bluuebunny/crossref_metadata_2025 huggingface dataset:
Metropolis Parking Problems and Management Planning Solutions for Traffic Operation Effectiveness
Authors: Liu Yuejun , Wang Wuhong , Ding Chengxi , Guo Hongwei , Guo Weiwei , Yao Liya , Xiong Hui , Tan Huachun
Published: October 2012

Advances in mobility are clearly illustrated by the rapid development of urbanization and motorization in developing countries. Following the dramatic incensement of traffic demand, the parking problem has been becoming much more seriously important in many metropolises. With the aim of seeking solutions as to how the parking system could operate more efficiently by using new technologies and new methodologies, this paper discusses the application of geographic information system into the parking planning and management for traffic operation effectiveness in metropolis. The concentration of this paper includes the characteristics of parking demand and the causations of parking problems, especially the basic parking principle and strategies for solving parking problems from the perspective of geographic information system are discussed in enough detail in this paper.
Applying a Self-Made Automobile Heterodyne Interferometer to Measure the Parameters of Twisted Nematic Liquid Crystal
Authors: Wang Shinn-Fwu , Ke Pei-Cheng , Lai Wesley , Ma Hao , Su Yi-Zhan , Chiu Jyh-Shyan
Published: October 2012

A self-made automobile heterodyne interferometer with a closed control loop is presented. In addition, we will apply the self-made automobile heterodyne interferometer to measure the parameters of optically compensated twisted nematic liquid crystal (TN LC). It is worthy to be mentioned that the self-made automobile heterodyne interferometer has a compact size because all the optical components are installed in the mechanism of the system. Besides, the self-made automobile heterodyne interferometer has some much more merits, for example, automobile control, a simple setup, in real-time test, reliability, and so forth. Besides, it is very stable because of its common optical path insensitive to environmental disturbances. And its feasibility is demonstrated.
Scheduling Parallel Jobs Using Migration and Consolidation in the Cloud
Authors: Liu Xiaocheng , Chen Bin , Qiu Xiaogang , Cai Ying , Huang Kedi
Published: October 2012

An increasing number of high performance computing parallel applications leverages the power of the cloud for parallel processing. How to schedule the parallel applications to improve the quality of service is the key to the successful host of parallel applications in the cloud. The large scale of the cloud makes the parallel job scheduling more complicated as even simple parallel job scheduling problem is NP‐complete. In this paper, we propose a parallel job scheduling algorithm named MEASY. MEASY adopts migration and consolidation to enhance the most popular EASY scheduling algorithm. Our extensive experiments on well‐known workloads show that our algorithm takes very good care of the quality of service. For two common parallel job scheduling objectives, our algorithm produces an up to 41.1% and an average of 23.1% improvement on the average response time; an up to 82.9% and an average of 69.3% improvement on the average slowdown. Our algorithm is robust even in terms that it allows inaccurate CPU usage estimation and high migration cost. Our approach involves trivial modification on EASY and requires no additional technique; it is practical and effective in the cloud environment.
Multislot Antenna with a Screening Backplane for UWB WBAN Applications
Authors: Wei Yun-fei , Roblin Christophe
Published: October 2012

A novel multislot antenna with a conducting backplane reflector (MSA-BP) designed for ultrawideband wireless body area networks (WBANs) applications is presented. The objective is to achieve a desensitization of the antenna behavior regarding the proximity effects of the human body, thanks to the field screening operated by the backplane. Partly because of the latter, the antenna is fed with a tapered CPW. The influence of antenna parameters and human body proximity on the radiation characteristics of the MSA-BP is analyzed. Simulated results of the antenna close to a three-layer arm phantom are presented. Impedance and radiation measurements of the isolated antenna as well as propagation characteristics along the human body demonstrating the desensitization effect are also presented. The characteristics of the MSA-BP, in terms of the on-body total radiation efficiency, are significantly improved compared to any (quasi-) omnidirectional counterpart.
Realization of Radar Illusion Using Active Devices
Authors: Cao B. Z. , Sun L. , Mei Z. L.
Published: October 2012

A new method is proposed for realizing radar illusion of an electromagnetic target by using active devices. The devices are installed around the target but may closely cover the target or not, leading to closed or open configurations. The amplitudes and phases of the active devices are determined by using T-matrix method. The numerical computation is calculated using MATLAB, and the results show that this method is convenient, flexible, and efficient, which has important significances for implementation of novel electromagnetic devices.
Primary Renal Epithelioid Hemangioendothelioma
Authors: Roy S. , Parwani A. V.
Published: October 2012

Epithelioid hemangioendothelioma is a rare vascular tumor with intermediate biologic behavior and metastatic potential. Primary renal epithelioid hemangioendothelioma is extremely rare and we present the second report of this rare tumor in an interesting clinical scenario. A 59-year-old male with established history of widely metastatic high grade esophageal adenocarcinoma was found to have an isolated renal nodule on a followup computed tomography (CT) scan. Surgical excision, with the suspicion of metastatic carcinoma, and subsequent pathologic examination revealed an epithelioid hemangioendothelioma. The various differential diagnoses and use of morphological clues and immunohistochemistry are discussed.
Adaptive Sliding Mode Control of Single‐Phase Shunt Active Power Filter
Authors: Fei Juntao , Zhang Shenglei , Zhou Jian
Published: October 2012

