bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous laparoscopic splenectomy and right hemihepatectomy for littoral cell angiosarcoma accompanied with liver metastases
Authors: Wang Liang , Xiu Dianrong , Jiang Bin , Ma Zhaolai , Yuan Chunhui , Li Lei
Published: August 2013

Despite the wide acceptance of laparoscopic resection for treatment of abdominal tumors, only few cases of simultaneous laparoscopic removal of the spleen and the right liver have been reported to date. Littoral cell angiosarcoma (LCAS), which arises from the littoral cells lining the sinus channels of the splenic red pulp, is a rare condition, and there is limited literature on littoral cell angiosarcoma with liver metastases. We present the case of a 28-year-old woman with postoperative pathologically-proven LCAS with right liver metastases. The patient’s surgery was safely performed, and her postoperative course was uneventful until now. This case suggests that concomitant laparoscopic splenectomy (LS) and right hemihepatectomy is a suitable surgical option for selected patients.
Forecasting the absolute and relative shortage of physicians in Japan using a system dynamics model approach
Authors: Ishikawa Tomoki , Ohba Hisateru , Yokooka Yuki , Nakamura Kozo , Ogasawara Katsuhiko
Published: August 2013

Background

In Japan, a shortage of physicians, who serve a key role in healthcare provision, has been pointed out as a major medical issue. The healthcare workforce policy planner should consider future dynamic changes in physician numbers. The purpose of this study was to propose a physician supply forecasting methodology by applying system dynamics modeling to estimate future absolute and relative numbers of physicians.

Method

We constructed a forecasting model using a system dynamics approach. Forecasting the number of physician was performed for all clinical physician and OB/GYN specialists. Moreover, we conducted evaluation of sufficiency for the number of physicians and sensitivity analysis.

Result & conclusion

As a result, it was forecast that the number of physicians would increase during 2008–2030 and the shortage would resolve at 2026 for all clinical physicians. However, the shortage would not resolve for the period covered. This suggests a need for measures for reconsidering the allocation system of new entry physicians to resolve maldistribution between medical departments, in addition, for increasing the overall number of clinical physicians.
Cold shock Y-box protein-1 proteolysis autoregulates its transcriptional activities
Authors: van Roeyen Claudia RC , Scurt Florian G , Brandt Sabine , Kuhl Vanessa A , Martinkus Sandra , Djudjaj Sonja , Raffetseder Ute , Royer Hans-Dieter , Stefanidis Ioannis , Dunn Sandra E , Dooley Steven , Weng Honglei , Fischer Thomas , Lindquist Jonathan A , Mertens Peter R
Published: August 2013

Background

The Y-box protein-1 (YB-1) fulfills pleiotropic functions relating to gene transcription, mRNA processing, and translation. It remains elusive how YB-1 shuttling into the nuclear and cytoplasmic compartments is regulated and whether limited proteolysis by the 20S proteasome releases fragments with distinct function(s) and subcellular distribution(s).

Results

To address these questions, mapping of domains responsible for subcellular targeting was performed. Three nuclear localization signals (NLS) were identified. NLS-1 (aa 149-156) and NLS-2 (aa 185-194) correspond to residues with unknown function(s), whereas NLS-3 (aa 276-292) matches with a designated multimerization domain. Nuclear export signal(s) were not identified. Endoproteolytic processing by the 20S proteasome before glycine 220 releases a carboxy-terminal fragment (CTF), which localized to the nucleus, indicating that NLS-3 is operative. Genotoxic stress induced proteolytic cleavage and nuclear translocation of the CTF. Co-expression of the CTF and full-length YB-1 resulted in an abrogated transcriptional activation of the MMP-2 promoter, indicating an autoregulatory inhibitory loop, whereas it fulfilled similar trans-repressive effects on the collagen type I promoter.

Conclusion

Compartmentalization of YB-1 protein derivatives is controlled by distinct NLS, one of which targets a proteolytic cleavage product to the nucleus. We propose a model for an autoregulatory negative feedback loop that halts unlimited transcriptional activation.
Anti-tumour activity of longikaurin A (LK-A), a novel natural diterpenoid, in nasopharyngeal carcinoma
Authors: Zou Qing-Feng , Du Ji-Ke , Zhang Hua , Wang Hong-Bo , Hu Ze-Dong , Chen Shu-Peng , Du Yong , Li Man-Zhi , Xie Dan , Zou Juan , Sun Han-Dong , Pu Jian-Xin , Zeng Mu-Sheng
Published: August 2013

Background

Longikaurin A is a natural ent-kaurene diterpenoid isolated from Isodon genus. The ent-kaurene diterpenoids isolated from medicinal plants have been shown to have anti-disease effects. The present study was designed to examine the anti-tumour effects of longikaurin A (LK-A) in nasopharyngeal carcinoma in vitro and in vivo.

Methods

Apoptosis and cell cycle arrest were determined by flow cytometry analysis of the cells treated with Longikaurin A. The proteins of apoptosis signaling pathway were detected by western blotting analysis. Finally, we examined whether LK-A exhibits anti-tumour activity in xenograft models.

Results

Longikaurin A inhibited the cell growth by inducing apoptosis and cell cycle arrest. At low concentrations, longikaurin A induced S phase arrest and at higher concentrations, longikaurin A induced caspase-dependent apoptosis by regulating apoptotic molecules. Finally, longikaurin A significantly inhibited the tumour growth of CNE2 xenografts in vivo and showed no obvious effect on the body weights of the mice.

