bluuebunny/crossref_metadata_2025 huggingface dataset:
Upper Bounds on Performance Measures of Heterogeneous M/M/c Queues
Authors: Alves F. S. Q. , Yehia H. C. , Pedrosa L. A. C. , Cruz F. R. B. , Kerbache Laoucine
Published: July 2011

In many real‐life queueing systems, the servers are often heterogeneous, namely they work at different rates. This paper provides a simple method to compute tight upper bounds on two important performance measures of single‐class heterogeneous multi‐server Markovian queueing systems, namely the average number in queue and the average waiting time in queue. This method is based on an expansion of the state space that is followed by an approximate reduction of the state space, only considering the most probable states. In most cases tested, we were able to approximate the actual behavior of the system with smaller errors than those obtained from traditional homogeneous multiserver Markovian queues, as shown by GPSS simulations. In addition, we have correlated the quality of the approximation with the degree of heterogeneity of the system, which was evaluated using its Gini index. Finally, we have shown that the bounds are robust and still useful, even considering quite different allocation strategies. A large number of simulation results show the accuracy of the proposed method that is better than that of classical homogeneous multiserver Markovian formulae in many situations.
Approximate Quartic and Quadratic Mappings in Quasi‐Banach Spaces
Authors: Gordji M. Eshaghi , Khodaei H. , Kim Hark-Mahn
Published: July 2011

we establish the general solution for a mixed type functional equation of aquartic and a quadratic mapping in linear spaces. In addition, we investigate the generalized Hyers‐Ulam stability in p‐Banach spaces.
Spectral Shifted Jacobi Tau and Collocation Methods for Solving Fifth‐Order Boundary Value Problems
Authors: Bhrawy A. H. , Alofi A. S. , El-Soubhy S. I.
Published: July 2011

We have presented an efficient spectral algorithm based on shifted Jacobi tau method of linear fifth‐order two‐point boundary value problems (BVPs). An approach that is implementing the shifted Jacobi tau method in combination with the shifted Jacobi collocation technique is introduced for the numerical solution of fifth‐order differential equations with variable coefficients. The main characteristic behind this approach is that it reduces such problems to those of solving a system of algebraic equations which greatly simplify the problem. Shifted Jacobi collocation method is developed for solving nonlinear fifth‐order BVPs. Numerical examples are performed to show the validity and applicability of the techniques. A comparison has been made with the existing results. The method is easy to implement and gives very accurate results.
A Note on the Generalized q‐Bernoulli Measures with Weight α
Authors: Kim T. , Lee S. H. , Dolgy D. V. , Ryoo C. S.
Published: July 2011

We discuss a new concept of the q‐extension of Bernoulli measure. From those measures, we derive some interesting properties on the generalized
q‐Bernoulli numbers with weight α attached to χ.
Immune Dysregulation after Cardiothoracic Surgery and Incidental Thymectomy: Maintenance of Regulatory T Cells despite Impaired Thymopoiesis
Authors: Halnon Nancy J. , Cooper Paige , Chen Diana Yu Hui , Boechat M. Ines , Uittenbogaart Christel H.
Published: July 2011

Thymectomy is performed in infants during cardiothoracic surgery leaving many patients with reduced thympopoiesis. An association between immune disorders and regulatory T cells (Treg) after incidental thymectomy has not been investigated. Questionnaires soliciting symptoms of atopic or autoimmune disease and biomarkers were measured in children and adults with congenital heart disease and either reduced or preserved thymopoiesis. Tregs were examined. Atopic or autoimmune-like symptoms and elevated anti-dsDNA antibodies were common after surgery in individuals with low thymopoiesis. Total Treg number and function were maintained but with fewer naïve Treg. TCR spectratypes were similar to other memory T cells. These data suggest that thymectomy does not reduce total Treg number but homeostasis is affected with reduced naïve Treg. Prevalence of autoimmune or atopic symptoms after surgery is not associated with total number or proportion of Tregs but appears to be due to otherwise unknown factors that may include altered Treg homeostasis.
Distance Traveled and Cross-State Commuting to Opioid Treatment Programs in the United States
Authors: Rosenblum Andrew , Cleland Charles M. , Fong Chunki , Kayman Deborah J. , Tempalski Barbara , Parrino Mark
Published: July 2011

This study examined commuting patterns among 23,141 methadone patients enrolling in 84 opioid treatment programs (OTPs) in the United States. Patients completed an anonymous one-page survey. A linear mixed model analysis was used to predict distance traveled to the OTP. More than half (60%) the patients traveled <10 miles and 6% travelled between 50 and 200 miles to attend an OTP; 8% travelled across a state border to attend an OTP. In the multivariate model (n=17,792), factors significantly (P<.05) associated with distance were, residing in the Southeast or Midwest, low urbanicity, area of the patient's ZIP code, younger age, non-Hispanic white race/ethnicity, prescription opioid abuse, and no heroin use. A significant number of OTP patients travel considerable distances to access treatment. To reduce obstacles to OTP access, policy makers and treatment providers should be alert to patients' commuting patterns and to factors associated with them.
A Reliable Event-Driven Strategy for Real-Time Multiple Object Tracking Using Static Cameras
Authors: Sarhan Amany M. , Saleh Ahmed I. , Elsadek Ramy K.
Published: July 2011

