bluuebunny/crossref_metadata_2025 huggingface dataset:
Alkaline Stability and Ion Conductivity of Polysulfone Anion Exchange Membranes (AEMs) with Different Cation Chemistries
Authors: Arges Christopher G , Ramani Vijay K.
Published: March 2013

The use of several different NMR techniques (1H, 13C, 31P, 1H decoupled phosphorus, COSY, and 1H-X (X= 13C or 31P) HMQC) were employed to elucidate the chemical structure of degraded polysulfone (PSF) anion exchange membranes (AEMs) exposed to alkaline solutions. The NMR spectra revealed degradation products perpetrated by rearrangement reactions from ylide intermediates and direct nucleophilic attack for trimethylammonium (TMA+), 1,4-dimethylpiperazinium (DMP+), 1-methylimidazolium (1M+) and trimethylphosphonium (TMP+) cations. Stevens rearrangement was the only verified rearrangement reaction for the ammonium cations. Trimethylphosphonium PSF AEMs were observed to degrade through Somelet-Hauser rearrangement. The stability experiments demonstrated that the ylide mechanisms were more prevalent at lower concentrations of alkaline solutions (e.g. 1 M Na2CO3 and 1 M KOH) when compared to higher concentrations (e.g. 6 M KOH). Also, the NMR spectra provided evidence that the introduction of alkaline stable cation sites on PSF leads to ether hydrolysis of the backbone.
Electrode Degradation of Direct Methanol Fuel Cells Evidenced by X-ray Tomography
Authors: Li Qing , Spernjak Dusan , Zelenay Piotr , Kim Yu Seung
Published: March 2013

The direct methanol fuel cell (DMFC) offers a promise for portable power applications thanks to the high energy density of methanol, no need for fuel reforming, and an ease of fuel storage and refilling. However, the long-term performance degradation presents a challenge that has hindered DMFC commercialization. The focus of this study is on the degradation of Nafion®-based membrane electrode assemblies (MEAs) during continuous DMFC operation. The fuel cells in this work were subjected to 100-hour life tests using different methanol feed concentrations at different operating voltages (current densities). X-ray tomography was used to examine structural changes in the MEAs after life tests. DMFC performance degradation was found to be correlated to higher feed concentration of methanol as was the formation of micro-cracks in both the anode and the cathode.
Hydrogen Generation from Aluminum Corrosion in Aqueous Solutions
Authors: Chiu Yen-Wen , Chen Chiao-Hsin , Hsueh Kan-Lin , Hung Ju-Shei
Published: March 2013

The H2 can be generated from the aluminum water reaction. Hydrogen generation rate by using aluminum from soft drink was measured by immersing samples in H2SO4, Na2SO4, KOH, and NaOH solutions. No observable amount of hydrogen is generated in acidic or in neutral solutions. At a given concentration, the generation rate of H2 is higher in NaOH solution than in KOH solution. High generation rate of H2 is obtained in concentrated NaOH as well as in concentrated KOH solutions. The gas volume of H2 generation can be fitted into a semi-empirical equation as function of reaction time. The H2 generation rate can be divided into two stages. During the first stage, hydrogen generation rate increases as the reaction continued. It reaches a maximum then gradually reduced in the second stage of reaction.
Endoplasmic reticulum stress signaling: the microRNA connection
Authors: Maurel Marion , Chevet Eric
Published: March 2013

The endoplasmic reticulum (ER)-induced unfolded protein response (ERUPR) is an adaptive mechanism that is activated upon accumulation of misfolded proteins in the ER and aims at restoring ER homeostasis. The ERUPR is transduced by three major ER-resident stress sensors, namely PKR-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol requiring enzyme 1 (IRE1). Activation of these ER stress sensors leads to transcriptional reprogramming of the cells. Recently, microRNAs (miRNAs), small noncoding RNAs that generally repress gene expression, have emerged as key regulators of ER homeostasis and important players in ERUPR-dependent signaling. Moreover, the miRNAs biogenesis machinery appears to also be regulated upon ER stress. Herein we extensively review the relationships existing between “canonical” ERUPR signaling, control of ER homeostasis, and miRNAs. We reveal an intricate signaling network that might confer specificity and selectivity to the ERUPR in tissue- or stress-dependent fashion. We discuss these issues in the context of the physiological and pathophysiological roles of ERUPR signaling.
Effects of early versus late rehabilitative training on manual dexterity after corticospinal tract lesion in macaque monkeys
Authors: Sugiyama Yoko , Higo Noriyuki , Yoshino-Saito Kimika , Murata Yumi , Nishimura Yukio , Oishi Takao , Isa Tadashi
Published: March 2013