Conclusion

Our results suggest that Longikaurin A exhibited anti-tumour activity in nasopharyngeal carcinoma in vitro and in vivo.
Electronic structures and optical properties for Ag-N-codoped ZnO nanotubes
Authors: Feng Xian-Yang , Zhang Chang-Wen , Xu Xi-Jin , Wang Pei-Ji
Published: August 2013

The structural and electronic/optical properties of pure and Ag-N-codoped (8,0) ZnO nanotubes have been studied using first-principles calculations in the framework of the local spin density approximation. The configurations for Zn atoms replaced by Ag atoms are p-type semiconductor materials, and the bandgap increases when N atoms are doped into ZnO nanotube configurations. The optical studies based on dielectric function and reflectivity indicate that new transition peaks in the visible light range are observed, which can be ascribed to the Ag and N doping. Furthermore, there is a red shift observed with the increase of N concentration.
Fractalkine (CX3CL1) enhances hippocampal N-methyl-d-aspartate receptor (NMDAR) function via d-serine and adenosine receptor type A2 (A2AR) activity
Authors: Scianni Maria , Antonilli Letizia , Chece Giuseppina , Cristalli Gloria , Di Castro Maria Amalia , Limatola Cristina , Maggi Laura
Published: August 2013

Background

N-Methyl-d-aspartate receptors (NMDARs) play fundamental roles in basic brain functions such as excitatory neurotransmission and learning and memory processes. Their function is largely regulated by factors released by glial cells, including the coagonist d-serine. We investigated whether the activation of microglial CX3CR1 induces the release of factors that modulate NMDAR functions.

Methods

We recorded the NMDAR component of the field excitatory postsynaptic potentials (NMDA-fEPSPs) elicited in the CA1 stratum radiatum of mouse hippocampal slices by Shaffer collateral stimulation and evaluated d-serine content in the extracellular medium of glial primary cultures by mass spectrometry analysis.

Results

We demonstrated that CX3CL1 increases NMDA-fEPSPs by a mechanism involving the activity of the adenosine receptor type A2 (A2AR) and the release of the NMDAR coagonist d-serine. Specifically (1) the selective A2AR blocker 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261) and the genetic ablation of A2AR prevent CX3CL1 action while the A2AR agonist 5-(6-amino-2-(phenethylthio)-9H-purin-9-yl)-N-ethyl-3,4-dihydroxytetrahydrofuran-2-carboxamide (VT7) mimics CX3CL1 effect, and (2) the selective blocking of the NMDAR glycine (and d-serine) site by 5,7-dicholorokynurenic acid (DCKA), the enzymatic degradation of d-serine by d-amino acid oxidase (DAAO) and the saturation of the coagonist site by d-serine, all block the CX3CL1 effect. In addition, mass spectrometry analysis demonstrates that stimulation of microglia and astrocytes with CX3CL1 or VT7 increases d-serine release in the extracellular medium.

Conclusions

CX3CL1 transiently potentiates NMDAR function though mechanisms involving A2AR activity and the release of d-serine.
The PROBIT approach in estimating the prevalence of wasting: revisiting bias and precision
Authors: Blanton Curtis J , Bilukha Oleg O
Published: August 2013

Background

The PROBIT methodology was presented in the 1995 World Health Organization Technical Report on Anthropometry as an alternative to the standard prevalence based method of measuring malnutrition in children. Theoretically the PROBIT method will always give a smaller standard error than the standard prevalence method in measuring malnutrition. A recent article by Dale et al. assessed the PROBIT method for measuring global acute malnutrition measure and found that the method was biased and the precision was superior only for sample sizes less than 150 when compared to the standard method. In a manner similar to Dale, our study further investigated the bias and precision of the PROBIT method for different sample sizes using simulated populations.

Results

The PROBIT method showed bias for each of the ten simulated populations, but the direction and magnitude of the average bias was changed depending on the simulated population. For a given simulated population, the average bias was relatively constant for all sample sizes drawn. The 95% half-width confidence interval was lower for the PROBIT method than the standard prevalence method regardless of the sample size or simulated population. The absolute difference in the confidence limits showed the most gains for the PROBIT method for the smaller samples sizes, but the ratio of confidence intervals was relatively constant across all sample sizes.

Conclusions

The PROBIT method will provide gains in precision regardless of the sample size, but the method may be biased. The direction and magnitude of the bias depends on the population it is drawn from.
ProAlgaZyme subfraction improves the lipoprotein profile of hypercholesterolemic hamsters, while inhibiting production of betaine, carnitine, and choline metabolites
Authors: Geamanu Andreea , Goja Arvind , Saadat Nadia , Khosla Pramod , Gupta Smiti V
Published: August 2013

Background

Previously, we reported that ProAlgaZyme (PAZ) and its biologically active fraction improved plasma lipids in hypercholesterolemic hamsters, by significantly increasing the high density lipoprotein cholesterol (HDL-C) while reducing non-HDL cholesterol and the ratio of total cholesterol/HDL-C. Moreover, hepatic mRNA expression of genes involved in HDL/reverse cholesterol transport were significantly increased, while cholesteryl ester transfer protein (CETP) expression was partially inhibited. In the current study, we investigated the therapeutic efficacy of the biologically active fraction of PAZ (BaP) on the plasma lipid and plasma metabolomic profiles in diet induced hypercholesterolemic hamsters.

