bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of p-STAT3 Enhances IFN-α Efficacy against Metastatic Melanoma in a Murine Model
Authors: Kong Ling-Yuan , Gelbard Alexander , Wei Jun , Reina-Ortiz Chantal , Wang Yongtao , Yang Eric C. , Hailemichael Yared , Fokt Izabela , Jayakumar Arumugam , Qiao Wei , Fuller Gregory N. , Overwijk Willem W. , Priebe Waldemar , Heimberger Amy B.
Published: April 2010

Purpose: Melanoma is a common and deadly tumor that upon metastasis to the central nervous system has a median survival duration of <6 months. Activation of the signal transducer and activator of transcription 3 (STAT3) has been identified as a key mediator that drives the fundamental components of melanoma malignancy, including immune suppression in melanoma patients. We hypothesized that WP1193, a novel inhibitor of STAT3 signaling, would enhance the antitumor activity of IFN-α against metastatic melanoma.

Experimental Design: Combinational therapy of STAT3 blockade agents with IFN-α was investigated in a metastatic and an established syngeneic intracerebral murine tumor model of melanoma. The immunologic in vivo mechanisms of efficacy were investigated by T-cell and natural killer (NK) cell cytotoxic assays.

Results: IFN-α immunotherapy was synergistic with WP1193 showing marked in vivo efficacy against metastatic and established intracerebral melanoma. At autopsy, it was noted that there was a decreased trend in mice with melanoma developing leptomeningeal disease treated with combinational therapy. The combinational approach enhanced both NK-mediated and T-cell–mediated antitumor cytotoxicity.

Conclusions: The immune modulatory effects of STAT3 blockade can enhance the therapeutic efficacy of IFN-α immunotherapy by enhancing both innate and adaptive cytotoxic T-cell activities. This combination therapy has the potential in the treatment of metastatic melanoma that is typically refractory to this type of immune therapeutic approach. Clin Cancer Res; 16(9); 2550–61. ©2010 AACR.
Neurological Signs in Relation to White Matter Hyperintensity Volumes in Memory Clinic Patients
Authors: Staekenborg S.S. , de Waal H. , Admiraal-Behloul F. , Barkhof F. , Reiber J.H.C. , Scheltens P. , Pijnenburg Y.A.L. , Vrenken H. , van der Flier W.M.
Published: April 2010

Purpose: To determine the frequency of neurological signs in a memory clinic population and to explore their associations with white matter hyperintensity (WMH). Methods: We included patients with Alzheimer disease (AD; n = 210), vascular dementia (VaD; n = 34), mild cognitive impairment (MCI; n = 86) and subjective complaints (n = 153). The presence of extrapyramidal and unilateral signs was assessed from medical charts. On MRI, WMH volumes were extracted automatically. Results: Extrapyramidal signs were found in 10% and unilateral signs in 12% of the patients. Age- and sex-adjusted extrapyramidal signs occurred more often in VaD compared to patients with subjective complaints. Unilateral signs were more prevalent in all groups compared to patients with subjective complaints. Two-way analysis of variance (ANOVA) with WMH as the dependent variable showed a main effect of diagnosis (p < 0.001), but not of extrapyramidal signs (p = 0.62). In contrast, 2-way ANOVA showed main effects of diagnosis (p < 0.001) and unilateral signs (p = 0.001). Furthermore, there was an interaction between these factors (p = 0.04); if unilateral signs were present, patients with subjective complaints and VaD showed more WMH, whereas there was no relation in AD and MCI. Conclusion: Extrapyramidal and unilateral signs are common in memory clinic patients, but are only modestly related to WMH.
Framing Genomics, Public Health Research and Policy: Points to Consider
Authors: Knoppers B.M. , Leroux T. , Doucet H. , Godard B. , Laberge C. , Stanton-Jean M. , Fortin S. , Cousineau J. , Monardes C. , Girard N. , Levesque L. , Durand C. , Farmer Y. , Dion-Labrie M. , Bouthillier M.-E. , Avard D.
Published: April 2010

Genetic information can be used to target interventions that improve health and prevent disease. Indeed, the results of population genomics research could be useful for public health and national pandemic plans. Yet, firm scientific evidence originating from such research and the indicators of the role of health determinants, gene-gene and gene-environment interaction remain to be assessed and validated before being integrated into pandemic plans or public health programmes. It is not clear what is the role of the State in research on the elucidation of the determinants of gene-gene and gene-environment interactions and how, when, and if such data can be accessed and used for such planning. Over a period of 3 years, we sought to address these questions by gathering data and literature relevant to research in public health genomics, preparing issues papers and, finally, consulting with stakeholders on a provisional ‘points to consider’ document at various times. Examining in turn the issues of privacy, State powers, stakeholder perceptions, and public participation, we propose in this article, for each of these themes, a series of recommendations aiming to provide guidance on the role of the State in the use of genomic information for public health research, prevention and planning.
Current Information on Sacral Neuromodulation and Botulinum Toxin Treatment for Refractory Idiopathic Overactive Bladder Syndrome: A Review
Authors: Leong Randall K. , De Wachter Stefan G.G. , van Kerrebroeck Philip E.V.
Published: April 2010