Recently, because of its importance in computer vision and surveillance systems, object tracking has progressed rapidly over the last two decades. Researches on such systems still face several theoretical and technical problems that badly impact not only the accuracy of position measurements but also the continuity of tracking. In this paper, a novel strategy for tracking multiple objects using static cameras is introduced, which can be used to grant a cheap, easy installation and robust tracking system. The proposed tracking strategy is based on scenes captured by a number of static video cameras. Each camera is attached to a workstation that analyzes its stream. All workstations are connected directly to the tracking server, which harmonizes the system, collects the data, and creates the output spatial-tempo database. Our contribution comes in two issues. The first is to present a new methodology for transforming the image coordinates of an object to its real coordinates. The second is to offer a flexible event-based object tracking strategy. The proposed tracking strategy has been tested over a CAD of soccer game environment. Preliminary experimental results show the robust performance of the proposed tracking strategy.
Bambusae caulisin Liquamen Suppresses the Expression of Thymus and Activation-Regulated Chemokine and Macrophage-Derived Chemokine in Human Keratinocytes due to Antioxidant Effect
Authors: Qi Xu-Feng , Kim Dong-Heui , Yoon Yang-Suk , Song Soon-Bong , Teng Yung-Chien , Cai Dong-Qing , Lee Kyu-Jae
Published: July 2011

Bambusae caulisin Liquamen (BCL), traditional herbal medicine used in East Asia, is known to have antioxidative and immune-regulating properties. We hypothesized that the potential antioxidant effects of BCL might suppress the production of thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in human keratinocytes (HaCaT cell). The immune-regulating effect of BCL was demonstrated by antioxidant capacity using DPPH analysis and DCFH-DA analysis. We found that BCL had strong ROS scavenge effect in HaCaT cell. BCL also showed suppression of IFN-γ-induced expression of TARC and MDC, activation of NF-κB, and, moreover, significant block of IFN-γ-induced degradation and phosphorylation of IκB. However, it had no effects on phosphorylation of p38 MAPK. Collectively, these results suggest that BCL may have a therapeutic potential on skin disease such as atopic dermatitis by inhibiting Th2 chemokines which is due, at least in part, to its antioxidant capacities.
Immunoregulatory Molecule B7-H1 (CD274) Contributes to Skin Carcinogenesis
Authors: Cao Yujia , Zhang Lu , Ritprajak Pacharee , Tsushima Fumihiko , Youngnak-Piboonratanakit Pornpan , Kamimura Yosuke , Hashiguchi Masaaki , Azuma Miyuki
Published: July 2011

B7-H1 (CD274), a member of the B7 family of coinhibitory molecules, is often induced in human tumors and its expression is closely correlated with a poor prognosis or higher malignancy grade. Tumor-associated B7-H1 is implicated in mechanisms of immune escape. Under inflammatory conditions, B7-H1 is also inducible in normal epithelial cells, but little is known about its involvement in the conversion of normal cells to tumor cells. We recently found that skin-specific expression of B7-H1 accelerates chemically induced carcinogenesis of squamous cell carcinoma (SCC), despite impaired skin inflammatory responses, in B7-H1 transgenic (B7-H1tg) mice. B7-H1tg–derived keratinocytes (KC) and SCCs exhibited a marked reduction of E-cadherin, and B7-H1tg–originated SCCs showed elevated expression of the transcription factors Slug and Twist, suggesting that B7-H1 overexpression in KCs promotes the epithelial–mesenchymal transition and accelerates carcinogenesis. This review discusses the diverse functions of B7-H1 in carcinogenesis and cancer progression, and considers future directions for developing cancer therapy targeting B7-H1. Cancer Res; 71(14); 4737–41. ©2011 AACR.
Apoptotic Role of IKK in T-ALL Therapeutic Response
Authors: Riz Irene , Zweier-Renn Lynnsey A. , Toma Ian , Hawley Teresa S. , Hawley Robert G.
Published: July 2011

Despite considerable progress in the treatment of T cell acute lymphoblastic leukemia (T-ALL), it is still the highest risk malignancy among ALL. The outcome of relapsed patients remains dismal. The pro-survival role of NOTCH1 and NFκB in T-ALL is well documented; also, both factors were reported to be predictive of relapse. The NOTCH1 signaling pathway, commonly activated in T-ALL, was shown to enhance the transcriptional function of NFκB via several mechanisms. Thus, pharmacological inhibition of NOTCH1-NFκB signaling was suggested to be incorporated into existing T-ALL treatment protocols. However, conventional chemotherapy is based on activation of various types of stress, such as DNA damage, mitotic perturbations or endoplasmic reticulum overload. NFκB is frequently activated in response to stress and, depending on yet unknown mechanisms, it either protects cells from the drug action or mediates apoptosis. Here, we report that T-ALL cells respond to NFκB inhibition in opposite ways depending on whether they were treated with a stress-inducing chemotherapeutic agent or not. Moreover, we found that NOTCH1 enhances NFκB apoptotic function in the stressed cells. The data argue for further studies of NFκB status in T-ALL patients on different treatment protocols and the impact of activating NOTCH1 mutations on treatment response. Mol Cancer Res; 9(8); 979–84. ©2011 AACR.
A DNA Vaccine against ERBB2 Impairs Chemical Carcinogenesis in Random-Bred Hamsters
Authors: Berta Giovanni N. , Sprio Andrea E. , Iezzi Manuela , Spadaro Michela , Cappia Susanna , Salamone Paolina , Di Scipio Federica , Mognetti Barbara , Papotti Mauro , Musiani Piero , Forni Guido , Cavallo Federica
Published: July 2011