Dexterous hand movements can be restored with motor rehabilitative training after a lesion of the lateral corticospinal tract (l-CST) in macaque monkeys. To maximize effectiveness, the optimal time to commence such rehabilitative training must be determined. We conducted behavioral analyses and compared the recovery of dexterous hand movements between monkeys in which hand motor training was initiated immediately after the l-CST lesion (early-trained monkeys) and those in which training was initiated 1 mo after the lesion (late-trained monkeys). The performance of dexterous hand movements was evaluated by food retrieval tasks. In early-trained monkeys, performance evaluated by the success rate in a vertical slit task (retrieval of a small piece of food through a narrow vertical slit) recovered to the level of intact monkeys during the first 1–2 mo after the lesion. In late-trained monkeys, the task success rate averaged ∼30% even after 3 mo of rehabilitative training. We also evaluated hand performance with the Klüver board task, in which monkeys retrieved small spherical food pellets from cylindrical wells. Although the success rate of the Klüver board task did not differ between early- and late-trained monkeys, kinematic movement analysis showed that there was a difference between the groups: late-trained monkeys with an improved success rate frequently used alternate movement strategies that were different from those used before the lesion. These results suggest that early rehabilitative training after a spinal cord lesion positively influences subsequent functional recovery.
Suppression of competing speech through entrainment of cortical oscillations
Authors: Horton Cort , D'Zmura Michael , Srinivasan Ramesh
Published: March 2013

People are highly skilled at attending to one speaker in the presence of competitors, but the neural mechanisms supporting this remain unclear. Recent studies have argued that the auditory system enhances the gain of a speech stream relative to competitors by entraining (or “phase-locking”) to the rhythmic structure in its acoustic envelope, thus ensuring that syllables arrive during periods of high neuronal excitability. We hypothesized that such a mechanism could also suppress a competing speech stream by ensuring that syllables arrive during periods of low neuronal excitability. To test this, we analyzed high-density EEG recorded from human adults while they attended to one of two competing, naturalistic speech streams. By calculating the cross-correlation between the EEG channels and the speech envelopes, we found evidence of entrainment to the attended speech's acoustic envelope as well as weaker yet significant entrainment to the unattended speech's envelope. An independent component analysis (ICA) decomposition of the data revealed sources in the posterior temporal cortices that displayed robust correlations to both the attended and unattended envelopes. Critically, in these components the signs of the correlations when attended were opposite those when unattended, consistent with the hypothesized entrainment-based suppressive mechanism.
Development of on-off spiking in superior paraolivary nucleus neurons of the mouse
Authors: Felix Richard A. , Vonderschen Katrin , Berrebi Albert S. , Magnusson Anna K.
Published: March 2013

The superior paraolivary nucleus (SPON) is a prominent cell group in the auditory brain stem that has been increasingly implicated in representing temporal sound structure. Although SPON neurons selectively respond to acoustic signals important for sound periodicity, the underlying physiological specializations enabling these responses are poorly understood. We used in vitro and in vivo recordings to investigate how SPON neurons develop intrinsic cellular properties that make them well suited for encoding temporal sound features. In addition to their hallmark rebound spiking at the stimulus offset, SPON neurons were characterized by spiking patterns termed onset, adapting, and burst in response to depolarizing stimuli in vitro. Cells with burst spiking had some morphological differences compared with other SPON neurons and were localized to the dorsolateral region of the nucleus. Both membrane and spiking properties underwent strong developmental regulation, becoming more temporally precise with age for both onset and offset spiking. Single-unit recordings obtained in young mice demonstrated that SPON neurons respond with temporally precise onset spiking upon tone stimulation in vivo, in addition to the typical offset spiking. Taken together, the results of the present study demonstrate that SPON neurons develop sharp on-off spiking, which may confer sensitivity to sound amplitude modulations or abrupt sound transients. These findings are consistent with the proposed involvement of the SPON in the processing of temporal sound structure, relevant for encoding communication cues.
Circle of Willis Variants: Fetal PCA
Authors: Shaban Amir , Albright Karen C. , Boehme Amelia K. , Martin-Schild Sheryl
Published: March 2013