The overactive bladder syndrome (OAB) negatively affects the daily life of many people. Conservative treatments, such as antimuscarinics, do not always lead to sufficient improvement of the complaints and/or are often associated with considerable side effects resulting in treatment failure. In the case of failure or intolerable side effects, sacral neuromodulation (SNM) and botulinum toxin are minimally invasive and reversible alternatives. Currently, of these alternatives only SNM with InterStimTM therapy has FDA approval for use in OAB patients. This review attempts to provide an update on the current position of SNM and botulinum toxin in the second-line management of adults with idiopathic OAB, based on the available clinical evidence concerning the efficacy and safety.
Treatment of Ureteral Calculi with Semirigid Ureteroscopy: Where Should We Stop?
Authors: Yencilek F. , Sarica K. , Erturhan S. , Yagci F. , Erbagci A.
Published: April 2010

Objectives: To evaluate the efficacy of semirigid ureteroscopy in the management of ureteral stones located in different parts of the ureter. Methods: 1,503 patients were treated with semirigid ureteroscopy. All ureteral stones were either removed only by a basket catheter or disintegrated by pneumatic lithotripsy. Success rates, auxiliary procedures, complication rates and operation time were comparatively evaluated according to stone location. Results: Overall, mean stone size and age were 12.1 ± 3.7 mm and 43.2 ± 9.72 years, respectively. While 1,416 patients (94.2%) were completely stone-free, the procedure was unsuccessful in 87 cases (5.8%). The success rate was relatively low in the proximal ureter (71.7%) when compared with the mid (94.8%) and distal ureter (98.9%) (p = 0.021). Mean operation time was 25.4 ± 11.7 min. Longer duration of operation and higher complication rate were found in proximal ureteral calculi. Stone migration to the kidney and hematuria were the main reasons of failure in the proximal ureter and ureteral stenting was needed for 56.4% of patients with upper ureteral stone. Conclusions: Semirigid ureteroscopy can be the treatment of choice in lower and midureteral stones. However, it is an invasive and less successful treatment modality for proximal ureteral stones with relatively high complication rates.
Povidone Iodine Instillation into the Renal Pelvis in the Management of Chyluria: Our Experience
Authors: Ramana Murthy K.V. , Jayaram Reddy S. , Prasad D.V.S.R.K. , Purusotham G.
Published: April 2010

Purpose: We report our experience with the use of povidone iodine instillation into the renal pelvis for the treatment of chyluria. Materials and Methods: From August 2006 to November 2008, 26 patients with chyluria were treated. There were 18 males and 8 females ranging from 24–55 years of age. Cystoscopic localization of chylous efflux was done. Povidone iodine as a sclerosing agent was instilled through a ureteric catheter placed in the renal pelvis. A total of 9 doses were given at 8-hour intervals for 3 days. Unilateral instillation was done in 20 cases, and bilateral instillation was done in 6 patients. Results: Twenty-one of 26 patients showed complete clearance. In 4 patients, recurrence was noted and a repeat injection was given after 4 weeks, with success, in 2 patients. The other two patients required chylolymphatic disconnection. One patient was lost to follow-up. Conclusion: Our experience shows that povidone iodine is a safe and effective sclerosing agent in the management of chyluria.
Role of Surgical Resection in Adult Urological Soft Tissue Sarcoma: 25-Year Experience
Authors: Izumi Kouji , Mizokami Atsushi , Sugimoto Kazuhiro , Narimoto Kazutaka , Miyagi Tohru , Maeda Yuji , Kitagawa Yasuhide , Kadono Yoshifumi , Konaka Hiroyuki , Namiki Mikio
Published: April 2010

Introduction: As adult urological soft tissue sarcomas (STS) are rare, there have been few recent large-scale studies of these tumors. This report describes a single institutional experience of adult urological STS over 25 years. Patients and Methods: The study population consisted of 25 adult patients with histologically diagnosed STS arising in the urinary tract, male genital system, or retroperitoneum between January 1983 and July 2008. The study endpoint was overall survival. The crude probability of survival was estimated using the Kaplan-Meier method. Uni- and multivariate analysis of differences between patient groups was performed with the log rank test and the Cox proportional hazards model. Results: Overall survival rate at 5 years was 54.2%. On univariate analysis, unfavorable prognostic variables for overall survival were presence of metastasis at diagnosis (p = 0.0005), absence of surgical resection (p = 0.0003), histological subtype of rhabdomyosarcoma (p = 0.0068), and primary organs other than retroperitoneum (p = 0.0410). On multivariate analysis, absence of surgical resection remained a significant predictor of unfavorable prognosis (HR 2.67, 95% CI 1.03–7.76, p = 0.044). Conclusions: Surgical resection, regardless of status of surgical resection margin, contributed to a favorable prognosis in adult patients with locally advanced or metastatic urological STS.
A Placebo-Controlled Trial of the Effects of Hydrochlorothiazide on Nocturnal Enuresis
Authors: AlAwwa Izzat Ahmad , Matani Yousef Samih , Saleh Akram A. , Al-Ghazo Mohammed Ahmed
Published: April 2010

