bluuebunny/crossref_metadata_2025 huggingface dataset:
A survey of appearance models in visual object tracking
Authors: Li Xi , Hu Weiming , Shen Chunhua , Zhang Zhongfei , Dick Anthony , Hengel Anton Van Den
Published: October 2013

Visual object tracking is a significant computer vision task which can be applied to many domains, such as visual surveillance, human computer interaction, and video compression. Despite extensive research on this topic, it still suffers from difficulties in handling complex object appearance changes caused by factors such as illumination variation, partial occlusion, shape deformation, and camera motion. Therefore, effective modeling of the 2D appearance of tracked objects is a key issue for the success of a visual tracker. In the literature, researchers have proposed a variety of 2D appearance models.

To help readers swiftly learn the recent advances in 2D appearance models for visual object tracking, we contribute this survey, which provides a detailed review of the existing 2D appearance models. In particular, this survey takes a module-based architecture that enables readers to easily grasp the key points of visual object tracking. In this survey, we first decompose the problem of appearance modeling into two different processing stages: visual representation and statistical modeling. Then, different 2D appearance models are categorized and discussed with respect to their composition modules. Finally, we address several issues of interest as well as the remaining challenges for future research on this topic.

The contributions of this survey are fourfold. First, we review the literature of visual representations according to their feature-construction mechanisms (i.e., local and global). Second, the existing statistical modeling schemes for tracking-by-detection are reviewed according to their model-construction mechanisms: generative, discriminative, and hybrid generative-discriminative. Third, each type of visual representations or statistical modeling techniques is analyzed and discussed from a theoretical or practical viewpoint. Fourth, the existing benchmark resources (e.g., source codes and video datasets) are examined in this survey.
COM
Authors: Rashidi Parisa , Cook Diane J.
Published: October 2013

The increasing aging population in the coming decades will result in many complications for society and in particular for the healthcare system due to the shortage of healthcare professionals and healthcare facilities. To remedy this problem, researchers have pursued developing remote monitoring systems and assisted living technologies by utilizing recent advances in sensor and networking technology, as well as in the data mining and machine learning fields. In this article, we report on our fully automated approach for discovering and monitoring patterns of daily activities. Discovering and tracking patterns of daily activities can provide unprecedented opportunities for health monitoring and assisted living applications, especially for older adults and individuals with mental disabilities. Previous approaches usually rely on preselected activities or labeled data to track and monitor daily activities. In this article, we present a fully automated approach by discovering natural activity patterns and their variations in real-life data. We will show how our activity discovery component can be integrated with an activity recognition component to track and monitor various daily activity patterns. We also provide an activity visualization component to allow caregivers to visually observe and examine the activity patterns using a user-friendly interface. We validate our algorithms using real-life data obtained from two apartments during a three-month period.
CUDIA
Authors: Park Yubin , Ghosh Joydeep
Published: October 2013

In healthcare-related studies, individual patient or hospital data are not often publicly available due to privacy restrictions, legal issues, or reporting norms. However, such measures may be provided at a higher or more aggregated level, such as state-level, county-level summaries or averages over health zones, such as hospital referral regions (HRR) or hospital service areas (HSA). Such levels constitute partitions over the underlying individual level data, which may not match the groupings that would have been obtained if one clustered the data based on individual-level attributes. Moreover, treating aggregated values as representatives for the individuals can result in the ecological fallacy. How can one run data mining procedures on such data where different variables are available at different levels of aggregation or granularity? In this article, we seek a better utilization of variably aggregated datasets, which are possibly assembled from different sources. We propose a novel cross-level imputation technique that models the generative process of such datasets using a Bayesian directed graphical model. The imputation is based on the underlying data distribution and is shown to be unbiased. This imputation can be further utilized in a subsequent predictive modeling, yielding improved accuracies. The experimental results using a simulated dataset and the Behavioral Risk Factor Surveillance System (BRFSS) dataset are provided to illustrate the generality and capabilities of the proposed framework.
Validation of an ontological medical decision support system for patient treatment using a repository of patient data
Authors: Khan Atif , Doucette John A. , Cohen Robin
Published: October 2013

In this article, we begin by presenting OMeD, a medical decision support system, and argue for its value over purely probabilistic approaches that reason about patients for time-critical decision scenarios. We then progress to present Holmes, a Hybrid Ontological and Learning MEdical System which supports decision making about patient treatment. This system is introduced in order to cope with the case of missing data. We demonstrate its effectiveness by operating on an extensive set of real-world patient health data from the CDC, applied to the decision-making scenario of administering sleeping pills. In particular, we clarify how the combination of semantic, ontological representations, and probabilistic reasoning together enable the proposal of effective patient treatments. Our focus is thus on presenting an approach for interpreting medical data in the context of real-time decision making. This constitutes a comprehensive framework for the design of medical recommendation systems for potential use by medical professionals and patients both, with the end result being personalized patient treatment. We conclude with a discussion of the value of our particular approach for such diverse considerations as coping with misinformation provided by patients, performing effectively in time-critical environments where real-time decisions are necessary, and potential applications facilitating patient information gathering.
A semantic framework for intelligent matchmaking for clinical trial eligibility criteria
Authors: Lee Yugyung , Krishnamoorthy Saranya , Dinakarpandian Deendayal
Published: October 2013