This paper presents a thorough study of the adaptive sliding mode technique with application to single‐phase shunt active power filter (APF). Based on the basic principle of single‐phase shunt APF, the approximate dynamic model is derived. A model reference adaptive sliding mode control algorithm is proposed to implement the harmonic compensation for the single‐phase shunt APF. This method will use the tracking error of harmonic and APF current as the control input and adopt the tracking error of reference model and APF output as the control objects of adaptive sliding mode. In the reference current track loop, a novel adaptive sliding mode controller is implemented to tracking the reference currents, thus improving harmonic treating performance. Simulation results demonstrate the satisfactory control performance and rapid compensation ability of the proposed control approach under different conditions of the nonlinear load current distortion and the mutation load, respectively.
Screening Tests of Reproductive Immunology in Systemic Lupus Erythematosus
Authors: Ulcova-Gallova Zdenka , Mockova Alice , Cedikova Miroslava
Published: October 2012

Female patients in reproductive age with systemic lupus erythematosus and fertility complications together are observed by rheumatologists, gynecologists, and reproductive immunologists. The paper notes the presence of autoantibodies to zona pellucida, to phospholipids (phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl inositol, phosphatidyl glycerol, phosphatidic acid, annexin V, beta-2 glycoprotein I, and cardiolipin) and of isoantibodies to sperm cells. Isoantibodies to sperm cells are not significantly predominant, but autoimmunity is well expressed in IgG positivity against phosphatidyl inositol, phosphatidyl ethanolamine, phosphatidyl serine, cardiolipin, and beta-2 glycoprotein I, as well as antizona pellucida antibodies in IgG isotype. According to the levels of autoantibodies we have to choose preventive treatment to protect mother and her foetus.
Data‐Driven Adaptive Observer for Fault Diagnosis
Authors: Yin Shen , Yang Xuebo , Karimi Hamid Reza
Published: October 2012

This paper presents an approach for data‐driven design of fault diagnosis system. The proposed fault diagnosis scheme consists of an adaptive residual generator and a bank of isolation observers, whose parameters are directly identified from the process data without identification of complete process model. To deal with normal variations in the process, the parameters of residual generator are online updated by standard adaptive technique to achieve reliable fault detection performance. After a fault is successfully detected, the isolation scheme will be activated, in which each isolation observer serves as an indicator corresponding to occurrence of a particular type of fault in the process. The thresholds can be determined analytically or through estimating the probability density function of related variables. To illustrate the performance of proposed fault diagnosis approach, a laboratory‐scale three‐tank system is finally utilized. It shows that the proposed data‐driven scheme is efficient to deal with applications, whose analytical process models are unavailable. Especially, for the large‐scale plants, whose physical models are generally difficult to be established, the proposed approach may offer an effective alternative solution for process monitoring.
Genetic Algorithm for Job Scheduling with Maintenance Consideration in Semiconductor Manufacturing Process
Authors: Lee Seungchul , Ni Jun
Published: October 2012

This paper presents wafer sequencing problems considering perceived chamber conditions and maintenance activities in a single cluster tool through the simulation‐based optimization method. We develop optimization methods which would lead to the best wafer release policy in the chamber tool to maximize the overall yield of the wafers in semiconductor manufacturing system. Since chamber degradation will jeopardize wafer yields, chamber maintenance is taken into account for the wafer sequence decision‐making process. Furthermore, genetic algorithm is modified for solving the scheduling problems in this paper. As results, it has been shown that job scheduling has to be managed based on the chamber degradation condition and maintenance activities to maximize overall wafer yield.
Cocoa Polyphenols and Their Potential Benefits for Human Health
Authors: Andújar I. , Recio M. C. , Giner R. M. , Ríos J. L.
Published: October 2012

This paper compiles the beneficial effects of cocoa polyphenols on human health, especially with regard to cardiovascular and inflammatory diseases, metabolic disorders, and cancer prevention. Their antioxidant properties may be responsible for many of their pharmacological effects, including the inhibition of lipid peroxidation and the protection of LDL-cholesterol against oxidation, and increase resistance to oxidative stress. The phenolics from cocoa also modify the glycemic response and the lipid profile, decreasing platelet function and inflammation along with diastolic and systolic arterial pressures, which, taken together, may reduce the risk of cardiovascular mortality. Cocoa polyphenols can also modulate intestinal inflammation through the reduction of neutrophil infiltration and expression of different transcription factors, which leads to decreases in the production of proinflammatory enzymes and cytokines. The phenolics from cocoa may thus protect against diseases in which oxidative stress is implicated as a causal or contributing factor, such as cancer. They also have antiproliferative, antimutagenic, and chemoprotective effects, in addition to their anticariogenic effects.
Creep Modeling in a Composite Rotating Disc with Thickness Variation in Presence of Residual Stress
Authors: Gupta Vandana , Singh S. B.
Published: October 2012