Objective: To assess the efficacy, tolerability and side effects of the diuretic hydrochlorothiazide (HCTZ) in the management of monosymptomatic nocturnal enuresis by a placebo-controlled double-blind crossover trial. Patients and Methods: Forty patients suffering from nocturnal enuresis were blindly randomized into 2 groups of equal numbers. Group 1 first received placebo for 3 months, and group 2 received oral HCTZ once daily for the same period. Both groups, after a 2-week wash-out period, were crossed over in their medication and continued treatment for another 3 months. The main outcome measure (variable) for the assessment of drug efficacy was taken to represent the average reduction in the percentage of wet nights as compared to the baseline enuresis pattern. Statistical analysis was based on a t test (p ≤ 0.05). A subjective scale was also used to assess patients’ and their parents’ satisfaction. Tolerability and side effects were also documented in the study. Results: Both HCTZ and placebo were statistically effective in reducing the average percentage of wet nights. HCTZ resulted in a significantly better reduction than placebo (41.1 vs. 32.5%; p ≤ 0.023). Overall short-term clinical cure and improvement, on the other hand, were comparable to those of placebo according to the standards of the International Children’s Continence Society. Satisfaction, as a crude measure of success, was expressed more frequently in patients who received HCTZ (20 vs. 9). Both drugs were well-tolerated. Conclusion: The use of HCTZ in the treatment of nocturnal enuresis has never been previously evaluated. The drug, in this pilot study, has a promising statistical superiority to placebo. Its clinical value, however, deserves further definition in future controlled trials.
Cauda Equina Symptoms Are Closely Related to Male Lower Urinary Tract Symptoms
Authors: Imai Atsushi , Yamamoto Hayato , Hatakeyama Shingo , Iwabuchi Ikuya , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Kamimura Noritaka , Danjo Kazuma , Ono Atsushi , Ohyama Chikara
Published: April 2010

Introduction: To determine the impact of cauda equina symptoms on male lower urinary tract function, we investigated the related risk factors in healthy Japanese men. Methods: Subjects included 345 healthy males (average age 56 years; range 26–83) who participated in the Iwaki Health Promotion Project in 2006. They were residents of Iwaki district, Hirosaki City, northern Japan. Using a self-administered, self-reported questionnaire for lumbar spinal stenosis and International Prostate Symptom Score (IPSS), we investigated the prevalence of cauda equina symptoms. We also measured body mass index; blood pressure; and triglyceride, cholesterol, glucohemoglobin, and prostate-specific antigen levels. Results: Nineteen participants (5.5%) were positive for cauda equina symptoms; 270 participants (78.3%) scored 0–7 points on the total IPSS survey, 65 (18.8%) scored 8–19, and 10 (2.9%) scored 20–35. The total IPSS, and storage and voiding symptom scores of participants negative for cauda equina symptoms were significantly lower than those who were positive. Multiple logistic regression analysis revealed that age and cauda equina symptoms were independent significant risk factors for total IPSS and storage symptoms. Conclusions: Cauda equina symptoms are closely related to lower urinary tract symptoms in healthy Japanese men.
Prognostic Role of Pigment Epithelium-Derived Factor in Clear Cell Renal Cell Carcinoma
Authors: Jiang Zhaohui , Fang Zhujun , Ding Qiang
Published: April 2010

Aims: The purpose of this study was to investigate the prognostic significance of pigment epithelium-derived factor (PEDF) in human clear cell renal cell carcinoma (CCRCC) tissues. Patients and Methods: We investigated the expression of PEDF and its correlation with clinicopathological features in 203 patients who underwent radical nephrectomy for CCRCC. Expression of PEDF and CD34-positive vessels (microvessel density, MVD) in tumor samples was examined by immunohistochemistry. The relationship between PEDF expression and clinicopathologic features including tumor diameter, MVD, and survival was evaluated by univariate and multivariate analyses. Results: Of 203 patients, 116 cases (57.1%) were positive for PEDF. A significant association was found between PEDF expression and high MVD (p = 0.012). PEDF expression was inversely correlated with grade (p = 0.004) and pT stage (p = 0.001). Multivariate analysis using the Cox regression model indicated that PEDF expression was an independent favorable prognostic factor (risk ratio, 4.105; p = 0.001). However, no significant correlation was found between PEDF expression and age, gender, tumor diameter or lymph node invasion. Conclusion: Our findings suggest that PEDF may be a favorable prognostic indicator in patients with CCRCC.
Testicular Steroidogenesis Is Decreased by Hyperthermia in Old Rats
Authors: Hwang Eu Chang , Min Kyung Dai , Jung Seung Il , Ryu Soo Bang , Ahn Kyu Youn , Lee Keesook , Park Kwangsung
Published: April 2010

Purpose: To evaluate the effects of hyperthermia on testicular steroidogenesis in a rat model. Materials and Methods: Three-month-old and 20-month-old male Sprague-Dawley rats were randomly divided into 4 groups of 10 rats each, a control group and a hot-bath group for each age. The rats in the hot-bath groups received multiple 10-min treatments in a hot bath (41–43°C) over a period of 4 weeks. Testicular testosterone, serum testosterone and serum luteinizing hormone levels were measured. The protein levels of 2 steroidogenic enzymes, StAR and P450c17, were measured by Western blot. The testes were examined histologically by light microscopy. Results: Testicular testosterone levels of the 20-month-old, but not the 3-month-old, rats in the hot-bath group were significantly lower than those in the control group (p < 0.05). Serum testosterone levels of both the old and the young hot-bath groups tended to decrease compared with their corresponding controls, although the differences were not statistically significant. Serum luteinizing hormone levels changed insignificantly after the hot baths in both age groups. The hot-bath treatment had no significant effect on P450c17 protein levels, whereas the protein level of StAR was significantly lower in the old hot-bath group than in the same-age control group (p < 0.05). Conclusions: Hyperthermia significantly decreased the testicular testosterone level in old male rats and significantly lowered the StAR protein level. These data imply that frequent hot baths might impair testicular steroidogenesis, especially in old men.
Enhancement of the Sensitivity of Renal Cell Carcinoma Cells to Fas-Mediated Cytotoxicity and Apoptosis by the Selective Cyclooxygenase-2 Inhibitor JTE-522
Authors: Sato Nodoka , Mizutani Yoichi , Li Yong Nan , Fujiwara Jun , Ishida Hirokazu , Toiyama Daisuke , Abe Koichi , Hayashi Issei , Nakanishi Hiroyuki , Kawauchi Akihiro , Miki Tsuneharu
Published: April 2010