An integral step in the discovery of new treatments for medical conditions is the matching of potential subjects with appropriate clinical trials. Eligibility criteria for clinical trials are typically specified as inclusion and exclusion criteria for each study in freetext form. While this is sufficient for a human to guide a recruitment interview, it cannot be reliably and computationally construed to identify potential subjects. Standardization of the representation of eligibility criteria can enhance the efficiency and accuracy of this process. This article presents a semantic framework that facilitates intelligent matchmaking by identifying a minimal set of eligibility criteria with maximal coverage of clinical trials. In contrast to existing top-down manual standardization efforts, a bottom-up data driven approach is presented to find a canonical nonredundant representation of an arbitrary collection of clinical trial criteria. The methodology has been validated with a corpus of 709 clinical trials related to Generalized Anxiety Disorder containing 2,760 inclusion and 4,871 exclusion eligibility criteria. This corpus is well represented by a relatively small number of 126 inclusion clusters and 175 exclusion clusters, each of which corresponds to a semantically distinct criterion. Internal and external validation measures provide an objective evaluation of the method. An eligibility criteria ontology has been constructed based on the clustering. The resulting model has been incorporated into the development of the MindTrial clinical trial recruiting system. The prototype for clinical trial recruitment illustrates the effectiveness of the methodology in characterizing clinical trials and subjects and accurate matching between them.
LocateMe
Authors: Subbu Kalyan Pathapati , Gozick Brandon , Dantu Ram
Published: October 2013

Fine-grained localization is extremely important to accurately locate a user indoors. Although innovative solutions have already been proposed, there is no solution that is universally accepted, easily implemented, user centric, and, most importantly, works in the absence of GSM coverage or WiFi availability. The advent of sensor rich smartphones has paved a way to develop a solution that can cater to these requirements.

By employing a smartphone's built-in magnetic field sensor, magnetic signatures were collected inside buildings. These signatures displayed a uniqueness in their patterns due to the presence of different kinds of pillars, doors, elevators, etc., that consist of ferromagnetic materials like steel or iron. We theoretically analyze the cause of this uniqueness and then present an indoor localization solution by classifying signatures based on their patterns. However, to account for user walking speed variations so as to provide an application usable to a variety of users, we follow a dynamic time-warping-based approach that is known to work on similar signals irrespective of their variations in the time axis.

Our approach resulted in localization distances of approximately 2m--6m with accuracies between 80--100% implying that it is sufficient to walk short distances across hallways to be located by the smartphone. The implementation of the application on different smartphones yielded response times of less than five secs, thereby validating the feasibility of our approach and making it a viable solution.
Synaptic Laminae in the Visual System: Molecular Mechanisms Forming Layers of Perception
Authors: Baier Herwig
Published: October 2013

Synaptic connections between neurons form the basis for perception and behavior. Synapses are often clustered in space, forming stereotyped layers. In the retina and optic tectum, multiple such synaptic laminae are stacked on top of each other, giving rise to stratified neuropil regions in which each layer combines synapses responsive to a particular sensory feature. Recently, several cellular and molecular mechanisms that underlie the development of multilaminar arrays of synapses have been discovered. These mechanisms include neurite guidance and cell-cell recognition. Molecules of the Slit, Semaphorin, Netrin, and Hedgehog families, binding to their matching receptors, bring axons and dendrites into spatial register. These guidance cues may diffuse over short distances or bind to sheets of extracellular matrix, thus conditioning the local extracellular milieu, or are presented on the surface of cells bordering the future neuropil. In addition, mutual recognition of axons and dendrites through adhesion molecules with immunoglobulin domains ensures cell type–specific connections within a given layer. Thus, an elaborate genetic program assembles the parallel processing channels that underlie visual perception.
Bacterial Communities in Polluted Seabed Sediments: A Molecular Biology Assay in Leghorn Harbor
Authors: Chiellini Carolina , Iannelli Renato , Verni Franco , Petroni Giulio
Published: October 2013

Seabed sediments of commercial ports are often characterized by high pollution levels. Differences in number and distribution of bacteria in such areas can be related to distribution of pollutants in the port and to sediment conditions. In this study, the bacterial communities of five sites from Leghorn Harbor seabed were characterized, and the main bacterial groups were identified. T‐RFLP was used for all samples; two 16S rRNA libraries and in silico digestion of clones were used to identify fingerprint profiles. Library data, phylogenetic analysis, and T‐RFLP coupled with in silico digestion of the obtained sequences evidenced the dominance of Proteobacteria and the high percentage of Bacteroidetes in all sites. The approach highlighted similar bacterial communities between samples coming from the five sites, suggesting a modest differentiation among bacterial communities of different harbor seabed sediments and hence the capacity of bacterial communities to adapt to different levels and types of pollution.
Albumin Reduces Paracentesis-Induced Circulatory Dysfunction and Reduces Death and Renal Impairment among Patients with Cirrhosis and Infection: A Systematic Review and Meta-Analysis
Authors: Kwok Chun Shing , Krupa Lukasz , Mahtani Ash , Kaye Duncan , Rushbrook Simon M. , Phillips Martin G. , Gelson William
Published: October 2013