Steady-state creep response in a rotating disc made of Al-SiC (particle) composite having linearly varying thickness has been carried out using isotropic/anisotropic Hoffman yield criterion and results are compared with those using von Mises yield criterion/Hill's criterion ignoring difference in yield stresses. The steady-state creep behavior has been described by Sherby's creep law. The material parameters characterizing difference in yield stresses have been used from the available experimental results in literature. Stress and strain rate distributions developed due to rotation have been calculated. It is concluded that the stress and strain distributions got affected from the thermal residual stress in an isotropic/anisotropic rotating disc, although the effect of residual stress on creep behavior in an anisotropic rotating disc is observed to be lower than those observed in an isotropic disc. Thus, the presence of residual stress in composite rotating disc with varying thickness needs attention for designing a disc.
Comparative Study on Molecular Weight of Konjac Glucomannan by Gel Permeation Chromatography-Laser Light Scattering-Refractive Index and Laser Light-Scattering Methods
Authors: Xu Mei , Li Dong-Sheng , Li Bin , Wang Chao , Zhu Yu-Peng , Lv Wen-Ping , Xie Bi-Jun
Published: October 2012

The gel permeation chromatography, combined with laser light scattering and refractive index (GPC-LLS-RI) online method and laser light scattering (LLS) single method, researched the weight-average molecular weight (Mw) of konjac glucomannan (KGM) in this paper. The results show that the determination results of molecular weight of KGM are similar by two method, the molecular weight of KGM is2.476×105 g/mol by online method measured, and it is2.508×105 g/mol by single method measured, compared with only 1.3% difference between the two methods. At the same time, the molecular weight distributions of KGM and conformation index were analyzed by online method, while the second virial coefficient (A2) that characterizes the interaction between KGM molecules and solvent molecules was acquired by single method, which can provide reliable foundation for the molecular chain morphology research of KGM.
Adoptive Transfer of Autologous T Cells Improves T-cell Repertoire Diversity and Long-term B-cell Function in Pediatric Patients with Neuroblastoma
Authors: Grupp Stephan A. , Prak Eline Luning , Boyer Jean , McDonald Kenyetta R. , Shusterman Suzanne , Thompson Edward , Callahan Colleen , Jawad Abbas F. , Levine Bruce L. , June Carl H. , Sullivan Kathleen E.
Published: October 2012

Purpose: Children with high-risk neuroblastoma have a poor prognosis with chemotherapy alone, and hematopoietic stem cell transplantation offers improved survival. As a dose-escalation strategy, tandem transplants have been used, but are associated with persistent immunocompromise. This study evaluated the provision of an autologous costimulated, activated T-cell product to support immunologic function.

Experimental Design: Nineteen subjects with high-risk neuroblastoma were enrolled in a pilot phase and 23 subjects were entered in to the randomized study. Immunologic reconstitution was defined by flow cytometric and functional assays. Next-generation sequencing was conducted to identify changes to the T-cell repertoire. Twenty-two patients were vaccinated to define effects on antibody responses.

Results: Subjects who received their autologous costimulated T-cell product on day 2 had significantly superior T-cell counts and T-cell proliferation compared with those who received T cells on day 90. Early administration of autologous T cells suppressed oligoclonality and enhanced repertoire diversity. The subjects who received the day 2 T-cell product also had better responses to the pneumococcal vaccine.

Conclusions: The infusion of activated T cells can improve immunologic function especially when given early after transplant. This study showed the benefit of providing cell therapies during periods of maximum lymphopenia. Clin Cancer Res; 18(24); 6732–41. ©2012 AACR.
Phase I and Pharmacologic Trial of Cytosine Arabinoside with the Selective Checkpoint 1 Inhibitor Sch 900776 in Refractory Acute Leukemias
Authors: Karp Judith E. , Thomas Brian M. , Greer Jacqueline M. , Sorge Christopher , Gore Steven D. , Pratz Keith W. , Smith B. Douglas , Flatten Karen S. , Peterson Kevin , Schneider Paula , Mackey Karen , Freshwater Tomoko , Levis Mark J. , McDevitt Michael A. , Carraway Hetty E. , Gladstone Douglas E. , Showel Margaret M. , Loechner Sabine , Parry David A. , Horowitz Jo Ann , Isaacs Randi , Kaufmann Scott H.
Published: October 2012

Purpose: Incorporation of cytarabine into DNA activates checkpoint kinase 1 (Chk1), which stabilizes stalled replication forks, induces S-phase slowing, and diminishes cytarabine cytotoxicity. The selective Chk1 inhibitor SCH 900776 abrogates cytarabine-induced S-phase arrest and enhances cytarabine cytotoxicity in acute leukemia cell lines and leukemic blasts in vitro. To extend these findings to the clinical setting, we have conducted a phase I study of cytarabine and SCH 900776.

Experimental Design: Twenty-four adults with relapsed and refractory acute leukemias received timed sequential, continuous infusion cytarabine 2 g/m2 over 72 hours (667 mg/m2/24 hours) beginning on day 1 and again on day 10. SCH 900776 was administered as a 15- to 30-minute infusion on days 2, 3, 11, and 12. The starting dose of SCH 900776 was 10 mg/m2/dose.

Results: Dose-limiting toxicities consisting of corrected QT interval prolongation and grade 3 palmar-plantar erythrodysesthesia occurred at 140 mg flat dosing (dose level 5, equivalent to 80 mg/m2). Complete remissions occurred in 8 of 24 (33%) patients, with 7 of 8 at 40 mg/m2 or higher. SCH 900776 did not accumulate at any dose level. Marrow blasts obtained pretreatment and during therapy showed increased phosphorylation of H2Ax after SCH 900776 beginning at 40 mg/m2, consistent with unrepaired DNA damage.