Background: Cyclooxygenase-2 (COX-2) is a key enzyme involved in the production of prostaglandins and its inhibitors have been shown to induce apoptosis in a variety of cancer cells. We reasoned that combination treatment of renal cell carcinoma (RCC) cells with COX-2 inhibitors and anticancer agents may result in synergistic apoptosis. We examined whether the selective COX-2 inhibitor JTE-522 synergizes with anticancer agents in cytotoxicity and apoptosis against RCC cells. Methods: The cytotoxicity of the selective COX-2 inhibitor JTE-522 and other anticancer agents against the RCC cell lines and the normal renal cell line was determined by the microculture tetrazolium dye assay. Results: JTE-522 was cytotoxic against the Caki-1 RCC cell line. JTE-522 and anti-Fas monoclonal antibody (CH-11) exhibited a synergistic cytotoxic effect against Caki-1 cells. In contrast, JTE-522 in combination with 5-fluorouracil, adriamycin, cis-diamminedichloroplatinum, or interferon-α, all commonly used clinically, resulted in an additive cytotoxic effect. Synergy achieved in cytotoxicity with JTE-522 and CH-11 was shown to be due to apoptosis. Conclusions: The present study demonstrated that the selective COX-2 inhibitor JTE-522 had a cytotoxic effect on RCC and that synergistic cytotoxicity against RCC was obtained with JTE-522 in combination with anti-Fas monoclonal antibody. These results suggest that selective COX-2 inhibitors in combination with immunotherapy may be useful in treating patients with RCC.
WAIS-R Features of Preclinical Huntington’s Disease: Implications for Early Detection
Authors: Robins Wahlin Tarja-Brita , Larsson Maria U. , Luszcz Mary A. , Byrne Gerard J.
Published: April 2010

Background/Aims: The main purpose of the study was to determine whether the predicted age of onset of Huntington’s disease (HD) affects cognitive function as measured by the Wechsler Adult Intelligence Scale-Revised (WAIS-R). The subscales and subtests, and their potential selectivity were examined in preclinical HD (30 mutation carriers and 34 noncarriers) with no motor or neuropsychiatric signs of HD. Methods: The predicted age of onset in mutation carriers was calculated by a regression equation allowing this group to be divided according to whether onset was predicted as within 12 years (HD+CLOSE) or longer than this (HD+DISTANT). Results: The HD+CLOSE group scored significantly lower on Verbal, Performance, and Full Scale IQ compared to noncarriers and performed significantly lower on 7 of the 11 WAIS-R subtests, with low average scores in language abilities, attention, abstract thinking, problem solving, visuospatial ability, and psychomotor speed. Conclusion: These low average scores affect general intelligence and functioning of HD+CLOSE carriers and are likely to reflect dysfunction of frontal cortex and frontostriatal circuits more than a decade before manifest symptoms. Our findings support a continuous linear model of slow cognitive decline in HD.
Delta-Centralization Fails to Control for Population Stratification in Genetic Association Studies
Authors: Dadd Tony , Lewis Cathryn M. , Weale Michael E.
Published: April 2010

Objective: To investigate the validity of simulations and assumptions used to underpin the delta-centralization (DC) method for correcting for population stratification in genetic association studies; to assess the effectiveness of DC compared to genomic control (GC) under valid simulation conditions; and to highlight other studies employing similarly flawed simulations. Methods: DC and GC use data from unlinked null loci to correct the test statistic at the target locus, but differ in the way the correction is performed. We compare DC and GC under two simulation approaches: an invalid approach adopted by the originators of DC, which permits subpopulation allele frequency matching of null markers to the target locus; and a valid approach, based on the Balding-Nichols model, which does not allow subpopulation matching. Results: DC works under invalid simulation conditions (subpopulation allele frequency matching), but not under our valid ones. We use theoretical arguments to assert that there are no valid conditions under which DC might work. We identify several studies which have adopted similarly invalid simulation approaches in this field. Conclusion: DC fails to control for population stratification and should not be used. Other results from studies which have used the same invalid simulation approach should be treated cautiously.
Central Precocious Puberty due to Hypothalamic Hamartomas Correlates with Anatomic Features but Not with Expression of GnRH, TGFα, or KISS1
Authors: Chan Yee-Ming , Fenoglio-Simeone Kristina A. , Paraschos Sophia , Muhammad Laura , Troester Matthew M. , Ng Yu-tze , Johnsonbaugh Roger E. , Coons Stephen W. , Prenger Erin C. , Kerrigan, Jr. John F. , Seminara Stephanie B.
Published: April 2010