Vaccines against oncoantigens halt early neoplastic lesions in several cancer-prone, genetically engineered mouse models, whereas their ability to prevent chemical carcinogenesis has not been explored. This is a significant issue, as exposure to chemical mutagens is responsible for a substantial percentage of cancers worldwide. Here, we show that the archetypal oncoantigen ERBB2 is transiently overexpressed in Syrian hamsters during the early stages of 7,12-dimethylbenz[α]anthracene (DMBA)-induced oral carcinogenesis. Repeated DNA vaccinations against ERBB2 significantly reduce the number, size, and severity of oral lesions in a manner directly proportional to the anti-ERBB2 antibody response. These results support the prospects of vaccines as a fresh strategy in the management of individuals at risk for exposure to defined carcinogenic agents. Cancer Prev Res; 4(7); 994–1001. ©2011 AACR.
EarlyCDT-Lung: An Immunobiomarker Test as an Aid to Early Detection of Lung Cancer
Authors: Lam Stephen , Boyle Peter , Healey Graham F. , Maddison Paul , Peek Laura , Murray Andrea , Chapman Caroline J. , Allen Jared , Wood William C. , Sewell Herb F. , Robertson John F.R.
Published: July 2011

Recent publications have reported the technical and clinical validation of EarlyCDT-Lung, an autoantibody test which detected elevated autoantibodies in 40% of lung cancers at diagnosis. This manuscript reports the results of EarlyCDT-Lung run on four new (postvalidation) data sets. The following four cohorts of patients (n = 574) with newly diagnosed lung cancer were identified: group 1 (n = 122), 100% small cell lung cancer (SCLC); group 2 (n = 249), 97% non-small cell lung cancer (NSCLC); group 3 (n = 122), 100% NSCLC; group 4 (n = 81), 62% NSCLC. Serum samples were obtained after diagnosis, prior to any anticancer treatment. Autoantibody levels were measured against a panel of six tumor-related antigens (p53, NY-ESO-1, CAGE, GBU4–5, Annexin 1, and SOX2) in the EarlyCDT-Lung panel and previously established cutoffs applied. In groups 2, 3, and 4, patients were individually matched by gender, age, and smoking history to a control individual with no history of malignant disease. Assay sensitivity was tested in relation to cancer type and stage, and in the matched normals to demographic variables. The autoantibody panel showed sensitivity/specificity of 57%/n.d (not done) for SCLC in group 1, 34%/87% for NSCLC in group 2, 31% and 84% for NSCLC in group 3, and 35%/89% for NSCLC and 43%/89% for SCLC in group 4. There was no significant difference in positivity of EarlyCDT-Lung and different lung cancer stages. These studies confirm the value of an autoantibody assay, EarlyCDT-Lung, as an aid to detecting lung cancer in patients at high risk of the disease. Cancer Prev Res; 4(7); 1126–34. ©2011 AACR.
Decreased Prostate Cancer-Specific Survival of Men with BRCA2 Mutations from Multiple Breast Cancer Families
Authors: Thorne Heather , Willems Amber J. , Niedermayr Eveline , Hoh Ivan M.Y. , Li Jason , Clouston David , Mitchell Gillian , Fox Stephen , Hopper John L. ,   on behalf of the Kathleen Cunningham Consortium for Research in Familial Breast Cancer Consortium (kConFab), Bolton Damien
Published: July 2011

The role of a germ-line BRCA2 mutation in the development of prostate cancer is established, but the clinical presentation linked to outcome for this group of men has not been well described.

A total of 148 men from 1,423 families were ascertained from the kConFab consortium. Each participant met the following criteria: (i) a verified case of prostate cancer; (ii) confirmed as either a carrier or noncarrier of a family-specific BRCA pathogenic mutation; (iii) comprehensive clinical and treatment data were available. Clinical data were linked to treatment received and overall survival was analyzed by Kaplan–Meier.

Prostate cancer in men from breast cancer-prone families has a high risk of disease progression, irrespective of mutation status. BRCA2 mutation carriers have an increased risk of death and prostate cancer-related death [HR (95% CI) 4.5 (2.12–9.52), P = 8.9 × 10−5] by comparison with noncarriers. Serum PSA readings taken prior to diagnosis in 90% of all men, age adjusted, were above clinical significance. Following D'Amico risk stratification, 77.5% of BRCA2 mutation carriers and 58.7% of noncarriers had high-risk disease. BRCA2 mutation status was also an independent prognostic indicator of overall survival. Furthermore, there was a poor overall survival outcome for both the BRCA2 mutation carriers and noncarriers given curative-intent treatment.

All men in breast cancer-prone families are at risk of developing aggressive prostate cancer. This information is significant and should be included in discussions with genetic counselors and medical professionals when discussing prostate cancer treatment options for men in these families, irrespective of mutation status. Cancer Prev Res; 4(7); 1002–10. ©2011 AACR.
The BATTLE to Personalize Lung Cancer Prevention through Reverse Migration
Authors: Gold Kathryn A. , Kim Edward S. , Lee J. Jack , Wistuba Ignacio I. , Farhangfar Carol J. , Hong Waun Ki
Published: July 2011

Agents can enter clinical development for cancer prevention either initially or after previous development for a different indication, such as arthritis, with both approaches consuming many years of development before an agent is fully evaluated for cancer prevention. We propose the following, third approach: reverse migration, that is, importing agents, targets, and study designs to personalize interventions and concepts developed in advanced cancer to the setting of cancer prevention. Importing these “ready-made” features from therapy will allow reverse migration to streamline preventive agent development. We recently reported the Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial of personalized lung cancer therapy and now propose the reverse migration development of personalized lung cancer prevention based on the BATTLE model. Cancer Prev Res; 4(7); 962–72. ©2011 AACR.
Cancer Vaccines: Moving toward Prevention?
Authors: Kwak Larry W.
Published: July 2011