Conclusions: These data support a randomized phase II trial of cytarabine +/− SCH 900776 at a recommended flat dose of 100 mg (equivalent to 56 mg/m2) for adults with poor-risk leukemias. The trial (SP P05247) was registered at www.clinicaltrials.gov as NCT00907517. Clin Cancer Res; 18(24); 6723–31. ©2012 AACR.
Different Pattern of Clinical Deficits in Stroke Mimics Treated with Intravenous Thrombolysis
Authors: Sarikaya Hakan , Yilmaz Murat , Luft Andreas R. , Gantenbein Andreas R.
Published: October 2012

Background: Guidelines recommend intravenous thrombolysis (IVT) to be applied as early as possible in ischemic stroke (IS), while clinical presentation is often assessed by using the National Institutes of Health Stroke Scale (NIHSS). However, diagnostic workup under time pressure bears the risk of misdiagnosis. Little is known about whether NIHSS could help to differentiate between IS and stroke mimics (SM) in patients being evaluated for IVT. Methods: Prospectively collected data of 326 consecutive patients treated with IVT were analyzed. Baseline characteristics and NIHSS subscores were compared between SM and IS. Results: Among 326 patients, 23 (7%) had a final diagnosis other than IS. Age and vascular risk factors were comparable in both groups. Patients with SM less often had oculomotor disturbance (0 vs. 37%, p < 0.001), dysarthria (9 vs. 51%, p < 0.001), hemineglect (0 vs. 30%, p < 0.01), hemianopia (0 vs. 22%, p < 0.01) and facial palsy (33 vs. 70%, p < 0.01). On the other hand, global aphasia without hemiparesis was more prevalent in SM patients (43 vs. 6%, p < 0.001). Conclusion: Our study suggests that patients with SM undergoing IVT present with a different pattern of clinical deficits than patients with IS.
Factors Associated with Low Self-Esteem in Children with Overweight*
Authors: Danielsen Yngvild Sørebø , Stormark Kjell Morten , Nordhus Inger Hilde , Mæhle Magne , Sand Liv , Ekornås Belinda , Pallesen Ståle
Published: October 2012

Objective: Low self-esteem is one of the main psychosocial factors related to childhood overweight. Yet not all overweight children are affected. Little is known about what characterises the group of overweight children with the lowest self-esteem. Our aim was to identify factors related to low domain-specific self-esteem in children with overweight/obesity. Methods: Children (aged 10–13; N = 5,185) and parents from a large population-based sample completed the Eating Disturbance Scale, the Self-Perception Profile for Children, and questions about bullying and socio-economic status (SES). Parents reported the child’s weight and height. 545 children with overweight/obesity were identified in the overall sample and selected for the current analyses. Self-esteem scores from this group were compared to scores from children with normal weight. Factors examined in relation to self-esteem in children with overweight/obesity were: age, gender, SES, disturbed eating, bullying, parents’ evaluation of weight status and degree of overweight. Results: Children with overweight scored significantly lower than normal-weight children on all self-esteem domains. Athletic competence and physical appearance were most impaired. Disturbed eating and bullying were related to low physical appearance as well as scholastic, social and athletic self-esteem. Being female, a pre-teen, having a higher BMI and being evaluated as overweight by parents were associated with lower satisfaction with physical appearance. Conclusions: Disturbed eating and bullying are significantly related to low self-esteem in the overweight group.
Clinical Characteristics of Patients with Mycoplasma pneumoniae-Related Acute Hepatitis
Authors: Shin Su Rin , Park Sang Hoon , Kim Joo-Hee , Ha Jun-Wook , Kim Yu Jin , Jung Sung Won , Kim Jin Bae , Lee Myung Seok , Park Choong Kee
Published: October 2012

Background/Aims: Although the hepatobiliary manifestations of Mycoplasma pneumoniae infection have been described in several previous studies, controversies still remain. The aim of this study was to evaluate the clinical characteristics of patients with M. pneumoniae-related hepatitis and compare to those with M. pneumoniae infection but not hepatitis. Methods: We reviewed the medical chart of patients diagnosed with M. pneumoniae infection serologically. Results: Among the 117 patients with M. pneumoniae infection enrolled in the study, 25 showed acute hepatitis without any evidence of another cause. Patients with hepatitis presented with prodromal symptoms more frequently and also had a higher body temperature and C-reactive protein (CRP) levels than patients without hepatitis. Frequencies of respiratory tract involvement were not different between two groups. Clinical signs recovered within three weeks in both groups following the institution of antibiotic therapy. Multivariate analysis revealed that male sex, age <40 years, and high CRP levels were significantly linked to M. pneumoniae-related hepatitis. Conclusions: We found that acute hepatitis associated with M. pneumoniae occurred in about 21% of all M. pneumoniae infections, and gender, age, and CRP levels were factors related to the occurrence of M. pneumoniae-related hepatitis.
Promotion of Hepatocellular Carcinoma by Hepatitis C Virus
Authors: Bühler Sandra , Bartenschlager Ralf
Published: October 2012