We sought to determine the prevalence of fetal posterior cerebral artery (fPCA) and if fPCA was associated with specific stroke etiology and vessel territory affected. This paper is a retrospective review of prospectively identified patients with acute ischemic stroke from July 2008 to December 2010. We defined complete fPCA as absence of a P1 segment linking the basilar with the PCA and partial fPCA as small segment linking the basilar with the PCA. Patients without intracranial vascular imaging were excluded. We compared patients with complete fPCA, partial fPCA, and without fPCA in terms of demographics, stroke severity, distribution, and etiology and factored in whether the stroke was ipsilateral to the fPCA. Of the 536 included patients, 9.5% () had complete fPCA and 15.1% () had partial fPCA. Patients with complete fPCA were older and more often female than partial fPCA and no fPCA patients, and significant variation in TOAST classification was detected across groups (). Patients with complete fPCA had less small vessel and more large vessel strokes than patients with no fPCA and partial fPCA. Fetal PCA may predispose to stroke mechanism, but is not associated with vascular distribution, stroke severity, or early outcome.
Analysis of Structures and Epitopes of Surface Antigen Glycoproteins Expressed in Bradyzoites ofToxoplasma gondii
Authors: Cong Hua , Zhang Min , Zhang Qingli , Gong Jing , Cong Haizi , Xin Qing , He Shenyi
Published: March 2013

Toxoplasma gondiiis a protozoan parasite capable of infecting humans and animals. Surface antigen glycoproteins, SAG2C, -2D, -2X, and -2Y, are expressed on the surface of bradyzoites. These antigens have been shown to protect bradyzoites against immune responses during chronic infections. We studied structures of SAG2C, -2D, -2X, and -2Y proteins using bioinformatics methods. The protein sequence alignment was performed by T-Coffee method. Secondary structural and functional domains were predicted using software PSIPRED v3.0 and SMART software, and 3D models of proteins were constructed and compared using the I-TASSER server, VMD, and SWISS-spdbv. Our results showed that SAG2C, -2D, -2X, and -2Y are highly homologous proteins. They share the same conserved peptides and HLA-I restricted epitopes. The similarity in structure and domains indicated putative common functions that might stimulate similar immune response in hosts. The conserved peptides and HLA-restricted epitopes could provide important insights on vaccine study and the diagnosis of this disease.
Study of the Effect of Breast Tissue Density on Detection of Masses in Mammograms
Authors: García-Manso A. , García-Orellana C. J. , González-Velasco H. M. , Gallardo-Caballero R. , Macías-Macías M.
Published: March 2013

One of the parameters that are usually stored for mammograms is the BI-RADS density, which gives an idea of the breast tissue composition. In this work, we study the effect of BI-RADS density in our ongoing project for developing an image-based CAD system to detect masses in mammograms. This system consists of two stages. First, a blind feature extraction is performed for regions of interest (ROIs), using Independent Component Analysis (ICA). Next, in the second stage, those features form the input vectors to a classifier, neural network, or SVM classifier. To train and test our system, the Digital Database for Screening Mammography (DDSM) was used. The results obtained show that the maximum variation in the performance of our system considering only prototypes obtained from mammograms with a concrete value of density (both for training and test) is about 7%, yielding the best values for density equal to 1, and the worst for density equal to 4, for both classifiers. Finally, with the overall results (i.e., using prototypes from mammograms with all the possible values of densities), we obtained a difference in performance that is only 2% lower than the maximum, also for both classifiers.
Combining Kalman Filtering with ZigBee Protocol to Improve Localization in Wireless Sensor Network
Authors: El Madani Bouchra , Yao Anne Paule , Lyhyaoui Abdelouahid
Published: March 2013