Background.Studies have suggested that albumin has a value in cirrhotic patients undergoing paracentesis but its value in infection and sepsis is less clear. We planned to perform a meta-analysis of the risk of adverse outcomes in cirrhotic patients with and without albumin use.Methods.We searched MEDLINE and EMBASE in January 2013 for randomized studies of cirrhotic patients that reported the risk of adverse events and mortality with albumin and no albumin exposure. We performed random effects meta-analysis and assessed heterogeneity using theI2statistic.Results.Our review included 16 studies covering 1,518 patients. The use of albumin in paracentesis was associated with significantly reduced risk of paracentesis-induced circulatory dysfunction (OR 0.26 95%, CI 0.08–0.93) and there was a nonsignificant difference in death, encephalopathy, hyponatraemia, readmission, and renal impairment. Compared to the other volume expanders, albumin use showed no difference in clinical outcomes. In cirrhotic patients with any infection, there was a significant reduction in mortality (OR 0.46 95%, CI 0.25–0.86) and renal impairment (OR 0.34 95%, CI 0.15–0.75) when albumin was used.Conclusion.The use of albumin in cirrhotic patients is valuable in patients with any infection and it reduces the risk of circulatory dysfunction among patients undergoing paracentesis.
Acute on Chronic Venous Thromboembolism on Therapeutic Anticoagulation
Authors: Bassi Byron , Nickels L. Connor , Flach F. Eike , DePortu Guiliano , Ganti Latha
Published: October 2013

A case of proximal venous thromboembolism in a patient who presented to the ED with lower extremity pain is presented. Making this diagnosis is very important as fifty percent of patients with symptomatic proximal DVTs will go on to develop PE without treatment. This report underscores the utility of bedside ultrasonography in the emergency department.
Weak Target Detection within the Nonhomogeneous Ionospheric Clutter Background of HFSWR Based on STAP
Authors: Zhang Xin , Yang Qiang , Deng Weibo
Published: October 2013

High Frequency Surface Wave Radar (HFSWR) can perform the functions of ocean environment monitoring, target detection, and target tracking over the horizon. However, its system's performance is always limited by the severe ionospheric clutter environment, especially by the nonhomogeneous component. The nonhomogeneous ionospheric clutter generally can cover a few Doppler shift units and a few angle units. Consequently, weak targets masked by the nonhomogeneous ionospheric clutter are difficult to be detected. In this paper, a novel algorithm based on angle-Doppler joint eigenvector which considers the angle-Doppler map of radar echoes is adopted to analyze the characteristics of the nonhomogeneous ionospheric clutter. Given the measured data set, we first investigate the correlation between the signal of interest (SOI) and the nonhomogeneous ionospheric clutter and then the correlation between the nonhomogeneous ionospheric clutters in different two ranges. Finally, a new strategy of training data selection is proposed to improve the joint domain localised (JDL) algorithm. Simulation results show that the improved-JDL algorithm is effective and the performance of weak target detection within nonhomogeneous ionospheric clutter is improved.
Impediments for the Uptake of the Botswana Government′s Male Circumcision Initiative for HIV Prevention
Authors: Sabone Motshedisi , Magowe Mabel , Busang Lesego , Moalosi Jonathan , Binagwa Benjamin , Mwambona Janet
Published: October 2013

Botswana remains one of the countries with high prevalence of HIV infection with a population prevalence rate of 17.6 in 2008. In 2009, the Ministry of Health launched male circumcision as an additional strategy to the already existing HIV preventive efforts. The purpose of this paper is to share what the participants of a survey to evaluate a short‐term male circumcision communication strategy in seven health districts of Botswana reported as impediments for the program′s uptake. Qualitative data were obtained from 32 key informants and 36 focus group discussions in 2011. Content analysis method was used to analyze data and to derive themes and subthemes. Although male circumcision was generally acceptable to communities in Botswana, the uptake of the program was slow, and participants attributed that to a number of challenges or impediments that were frustrating the initiative. The impediments were organized into sociocultural factors, knowledge/informational factors, and infrastructural and system factors.
Evaluation of Wall Correction Factor of INER's Air-Kerma Primary Standard Chamber and Dose Variation by Source Displacement for HDR192Ir Brachytherapy
Authors: Lee J. H. , Wang J. N. , Huang T. T. , Su S. H. , Chang B. J. , Su C. H. , Hsu S. M.
Published: October 2013

The aim of the present study was to estimate the wall effect of the self-made spherical graphite-walled cavity chamber with the Monte Carlo method for establishing the air-kerma primary standard of high-dose-rate (HDR)192Ir brachytherapy sources at the Institute of Nuclear Energy Research (INER, Taiwan). The Monte Carlo method established in this paper was also employed to respectively simulate wall correction factors of the192Ir air-kerma standard chambers used at the National Institute of Standards and Technology (NIST, USA) and the National Physical Laboratory (NPL, UK) for comparisons and verification. The chamber wall correction calculation results will be incorporated into INER's HDR192Ir primary standard in the future. For the brachytherapy treatment in the esophagus or in the bronchi, the position of the isotope may have displacement in the cavity. Thus the delivered dose would differ from the prescribed dose in the treatment plan. We also tried assessing dose distribution due to the position displacement of HDR192Ir brachytherapy source in a phantom with a central cavity by the Monte Carlo method. The calculated results could offer a clinical reference for the brachytherapy within the human organs with cavity.
Effects of Urban Configuration on Human Thermal Conditions in a Typical Tropical African Coastal City
Authors: Ndetto Emmanuel Lubango , Matzarakis Andreas
Published: October 2013

