to identify cis-NATs and heat responsive nat-siRNAs inB. rapa.

Results

Analyses of four RNA sequencing datasets revealed 1031cis-NATsB. rapassp.chinensiscv Wut andB. rapassp.pekinensiscv. Bre. Based on sequence homology betweenArabidopsis thalianaandB. rapa, 303 conservedcis-NATs inB. rapawere found to correspond to 280 cis-NATs inArabidopsis; the remaining 728 novelcis-NATs were identified asBrassica-specific ones. Using six sRNA libraries, 4846 nat-siRNAs derived from 150cis-NATs were detected. Differential expression analysis revealed that nat-siRNAs derived from 12 cis-NATs were responsive to heat stress, and most of them showed strand bias. Real-time PCR indicated that most of the transcripts generating heat-responsive nat-siRNAs were upregulated under heat stress, while the transcripts from the opposite strands of the same loci were downregulated.

Conclusions

Our results provide the first subsets of genome-wide cis-NATs and heat-responsive nat-siRNAs inB. rapa; these sRNAs are potentially useful for the genetic improvement of heat tolerance inB. rapaand other crops.