We propose a low-cost and low-power-consumption localization scheme for ZigBee-based wireless sensor networks (WSNs). Our design is based on the link quality indicator (LQI)—a standard feature of the ZigBee protocol—for ranging and the ratiometric vector iteration (RVI)—a light-weight distributed algorithm—modified to work with LQI measurements. To improve performance and quality of this system, we propose three main ideas: a cooperative approach, a coefficient delta () to regulate the speed of convergence of the algorithm, and finally the filtering process with the extended Kalman filter. The results of experiment simulations show acceptable localization performance and illustrate the accuracy of this method.
Selective Intermittent Preventive Treatment of Vivax Malaria: Reduction of Malaria Incidence in an Open Cohort Study in Brazilian Amazon
Authors: Katsuragawa Tony Hiroshi , Gil Luiz Herman Soares , Lima Alzemar Alves de , Freitag Elci Marlei , Santos Tatiana Marcondes dos , Nascimento Filha Maria Teixeira do , Santos Júnior Alcides Procópio Justiniano dos , Silva Josiane Mendes da , Rodrigues Aline de Freitas , Tada Mauro Shugiro , Fontes Cor Jesus Fernandes , Pereira da Silva Luiz Hildebrando
Published: March 2013

In children, the Intermittent Preventive Treatment (IPTc), currently called Seasonal Malaria Chemoprevention (SMC), was considered effective on malaria control due to the reduction of its incidence in Papua New Guinea and in some areas with seasonal malaria in Africa. However, the IPT has not been indicated because of its association with drug resistance and for hindering natural immunity development. Thus, we evaluated the alternative IPT impact on malaria incidence in three riverside communities on Madeira River, in the municipality of Porto Velho, RO. We denominate this scheme Selective Intermittent Preventive Treatment (SIPT). The SIPT consists in a weekly dose of two 150 mg chloroquine tablets for 12 weeks, for adults, and an equivalent dose for children, after complete supervised treatment for P. vivax infection. This scheme is recommend by Brazilian Health Ministry to avoid frequent relapses. The clinic parasitological and epidemiological surveillance showed a significant reduction on vivax malaria incidence. The results showed a reduction on relapses and recurrence of malaria after SIPT implementation. The SIPT can be effective on vivax malaria control in localities with high transmission risk in the Brazilian Amazon.
Increases in Xu Zheng and Yu Zheng among Patients with Breast Cancer Receiving Different Anticancer Drug Therapies
Authors: Huang Sheng-Miauh , Chien Li-Yin , Tai Cheng-Jeng , Tseng Ling-Ming , Chen Ping-Ho , Tai Chen-Jei
Published: March 2013

Aim. The objectives of this study were to compare yang-xu, yin-xu, and yu among patients with breast cancer right before, one month after, and three months after receiving target, chemo, or combined therapy.Method. After recruiting 126 patients from 4 hospitals in northern Taiwan, a longitudinal study was carried out with 61 patients receiving chemotherapy, 30 receiving target therapy, and 35 receiving combined therapy. Yang-xu, yin-xu, and yu were assessed using the Traditional Chinese Medical Constitutional Scale (TCMCS), with higher scores indicating more xu and yu.Results. There were significant increases in yang-xu, yin-xu, and yu at 1 month and 3 months after than before the start of the chemotherapy, target, or combined therapy. Patients receiving combined therapy had significantly higher scores in yang-xu and yin-xu than patients receiving chemo or target therapy. A history of coronary heart disease was associated with more yin-xu. Those patients who had undergone a mastectomy were associated with less yu zheng than those patients who had not.Conclusion and Implications. TCM doctors should focus their treatment on dealing with xu and yu in order to support their patients, as they complete their modern anticancer treatments.
A Multiple Case Series Analysis of Six Variants of Attentional Bias Modification for Depression
Authors: Kruijt Anne-Wil , Putman Peter , Van der Does Willem
Published: March 2013

Background. Attention bias modification (ABM) is a new treatment for affective disorders. A meta-analysis of ABM for anxiety disorders showed that the effect size may be large but the number of studies is low. The working mechanism is still unclear, and little is known about the optimal treatment parameters. ABM for depression is much less studied. A few studies claimed positive effects but the sample sizes are low. Furthermore, the treatment parameters varied widely and differed from the anxiety literature. Aim. To select the most promising version of ABM for depression for further evaluation in clinical trials. Methods. Multiple case series design. We tested six versions of ABM that varied on stimulus duration and training direction. Thirty students with mild to moderate symptoms of depression underwent four sessions of ABM. Change of attentional bias was measured during each session. Generalization of treatment effects and the role of awareness of receiving training were also investigated. Results. None of the investigated versions of ABM had a consistent effect on attentional bias. Changes of attentional bias in individual participants the effects did not generalize to untrained stimuli. Conclusion. It is unlikely that any of these ABM versions will have a specific effect on symptoms in controlled studies.
PH1: An Archaeovirus ofHaloarcula hispanicaRelated to SH1 and HHIV-2
Authors: Porter Kate , Tang Sen-Lin , Chen Chung-Pin , Chiang Pei-Wen , Hong Mei-Jhu , Dyall-Smith Mike
Published: March 2013