A long-term simulation of urban climate was done using the easily available long-term meteorological data from a nearby synoptic station in a tropical coastal city of Dar es Salaam, Tanzania. The study aimed at determining the effects of buildings’ height and street orientations on human thermal conditions at pedestrian level. The urban configuration was represented by a typical urban street and a small urban park near the seaside. The simulations were conducted in the microscale applied climate model of RayMan, and results were interpreted in terms of the thermal comfort parameters of mean radiant (Tmrt) and physiologically equivalent (PET) temperatures. PET values, high as 34°C, are observed to prevail during the afternoons especially in the east-west oriented streets, and buildings’ height of 5 m has less effect on the thermal comfort. The optimal reduction ofTmrtand PET values for pedestrians was observed on the nearly north-south reoriented streets and with increased buildings’ height especially close to 100 m. Likewise, buildings close to the park enhance comfort conditions in the park through additional shadow. The study provides design implications and management of open spaces like urban parks in cities for the sake of improving thermal comfort conditions for pedestrians.
Application of HPLC with ELSD Detection for the Assessment of Azelaic Acid Impurities in Liposomal Formulation
Authors: Han Stanislaw , Karlowicz-Bodalska Katarzyna , Szura Dorota , Ozimek Lukasz , Musial Witold
Published: October 2013

In the course of research and development of a new pharmaceutical formulation of azelaic acid in the liposomal form, we developed a rapid and accurate method for the detection of impurities using high‐performance liquid chromatography. A chromatographic column from Merck (Purospher Star RP C18, 250–4 mm (5 μm) was used in the assay, and the mobile phase gradient consisted of three phases: A—methanol : water (5 : 95) + 1.5% (v/v) acetic acid; B—water : methanol (5 : 95) + 1.5% (v/v) acetic acid; and C—chloroform. Detection of the impurities and the active substance was performed by an evaporative light‐scattering detector. The method was validated for selectivity, system precision, method precision, limit of detection, and response rates. The proposed method can be used to detect impurities in the liposomal formulation of azelaic acid. The method enables separation of azelaic acid from the identified and unidentified impurities and from the excipients used in the drug form.
Preparation and Characterization of Highly Efficient and Stable Visible‐Light‐Responsive Photocatalyst AgBr/Ag3PO4
Authors: Jinfeng Zhang , Tao Zhang
Published: October 2013

AgBr/Ag3PO4 photocatalyst was synthesized using a facile coprecipitation method. The photocatalyst was characterized by X‐ray powder diffraction (XRD), UV‐Vis diffuse reflectance spectroscopy (DRS), scanning electron microscopy (SEM), Brunauer‐Emmett‐Teller (BET) surface areas, and photoluminescence (PL) technique. The activity of the photocatalyst was evaluated by the degradation of methyl orange (MO) and rhodamine B (RhB). The results showed that the prepared AgBr/Ag3PO4 exhibited excellent performance and much higher photocatalytic activity than the single one under visible‐light irradiation. The optimum mole ratio of Br/P in AgBr/Ag3PO4 samples is 0.3. The prepared AgBr/Ag3PO4 photocatalyst was transformed to Ag/AgBr/Ag3PO4 system with excellent property and good stability in the photocatalytic process. The possible mechanisms of the enhanced photocatalytic activity for the AgBr/Ag3PO4 were also discussed in detail.
Antileukemic Efficacy of Monomeric Manganese-Based Metal Complex on KG-1A and K562 Cell Lines
Authors: Dash Sandeep Kumar , Chattopadhyay Sourav , Ghosh Totan , Tripathy Satyajit , Das Sabyasachi , Das Debasis , Roy Somenath
Published: October 2013

Transitional metals and metal compounds have been used in versatile platforms for biomedical applications and therapeutic intervention. Severe side effects of anticancer drugs produce an urgent urge to develop new classes of anticancer agents with great potency as well as selectivity. In this background, recent studies demonstrate that monomeric manganese (MnII) thiocyanate complex (MMTC) holds great promise to exert effective antileukemic effects. MMTC was developed by a simple chemical reaction and characterized by elemental analyses, thermal analyses, and Fourier transform infrared (FTIR) spectroscopy. Anti-leukemic efficacy of the developed MMTC was estimated in KG-1A (AML) and K562 (CML) cell lines. Cell viability study, drug uptake assay, cellular redox balance (GSH and GSSG level), nitric oxide (NO) release level, reactive oxygen species (ROS) formation, alteration of mitochondrial membrane potential (MMP), and DNA fragmentation revealed that MMTC was able to produce significant antiproliferative effects on both cell lines at 25 μg mL−1 without showing any toxicological impact on normal lymphocytes. These findings will enlighten the biomedical application of manganese-based metal complexes as anti-leukemic agents.
Possible Mechanisms of Fullerene C60Antioxidant Action
Authors: Chistyakov V. A. , Smirnova Yu. O. , Prazdnova E. V. , Soldatov A. V.
Published: October 2013