Methods

Fifty male Golden Syrian hamsters were fed a high fat diet for 4 weeks prior to randomization into 6 groups, based on the number of days they received subsequent treatment. Thus animals in T0, T3, T7, T10, T14, and T21 groups received BaP for 0, 3, 7, 10, 14, and 21 days, respectively, as their drinking fluid. Plasma lipids were assayed enzymatically, while real-time reverse transcriptase polymerase chain reaction (RT-PCR) provided the transcription levels of the Apolipoprotein (Apo) A1 gene. The plasma metabolomic profile was determined using 1H nuclear magnetic resonance (NMR) spectroscopy in conjunction with multivariate analysis.

Results

Plasma HDL-C was significantly increased in T3 (P < 0.05) and T21 (P < 0.001), while non-HDL cholesterol was significantly reduced in T3, T7, T10 (P < 0.001) and T14, T21 (P < 0.01). Moreover, the ratio of total cholesterol/HDL-C was significantly lower in all BaP treated groups (P < 0.001) as compared with T0. Quantitative RT-PCR showed an increase in Apo A1 expression in T10 (3-fold) and T21 (6-fold) groups. NMR data followed by multivariate analysis showed a clear separation between T0 and T21 groups, indicating a difference in their metabolomic profiles. Plasma concentrations of metabolites associated with a risk for atherosclerosis and cardiovascular disease, including choline, phosphocholine, glycerol-phosphocholine, betaine and carnitine metabolites were significantly lower in the T21 group.

Conclusion

Treatment with BaP significantly improved the plasma lipid profile by increasing HDL-C and lowering non-HDL cholesterol. In addition, BaP potentially improved the plasma metabolomic profile by reducing the concentration of key metabolites associated with risk for atherosclerosis and cardiovascular disease.
Characterization of a case of follicular lymphoma transformed into B-lymphoblastic leukemia
Authors: Ning Yi , Foss Aubry , Kimball Amy S , Neill Nicholas , Matz Tricia , Schultz Roger
Published: August 2013

Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma with an ability to transform into a more aggressive disease, albeit infrequently to B-lymphoblastic leukemia/lymphoma. While t(14;18)(q32;q21) has been associated with approximately 90% cases of FL, that alteration alone is insufficient to cause FL and associated mutations are still being elucidated. The transformation of FL to B-lymphoblastic leukemia generally includes the dysregulation of MYC gene expression, typically through IGH rearrangement. Such cases of “double-hit” leukemia/lymphoma with both BCL2 and MYC translocations warrant further study as they are often not identified early, are associated with a poor prognosis, and are incompletely understood in molecular terms. Here we describe a patient with a diagnosis of FL that transformed to B-lymphoblastic leukemia. Detailed cytogenetic characterization of the transformed specimen using karyotype, fluorescence in situ hybridization, microarray and gene rearrangement analyses revealed a complex karyotype comprised principally of whole chromosome or whole arm copy number gains or losses. Smaller, single-gene copy number alterations identified by microarray were limited in number, but included amplification of a truncated EP300 gene and alterations in NEIL1 and GPHN. Analyses defined the presence of an IGH/BCL2 fusion due to a translocation as well as a MYC/IGH fusion due to an insertion, with both rearrangements involving the same IGH allele. The data illustrate the value in characterizing double-hit lymphoma cases with both traditional and novel technologies in the detailed cytogenetic workup.
Identification of key structural elements for neuronal calcium sensor-1 function in the regulation of the temperature-dependency of locomotion in C. elegans
Authors: Martin Victoria M , Johnson James R , Haynes Lee P , Barclay Jeff W , Burgoyne Robert D
Published: August 2013

Background

Intracellular Ca2+ regulates many aspects of neuronal function through Ca2+ binding to EF hand-containing Ca2+ sensors that in turn bind target proteins to regulate their function. Amongst the sensors are the neuronal calcium sensor (NCS) family of proteins that are involved in multiple neuronal signalling pathways. Each NCS protein has specific and overlapping targets and physiological functions and specificity is likely to be determined by structural features within the proteins. Common to the NCS proteins is the exposure of a hydrophobic groove, allowing target binding in the Ca2+-loaded form. Structural analysis of NCS protein complexes with target peptides has indicated common and distinct aspects of target protein interaction. Two key differences between NCS proteins are the size of the hydrophobic groove that is exposed for interaction and the role of their non-conserved C-terminal tails.

Results

We characterised the role of NCS-1 in a temperature-dependent locomotion assay in C. elegans and identified a distinct phenotype in the ncs-1 null in which the worms do not show reduced locomotion at actually elevated temperature. Using rescue of this phenotype we showed that NCS-1 functions in AIY neurons. Structure/function analysis introducing single or double mutations within the hydrophobic groove based on information from characterised target complexes established that both N- and C-terminal pockets of the groove are functionally important and that deletion of the C-terminal tail of NCS-1 did not impair its ability to rescue.