Background/Aims: Hypothalamic hamartomas are the most common identifiable cause of central precocious puberty (CPP). Hamartoma characteristics proposed to be associated with CPP include specific anatomic features and expression of molecules such as gonadotropin-releasing hormone (GnRH), transforming growth factor α (TGFα), and GRM1A, which encodes the type 1 metabotropic glutamate receptor α isoform. We sought to determine whether hamartomas that cause CPP could be distinguished by anatomic features, expression of these molecules, or expression of KISS1, whose products signal through the receptor GPR54 to stimulate GnRH release. Methods: Clinical records and radiologic images were reviewed for 18 patients who underwent hamartoma resection for intractable seizures; 7 had precocious puberty. Resected tissue was examined for expression of GnRH, GnRH receptor (GnRHR), TGFα, KISS1, GPR54, and GRM1A. Results: Hypothalamic hamartomas associated with CPP were more likely to contact the infundibulum or tuber cinereum and were larger than hamartomas not associated with CPP. GnRH, TGFα, and GnRHR were expressed by all hamartomas studied. Expression of KISS1, GPR54, and GRM1A did not differ significantly between hamartomas associated and not associated with CPP. Conclusion: Anatomic features rather than expression patterns of candidate molecules distinguish hypothalamic hamartomas that are associated with CPP from those that are not.
Expression and Protein Content of IGF-I and IGF-I Receptor in Placentas from Small, Adequate and Large for Gestational Age Newborns
Authors: Iñiguez G. , González C.A. , Argandoña F. , Kakarieka E. , Johnson M.C. , Cassorla F.
Published: April 2010

In humans, a direct relationship between IGF-I cord blood levels and birth weight has been demonstrated. To determine the placental IGF-I, IGF-II and IGF-IR mRNA and protein contents in full-term pregnancies from appropriate for gestational age (AGA), small for gestational age (SGA) and large for gestational age (LGA) newborns, we studied the placentas from 35 AGA, 30 SGA and 28 LGA pregnancies. The IGF-I, IGF-II and IGF-I receptor (IGF-IR) placental mRNA and protein contents were determined in the basal and chorionic plates of the placenta. IGF1 and IGF1R mRNA was higher in SGA compared to AGA and LGA placentas and lower in LGA compared with AGA placentas. In addition, a higher protein content of IGF-I and IGF-IR was observed in SGA compared with AGA and LGA placentas and lower contents in LGA compared with AGA placentas. These results suggest that the higher IGF-I and IGF-IR contents observed in SGA placentas and the lower contents observed in LGA placentas compared with AGA placentas may be influencing human fetal growth.
PROP1, HESX1, POU1F1, LHX3 and LHX4 Mutation and Deletion Screening and GH1 P89L and IVS3+1/+2 Mutation Screening in a Dutch Nationwide Cohort of Patients with Combined Pituitary Hormone Deficiency
Authors: de Graaff Laura C.G. , Argente Jesús , Veenma Danielle C.M. , Drent Madeleine L. , Uitterlinden André G. , Hokken-Koelega Anita C.S.
Published: April 2010

Background/Aims: Mutation frequencies of genes involved in combined pituitary hormone deficiency (CPHD) vary substantially between populations. The HYPOPIT study aims to obtain an overall picture of known and new genetic defects and variations in a nationwide cohort of Dutch (mostly) sporadic CPHD patients. Methods: We screened 79 CPHD patients from 78 families (regardless of MRI and hormonal phenotype) for mutations and deletions in PROP1, HESX1, POU1F1, LHX3 and LHX4, as well as the P89L and IVS3+1/+2 mutations in GH1, recently described to cause pituitary hormone impairment in addition to GH deficiency. Results: We did not find any mutation or deletion in PROP1, HESX1, LHX3 or LHX4, nor GH1 P89L and GH1 IVS3+1/+2 mutations. Among 12 patients with a typical ‘POU1F1 phenotype’, 1 patient was formerly known to have a POU1F1 mutation. This results in a POU1F1 mutation frequency in these patients of 8.3%. Conclusion: Thorough screening for mutations and deletions in PROP1, HESX1, POU1F1, LHX3, LHX4, as well as screening for GH1 P89L or GH1 IVS3+1/+2 mutations, did not reveal any genetic defect in our cohort of CPHD patients except for one formerly known POU1F1 mutation in 1 patient. Future research should focus on alternative explanations for CPHD, like other genes or environmental factors.
Validation of a New Method for Automated Determination of Bone Age in Japanese Children
Authors: Martin David D. , Sato Koshi , Sato Mari , Thodberg Hans Henrik , Tanaka Toshiaki
Published: April 2010

BoneXpert, an automated method for analysis of hand radiographs of children, has recently been developed and validated in European children. It determines Tanner-Whitehouse (TW) and Greulich Pyle (GP) bone ages (BA). The purpose of this work is to validate BoneXpert BA in Japanese children and determine the following two properties of the method: (1) The accuracy of the BA, i.e. the standard deviation from an experienced Japanese TW BA rater. (2) The precision of the BA, i.e. BoneXpert’s ability to yield the same BA value on a repeated radiograph. The data consist of two studies: 185 radiographs of 22 normal children followed longitudinally from approximately 7 years to full maturity, and 284 radiographs of 22 patients with growth hormone deficiency treated with growth hormone and gonadotropin-releasing hormone analogue followed from an age of 4–11 years to almost full maturity. All radiographs were rated manually according to the TW-Japan system. BoneXpert processed all images, and the accuracy (SD) of TW-Japan BA was 0.72 years (95% CI 0.68–0.76). The precision error (SD) on a single determination of GP BA was 0.17 years (95% CI 0.15–0.19). It is concluded that BoneXpert performs as well in Japanese children as it does in Caucasian children. This study accomplishes a calibration of BoneXpert to the TW-Japan standard, which performs well for the entire BA range from 4 years up to full maturity.
Malignant Profile Detected by CT Angiographic Information Predicts Poor Prognosis despite Thrombolysis within Three Hours from Symptom Onset
Authors: Puetz Volker , Dzialowski Imanuel , Hill Michael D. , Steffenhagen Nikolai , Coutts Shelagh B. , O’Reilly Christine , Demchuk Andrew M. ,   for the Calgary CTA Study Group
Published: April 2010