Novel mechanism of antioxidant activity of buckminsterfullerene C60based on protons absorbing and mild uncoupling of mitochondrial respiration and phosphorylation was postulated. In the present study we confirm this hypothesis using computer modeling based on Density Functional Theory. Fullerene's geroprotective activity is sufficiently higher than those of the most powerful reactive oxygen species scavengers. We propose here that C60has an ability to acquire positive charge by absorbing inside several protons and this complex could penetrate into mitochondria. Such a process allows for mild uncoupling of respiration and phosphorylation. This, in turn, leads to the decrease in ROS production.
Multiple Dental and Skeletal Abnormalities in an Individual with Filippi Syndrome
Authors: Sandhu Meera , Malik Pooja , Saha Rooposhi
Published: October 2013

Filippi syndrome is an autosomal recessive condition characterized by variable soft tissue syndactyly of the fingers and toes, microcephaly, pre- and postnatal growth retardation, mildly abnormal craniofacial appearance, and mental retardation. We report on a child with Filippi syndrome who shows syndactyly of fingers, severe postnatal growth retardation, postnatal microcephaly, and moderate to severe mental retardation. In addition, there is a mildly dysmorphic face along with ocular and a number of dental abnormalities. Radiologically, hands demonstrate bony syndactyly, without any hypoplasia of bones. This phenotype can easily be classified in the group of craniodigital syndromes, but it is difficult to make a more clearly defined diagnosis, based on other minor anomalies, because of the presence of overlapping features. On the basis of various pathognomic features, we conclude that our patient could be an additional case of Filippi syndrome. Moreover, newly recognised features in this patient may be due to variability in phenotypic expression.
CDK1 Phosphorylation of YAP Promotes Mitotic Defects and Cell Motility and Is Essential for Neoplastic Transformation
Authors: Yang Shuping , Zhang Lin , Liu Miao , Chong Rong , Ding Shi-Jian , Chen Yuanhong , Dong Jixin
Published: October 2013

The Yes-associated protein, YAP, is a downstream effector of the Hippo pathway of cell-cycle control that plays important roles in tumorigenesis. Hippo-mediated phosphorylation YAP, mainly at S127, inactivates YAP function. In this study, we define a mechanism for positive regulation of YAP activity that is critical for its oncogenic function. Specifically, we found that YAP is phosphorylated in vitro and in vivo by the cell-cycle kinase CDK1 at T119, S289, and S367 during the G2–M phase of the cell cycle. We also found that ectopic expression of a phosphomimetic YAP mutant (YAP3D, harboring T119D/S289D/S367D) was sufficient to induce mitotic defects in immortalized epithelial cells, including centrosome amplification, multipolar spindles, and chromosome missegregation. Finally, we documented that mitotic phosphorylation of YAP was sufficient to promote cell migration and invasion in a manner essential for neoplastic cell transformation. In support of our findings, CDK1 inhibitors largely suppressed cell motility mediated by activated YAP-S127A but not the phosphomimetic mutant YAP3D. Collectively, our results reveal a previously unrecognized mechanism for controlling the activity of YAP that is crucial for its oncogenic function mediated by mitotic dysregulation. Cancer Res; 73(22); 6722–33. ©2013 AACR.
Targeting Src and Tubulin in Mucinous Ovarian Carcinoma
Authors: Liu Tao , Hu Wei , Dalton Heather J. , Choi Hyun Jin , Huang Jie , Kang Yu , Pradeep Sunila , Miyake Takahito , Song Jian H. , Wen Yunfei , Lu Chunhua , Pecot Chad V. , Bottsford-Miller Justin , Zand Behrouz , Jennings Nicholas B. , Ivan Cristina , Gallick Gary E. , Baggerly Keith A. , Hangauer David G. , Coleman Robert L. , Frumovitz Michael , Sood Anil K.
Published: October 2013

Purpose: To investigate the antitumor effects of targeting Src and tubulin in mucinous ovarian carcinoma.

Experimental Design: The in vitro and in vivo effects and molecular mechanisms of KX-01, which inhibits Src pathway and tubulin polymerization, were examined in mucinous ovarian cancer models.

Results: In vitro studies using RMUG-S and RMUG-L cell lines showed that KX-01 inhibited cell proliferation, induced apoptosis, arrested the cell cycle at the G2–M phase, and enhanced the cytotoxicity of oxaliplatin in the KX-01–sensitive cell line, RMUG-S. In vivo studies showed that KX-01 significantly decreased tumor burden in RMUG-S and RMUG-L mouse models relative to untreated controls, and the effects were greater when KX-01 was combined with oxaliplatin. KX-01 alone and in combination with oxaliplatin significantly inhibited tumor growth by reducing cell proliferation and inducing apoptosis in vivo. PTEN knock-in experiments in RMUG-L cells showed improved response to KX-01. Reverse phase protein array analysis showed that in addition to blocking downstream molecules of Src family kinases, KX-01 also activated acute stress-inducing molecules.