Persistent infection with the hepatitis C virus (HCV) is a major global health problem. Around 2–3% of the world’s population are chronically infected, and infected individuals are at high risk of developing steatosis, fibrosis, and liver cirrhosis. The latter is a major predisposing factor for the development of hepatocellular carcinoma (HCC). It is generally accepted that an inflammatory response triggered by persistent HCV infection leads to increased cell proliferation and fibrogenesis that in turn promotes cirrhosis and ultimately HCC development. This indirect mechanism of tumor induction would explain the long incubation period from primary HCV infection to HCC and the requirement for additional cofactors such as toxins or drugs (most notably alcohol), metabolic liver diseases, steatosis, nonalcoholic liver disease, or diabetes. With the advent of adequate cell culture systems for HCV it is, however, becoming increasingly clear that the virus also contributes directly to HCC formation. Examples are the continuous induction of stress response or the massive accumulation of intracellular lipids. Moreover, viral proteins can bind to and sequester cell cycle control factors such as the retinoblastoma protein or the tumor suppressor DDX3. Thus, HCV-associated liver cancer is most likely promoted by the combined action of long-term chronic inflammation and targeted perturbations of cellular key pathways involved in metabolic homeostasis as well as cell cycle control.
Age of Onset: Can We Rely on Essential Tremor Patients to Report This? Data from a Prospective, Longitudinal Study
Authors: Louis Elan D.
Published: October 2012

Background: Essential tremor (ET) is among the most prevalent neurological diseases. Age of onset, a key variable in neuroepidemiological and genetic research, is chiefly assessed by self-report rather than medical record review; the latter may be of little use. As a researcher, one wonders about the quality of this self-report. Is age of onset something which can be reproducibly self-reported by patients? There are few published data to aid researchers. Methods: Age of onset was self-reported at two time points (baseline and follow-up) in 86 ET cases in a longitudinal epidemiological study in New York. Results: The mean follow-up interval was 5.7 ± 2.5 (maximum = 14) years. Overall, agreement between the baseline and follow-up reports was high (ρ = 0.85, p < 0.001). Yet the difference (age of onset baseline – age of onset follow-up) ranged widely (from –47 to 32 years), and in one fifth of cases was ≥10 years. Greater agreement was associated with several clinical factors including age, medication use, embarrassment, depressive symptoms, cognitive test score and disease duration. Conclusions: Differences in reported age of onset in ET may vary widely, and in up to one fifth of patients may be substantial. Investigators should approach these self-reports with caution.
Extracorporeal Liver Support
Authors: Leckie Pamela , Davenport Andrew , Jalan Rajiv
Published: October 2012

Mortality of patients with liver failure remains unacceptably high. As the liver has an enormous potential to regenerate, extracorporeal liver support devices may allow patients with liver failure to be bridged to recovery. Alternatively, liver assist may allow patients with advanced liver disease to be managed until a suitable organ for transplant is available. Current approaches to liver support include the use of biological devices that contain hepatocytes and those that function as detoxification devices, and artificial liver support systems. This review describes the current state of the art and existing data on the use of these devices to treat patients with liver failure.
Pediatric Renal Replacement Therapy in the Intensive Care Unit
Authors: Bridges Brian C. , Askenazi David J. , Smith Jessimene , Goldstein Stuart L.
Published: October 2012

Renal replacement therapy (RRT) is used in a wide variety of pediatric populations. In this article, we will review the advantages and disadvantages of the different RRT modalities and the technical aspects of providing pediatric RRT. In addition, we will review the use of RRT with extracorporeal membrane oxygenation, the use of continuous RRT in the critically ill child with acute kidney injury and fluid overload, and the use of RRT for the removal of toxins and treatment of inborn errors of metabolism.
Elevated Red Blood Cell Distribution Width Is Associated with Higher Recourse to Coronary Artery Bypass Graft
Authors: Ephrem Georges , Kanei Yumiko
Published: October 2012

Background: Red blood cell distribution width (RDW) is a measure of heterogeneity in erythrocyte size used in the differential diagnosis of anemia. High levels are associated with elevated cardiovascular biomarkers and increased mortality. The hypothesis of this study is that high RDW levels on admission are associated with higher recourse to coronary artery bypass graft (CABG) in unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI) patients. Methods: An observational, cross-sectional study of all adult patients undergoing coronary angiography admitted to an urban tertiary care center in 2007 with UA or NSTEMI was conducted. Data was gathered by review of inpatient charts. RDW was considered ‘high’ if it exceeded the 95th percentile (16.3%). Results: Among the 503 subjects included in the analysis, high RDW was independently associated with higher recourse to CABG versus a nonsurgical approach [OR = 2.39 (1.04–5.50); p = 0.041] but not with conservative management [OR = 0.97 (0.51–1.84); p = 0.922] or percutaneous coronary intervention [OR = 0.67 (0.36–1.25); p = 0.208]. Conclusions: This study of patients with UA or NSTEMI demonstrated an independent association of elevated RDW with higher recourse to CABG. RDW should be considered in the stratification of patients presenting with UA or NSTEMI.
Desmoplastic Malignant Melanoma: A Study of Ten Cases and Status of BRAF Mutation
Authors: Coupelon S. , Franck F. , Jarrousse A.S. , Déchelotte P. , Souteyrand P. , D’Incan M.
Published: October 2012