Objective: A malignant profile of early brain ischemia has been demonstrated in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) trial. Patients with a malignant profile had a low chance for an independent functional outcome despite thrombolysis within 3–6 h. We sought to determine whether CT angiography (CTA) could identify a malignant imaging profile within 3 h from symptom onset. Methods: We studied consecutive patients (04/02–09/07) with anterior circulation stroke who received CTA before intravenous thrombolysis within 3 h. We assessed the Alberta Stroke Program Early CT Score (ASPECTS) on CTA source images (CTASI). Intracranial thrombus burden on CTA was assessed with a novel 10-point clot burden score (CBS). We analyzed percentages independent (modified Rankin Scale score ≤2) and fatal outcome at 3 months and parenchymal hematoma rates across categorized combined CTASI-ASPECTS + CBS score groups where 20 is best and 0 is worst. Results: We identified 114 patients (median age 73 years [interquartile range 61–80], onset-to-tPA time 129 min [95–152]). Among 24 patients (21%) with extensive hypoattenuation on CTASI and extensive thrombus burden (combined score ≤10), only 4% (1/24) were functionally independent whereas mortality was 50% (12/24). In contrast, 57% (51/90) of patients with less affected scores (combined score 11–20) were functionally independent and mortality was 10% (9/90; p < 0.001). Parenchymal hematoma rates were 30% (7/23) vs. 8% (7/88), respectively (p = 0.008). Conclusion: CTA identifies a large hyperacute stroke population with high mortality and low likelihood for independent functional outcome despite early thrombolysis.
Sick Sinus Syndrome, Progressive Cardiac Conduction Disease, Atrial Flutter and Ventricular Tachycardia Caused by a Novel SCN5A Mutation
Authors: Holst Anders G. , Liang Bo , Jespersen Thomas , Bundgaard Henning , Haunso Stig , Svendsen Jesper Hastrup , Tfelt-Hansen Jacob
Published: April 2010

Mutations in the cardiac sodium channel encoded by the gene SCN5A can result in a wide array of phenotypes. We report a case of a young male with a novel SCN5A mutation (R121W) afflicted by sick sinus syndrome, progressive cardiac conduction disorder, atrial flutter and ventricular tachycardia. His father carried the same mutation, but had a milder phenotype, presenting with progressive cardiac conduction later in life. The mutation was found to result in a loss-of-function in the sodium current. In conclusion, the same SCN5A mutation can result in a wide array of clinical phenotypes and perhaps the spectrum of SCN5A loss-of-function associated disease entities should be viewed as one syndrome.
Tissue Factor and Thrombosis Models
Authors: Kretz Colin A. , Vaezzadeh Nima , Gross Peter L.
Published: April 2010

Mouse models of thrombosis have extended our understanding of the role of tissue factor (TF) in thrombogenesis. Because tissue factor deficiency is embryonic lethal in mice, inventive genetic models are required to probe the role of TF in thrombosis. TF is expressed by different cell types, including vascular smooth muscle cells, cardiomyocytes, fibroblasts, and monocytes. Platelets and endothelial cells also express TF under certain conditions, but the importance of this TF remains controversial. Animal models are commonly used to evaluate the contribution of TF from each cell type to thrombogenesis. Although a variety of well-established injury techniques are used to induce thrombosis, it is likely that the sources of TF that drive thrombosis are model dependent. Therefore, rigorous controls are needed before thrombogenesis can be attributed to TF from a particular cell type. This review summarizes data from mouse models that have attempted to delineate the role of TF in thrombus formation in response to various types of vascular injury. We have consolidated this information to generate unifying concepts that require testing in future studies.
Treatment and Risk in Heart Failure
Authors: Peterson Pamela N. , Rumsfeld John S. , Liang Li , Hernandez Adrian F. , Peterson Eric D. , Fonarow Gregg C. , Masoudi Frederick A.
Published: April 2010

Background—

Although the absolute benefits of an intervention are proportional to patients’ underlying risk, studies in heart failure have noted a paradoxical inverse relationship between treatment and risk. The extent to which this reflects higher rates of contraindications in patients with higher risk or larger gaps in care quality has not been explored.

Methods and Results—

We studied 18 307 patients with left ventricular systolic dysfunction surviving hospitalization between January 2005 and June 2007 from 194 hospitals participating in Get With The Guidelines (GWTG)–Heart Failure. Patients were categorized according to their estimated risk for in-hospital mortality using a validated risk score. The proportions of patients with documented contraindications to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and β-blockers as well as the use of these medications among patients without contraindications at hospital discharge was determined across levels of risk. For each therapy, the proportion of patients with contraindications was significantly higher with increasing patient risk (
P
<0.001 for each). Even after excluding those with contraindications, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and β-blockers was significantly lower with increasing risk (
P
<0.001 for each).