Conclusion: Our results showed that targeting both the Src pathway and tubulin with KX-01 significantly inhibited tumor growth in preclinical mucinous ovarian cancer models, suggesting that this may be a promising therapeutic approach for patients with mucinous ovarian carcinoma. Clin Cancer Res; 19(23); 6532–43. ©2013 AACR.
Polyamine-Blocking Therapy Reverses Immunosuppression in the Tumor Microenvironment
Authors: Hayes Candace S. , Shicora Allyson C. , Keough Martin P. , Snook Adam E. , Burns Mark R. , Gilmour Susan K.
Published: October 2013

Correcting T-cell immunosuppression may unleash powerful antitumor responses; however, knowledge about the mechanisms and modifiers that may be targeted to improve therapy remains incomplete. Here, we report that polyamine elevation in cancer, a common metabolic aberration in aggressive lesions, contributes significantly to tumor immunosuppression and that a polyamine depletion strategy can exert antitumor effects that may also promote immunity. A polyamine-blocking therapy (PBT) that combines the well-characterized ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO) with AMXT 1501, a novel inhibitor of the polyamine transport system, blocked tumor growth in immunocompetent mice but not in athymic nude mice lacking T cells. PBT had little effect on the proliferation of epithelial tumor cells, but it increased the number of apoptotic cells. Analysis of CD45+ tumor immune infiltrates revealed that PBT decreased levels of Gr-1+CD11b+ myeloid suppressor cells and increased CD3+ T cells. Strikingly, in a model of neoadjuvant therapy, mice administered with PBT one week before surgical resection of engrafted mammary tumors exhibited resistance to subsequent tumor rechallenge. Collectively, our results indicate that therapies targeting polyamine metabolism do not act exclusively as antiproliferative agents, but also act strongly to prevent immune escape by the tumor. PBT may offer a general approach to heighten immune responses in cancer. Cancer Immunol Res; 2(3); 274–85. ©2013 AACR.
Anti-PD1 Following Ipilimumab for Mucosal Melanoma: Durable Tumor Response Associated with Severe Hypothyroidism and Rhabdomyolysis
Authors: Min Le , Hodi F. Stephen
Published: October 2013

Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important. Cancer Immunol Res; 2(1); 15–18. ©2014 AACR.
The Role of Th17/IL-17 in the Pathogenesis of Primary Nephrotic Syndrome in Children
Authors: Wang Li , Li Qiu , Wang Lijia , Li Cuicui , Yang Haiping , Wang Xiaoli , Tao Hong
Published: October 2013

Background: This work aims to explore the role of Th17 and IL-17 signaling in the pathogenesis of primary nephrotic syndrome (PNS) in children and podocyte injury, children with PNS were divided into minimal change nephrotic syndrome (MCNS) and non-minimal change nephrotic syndrome [NMCNS, including mesangial proliferative glomerulonephritis (MsPGN) and focal segmental glomerulosclerosis (FSGS)]. Methods: Flow cytometry (FCM) was used to observe the circulating frequency of Th17 cells and the apoptosis of podocytes by annexinV-FITC/PI. Serum IL-1β and IL-6 levels were measured using enzyme-linked immunosorbent assay. The Fas and FasL expressions in podocytes were examined by FCM analysis using a direct immunofluorescence method. Reverse transcription polymerase chain reaction was applied to measure the mRNA expressions of RORc, IL-23p19, Nephrin, WT1, Synaptopodin, Podocalyxin, Fas, and FasL. The IL-17 and IL-1β expression in renal biopsy tissue was detected by immunohistochemistry. The expressions of WT1, Caspase 8, and Caspase 3 in podocyte cell culture were also measured using immunocytochemistry. Results: Circulating frequencies of Th17 cells, mRNA levels of RORc and IL-23p19, and serum levels of IL-6 and IL-1β were higher in the MCNS and NMCNS groups than in the control group (all P < 0.05), and were higher in the NMCNS group than in the MCNS group (all P < 0.05). The expressions of IL-17 and IL-1β in renal biopsy tissue were higher in the MCNS, MsPGN, and FSGS groups than in the control group (all P < 0.05). Recombinant murine IL-17 (rmIL-17) had no effect on the expressions of Nephrin, Synaptopodin, and WT1 of mouse podocytes, but caused an decrease in the expression of podocalyxin as well as promoted apoptosis in a dose- and time-dependent fashion. Moreover, rmIL-17 increased the expression of Fas, Casepase-8, and Casepase-3, but had no effect on that of FasL. Conclusion: Th17/IL-17 may contribute to the pathogenesis of PNS by decreasing the podocalyxin level and inducing podocyte apoptosis.
Donor Satisfaction with a New German Blood Donor Questionnaire and Intention of the Donor to Return for Further Donations
Authors: Weidmann Christian , Müller-Steinhardt Michael , Schneider Sven , Weck Eberhard , Klüter Harald
Published: October 2013

Background: The aim of this study was to describe donor satisfaction regarding different aspects of the new German blood donor questionnaire (BDQ) and to assess whether donor satisfaction is associated with the intention to return for further donations. Methods: A random number of 6,600 blood donors, donating at the German Red Cross Blood Service Baden-Wuerttemberg - Hessen, were asked to rate their satisfaction with four different aspects of the BDQ. Chi-square statistics was used to test for associations between satisfaction and the intention to return. Results: Most of the donors were satisfied with format and layout (72.7%) and the clarity of the questions (72.5%). However, only 39.5% of the donors were satisfied with the scope of the BDQ and 44.3% with the questions about sexual risk behavior. The lowest satisfaction seemed to be among experienced donors and among donors from small municipalities. Among experienced and very experienced donors, a significant association between the satisfaction with the different aspects and the intention to return became apparent. Conclusion: When considering the implementation of the BDQ, Blood Donor Services have to weigh up the advantages of increased deferral rates among donors with high-risk behavior against the potential drop-out of dissatisfied blood donors.
Magnetic Resonance Imaging versus Computed Tomography in Transient Ischemic Attack and Minor Stroke: The More Υou See the More You Know
Authors: Moreau François , Asdaghi Negar , Modi Jayesh , Goyal Mayank , Coutts Shelagh B.
Published: October 2013