After several decades of research, recent successful phase III controlled clinical trials have renewed enthusiasm for vaccine treatment of cancer. This perspective on the report by Berta and colleagues in this issue of the journal (beginning on page 994) discusses the potential prevention of oral cancer through vaccine strategies and, in the broader context, ideal characteristics of tumor antigens as candidates for vaccines for both treating and preventing cancer, potential primary and secondary prevention settings for vaccines, desirable types of immune effectors induced by vaccines, and safety. Cancer Prev Res; 4(7); 954–6. ©2011 AACR.
The Dawn of a Revolution in Personalized Lung Cancer Prevention
Authors: Khuri Fadlo R.
Published: July 2011

Lung cancer prevention and early detection, which have fallen on hard times for more than the past 20 years, seem to have turned a corner toward better times ahead. Exciting new results of randomized controlled trials that targeted the arachidonic acid pathway, including a celecoxib trial reported by Mao and colleagues in this issue of the journal (beginning on page 984) and a trial of the prostacyclin analog iloprost, complement recently reported 20%–30% lung cancer mortality reductions, either with aspirin in targeting the arachidonic acid pathway or with computed tomography screening. The new results show encouraging activity personalized to former smokers and/or people expressing predictive biomarkers. These trials and technological advances in molecular profiling and imaging herald substantial clinical advances on the horizon of this field. Cancer Prev Res; 4(7); 949–53. ©2011 AACR.
Genome-Wide Linkage Analysis to Identify Genetic Modifiers of ALK Mutation Penetrance in Familial Neuroblastoma
Authors: Devoto Marcella , Specchia Claudia , Laudenslager Marci , Longo Luca , Hakonarson Hakon , Maris John , Mossé Yael
Published: July 2011

Background: Neuroblastoma (NB) is an important childhood cancer with a strong genetic component related to disease susceptibility. Approximately 1% of NB cases have a positive family history. Following a genome-wide linkage analysis and sequencing of candidate genes in the critical region, we identified ALK as the major familial NB gene. Dominant mutations in ALK are found in more than 50% of familial NB cases. However, in the families used for the linkage study, only about 50% of carriers of ALK mutations are affected by NB. Methods: To test whether genetic variation may explain the reduced penetrance of the disease phenotype, we analyzed genome-wide genotype data in ALK mutation-positive families using a model-based linkage approach with different liability classes for carriers and non-carriers of ALK mutations. Results: The region with the highest LOD score was located at chromosome 2p23–p24 and included the ALK locus under models of dominant and recessive inheritance. Conclusions: This finding suggests that variants in the non-mutated ALK gene or another gene linked to it may affect penetrance of the ALK mutations and risk of developing NB in familial cases.
Ego Disturbances in the Sense of Kurt Schneider: Historical and Phenomenological Aspects
Authors: Bürgy Martin
Published: July 2011

The phenomena which were grouped together by Kurt Schneider to constitute the ego disturbances have always been of particular diagnostic relevance for schizophrenia. The manner in which these symptoms are described and distinguished from other psychopathological symptoms has generally been rather imprecise. The introduction of phenomenological methods into the field of psychiatry led to considerable improvements in symptom descriptions and to a clearer distinction between psychotic and nonpsychotic experience. Continued developments in phenomenology have further incorporated aspects of schizophrenic symptom development and in doing so have brought so-called transitional phenomena and the core schizophrenic syndrome into focus. The ego disturbances accordingly appear to stem from a particular form of depersonalization which is described as a modified sense of mineness and which can be distinguished from the neurotic experience of depersonalization.
Treatment of Alice in Wonderland Syndrome and Verbal Auditory Hallucinations Using Repetitive Transcranial Magnetic Stimulation: A Case Report with fMRI Findings
Authors: Blom Jan Dirk , Looijestijn Jasper , Goekoop Rutger , Diederen Kelly M.J. , Rijkaart Anne-Marije , Slotema Christina W. , Sommer Iris E.C.
Published: July 2011

Background: Alice in Wonderland syndrome (AIWS) is a rare cluster of CNS symptoms characterized by visual distortions (i.e. metamorphopsias), body image distortions, time distortions, and déjà experiences. Verbal auditory hallucinations (VAHs) are the most prevalent type of hallucination in adults with or without a history of psychiatric illness. Here, we report the case of a woman with AIWS, long-lasting VAHs, and various additional perceptual and mood symptoms. Methods: Semi-structured interviews were used to assess symptoms, and functional MRI (fMRI) was employed to localize cerebral activity during self-reported VAHs. Treatment consisted of repetitive transcranial magnetic stimulation (rTMS) at a frequency of 1 Hz at T3P3, overlying Brodmann’s area 40. Results: Activation during VAHs was observed bilaterally in the basal ganglia, the primary auditory cortex, the association auditory cortex, the temporal poles, and the anterior cingulated gyrus. The left and right inferior frontal gyri (Broca’s area and its contralateral homologue) were involved, along with the dorsolateral prefrontal cortex. Interestingly, synchronized activation was observed in the primary visual cortex (areas V1 and V2), and the bilateral dorsal visual cortex. The higher visual association cortex also showed significant, but less prominent, activation. During the second week of rTMS treatment, not only the VAHs, but also the other sensory deceptions/distortions and mood symptoms showed complete remission. The patient remained free of any symptoms during a 4-month follow-up phase. After 8 months, when many of the original symptoms had returned, a second treatment phase with rTMS was again followed by complete remission. Conclusions: This case indicates that VAHs and metamorphopsias in AIWS are associated with synchronized activation in both auditory and visual cortices. It also indicates that local rTMS treatment may have global therapeutic effects, suggesting an effect on multiple brain regions in a distributed network. Although a placebo effect cannot be ruled out, this case warrants further investigation of the effects of rTMS treatment in AIWS.
Hypertonic Stress Promotes the Upregulation and Phosphorylation of Zonula Occludens 1
Authors: Then Cornelia , Bergler Tobias , Jeblick Roland , Jung Bettina , Banas Bernhard , Krämer Bernhard K.
Published: July 2011