Conclusions

The current work has allowed physiological assessment of suggestions from structural studies on the key structural features that underlie the interaction of NCS-1 with its target proteins. The results are consistent with the notion that full length of the hydrophobic groove is required for the regulatory interactions underlying NCS-1 function whereas the C-terminal tail of NCS-1 is not essential. This has allowed discrimination between two potential modes of interaction of NCS-1 with its targets.
Synthesis of some novel 4-arylidene pyrazoles as potential antimicrobial agents
Authors: Khloya Poonam , Kumar Pawan , Mittal Arpana , Aggarwal Neeraj K , Sharma Pawan K
Published: August 2013

Background

Pyrazole and pyrazolone motifs are well known for their wide range of biological activities such as antimicrobial, anti-inflammatory, and antitumor activities. The incorporation of more than one pharmacophore in a single scaffold is a well known approach for the development of more potent drugs. In the present investigation, a series of differently substituted 4-arylidene pyrazole derivatives bearing pyrazole and pyrazolone pharmacophores in a single scaffold was synthesized.

Results

The synthesis of novel 4-arylidene pyrazole compounds is achieved through Knovenagel condensation between 1,3-diaryl-4-formylpyrazoles and 3-methyl-1-phenyl-1H-pyrazol-5-(4H)-ones in good yields. All compounds were evaluated for their in vitro antimicrobial activity.

Conclusions

A series of 4-arylidene pyrazole derivatives was evaluated for their in vitro antimicrobial activity against two Gram-positive (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative bacteria (Pseudomonas fluorescens and Escherichia coli), as well as two pathogenic fungal strains (Candida albicans and Saccharomyces cerevisiae). The majority of the compounds displayed excellent antimicrobial profile against the Gram-positive (B. subtilis and S. aureus), and some of them are even more potent than the reference drug ciprofloxacin.
New pulse wave measurement method using different hold-down wrist pressures according to individual patient characteristics
Authors: Yoo Seong Ki , Shin Ki Young , Lee Tae Bum , Jin Seung Oh
Published: August 2013

In traditional Chinese and Korean medicine, doctors first observe a patient’s pulse by gently and strongly pressing their fingers onto the wrist, and then make a diagnosis based on the observed pulse waves. The most common method to implement this diagnostic technique is to mechanically extract the pulse waves by applying a fixed range of pressures for all patients. However, this method does not consider the patients individual characteristics such as age, sex, and skin thickness. In the present study, we propose a new method of pulse wave extraction that incorporates the personal characteristics of the patients. This method measures the pulse wave signal at varying hold-down pressures, rather than applying a fixed hold-down pressure for all patients. To compare this new technique with existing methods, we extracted pulse waves from 20 subjects, and then determined the actual applied pressure at each step, the coefficient of floating and sinking pulse (CFS), and the distinction of floating/sinking pulse for each group. Consequently, each subject had a different pressure range in our proposed method, whereas all subjects had a similar pressure range in the existing method. Four of 20 subjects exhibited different floating/sinking pulse patterns due to the value of the first pressure step and the range of hold-down pressures. These four subjects were categorized as overweight based on BMI. In addition, the moving distance of the proposed method was longer than the existing method (p = 0.003, paired t-test), and the correlation coefficient between CFS values of two different methods was 0.321, indicating that there was no correlation.
p53 activation and mitochondria-mediated pathway are involved during hanging death-induced neuronal cell apoptosis in dentate gyrus region of the rat brain
Authors: Khatun Sabana , Chaube Shail K , Bhattacharyya Chandra N
Published: August 2013

The goal of this study was to understand the molecular event in the brain caused by hanging death (HD). Animals were subjected to either cervical dislocation (CD) or HD. Brain was collected at various times (0, 1, 3, 6 and 12 h) after death. Brain expression of p53 and Bax, cytochrome c concentration, caspases activity and DNA fragmentation were analyzed. Compared to that of CD, HD increased p53 and Bax proteins expressions, cytochrome c concentration, caspases activity and DNA fragmentation during the early period (0–6 h) of HD, whereas CD induced necrosis 3 h post- CD and thereafter. These data support that HD induces neuronal cell apoptosis, in part, through mitochondria-mediated pathways. These data also suggest that neuronal apoptosis could be a potential marker and an aid to forensic science of HD.
The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery
Authors: Laing Roz , Kikuchi Taisei , Martinelli Axel , Tsai Isheng J , Beech Robin N , Redman Elizabeth , Holroyd Nancy , Bartley David J , Beasley Helen , Britton Collette , Curran David , Devaney Eileen , Gilabert Aude , Hunt Martin , Jackson Frank , Johnston Stephanie L , Kryukov Ivan , Li Keyu , Morrison Alison A , Reid Adam J , Sargison Neil , Saunders Gary I , Wasmuth James D , Wolstenholme Adrian , Berriman Matthew , Gilleard John S , Cotton James A
Published: August 2013

Background

The small ruminant parasite Haemonchus contortus is the most widely used parasitic nematode in drug discovery, vaccine development and anthelmintic resistance research. Its remarkable propensity to develop resistance threatens the viability of the sheep industry in many regions of the world and provides a cautionary example of the effect of mass drug administration to control parasitic nematodes. Its phylogenetic position makes it particularly well placed for comparison with the free-living nematode Caenorhabditis elegans and the most economically important parasites of livestock and humans.