Background: Magnetic resonance imaging (MRI) is proposed as the preferred imaging modality to investigate patients with transient ischemic attack (TIA). This is mainly based on a higher yield of small acute ischemic lesions; however, direct prospective comparisons are lacking. In this study, we aimed to directly compare the yield of acute ischemic lesions on MRI and computed tomography (CT) in the emergency diagnosis of suspected TIA or minor stroke. Methods: Consecutive patients aged 18 years or older presenting with minor stroke (NIHSS <4) or high-risk TIA and who were examined by a stroke neurologist within 24 h of symptom onset were prospectively enrolled in the CATCH study. Patients who had undergone both a baseline CT and an MRI within 24 h of symptom onset were included in this substudy. Baseline MRI and CT were interpreted independently to identify an acute ischemic lesion. The rates of acute ischemic lesions on CT and MRI were compared, and the volume of acute ischemic lesions was measured on MRI. In addition, the volume of acute ischemic lesions on MRI was compared between patients who had evidence of acute ischemia on CT and in those who did not. Results: A total of 347 patients were included, 168 with TIAs, 147 with minor strokes and 32 with a final diagnosis of a mimic. Acute ischemic lesions were detected in 39% of TIAs by using MRI versus 8% by using CT (p < 0.0001) and in 86% of minor strokes by using MRI versus 18% by using CT (p < 0.0001). Compared to MRI, CT had a sensitivity of 20% and a specificity of 98% in identifying an acute ischemic lesion. The infarct volume on diffusion-weighted MRI was larger in cases where the CT also showed an acute ischemic lesion (median 5.07 ml, IQR 10) as compared to lesions seen only on MRI (median 0.68 ml, IQR 1.31, p < 0.0001). Conclusion: MRI is superior to CT in detecting the small ischemic lesions occurring after TIA and minor stroke. Since these lesions are clinically relevant, MRI should be the preferred imaging modality in this setting.
Novel Approach to Estimate Kidney and Cyst Volumes Using Mid-Slice Magnetic Resonance Images in Polycystic Kidney Disease
Authors: Bae Kyongtae T. , Tao Cheng , Wang Jinhong , Kaya Diana , Wu Zhiyuan , Bae Junu T. , Chapman Arlene B. , Torres Vicente E. , Grantham Jared J. , Mrug Michal , Bennett William M. , Flessner Michael F. , Landsittel Doug P. ,   for the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP)
Published: October 2013

Objective: To evaluate whether kidney and cyst volumes can be accurately estimated based on limited area measurements from magnetic resonance (MR) images of patients with autosomal dominant polycystic kidney disease (ADPKD). Materials and Methods: MR coronal images of 178 ADPKD participants from the Consortium for Radiologic Imaging Studies of ADPKD (CRISP) were analyzed. For each MR image slice, we measured kidney and renal cyst areas using stereology and region-based thresholding methods, respectively. The kidney and cyst ‘observed' volumes were calculated by summing up the area measurements of all the slices covering the kidney. To estimate the volume, we selected a coronal mid-slice in each kidney and multiplied its area by the total number of slices (‘PANK2' for kidney and ‘PANC2' for cyst). We then compared the kidney and cyst volumes predicted from PANK2 and PANC2, respectively, to the corresponding observed volumes, using a linear regression analysis. Results: The kidney volume predicted from PANK2 correlated extremely well with the observed kidney volume (R2 = 0.994 for the right kidney and 0.991 for the left kidney). The linear regression coefficient multiplier to PANK2 that best fit the kidney volume was 0.637 (95% CI: 0.629-0.644) for the right kidney and 0.624 (95% CI: 0.616-0.633) for the left kidney. The correlation between the cyst volume predicted from PANC2 and the observed cyst volume was also very high (R2 = 0.984 for the right kidney and 0.967 for the left kidney). The least squares linear regression coefficient for PANC2 was 0.637 (95% CI: 0.624-0.649) for the right kidney and 0.608 (95% CI: 0.591-0.625) for the left kidney. Conclusion: Kidney and cyst volumes can be closely approximated by multiplying the product of the mid-slice area measurement and the total number of slices in the coronal MR images of ADPKD kidneys by 0.61-0.64. This information will help save processing time needed to estimate total kidney and cyst volumes of ADPKD kidneys.
An Individual, Community-Based Treatment for Obese Children and Their Families: The Solution-Focused Approach
Authors: Kreier Felix , Genco Şükrü M. , Boreel Maggie , Langkemper Mieke P. , Nugteren Ineke C. , Rijnveld Viola , Thissen Vivianne , Deden Sonja , Keessen Marina
Published: October 2013