Background: Desmoplastic malignant melanoma (DM) is a rare variant of melanoma. BRAF gene mutations have been poorly explored in this entity. Objective: To detect BRAF gene mutation in a series of DM. Methods: This is a single-center retrospective study of ten patients with DM, with a biomolecular analysis of BRAF mutation. Results: The male:female ratio was 2.3:1, with a mean patient age of 66.5 years. Melanoma arose in the head and neck region in 3 cases. The mean tumor thickness was 7.97 mm, Clark level was IV or V in all cases. Six melanomas were of the pure DM variant. Three patients had at least one local recurrence, two had regional node metastases, and two experienced systemic metastases which they died of (average follow-up 34.1 months). A V600E BRAF mutation was detected in only one patient. Conclusion: BRAF mutation seems to be a rare event in DM contrary to other melanoma variants.
Endothelial Nitric Oxide Synthase in Dorsal Root Ganglia during Chronic Inflammatory Nociception
Authors: Borsani Elisa , Giovannozzi Sara , Cocchi Marco Angelo , Boninsegna Ramon , Rezzani Rita , Rodella Luigi F.
Published: October 2012

Nitric oxide (NO) is a gaseous molecule implicated both in vascular tone and nociceptive transmission. The capillary blood supply to the dorsal root ganglia (DRG) is unique because it is highly permeable to several low and high molecular-weight compounds. This anatomical situation leads to a potential role of endothelial nitric oxide synthase (eNOS) in inflammatory nociception, which is not well established. Therefore, we examined the role of eNOS in DRG in a murine chronic inflammatory pain model induced by complete Freund’s adjuvant using L-N5-(1-iminoethyl)ornithine (L-NIO), a potent inhibitor of eNOS activity. Pain state was examined using a behavioral test. The expression of eNOS, platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor (VEGF) was examined by immunofluorescence. In control animals, CD31 was detected in vessels; VEGF was localized both in vessels and neurons while a weak eNOS immunopositivity was detected in both vessels and in neurons. Under inflammatory pain conditions, eNOS, CD31 and VEGF immunopositivity increased. Administration of L-NIO significantly attenuated thermal hyperalgesia by 24 h and decreased eNOS activity and CD31 immunopositivity by 7 days. VEGF was unaffected. Our results show that eNOS plays a nociceptive role in the early phases of inflammation while in the later phases it may be involved in neurotrophic support.
GH-Releasing Hormone Receptor Gene: A Novel Splice-Disrupting Mutation and Study of Founder Effects
Authors: Marui Suemi , Trarbach Ericka B. , Boguszewski Margaret C.S. , França Marcela M. , Jorge Alexander A.L. , Inoue Hiroshi , Nishi Mirian Y. , de Lacerda Filho Luiz , Aguiar-Oliveira Manuel H. , Mendonca Berenice B. , Arnhold Ivo J.P.
Published: October 2012

Background: Mutations in GH-releasing hormone receptor gene (GHRHR) are emerging as the most common cause of autosomal recessive isolated GH deficiency (IGHD). Objective: To search for GHRHR mutations in patients with familial or sporadic IGHD and to investigate founder effects in recurring mutations. Methods: The coding region of GHRHR was entirely amplified and sequenced from DNA of 18 patients with IGHD (16 unrelated) with topic posterior pituitary lobe on MRI. Haplotypes containing promoter SNPs and microsatellites flanking GHRHR were analyzed in patients with c.57+1G>A (IVS1+1G>A) mutation of our previously published kindred and also a Brazilian patient and 2 previously reported Japanese sisters with c.1146G>A (p.E382E) mutation. Results: A novel homozygous intronic GHRHR c.752-1G>A (IVS7-1G>A) mutation, predicting loss of the constitutive splice acceptor site, was identified in two siblings with IGHD. A compound heterozygous c.[57+1G>A];[1146G>A] and a heterozygous c.527C>T (p.A176V) were found in two sporadic cases. Haplotype analysis provided evidence for a founder effect for the c.57+1G>A mutation and independent recurrence for the c.1146G>A mutation. Conclusion: We report a novel splice-disrupting mutation in GHRHR in 2 siblings and provide evidence that all c.57+1G>A (IVS1+1G>A) mutant chromosomes have the same haplotype ancestor, indicating the occurrence of a founder effect in Brazilian patients with IGHD.
Significance of Gleason Grading of Low-Grade Carcinoma of the Prostate with Therapeutic Option of Active Surveillance
Authors: Helpap Burkhard , Kristiansen Glen , Köllermann Jens , Adler David , Wernert Nicolas , Oehler Ulrich , Fellbaum Christian
Published: October 2012

Introduction: Active surveillance needs a precise grading diagnosis of a low-grade carcinoma of the prostate (Gleason score (GS) 6) within a small organ-confined tumor. However, how accurate is the gold standard of GS 6 in predicting a small pT2 carcinoma? To answer this question, we have analyzed grading systems in this study. Methods: Prostatic carcinomas in biopsy and corresponding radical prostatectomy (RP) specimens of 960 patients were graded by the Gleason system in which glandular fusions and nucleolar stage (prominence and location) were considered. Results: Using the modified Gleason grading, a high upgrading rate from the biopsy to RP specimens (GS 6–7) and in even 30% a non-organ-confined growth pattern (pT3) of GS 6 carcinoma in RP was found. When considering glandular fusion and the incorporation of the state of nucleoli within the Gleason grading, the agreement of score 6 between biopsy and RP specimens as well as the prediction of a pT2a tumor increased from about 80 to 90%. Conclusion: The combination of Gleason grading and grading of the nuclear and nucleolar features may help to identify patients eligible for active surveillance.
Urine Gonadotropin and Testosterone Levels in Male Very-Low-Birthweight Infants
Authors: de Jong M. , Rotteveel J. , Heijboer A.C. , Cranendonk A. , Twisk J.W.R. , van Weissenbruch M.M.
Published: October 2012