Tight junction molecules form a barrier between adjacent cells and mediate the cells’ ability to develop membranes that constitute boundaries of different compartments within the body. Membranes with selective ion and water passage are important for the electrolyte and water homeostasis in the kidney. Due to their role in the urinary concentration process, renal medullary cells are exposed to hyperosmotic stress. Therefore, we were interested in the question of how mouse inner medullary collecting duct cells (mIMCD3) manage to maintain their cell-cell contacts, despite hypertonicity-induced cell shrinkage. Employing mRNA expression analysis, we found that the zonula occludens type 1 (Zo-1), multi-PDZ domain protein 1 (MUPP1) and cortactin mRNA levels were upregulated in a tonicity-dependent manner. Using Western blot analysis, immunoprecipitation and immunofluorescence, we show that the Zo-1 protein is upregulated, phosphorylated and linked to the actin cytoskeleton in response to hypertonic stress. After cell exposure to hypertonicity, rearrangement of the actin cytoskeleton resulted in a stronger colocalization of actin fibres with Zo-1. Urea, which generates hyperosmolality, but no transcellular gradient, did not induce changes in Zo-1 protein expression or actin rearrangement. This data indicates that Zo-1 is a response protein to inner medullary tonicity and that extracellular stressors can promote Zo-1 protein expression, tyrosine phosphorylation and cytoskeleton association.
Efficacy of Noninvasive Positive Pressure Ventilation in Elderly Patients with Acute Hypercapnic Respiratory Failure
Authors: Kida Yohei , Minakata Yoshiaki , Yamada Yoichi , Ichinose Masakazu
Published: July 2011

Background: There have been no reports on the efficacy of noninvasive positive pressure ventilation (NPPV) in elderly patients. Objectives: The purpose of this study was to clarify the efficacy and identify the predictors of a successful outcome of NPPV in patients over the age of 75 years with acute hypercapnic respiratory failure (AHRF). Methods: We retrospectively evaluated the data of 42 patients (21 men) with AHRF who were treated at our unit. The patients were divided into survivor and nonsurvivor groups, and the clinical parameters measured prior to the initiation of NPPV were compared between the 2 groups. Results: The mean age of the patients was 83.0 ± 6.3 years. The etiology of the respiratory failure was acute exacerbation of chronic obstructive pulmonary disease in 19 patients, acute cardiogenic pulmonary edema in 18 patients, idiopathic pulmonary fibrosis in 3 patients, sequelae of tuberculosis in 1 patient, and asthma in 1 patient. Of the 42 patients, 33 (78.6%) survived. All patients with a Glasgow Coma Scale (GCS) score ≥9 and/or an APACHE II score <29 survived after the initiation of NPPV. Conclusion: An APACHE II score <29 and a GCS score ≥9 were predictors of a successful outcome of NPPV in elderly people.
Expression of Keratin 19 Is Related to High Recurrence of Hepatocellular Carcinoma after Radiofrequency Ablation
Authors: Tsuchiya Kaoru , Komuta Mina , Yasui Yutaka , Tamaki Nobuharu , Hosokawa Takanori , Ueda Ken , Kuzuya Teiji , Itakura Jun , Nakanishi Hiroyuki , Takahashi Yuka , Kurosaki Masayuki , Asahina Yasuhiro , Enomoto Nobuyuki , Sakamoto Michiie , Izumi Namiki
Published: July 2011

Objective: Keratin (K) 19 positivity has been reported to be a useful predictive marker for recurrence in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection. We investigated the clinical usefulness of K19 positivity in patients who had received curative radiofrequency ablation (RFA). Methods: We retrospectively evaluated the clinicopathological features, including imaging and K19 expression, in 246 patients with HCC who were within the Milan criteria and had received curative RFA. Using a two-step insertion method, tumor biopsies were obtained just prior to RFA and were evaluated histologically. Results: Tumor seeding due to liver biopsy and RFA was not observed. Ten patients (4.1%) had K19-positive HCC. Imaging findings were similar between K19-positive and -negative HCC (p = 0.187). Nine out of 10 patients (90%) who had K19-positive HCC had recurrence of HCC after RFA, and intrahepatic recurrences were observed within 12 months in 6 out of 10 (60.0%). K19 positivity was a significant risk factor for recurrence (p < 0.0001) and early recurrence (<1 year after RFA; p =0.012). K19 expression (p = 0.016) was an independent risk factor for tumor status exceeding the Milan criteria after RFA. Conclusion: Expression of K19 is related to high recurrence of HCC after curative RFA.
Neuropsychological Correlates of the Proportional Impact of White Matter Hyperintensities on Mild to Moderate Dementia: The MRI 300 Study
Authors: Ku Bon D. , Na Duk L. , Moon So Young , Kim Seong Yoon , Seo Sang Won , Cheong Hae-Kwan , Park Kyung Won , Park Kee Hyung , Lee Jun-Young , Cha Kyung Ryeol , Shim Yong S. , Youn Young Chul , Chung Chan-Seung , Kim Jung Eun , Kang Hee Young , Kim Sang Yun , Choi Seong Hye , Han Seol-Heui
Published: July 2011