Background: This study evaluates an individual, community-based treatment for obese children and their families. In this program, a treatment team applied solution-focused techniques to develop a custom-made treatment plan in collaboration with the participants. The treatment plan consisted of community-based lifestyle activities. Methods: 559 obese children with an average BMI z-score of 2.76 ± 0.54 took part in the 12-month study, and 372 children with an average BMI z-score of 2.75 ± 0.52 took part in the 24-month study. At the start of the study, ethnicity and special school needs were recorded. Before, after 12 months, and after 24 months of the treatment, body weight and height were measured. The effect of the treatment on body weight was evaluated using BMI z-scores. Results: 291 children (52%) completed 12 months of treatment, whereas 22 children (4%) were dismissed earlier due to a good response. After 12 months, the children showed a significant decrease in BMI z-score by 0.16 (95% confidence interval (CI) 0.11-0.20; p < 0.005). After 24 months, 103 children (28%) were participating in the program, with a significant decrease in BMI z-score of 0.15 (95% CI 0.07-0.22; p < 0.005). 50 children (13%) were dismissed before the end of the second year due to significant weight loss (standard deviation z-score reduction -0.38; 95% CI 0.30-0.46; p < 0.005; with an average treatment duration of 12.9 ± 6.4 months). There was a negative correlation of age and reduction in BMI z-score: children younger than 6 years showed a decrease in BMI z-score of 0.45 (95% CI 0.26-0.65) and 0.31 (95% CI 0.11-0.53) after 12 and after 24 months, respectively. Conclusions: Children showed a significant decrease in BMI z-score after the treatment. We found a negative correlation of age and weight loss. Special attention to patients with a high risk of drop-out might further improve these results. We advise a referral to obesity treatment as early as possible since a ‘wait and see' policy might have adverse results in obese children.
Effect of Combined Systolic and Diastolic Functional Parameter Assessment for Differentiation of Cardiac Amyloidosis From Other Causes of Concentric Left Ventricular Hypertrophy
Authors: Liu Dan , Hu Kai , Niemann Markus , Herrmann Sebastian , Cikes Maja , Störk Stefan , Gaudron Philipp Daniel , Knop Stefan , Ertl Georg , Bijnens Bart , Weidemann Frank
Published: October 2013

Background—

Differentiation of cardiac amyloidosis (CA) from other causes of concentric left ventricular hypertrophy remains a clinical challenge, especially in patients with preserved ejection fraction at the early disease stages.

Methods and Results—

Consecutive hypertrophic patients with CA, isolated arterial hypertension, Fabry disease, and Friedreich ataxia (n=25 per group) were investigated; 25 healthy volunteers served as a control group. Standard echocardiography was performed, and segmental longitudinal peak systolic strain (LSsys) in the septum was assessed by 2-dimensional speckle tracking imaging. Indices of left ventricular hypertrophy and ejection fraction were similar among all patient groups. Deceleration time of early filling was significantly lower in patients with CA (147±46 milliseconds) compared with those with isolated arterial hypertension, Fabry disease, or control subjects (all
P
<0.0125). Septal basal LSsys (−6±2%) was significantly lower in patients with CA compared with those with isolated arterial hypertension (−14±6%), Fabry disease (−12±5%), Friedreich ataxia (−16±2%), or control subjects (−17±3%; all
P
<0.001), whereas septal apical LSsys was similar among all patient groups and control subjects (all
P
>0.05). A data-driven cutoff value for the ratio of septal apical to basal LSsys ratio >2.1 differentiated CA from other causes of left ventricular hypertrophy (sensitivity, 88%; specificity, 85%; positive predictive value, 67%; negative predictive value, 96%). The prevalence of septal apical to basal LSsys ratio >2.1 plus deceleration time of early filling <200 milliseconds was 88% in CA but 0% in all other groups.

Conclusions—

A systolic septal longitudinal base-to-apex strain gradient (septal apical to basal LSsys ratio >2.1), combined with a shortened diastolic deceleration time of early filling (deceleration time of early filling <200 milliseconds), aids in differentiating CA from other causes of concentric left ventricular hypertrophy.
The Screamers
Authors: Burke Patrick
Published: October 2013

While screaming during popular music performances (at least loudly amplified ones) has become unremarkable and even expected, the mid-twentieth-century United States witnessed a series of debates over the appropriateness and significance of screaming. These debates, fraught with moral judgment and often open panic, focused on issues central to American popular music: sexuality, race, class, and the rights and responsibilities of the individual. Tracing the discourse surrounding screaming audiences from the nineteenth century to the present reveals that observers have associated female screamers primarily with sexual impropriety while male screamers more often have been depicted as a potentially violent mob. While commentary on screaming often reinforces racial and gender stereotypes, screaming maintains its subversive power because it effectively dramatizes the tension among social expectations, group solidarity, and individual freedom.
Fancy Meeting You Here: Pioneers of the Concept Album
Authors: Decker Todd
Published: October 2013

The introduction of the long-playing record in 1948 was the most aesthetically significant technological change in the century of the recorded music disc. The new format challenged record producers and recording artists of the 1950s to group sets of songs into marketable wholes and led to a first generation of concept albums that predate more celebrated examples by rock bands from the 1960s. Two strategies used to unify concept albums in the 1950s stand out. The first brought together performers unlikely to collaborate in the world of live music making. The second strategy featured well-known singers in songwriter-or performer-centered albums of songs from the 1920s, 1930s, and 1940s recorded in contemporary musical styles. Recording artists discussed include Fred Astaire, Ella Fitzgerald, and Rosemary Clooney, among others.