Results

Here we report the detailed analysis of a draft genome assembly and extensive transcriptomic dataset for H. contortus. This represents the first genome to be published for a strongylid nematode and the most extensive transcriptomic dataset for any parasitic nematode reported to date. We show a general pattern of conservation of genome structure and gene content between H. contortus and C. elegans, but also a dramatic expansion of important parasite gene families. We identify genes involved in parasite-specific pathways such as blood feeding, neurological function, and drug metabolism. In particular, we describe complete gene repertoires for known drug target families, providing the most comprehensive understanding yet of the action of several important anthelmintics. Also, we identify a set of genes enriched in the parasitic stages of the lifecycle and the parasite gut that provide a rich source of vaccine and drug target candidates.

Conclusions

The H. contortus genome and transcriptome provide an essential platform for postgenomic research in this and other important strongylid parasites.
Prognostic Significance of MTOR Pathway Component Expression in Neuroendocrine Tumors
Authors: Qian Zhi Rong , Ter-Minassian Monica , Chan Jennifer A. , Imamura Yu , Hooshmand Susanne M. , Kuchiba Aya , Morikawa Teppei , Brais Lauren K. , Daskalova Anastassia , Heafield Rachel , Lin Xihong , Christiani David C. , Fuchs Charles S. , Ogino Shuji , Kulke Matthew H.
Published: August 2013

Purpose

Clinical studies have implicated the mechanistic target of rapamycin (serine/threonine kinase; MTOR) pathway in the regulation of neuroendocrine tumor (NET) growth. We explored whether expression of MTOR pathway components has prognostic significance in NET patients.

Patients and Methods

We evaluated immunohistochemical expression of MTOR and phospho (p) –MTOR; its downstream targets RPS6KB1, RPS6, and EIF4EBP1; and its upstream regulators, in a cohort of 195 archival neuroendocrine tumors. We correlated expression levels with clinical outcomes, after adjusting for other prognostic variables.

Results

We observed anticipated correlations between expression of upstream components of the MTOR pathway and their downstream targets. Expression of PIK3CA, MTOR, or p-EIF4EBP1 was associated with high MKI67 (Ki-67) labeling index. We failed to identify clinical correlations associated with expression of the upstream regulators TSC1, TSC2, AKT, p-AKT, PDPK1, PTEN, PIK3R1, or PIK3CA. In contrast, high expression of MTOR or its activated downstream targets p-RPS6KB1, p-RPS6, or p-EIF4EBP1 was associated with adverse clinical outcomes.

Conclusion

Our observations suggest that expression of MTOR or its downstream targets may be adverse prognostic factors in neuroendocrine tumors.
German Adjuvant Intergroup Node-Positive Study: A Phase III Trial to Compare Oral Ibandronate Versus Observation in Patients With High-Risk Early Breast Cancer
Authors: von Minckwitz Gunter , Möbus Volker , Schneeweiss Andreas , Huober Jens , Thomssen Christoph , Untch Michael , Jackisch Christian , Diel Ingo J. , Elling Dirk , Conrad Bettina , Kreienberg Rolf , Müller Volkmar , Lück Hans-Joachim , Bauerfeind Ingo , Clemens Michael , Schmidt Marcus , Noeding Stefanie , Forstbauer Helmut , Barinoff Jana , Belau Antje , Nekljudova Valentina , Harbeck Nadia , Loibl Sibylle
Published: August 2013

Purpose

Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer. Their effect in early breast cancer is controversial. Ibandronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile. It therefore qualifies as potential agent for adjuvant use.

Patients and Methods

The GAIN (German Adjuvant Intergroup Node-Positive) study was an open-label, randomized, controlled phase III trial with a 2 × 2 factorial design. Patients with node-positive early breast cancer were randomly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ibandronate 50 mg per day orally for 2 years or observation. In all, 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival (DFS) by ibandronate from 75% to 79.5% by using a two-sided α = .05 and 1-β of 80%. We report here the efficacy analysis for ibandronate, which was released by the independent data monitoring committee because the futility boundary was not crossed after 50% of the required DFS events were observed.

Results

Between June 2004 and August 2008, 2,015 patients were randomly assigned to ibandronate and 1,008 to observation. Patients randomly assigned to ibandronate showed no superior DFS or overall survival (OS) compared with patients randomly assigned to observation (DFS: hazard ratio, 0.945; 95% CI, 0.768 to 1.161; P = .589; OS: HR, 1.040; 95% CI, 0.763 to 1.419; P = .803). DFS was numerically longer if ibandronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years (test for interaction P = .093).

Conclusion

Adjuvant treatment with oral ibandronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy.
Brivanib in Patients With Advanced Hepatocellular Carcinoma Who Were Intolerant to Sorafenib or for Whom Sorafenib Failed: Results From the Randomized Phase III BRISK-PS Study
Authors: Llovet Josep M. , Decaens Thomas , Raoul Jean-Luc , Boucher Eveline , Kudo Masatoshi , Chang Charissa , Kang Yoon-Koo , Assenat Eric , Lim Ho-Yeong , Boige Valerie , Mathurin Philippe , Fartoux Laetitia , Lin Deng-Yn , Bruix Jordi , Poon Ronnie T. , Sherman Morris , Blanc Jean-Frédéric , Finn Richard S. , Tak Won-Young , Chao Yee , Ezzeddine Rana , Liu David , Walters Ian , Park Joong-Won
Published: August 2013

Purpose

Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib.

Patients and Methods

In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety.

Results

Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%).