Conclusions—

The use of evidence-based therapies is lower in patients with heart failure at higher risk of mortality both because of higher rates of contraindications to therapy and lower rates of use among eligible patients. Optimizing heart failure outcomes will require both the expansion of the evidence base for treating the highest-risk patients as well as the development of effective strategies to assure that eligible high-risk patients receive all appropriate therapies.
Using a P300 Brain–Computer Interface in an Immersive Virtual Environment
Authors: Donnerer Michael , Steed Anthony
Published: April 2010

Brain–computer interfaces (BCIs) provide a novel form of human–computer interaction. The purpose of these systems is to aid disabled people by affording them the possibility of communication and environment control. In this study, we present experiments using a P300 based BCI in a fully immersive virtual environment (IVE). P300 BCIs depend on presenting several stimuli to the user. We propose two ways of embedding the stimuli in the virtual environment: one that uses 3D objects as targets, and a second that uses a virtual overlay. Both ways have been shown to work effectively with no significant difference in selection accuracy. The results suggest that P300 BCIs can be used successfully in a 3D environment, and this suggests some novel ways of using BCIs in real world environments.
Hypercommercialism, Televisuality, and the Changing Nature of College Sports Sponsorship
Authors: McAllister Matthew P.
Published: April 2010

This article updates previous research that critiqued the level and categories of commercial intrusion in national college football championship television broadcasts. Arguing that the “hypercommercialism” of television continues to increase due to a variety of contextual reasons and technological advances that enhance the distinctive “televisual” style of television, the article applies content and textual analyses of the 2007 BCS National Championship football broadcast on the U.S. television network Fox and compares these findings to a similar study conducted on the 1996 national championship broadcast. Results indicate a significant decrease in “advertising-free” broadcast time, mainly resulting from an increase in the use of on-screen graphics with commercial iconography. In addition, the broadcast is characterized by the integrated marketing techniques that blur distinctions between content categories. The essay concludes with a discussion of the implications of hypercommercialism of sports and broadcasting for the vibrancy of the public sphere.
Measuring the Mathematical Attitudes of Elementary Students: The Effects of a 4-Point or 5-Point Likert-Type Scale
Authors: Adelson Jill L. , McCoach D. Betsy
Published: April 2010

The purpose of this study was to compare how students in Grades 3 to 6 respond to a mathematics attitudes instrument with a 4-point Likert-type scale compared with one with an additional neutral point (a 5-point Likert-type scale). The 606 participating students from six elementary and middle schools randomly received either the 4-point or 5-point format of the Math and Me Survey. Regardless of whether a neutral midpoint was offered or not, the structure of the instrument was virtually the same, with equal intercepts, means, variances and covariances, pattern coefficients, and nearly all residuals. The 5-point scale is preferred with this population because with this format the reliability estimate for the Mathematical Self-Perceptions subscale was higher ( p = .049), and the pattern coefficients were stronger. Additionally, this format provided less model misfit than the 4-point format. Based on these findings, the authors recommend administration of the Math and Me Survey in the 5-point format. These findings also indicate that despite what some educators and educational experts believe, children in Grades 3 to 6 are capable of discriminating among five response options and do not tend toward the neutral point more so than with a 4-point scale.
The Sevenfold Form of the Lord’s Prayer in Matthew’s Gospel
Authors: Wenham David
Published: April 2010

The Lord’s Prayer, in the form we find it in Matthew’s gospel, consists of seven petitions, carefully and chiastically arranged: the first three clauses go together and ask for God’s glory, the last three ask for help in our struggle with evil; the fourth is different, linking the two groups and asking the Father in heaven to supply our down-to-earth needs. This rarely noted structure reflects Matthew’s artistry, his belief in Jesus as the teacher and embodiment of God’s perfection and the Sermon on the Mount’s concern for God’s kingdom and the Father’s provision for his children.
The Politicization of Paul: Romans 13:1-7 in Recent Discussion
Authors: Cassidy Ron
Published: April 2010

To those who regard the Letter to the Romans as part of a thoroughgoing critique of Roman power and ideology on the part of Paul, the first seven verses of Chapter 13 represent a major problem of interpretation, since they appear to represent endorsement rather than criticism of the prevailing political authorities. This paper looks at the way the text has been handled by those involved in the debate, as well as making some suggestions as to how the passage should be understood in its context.
Evolution through kenōsis
Authors: Williams David T
Published: April 2010

Despite the evidence for evolution, it remains unproven, and has several unresolved issues, notably its relation to entropy and its possibility in the accepted timescale. Christians also continue to debate how it relates to the biblical account of creation. A solution is that as God has limited himself to allow the independent existence of the universe, he also allowed its development by evolution. This is consistent with both theism and God’s sovereignty. Among others, two significant proposals are of ‘theistic evolution’, by which God created in such a way that evolution would proceed according to his will, and ‘intelligent design’, which sees a limited number of direct divine interventions. A combination of these is proposed as most in keeping with the evidence.
Effects of materialism on work-related personal well-being
Authors: Deckop John R , Jurkiewicz Carole L , Giacalone Robert A
Published: April 2010