Background: White matter hyperintensities (WMH) increase cognitive impairment in patients with dementia. Objective: We investigated the impact of WMH on the neuropsychological profiles in patients with mild to moderate dementia. Methods: We consecutively recruited newly diagnosed patients with mild to moderate dementia across South Korea for 1 year. The participants completed neuropsychological tests, magnetic resonance imaging, and structured neurological evaluations. The patients were divided into 3 categories, i.e. minimal, moderate, and severe WMH groups, according to the proportional degree of WMH. Results: 289 patients were recruited; 140 (48.3%) for the minimal WMH group, 99 (34.2%) for the moderate group, and 50 (17.5%) for the severe group. Both advanced age and low general cognitive level were significant contributors to WMH in patients with dementia. After adjusting for age, the neuropsychological correlates of the proportional impact of WMH were frontal executive, language, and attention profiles. However, the only significant neuropsychological correlate was the recognition memory profile after adjusting for both age and general cognitive level simultaneously. Conclusion: The results suggest that the most significant neuropsychological profile impacting the burden of WMH in patients with mild to moderate dementia was the recognition memory profile, regardless of age and general cognitive function.
Subjective Evaluation of Voice and Working Conditions and Phoniatric Examination in Kindergarten Teachers
Authors: Kankare E. , Geneid A. , Laukkanen A.-M. , Vilkman E.
Published: July 2011

Aims: This study evaluated the prevalence of voice problems in kindergarten teachers and investigated some background factors affecting vocal health. Methods: One hundred and nineteen female kindergarten teachers volunteered by responding to an Internet questionnaire on voice habits, voice symptoms, and the amount of negative impact various working conditions may have on their voices. Phoniatric examination was carried out with a rigid laryngoscope. Results: Of the subjects, 71.5% reported frequent strain on the voice (monthly or more often), and 56.3% reported hoarseness without infection. Eighty-six percent reported that when their voice got tired during the working day it recovered quite well, well or remarkably well by the next day. Noise at work was considered most detrimental to the voice. Clear organic findings were observed in 10.9% of the cases and did not correlate with subjective voice symptoms. Conclusions: The results confirmed earlier findings that a remarkable number of kindergarten teachers suffer from voice problems and consider noise in the environment especially to be harmful to their voices. However, the majority reported recovering well from vocal symptoms. Further studies are needed on individual speech habits, working day-related voice evaluation, recovery time and work-environmental factors. A follow-up is warranted to identify the main factors leading to voice problems.
High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients
Authors: Lee Soo Hyeon , Chang Myung Hee , Baek Kyung Kee , Han Boram , Lim Taekyu , Lee Jeeyun , Park Joon Oh
Published: July 2011

Introduction: For patients with refractory bone and soft tissue sarcoma (STS), treatment options have been limited. Ifosfamide is an alkylating agent with well-demonstrated efficacy against STS, and dose-dependent activity. The aim of this retrospective study was to evaluate the response rate, progression-free survival (PFS), progression-free rate (PFR), and median duration of response to high-dose ifosfamide (HDI) as at least second-line chemotherapy for patients with advanced bone sarcoma and STS. Patients and Methods: Thirty metastatic, unresectable sarcoma patients who were treated with HDI chemotherapy between May 1999 and November 2007 were included in the analysis. In total, 106 cycles (median 3 cycles; range 1–8 cycles) were administered. Twenty-one patients received treatment as second-line chemotherapy, and 9 patients as third-line treatment. HDI was given at a dose of 2 g/m2 over 3 h, and at a dose of 2 g/m2 per day; continuous infusion was administered on 6 consecutive days (2 g/m2/6 days) every 3 weeks. Results: After a median follow-up of 49 months (range 10–114), median PFS was 2.9 months (range 0.4–9.3) and median overall survival 8.7 months (range 0.4–57.8). The 3- and 6-month PFR were 47% (SE 9.1%) and 20% (SE 7.3%), respectively. Median response duration of HDI was 2.9 months (range 0.7–7.6). Of the 28 evaluable patients, 2 (7%) achieved complete response, 5 (18%) partial response, and 4 (14%) stable disease, and overall disease control was 39%. Two responders out of 7 (28.5%) and 4 patients out of 11 (36%) with controlled disease by HDI had a synovial sarcoma. Two patients were not evaluable because they were switched to another treatment due to ifosfamide-induced encephalopathy. Grade 3–4 neutropenia was seen in 13 (43%) patients, and treatment-related death was observed in one patient. Conclusion: HDI at a total dose of 14 g/m2 with mesna is still an active salvage regimen, particularly in patients with synovial sarcomas.
A Dimension Reduction Approach for Modeling Multi-Locus Interaction in Case-Control Studies
Authors: Basu Saonli , Pan Wei , Oetting William S.
Published: July 2011