Conclusion

In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.
Processing Speed, Attention, and Working Memory After Treatment for Medulloblastoma: An International, Prospective, and Longitudinal Study
Authors: Palmer Shawna L. , Armstrong Carol , Onar-Thomas Arzu , Wu Shengjie , Wallace Dana , Bonner Melanie J. , Schreiber Jane , Swain Michelle , Chapieski Lynn , Mabbott Donald , Knight Sarah , Boyle Robyn , Gajjar Amar
Published: August 2013

Purpose

The current study prospectively examined processing speed (PS), broad attention (BA), and working memory (WM) ability of patients diagnosed with medulloblastoma over a 5-year period.

Patients and Methods

The study included 126 patients, ages 3 to 21 years at diagnosis, enrolled onto a collaborative protocol for medulloblastoma. Patients were treated with postsurgical risk-adapted craniospinal irradiation (n = 36 high risk [HR]; n = 90 average risk) followed by four cycles of high-dose chemotherapy with stem-cell support. Patients completed 509 neuropsychological evaluations using the Woodcock-Johnson Tests of Cognitive Abilities Third Edition (median of three observations per patient).

Results

Linear mixed effects models revealed that younger age at diagnosis, HR classification, and higher baseline scores were significantly associated with poorer outcomes in PS. Patients treated as HR and those with higher baseline scores are estimated to have less favorable outcomes in WM and BA over time. Parent education and marital status were significantly associated with BA and WM baseline scores but not change over time.

Conclusion

Of the three key domains, PS was estimated to have the lowest scores at 5 years after diagnosis. Identifying cognitive domains most vulnerable to decline should guide researchers who are aiming to develop efficacious cognitive intervention and rehabilitation programs, thereby improving the quality of survivorship for the pediatric medulloblastoma population.
Solute Size-dependent Rotational Diffusion of Nitroxide Radicals in Ionic Liquids as Studied by EPR Spectroscopy
Authors: Miyake Yusuke , Akai Nobuyuki , Shibuya Kazuhiko , Kawai Akio
Published: August 2013

Rotational correlation time of five nitroxide radicals with various molecular volume and shape was determined in ionic liquids by EPR spectroscopy. Gierer–Wirtz theory for rotational diffusion well explains the experimental results obtained in a wide range of solute volume.
S6:S18 ribosomal protein complex interacts with a structural motif present in its own mRNA
Authors: Matelska Dorota , Purta Elzbieta , Panek Sylwia , Boniecki Michal J. , Bujnicki Janusz M. , Dunin-Horkawicz Stanislaw
Published: August 2013

Prokaryotic ribosomal protein genes are typically grouped within highly conserved operons. In many cases, one or more of the encoded proteins not only bind to a specific site in the ribosomal RNA, but also to a motif localized within their own mRNA, and thereby regulate expression of the operon. In this study, we computationally predicted an RNA motif present in many bacterial phyla within the 5′ untranslated region of operons encoding ribosomal proteins S6 and S18. We demonstrated that the S6:S18 complex binds to this motif, which we hereafter refer to as the S6:S18 complex-binding motif (S6S18CBM). This motif is a conserved CCG sequence presented in a bulge flanked by a stem and a hairpin structure. A similar structure containing a CCG trinucleotide forms the S6:S18 complex binding site in 16S ribosomal RNA. We have constructed a 3D structural model of a S6:S18 complex with S6S18CBM, which suggests that the CCG trinucleotide in a specific structural context may be specifically recognized by the S18 protein. This prediction was supported by site-directed mutagenesis of both RNA and protein components. These results provide a molecular basis for understanding protein-RNA recognition and suggest that the S6S18CBM is involved in an auto-regulatory mechanism.
Neuron-derived IgG Protects Neurons from Complement-dependent Cytotoxicity
Authors: Zhang Jie , Niu Na , Li Bingjie , McNutt Michael A.
Published: August 2013

Passive immunity of the nervous system has traditionally been thought to be predominantly due to the blood-brain barrier. This concept must now be revisited based on the existence of neuron-derived IgG. The conventional concept is that IgG is produced solely by mature B lymphocytes, but it has now been found to be synthesized by murine and human neurons. However, the function of this endogenous IgG is poorly understood. In this study, we confirm IgG production by rat cortical neurons at the protein and mRNA levels, with 69.0 ± 5.8% of cortical neurons IgG-positive. Injury to primary-culture neurons was induced by complement leading to increases in IgG production. Blockage of neuron-derived IgG resulted in more neuronal death and early apoptosis in the presence of complement. In addition, FcγRI was found in microglia and astrocytes. Expression of FcγR I in microglia was increased by exposure to neuron-derived IgG. Release of NO from microglia triggered by complement was attenuated by neuron-derived IgG, and this attenuation could be reversed by IgG neutralization. These data demonstrate that neuron-derived IgG is protective of neurons against injury induced by complement and microglial activation. IgG appears to play an important role in maintaining the stability of the nervous system.
Brokering evaluations of partnerships in Australian community arts: Responding to enterpreneurial tendencies
Authors: Hadley Bree , Gattenhof Sandra
Published: August 2013