Materialism is a defining aspect of many societal cultures. Unfortunately, a large body of research has documented a negative relationship between materialism and indicators of non-work personal well-being. This study extends the materialism research into the organizational domain, investigating whether materialistic values are related to work-related indicators of personal well-being. Our field study results indicate that materialistic values are negatively associated with a range of indicators of work-related personal well-being, including intrinsic and extrinsic reward satisfaction, job satisfaction, and career satisfaction. Further analyses suggest that the relationship between materialism and work-related personal well-being is driven by the happiness and centrality dimensions of materialism, and not by the success dimension. Implications for future research and practice are presented.
From virtual teams to virtuality in teams
Authors: Dixon Keith R , Panteli Niki
Published: April 2010

In this article we propose to go beyond the dichotomy of virtual vs collocated teams to look instead at virtuality in teams. In so doing, we argue that technology-mediated interactions do not substitute but rather complement face-to-face interactions.We adopt a definition of virtuality in teams based on discontinuities and pursue an understanding of their dynamics in an in-depth case study of an inter-organizational virtual centre of excellence.The findings present evidence suggesting the formation of ‘virtual continuities’ that mitigate the effects that create discontinuities. This, we argue, enriches our understanding of the complex dynamics of virtuality. The theoretical implications are discussed.
The Emergence of the Independent Self: Autobiographical Memory as a Mediator of False Belief Understanding and Sociocultural Motive Orientation in Cameroonian and German Preschoolers
Authors: Chasiotis Athanasios , Bender Michael , Kiessling Florian , Hofer Jan
Published: April 2010

Applying a preschooler version of an instrument measuring implicit motives (Operant Multimotive Test), the authors investigated the interrelations of autobiographical memory, theory of mind, and implicit motives in the preschool years. Four- to 6-year-old children from Bamenda (Cameroon, N = 30) and Osnabrück (Germany, N = 52) were tested using a location false belief task, and a second order task as measures for theory of mind and a version of Wang and Leichtman’s task on children’s narratives as a measure of autobiographical memory coded with the Cognitive Complexity Scoring Manual. Regression analyses for mediator effects while controlling for moderating effects of culture show that cognitive complexity of autobiographical memory mediates the relationship of mentalistic abilities and sociocultural orientation of implicit motivation. Results are discussed within the framework of the independent-interdependent construal of the self.
Mapping a 40-Year History With Leximancer: Themes and Concepts in the Journal of Cross-Cultural Psychology
Authors: Cretchley Julia , Rooney David , Gallois Cindy
Published: April 2010

This article presents a study using Leximancer (a text-mining tool for visualizing the structure of concepts and themes in text) to track the history of the Journal of Cross-Cultural Psychology’ s ( JCCP’s) research articles. We included 1,416 articles mapped by decade. Results reveal a strong overall orientation toward experimental psychology, with an early emphasis on child development. In more recent years, there has been a strong emphasis on the features of culture including values, orientation, and acculturation, with the journal now situated more centrally in social psychology and personality. JCCP is the most broad-based journal in cross-cultural psychology, and its development over 40 years clearly represents changes in the field.
The Most Recent Years: The Journal of Cross-Cultural Psychology, 2004—2009
Authors: Best Deborah L. , Everett Brady S.
Published: April 2010

Recent trends in the content and characteristics of articles published in the Journal of Cross-Cultural Psychology from 2004 through 2009 are reviewed, completing the picture of the first 40 of publication. Consistent with earlier trends, empirical comparative studies are seen most frequently, self-report social behavior studies are predominate, and the majority of researchers are from the United States and English-speaking countries. Increased statistical and methodological sophistication continue to strengthen cross-cultural research and support the centrality of culture in psychology.
A Design Study of an Air-twist Nozzle by Analysis of Fluid Flow
Authors: Juraeva Makhsuda , Dong Joo Song  , Du Hwan Chun
Published: April 2010

The efficiency of the air-twist nozzle has a direct effect on the uniform tension of spandex yarn during the winding and unwinding process. The different geometries of the air-twist nozzle were studied as a reference. Compressed air coming out of the air orifice flows through the wall of the yarn channel in a twisting motion. The purpose of this research is to develop an air-twist nozzle geometry which has well-twisted motion, with reasonable vorticity strength and velocity. The paper presents investigations of the effects of the inlet pressure and the yarn channel shape of the air-twist nozzle. The Ansys CFX was used to perform steady simulations of jet flow inside the air-twist nozzles. Results of computational simulations for the two most promising cases were confirmed by experimental tests. The twist and flow patterns, specifically vorticity and velocity inside the air twist nozzles, are discussed in this paper. As a result of this research, an air-twist nozzle of improved design is now being produced for commercial use.
Dominant Corporate Agents and the Power Elite in France and Britain
Authors: Maclean Mairi , Harvey Charles , Chia Robert
Published: April 2010

Corporate elites are not a new phenomenon. However, the ways in which significant agents gain ascendancy to positions of power vary across nations and cultures. This paper analyses the ascension of a small minority of corporate agents to positions of dominance and the subsequent accession of a select few to the power elite. Our theoretical position builds upon the writings of Pierre Bourdieu on power and domination. These constructs are elaborated and made tangible through a cross-national comparative study of dominant corporate agents in France and Britain. Our results demonstrate the extent to which power remains concentrated in the French and British corporate sectors; highlighting equally pronounced similarities and differences between the two countries. It is suggested that power elites function through governance networks to promote institutional and organizational goals.