Studying one locus or one single nucleotide polymorphism (SNP) at a time may not be sufficient to understand complex diseases because they are unlikely to result from the effect of only one SNP. Each SNP alone may have little or no effect on the risk of the disease, but together they may increase the risk substantially. Analyses focusing on individual SNPs ignore the possibility of interaction among SNPs. In this paper, we propose a parsimonious model to assess the joint effect of a group of SNPs in a case-control study. The model implements a data reduction strategy within a likelihood framework and uses a test to assess the statistical significance of the effect of the group of SNPs on the binary trait. The primary advantage of the proposed approach is that the dimension reduction technique produces a test statistic with degrees of freedom significantly lower than a multiple logistic regression with only main effects of the SNPs, and our parsimonious model can incorporate the possibility of interaction among the SNPs. Moreover, the proposed approach estimates the direction of association of each SNP with the disease and provides an estimate of the average effect of the group of SNPs positively and negatively associated with the disease in the given SNP set. We illustrate the proposed model on simulated and real data, and compare its performance with a few other existing approaches. Our proposed approach appeared to outperform the other approaches for independent SNPs in our simulation studies.
Immunochemistry and Lung Cancer: Application in Diagnosis, Prognosis and Targeted Therapy
Authors: Nanguzgambo Aldoph B. , Razack Rubina , Louw Mercia , Bolliger Chris T.
Published: July 2011

Immunochemistry is now an established ancillary technique in lung cancer diagnosis. Not only does it help in supporting the morphological diagnosis of malignancy, but its role now extends to the determination of cell lineage, ascertaining the primary site of tumour origin and contributing to decisions on prognosis and treatment. Early detection and confirmation of lung cancer facilitate early treatment decisions. Lung cancer management now has a multidisciplinary approach which includes cytopathologists and clinicians. Some clinicians may not understand what immunochemistry is and what its role is in lung cancer diagnosis, prognosis and therapy. The purpose of this paper is to define immunochemistry, on the background of basic respiratory airway epithelial structure and cancer biology, and discuss its application in the diagnosis, treatment and determination of prognosis of lung cancer.
Final Results of ERASME-4: A Randomized Trial of First-Line Docetaxel plus either Capecitabine or Epirubicin for Metastatic Breast Cancer
Authors: Bachelot Thomas , Bajard Agathe , Ray-Coquard Isabelle , Provencal Jocelyne , Coeffic David , Agostini Cécile , Boisseau Martial , Kaphan Régis , Dramais Dominique , Oprea Corina , Ferri-Dessens Rose-Marie , Guastalla Jean-Paul , Perol David
Published: July 2011

Objective: To assess the efficacy of capecitabine plus docetaxel (XT) versus epirubicin plus docetaxel (ET) as first-line therapy for metastatic breast cancer (MBC). Patients and Methods: Patients with no prior chemotherapy for MBC were randomized to 3-weekly cycles of either XT (capecitabine 1,000 mg/m2 twice daily, days 1–14; docetaxel 75 mg/m2, day 1) or ET (epirubicin 75 mg/m2, day 1; docetaxel 75 mg/m2, day 1). The primary endpoint was non-progression rate 6 months after randomization. The planned sample size was 106 patients based on a randomized, phase II selection design. Results: Between April 2004 and January 2007, 68 patients were randomized, giving 82% power to select the best regimen according to a 6-month non-progression rate. Slow accrual led to premature study termination. Baseline characteristics were generally well balanced between arms. The 6-month non-progression rates were 75.8% with XT versus 65.7% with ET (p = 0.36). After 42 months’ median follow-up, median progression-free survival was 12.4 versus 6.8 months, respectively (p = 0.040). The safety profiles were consistent with previous experience. Conclusion: Further larger studies are warranted to validate these results. Despite more grade 3 hand-foot syndrome, first-line XT may be a valid alternative to ET, potentially improving efficacy.
Neural Correlates of Stroop Performance in Alzheimer’s Disease: A FDG-PET Study
Authors: Yun Je-Yeon , Lee Dong Young , Seo Eun Hyun , Choo Il Han , Park Shin Young , Kim Shin Gyeom , Woo Jong In
Published: July 2011

Background/Aims: The Stroop test is commonly applied in elderly subjects for the evaluation of cognitive impairment related to Alzheimer’s disease (AD) and related disorders. This study aimed to investigate the functional neural correlates of the Stroop performance in AD. Methods: In 136 probable AD patients and 54 cognitively normal elderly, a [18F]-fluorodeoxyglucose positron emission tomography scan and Stroop Color Word Test (SCWT) were performed. The correlations between the Stroop effect, which was measured by 6 different scoring methods, and regional cerebral glucose metabolism (rCMglc) were explored using a region-of-interest (ROI) approach and voxel-based analysis. Results: Among 6 Stroop interference measures, only 2 scores, including the SCWT color-word (CW) score, were significantly correlated with rCMglc of the dorsolateral prefrontal and anterior cingulate ROIs. Voxel-based analysis revealed significant positive correlations between SCWT CW scores and rCMglc in the inferior parietal lobule, middle temporal gyrus and middle frontal gyrus. Such correlations remained significant only in the less severe AD group. Conclusion: In AD patients, the Stroop effect depends on the functional integrity of the prefrontal cortices. Some parietotemporal regions also appear to be responsible for the Stroop effect in AD individuals.
Diagnostic Value of Vena Contracta Area in the Quantification of Mitral Regurgitation Severity by Color Doppler 3D Echocardiography
Authors: Zeng Xin , Levine Robert A. , Hua Lanqi , Morris Eleanor L. , Kang Yuejian , Flaherty Mary , Morgan Nina V. , Hung Judy
Published: July 2011

Background—

Accurate quantification of mitral regurgitation (MR) is important for patient treatment and prognosis. Three-dimensional echocardiography allows for the direct measure of the regurgitant orifice area (ROA) by 3D-guided planimetry of the vena contracta area (VCA). We aimed to (1) establish 3D VCA ranges and cutoff values for MR grading, using the American Society of Echocardiography–recommended 2D integrative method as a reference, and (2) compare 2D and 3D methods of ROA to establish a common calibration for MR grading.