This article examines motivations and methods for external evaluators in taking on a brokerage relationship between artists, arts managers and governments (national and local) during an appraisal process of community arts events. The argument is situated in our experience evaluating the Creating Queensland programme, a multifaceted community arts programme presented as part of the one of Australia’s largest arts events the Brisbane Festival, in 2009 and 2010. We use this case to identify a number of principles and processes that may assist in establishing an effective evaluation process – defined, for us, as a process in which partners representing different elements of the community arts project can share information in a learning network, or an innovation network, that embraces the idea of continuous improvement. We explain that we, as consultants, are not necessarily the only participants in the evaluation process in a position to broker the decision making about what to research and report on. We argue that empowering each of the delivery partners to act as brokers, using the principles, protocols and processes to negotiate what should be researched, when, how and how it should be shared, is something each delivery partner can do. This can help create a common understanding that can reduce anxieties about using warts-and-all evaluation data to learn, grow and improve in the arts. It can, as a result, be beneficial both for the participating partners and the community arts sector as a whole.
Qualidade de Vida e Promoção da Saúde
Authors: Leite Pollyanna Nayara Belém
Published: August 2013

Este estudo teve como objetivo revisar a literatura sobre Qualidade de Vida e Promoção da Saúde. Foram consultados 36 produções entre os livros científicos, revistas  e textos, para uma melhor reflexão sobre os conceitos de qualidade de vida. Esses conceitos abordaram vários aspectos, como o trabalho, a saúde, a família e as atividades das pessoas na sociedade. Como resultado, foi possível identificar as ligações entre saúde e condições de vida das pessoas. Também questões relacionadas às políticas públicas  em termos de qualidade de vida das pessoas, como um meio de promoção da saúde, através  de práticas que podem efetivamente, melhorar a forma como as pessoas em geral vivem. A avaliação adequada da qualidade de vida das pessoas é certamente, uma ferramenta importante, para que possamos discutir uma melhor compreensão da nossa realidade em termos de uma expectativa de vida mais saudável.
A Pele Humana e sua evolução no tempo
Authors: Figueiredo Mayara Santana Nóbrega de , Albuquerque Lisiene Siebra de Deus e
Published: August 2013

O presente estudo discorre acerca de algumas das mais importantes modificações ocorridas durante a sucessão de eventos na escalada da evolução antropogenética, em relação a pele humana. Através de uma abordagem simplificada dos seus componentes essenciais no tecido cutâneo, superficial do corpo e das funções desempenhadas por eles na homeostase,  foram discutidas  as mais determinantes alterações que acontecidas na pele humana ao longo do tempo. O objetivo foi buscar um embasamento fisiológico que, porventura as tenha motivado e, que benefícios as mesmas trouxeram para a sobrevivência do homem na Terra.
Spruce fiber properties after high-temperature thermomechanical pulping (HT-TMP)
Authors: Solala Iina , Antikainen Toni , Reza Mehedi , Johansson Leena-Sisko , Hughes Mark , Vuorinen Tapani
Published: August 2013

Spruce was submitted to high-temperature (150°C–170°C) refining for 2 or 5 min to produce thermomechanical pulp (TMP) fibers with decreased electrical energy consumption. The pulp was characterized in terms of specific energy consumption as well as tensile and surface properties. The fibers from high-temperature TMP contained more surface lignin even if all sample types usually broke at the S1–S2 cell wall region. They also produced significantly weaker paper sheets, whereas their dry zero-span strength did not suffer substantial losses, indicating decreased fiber-fiber bonding. Tensile strength properties were also determined of a bisphenol-A-epichlorohydrin-based epoxy resin mixed with 5% fiber as a test for fiber-matrix compatibility in composite applications. Based on these preliminary results, high-temperature TMP shows potential for composite reinforcement due to its lower tendency to aggregate and its better compatibility with the tested matrix material.
Industrial Methanol from Syngas: Kinetic Study and Process Simulation
Authors: De María Raquel , Díaz Ismael , Rodríguez Manuel , Sáiz Adrián
Published: August 2013

In this study, a detailed rigorous kinetic model is proposed for the industrial production of methanol taking into account changes in total mole flowrate. The kinetic model proposed is compared with the one proposed in literature (Rezaie et al., Chem Eng Process Process Intensification 2005;44:911–21), showing significant differences in terms of compositions and total mole flow. A complete simulation of the methanol production process is developed with a commercial software. The rigorous reactor model is integrated in the simulation using the CAPE OPEN standard. Flowsheet simulation is carried out, and results show small differences with those found in previous studies (Luyben, Ind Eng Chem Res 2010;49:6150–63).
Comments on “He's Homotopy Perturbation Method for Calculating Adomian Polynomials”
Authors: Jafari H. , Ghasempour S. , Khalique C. M.
Published: August 2013

In the paper “He's Homotopy Perturbation Method for Calculating Adomian Polynomials” by A. Ghorbani and J. Saberi-Nadjafi, [International Journal of Nonlinear Sciences and Numerical Simulation, 8(2) (2007) 229–232], the authors introduced the homotopy perturbation method to calculate Adomian polynomials, which they claim makes the calculation of Adomian polynomials easy. We discuss here the restrictions on their method for calculating Adomian Polynomials for nonlinear equations. We also prove analytically that the method given by Ghorbani and Saberi-Nadjafi is equivalent to the method used in [Applied Mathematics and Computation, 138(2–3) (2003) 523–529].
Mathematical Models for Erosion and the Optimal Transportation of Sediment
Authors: Birnir Bjorn , Rowlett Julie
Published: August 2013