Background/Aims: The postnatal activation of the hypothalamic-pituitary-gonadal axis is more exaggerated in preterm than in full-term-born infants, and may be important for reproductive function. Our objective was to investigate this activation of the hypothalamic-pituitary-gonadal axis in male very-low-birthweight (VLBW) infants. Methods: Twenty-one VLBW boys (gestational age 26.0–30.0 weeks), participating in the NIRTURE trial, were included. Gonadotropin and testosterone levels were measured in serial urine samples collected at 1 and 4 weeks’ postnatal age, at 32 weeks’ postmenstrual age, at expected date of delivery and at the corrected age of 3 and 6 months. Results: Longitudinal analysis shows that after birth LH and FSH levels peak at a mean postnatal age of 1–4 weeks (mean postmenstrual age of 30–32 weeks) and decrease until 38 weeks’ postnatal age (corrected age of 6 months). Testosterone levels decrease with increasing age, and this decrease is faster in infants receiving early insulin therapy. Conclusions: Serial urine sampling for measurement of gonadotropin and testosterone levels provides accurate information about the postnatal activation of the hypothalamic-pituitary-gonadal axis in VLBW boys. FSH and LH levels peak at 1–4 weeks of age. Insulin treatment causes faster decrease in testosterone levels.
Involvement of the P2X7 Purinergic Receptor and c-Jun N-Terminal and Extracellular Signal-Regulated Kinases in Cyclooxygenase-2 and Prostaglandin E2 Induction by LL-37
Authors: Chotjumlong Pareena , Bolscher Jan G. , Nazmi Kamran , Reutrakul Vichai , Supanchart Chayarop , Buranaphatthana Worakanya , Krisanaprakornkit Suttichai
Published: October 2012

Periodontal disease is caused by microorganisms and host-derived inflammation involving increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production. We previously demonstrated that human β-defensin-3 induces COX-2 and PGE2 in human gingival fibroblasts (HGFs). We, therefore, aimed to examine the inducible effects of LL-37, the only cathelicidin expressed in humans, on COX-2 expression and PGE2 synthesis in HGFs and to elucidate the relevant signaling pathways. The COX-2 expression was upregulated by LL-37 in dose- and time-dependent manners. Accordingly, the synthesis of PGE2 in cell-free culture supernatants was raised by LL-37 (p < 0.01) and blocked by NS-398, a specific COX-2 inhibitor (p < 0.01). P2X inhibitors and a neutralizing antibody against P2X7 purinergic receptor significantly abrogated COX-2 induction and PGE2 production by LL-37 (p < 0.01). LL-37 upregulated COX-2 expression and PGE2 synthesis via activation of extracellular signal-regulated kinase (ERK) and p46 c-Jun N-terminal kinase (JNK), while interleukin-1β did so via nuclear factor-ĸB and all three mitogen-activated protein kinases. In summary, LL-37 can control arachidonic acid metabolism by induction of COX-2 expression and PGE2 synthesis via the P2X7 receptor, ERK, and p46 JNK. The pro-inflammatory effects of LL-37 may be essential for initiating oral mucosal inflammation in periodontal disease.
Early Imaging of Macular Hole Closure: A Diagnostic Technique and Its Quality for Gas-Filled Eyes with Spectral Domain Optical Coherence Tomography
Authors: Yamashita Toshifumi , Yamashita Takehiro , Kawano Hiroki , Sonoda Yasushi , Yamakiri Keita , Sakamoto Taiji
Published: October 2012

Background/Aims: This study was conducted to establish a reliable method to determine macular hole (MH) closure of gas-filled eyes. Method: 21 consecutive eyes with MH underwent vitrectomy with gas tamponade, and spectral domain optical coherence tomography (SD-OCT) was performed using our diagnostic technique. The quality of OCT images was rated as signal strength (SS) and evaluated by masked observers. Results: The quality to determine MH closure (SS ≥4) was sufficient in all eyes. In addition, SD-OCT images (SS ≥6) obtained from 16/21 eyes showed detailed retinal structures including the inner segment/outer segment line. The next day after surgery, MH closure was confirmed in 12/21 eyes, and residual MH was observed in 9/21 eyes. Among these 9 eyes, 7 eyes were closed within 2 weeks. Conclusion: The present method provided clear SD-OCT images from gas-filled eyes, which is not only essential for the diagnosis of MH closure but also for establishing proper protocols and for studying the pathology of gas-filled eyes.
Heart Failure Associated with Metastatic Myocardial Calcification in a Hemodialysis Patient with Progressive Calcification of the Hand
Authors: Matsui Masaru , Okayama Satoshi , Takitsume Akihiro , Morimoto Katsuhiko , Samejima Kenichi , Uemura Shiro , Saito Yoshihiko
Published: October 2012