Methods and Results—

Eighty-three patients with at least mild MR underwent 2D and 3D echocardiography. Direct planimetry of VCA was performed by 3D echocardiography. Two-dimensional quantification of MR included 2D ROA by proximal isovelocity surface area (PISA) method, vena contracta width, and ratio of jet area to left atrial area. There were significant differences in 3D VCA among patients with different MR grades. As assessed by receiver operating characteristic analysis, 3D VCA at a best cutoff value of 0.41 cm
2
yielded 97% of sensitivity and 82% of specificity to differentiate moderate from severe MR. There was significant difference between 2D ROA and 3D VCA in patients with functional MR, resulting in an underestimation of ROA by 2D PISA method by 27% as compared with 3D VCA. Multivariable regression analysis showed functional MR as etiology was the only predictor of underestimation of ROA by the 2D PISA method.

Conclusions—

Three-dimensional VCA provides a single, directly visualized, and reliable measurement of ROA, which classifies MR severity comparable to current clinical practice using the American Society of Echocardiography–recommended 2D integrative method. The 3D VCA method improves accuracy of MR grading compared with the 2D PISA method by eliminating geometric and flow assumptions, allowing for uniform clinical grading cutoffs and ranges that apply regardless of etiology and orifice shape.
Echocardiographic Evaluation Before Bidirectional Glenn Operation in Functional Single-Ventricle Heart Disease
Authors: Stern Kenan W.D. , McElhinney Doff B. , Gauvreau Kimberlee , Geva Tal , Brown David W.
Published: July 2011

Background—

Cardiac catheterization is routinely performed in patients with single ventricle before bidirectional Glenn operation (BDG). There is interest in noninvasive evaluation alone before BDG, but concern for echocardiography successfully imaging the relevant anatomy persists. We evaluated the accuracy of echocardiographic imaging of vascular anatomy.

Methods and Results—

Diagnostic images of 130 patients who had echocardiography and catheterization before BDG were reviewed; diameters of the pulmonary arteries (PAs) and aortic arch were measured, and stenoses were recorded. Patient and procedural factors associated with echocardiographic imaging were analyzed. Median age at echocardiography was 4 months; the most common diagnosis was hypoplastic left heart syndrome (55%). The left PA was imaged by echocardiography in 83 patients (64%), with 4 of 21 stenoses (19%) diagnosed by catheterization identified; similarly, the right PA was imaged in 81 (62%), and 3 of 17 stenoses (18%) were identified. The distal aortic arch was visualized in 104 (80%), with successful identification of 21 of 27 (78%) of coarctations diagnosed by catheterization. Complete vascular echocardiography (visualization of PAs and aortic arch) occurred in 43% and was not obtained more frequently with sedation.

Conclusions—

In a large cohort of patients presenting for BDG, evaluation by echocardiography frequently failed to image the PAs and missed the majority of PA stenoses. Sedation did not appear to improve the performance of echocardiography for evaluation of the PAs. Echocardiography cannot be relied on as the sole investigation before BDG.
Protein Kinase D2 Controls Cardiac Valve Formation in Zebrafish by Regulating Histone Deacetylase 5 Activity
Authors: Just Steffen , Berger Ina M. , Meder Benjamin , Backs Johannes , Keller Andreas , Marquart Sabine , Frese Karen , Patzel Eva , Rauch Gerd-Jörg ,   Tübingen 2000 Screen Consortium, Katus Hugo A. , Rottbauer Wolfgang
Published: July 2011

Background—

The molecular mechanisms that guide heart valve formation are not well understood. However, elucidation of the genetic basis of congenital heart disease is one of the prerequisites for the development of tissue-engineered heart valves.

Methods and Results—

We isolated here a mutation in zebrafish,
bungee
(

bng
jh177

), which selectively perturbs valve formation in the embryonic heart by abrogating endocardial Notch signaling in cardiac cushions. We found by positional cloning that the
bng
phenotype is caused by a missense mutation (Y849N) in zebrafish
protein kinase D2
(
pkd2
). The
bng
mutation selectively impairs PKD2 kinase activity and hence Histone deacetylase 5 phosphorylation, nuclear export, and inactivation. As a result, the expression of Histone deacetylase 5 target genes Krüppel-like factor 2a and 4a, transcription factors known to be pivotal for heart valve formation and to act upstream of Notch signaling, is severely downregulated in
bungee
(
bng
) mutant embryos. Accordingly, the expression of Notch target genes, such as Hey1, Hey2, and HeyL, is severely decreased in
bng
mutant embryos. Remarkably, downregulation of Histone deacetylase 5 activity in homozygous
bng
mutant embryos can rescue the mutant phenotype and reconstitutes
notch1b
expression in atrioventricular endocardial cells.

Conclusions—

We demonstrate for the first time that proper heart valve formation critically depends on Protein kinase D2-Histone deacetylase 5-Krüppel-like factor signaling.