We investigate a mathematical theory for the erosion of sediment which begins with the study of a non-linear, parabolic, weighted 4-Laplace equation on a rectangular domain corresponding to a base segment of an extended landscape. Imposing natural boundary conditions, we show that the equation admits entropy solutions and prove regularity and uniqueness of weak solutions when they exist. We then investigate a particular class of weak solutions studied in previous work of the first author and produce numerical simulations of these solutions. After introducing an optimal transportation problem for the sediment flow, we show that this class of weak solutions implements the optimal transportation of the sediment.
Resuscitation at birth in neonates with meningomyelocele
Authors: da Silva Simone Aparecida Basso , de Almeida Maria Fernanda Branco , Moron Antonio Fernandes , Cavalheiro Sérgio , Dastoli Patrícia Alessandra , Guinsburg Ruth
Published: August 2013

Aims: Compare the need for neonatal resuscitation procedures between newborn infants with and without meningomyelocele (MMC).

Results: This retrospective case-control study included 94 neonates with MMC, defined as open spinal dysraphism with exposure of nervous tissue, and 94 controls without malformations, paired with MMC infants by gender, mode of delivery, gestational age and time of birth. Infants were born at a university hospital in São Paulo, Brazil, from 2001 to 2010. After adjusting for perinatal variables (prenatal care, maternal hypertension, birth during the day shift, cephalic presentation, meconium in the amniotic fluid, gestational age <37 weeks and small-for-gestational-age infants), MMC increased the chance of positive pressure ventilation at birth [odds ratio (OR) 4.55 95% confidence interval (CI) 1.82–11.41], intubation at birth (OR 3.94 95% CI 1.14–13.59) and 1-min Apgar score 95% CI 0.99–7.57).

Conclusion: MMC is an independent factor associated with the need for positive pressure ventilation and intubation at birth.
The prevalence and clinical features of twin-twin transfusion syndrome with onset during the third trimester
Authors: Murata Masaharu , Ishii Keisuke , Taguchi Takako , Mabuchi Aki , Kawaguchi Haruna , Yamamoto Ryo , Hayashi Shusaku , Mitsuda Nobuaki
Published: August 2013

Objective: To describe the incidence and clinical features of twin-twin transfusion syndrome (TTTS) with third trimester onset.

Methods: We performed a retrospective chart review of monochorionic diamniotic (MD) twin pregnancies delivered during a recent 4-year period. The inclusion criterion was women who received prenatal care at our center from the first trimester onward. Serial ultrasound examinations were performed at least every 2 weeks until delivery to evaluate fetal growth as well as to estimate amniotic fluid volume. The prevalence of TTTS onset after 28 weeks of gestation and clinical features, including neonatal outcomes and placental findings, were elucidated.

Results: Meeting our inclusion criterion were 143 MD twin pregnancies, including 15 TTTS cases (10%). Five cases (4%) developed TTTS during the third trimester and underwent a cesarean section immediately after the diagnosis. All of these women exhibited either abdominal distension or uterine contractions. Recipient twins tended to require more intensive cardiopulmonary treatment than donors, however, neither a recipient nor a donor twin suffered neonatal death or neurological impairment. Placental arterio-arterial anastomoses were detected in three out of five cases. Arteriovenous anastomoses were present in all cases, however, venovenous anastomoses were not found in any case.

Conclusions: TTTS is a relatively rare complication during the third trimester. It is imperative to be observant for the development of TTTS in MD twin pregnancies with any abdominal symptoms, even if they appear insignificant.
Influence of Aggregate Source and Warm-Mix Technologies on the Mechanical Properties of Asphalt Mixtures
Authors: Ahmed Taha A. , Hajj Elie Y. , Sebaaly Peter E. , Majerus Nate
Published: August 2013

This study evaluated the impact of three aggregate sources (limestone, quartzite, and natural gravel) and three different WMA processes (Advera, Evotherm, and plant foaming) on the properties of asphalt mixtures. The aggregate source and warm-mix process were found to have an impact on the mixing and compaction temperatures of the WMA. The performance of the WMA mixtures was evaluated in terms of moisture damage, rutting, thermal cracking, and fatigue cracking resistance. Based on the results of the analysis of variance (ANOVA) of the data, the aggregate source, WMA technology type, and the interaction between the two were shown to have moderate to significant effects on the performance of the asphalt mixtures for certain tests, whereas having no effect for other tests. Statistical differences were found when comparing indirect tensile strength and tensile strength ratio values, flow number, asphalt pavement analyzer rut depth, and fatigue cracking test results for the various mixtures. None of the WMA mixtures performed, as well as the HMA, except in the beam fatigue test. This was mainly related to the difference between the HMA and WMA short-term aging procedures. However, WMA mixtures exhibited similar or higher moisture damage, rutting, and fatigue cracking resistance than the HMA mixtures produced at the WMA temperatures or with 2-h short-term conditioning, instead of the recommended 4 h by Superpave. Dynamic modulus results showed that, on average, WMA mixtures had significantly lower dynamic modulus values than the HMA mixtures, but similar values to HMA mixtures produced at the WMA temperature and short-term conditioning. The thermal stress restrained specimen test (TSRST) showed that the reduction of production temperatures and short-term aging lowered the fracture temperature, whereas it did not impact the fracture stress. The impact of WMA technology on thermal cracking and fatigue characteristics depended on the type of aggregate.