Metastatic myocardial calcification is a frequent cause of heart failure in hemodialysis patients. However, early detection is difficult, often resulting in a poor prognosis. A 47-year-old man with hemodialysis-dependent end-stage renal disease presented with progressive dyspnea. Levels of serum phosphate, calcium, and intact parathyroid hormone were poorly controlled. He developed pain in his right thumb 1 year before presentation, and the pain gradually increased and extended to the entire right hand. Hand radiography 1 month earlier had revealed significant progressive calcification. Echocardiography showed severe, diffuse hypokinesis and pericardial effusion as well as possible anterior myocardial calcification with high echogenicity. Chest computed tomography revealed a severely dilated heart with anterior massive myocardial calcification and a large amount of pericardial effusion, which was not detected on computed tomography performed 20 months earlier. The patient was diagnosed with heart failure associated with metastatic myocardial calcification and died suddenly 2 weeks later. This experience suggests that progressive metastatic calcification of the skin and subcutaneous tissue is useful for predicting myocardial calcification.
Evaluating the Impact of Public Health Notification
Authors: Eisenstein Eric L. , Wojdyla Daniel , Anstrom Kevin J. , Brennan J. Matthew , Califf Robert M. , Peterson Eric D. , Douglas Pamela S.
Published: October 2012

Background—

Provider and public health interventions in the late 2006 sought to change the duration of clopidogrel use after drug-eluting stent (DES) implantation. We evaluated whether public health interventions were associated with changes in patient-reported clopidogrel use among DES patients.

Methods and Results—

We used interrupted time analyses to evaluate trends in duration of patient-reported clopidogrel use before, during, and after public and provider interventions. We included patients with significant coronary artery disease receiving an intracoronary stent between April 2004 and December 2007 at a single tertiary care center. The center supplemented national and regulatory messaging regarding the role of clopidogrel after DES implantation with direct-to-patient and to-their-provider notifications in December 2006. The combination of public and provider direct notification was associated with significant changes in the percent of DES patients reporting clopidogrel use at 6 months (16.55% increase,
P
=0.010) and 12 months (15.33% increase,
P
=0.004), but no change at 24-month follow-up (4.64,
P
=0.295). During the same period, there was no change in the percent of bare-metal stent patients reporting clopidogrel use at 6-month (−3.73%, 0.654), 12-month (−5.98%,
P
=0.389), and 24-month follow-up (−5.16,
P
=0.708). Although mortality rates through 24 months seemed to decrease between the pre- and postintervention periods, these changes were not significant (DES,
P
=0.086; bare-metal stent,
P
=0.296).

Conclusions—

The combination of national scientific and regulatory messaging supplemented by local, personal communications to DES patients and their primary healthcare providers was associated with a significant increase in patient-reported clopidogrel use.
Impact of Community Wealth on Use of Cardiac-Resynchronization Therapy With Defibrillators for Heart Failure Patients
Authors: Farmer Steven A. , Tuohy Elizabeth J. , Small Dylan S. , Wang Yongfei , Groeneveld Peter W.
Published: October 2012

Background—

Disparities in cardiovascular disease treatment are a major health policy concern. A complex interplay of patient, provider, and social contextual factors affect inequities in care.

Methods and Results—

We used data regarding 22 205 patient stays in the National Cardiovascular Data Registry to explore the effect of hospital resources on receipt of a heart failure therapy, cardiac-resynchronization therapy with defibrillation (CRT-D). When added to patient-level variables, hospital ownership, cardiac patient volume, cardiac procedure availability, CRT-D, implantable cardioverter-defibrillator implantation volumes, and hospital financial characteristics were individually predictive of CRT-D receipt. In the full hierarchical model, average median household income (
P
<0.0001) and implantable cardioverter-defibrillator implantation volume (
P
<0.001) remained significant predictors of CRT-D receipt. Patients treated at hospitals in affluent communities were more likely to receive CRT-D than patients treated in poor communities, despite accounting for other patient and hospital characteristics, including insurance status.

Conclusions—

These findings suggest that the likelihood of receiving CRT-D is mediated by community wealth and hospital resources, and that health policy targeting insurance coverage alone may be ineffective in resolving inequities in care.
Origins of Medical Innovation
Authors: Xu Shuai , Avorn Jerry , Kesselheim Aaron S.
Published: October 2012

Background—

Innovative medical devices make major contributions to patient welfare, and coronary stents have been among the most important device developments of recent decades. However, the origins of such breakthrough medical technologies remain poorly understood.

Methods and Results—

Using a comprehensive database of patents, we identified all individuals and institutions that developed intellectual property related to stent technology early in its development process. The patents were categorized and described using a predetermined qualitative coding strategy. We found 245 granted patents related to bare metal coronary artery stents from 1984 (when the first patent issued in this field) to 1994 (after the first stents were approved). Each year showed an increase in the number of patent filings: from 1 in 1984 to 97 in 1994. The largest fraction of patents was issued to private entities (44.9% of the total). Public companies, individual inventors, and nonprofit institutions represented 31.4%, 18.0%, and 5.7%, respectively. The top 10 most-cited patents in the field were dominated by 2 private entities, Expandable Grafts Partnership and Cook Inc, organizations created by or dependent on the work of independent academic physician-inventors.

Conclusions—

Coronary artery stent technology first arose from individual physician-inventors within academic medical centers and their associated private companies. After these initial innovations were in place, the field became dominated by large public companies. This history suggests that policies aimed at encouraging transformative medical device development would have their greatest effect if focused on individual inventors and scientists performing the early stages of technology development.