Halovirus PH1 infectsHaloarcula hispanicaand was isolated from an Australian salt lake. The burst size in single-step growth conditions was 50–100 PFU/cell, but cell density did not decrease until well after the rise (4–6 hr p.i.), indicating that the virus could exit without cell lysis. Virions were round, 51 nm in diameter, displayed a layered capsid structure, and were sensitive to chloroform and lowered salt concentration. The genome is linear dsDNA, 28,064 bp in length, with 337 bp terminal repeats and terminal proteins, and could transfect haloarchaeal species belonging to five different genera. The genome is predicted to carry 49 ORFs, including those for structural proteins, several of which were identified by mass spectroscopy. The close similarity of PH1 to SH1 (74% nucleotide identity) allowed a detailed description and analysis of the differences (divergent regions) between the two genomes, including the detection of repeat-mediated deletions. The relationship of SH1-like and pleolipoviruses to previously described genomic loci of virus and plasmid-related elements (ViPREs) of haloarchaea revealed an extensive level of recombination between the known haloviruses. PH1 is a member of the same virus group as SH1 and HHIV-2, and we propose the namehalosphaerovirusto accommodate these viruses.
Parallel Simulation of Population Balance Model-Based Particulate Processes Using Multicore CPUs and GPUs
Authors: Prakash Anuj V. , Chaudhury Anwesha , Ramachandran Rohit
Published: March 2013

Computer-aided modeling and simulation are a crucial step in developing, integrating, and optimizing unit operations and subsequently the entire processes in the chemical/pharmaceutical industry. This study details two methods of reducing the computational time to solve complex process models, namely, the population balance model which given the source terms can be very computationally intensive. Population balance models are also widely used to describe the time evolutions and distributions of many particulate processes, and its efficient and quick simulation would be very beneficial. The first method illustrates utilization of MATLAB's Parallel Computing Toolbox (PCT) and the second method makes use of another toolbox, JACKET, to speed up computations on the CPU and GPU, respectively. Results indicate significant reduction in computational time for the same accuracy using multicore CPUs. Many-core platforms such as GPUs are also promising towards computational time reduction for larger problems despite the limitations of lower clock speed and device memory. This lends credence to the use of highfidelity models (in place of reduced order models) for control and optimization of particulate processes.
Effect of Nitrogen Implantation on Metal Transfer during Sliding Wear under Ambient Conditions
Authors: Autry Luke , Marcus Harris
Published: March 2013

Nitrogen implantation in Interstitial-Free steel was evaluated for its impact on metal transfer and 1100 Al rider wear. It was determined that nitrogen implantation reduced metal transfer in a trend that increased with dose; the Archard wear coefficient reductions of two orders of magnitude were achieved using a dose of 2e17 ions/cm2, 100 kV. Cold-rolling the steel and making volumetric wear measurements of the Al-rider determined that the hardness of the harder material had little impact on volumetric wear or friction. Nitrogen implantation had chemically affected the tribological process studied in two ways: directly reducing the rider wear and reducing the fraction of rider wear that ended up sticking to the ISF steel surface. The structure of the nitrogen in the ISF steel did not affect the tribological behavior because no differences in friction/wear measurements were detected after postimplantation heat treating to decompose the as-implantedε-Fe3N toγ-Fe4N. The fraction of rider-wear sticking to the steel depended primarily on the near-surface nitrogen content. Covariance analysis of the debris oxygen and nitrogen contents indicated that nitrogen implantation enhanced the tribo-oxidation process with reference to the unimplanted material. As a result, the reduction in metal transfer was likely related to the observed tribo-oxidation in addition to the introduction of nitride wear elements into the debris. The primary Al rider wear mechanism was stick-slip, and implantation reduced the friction and friction noise associated with that wear mechanism. Calculations based on the Tabor junction growth formula indicate that the mitigation of the stick-slip mechanism resulted from a reduced adhesive strength at the interface during the sticking phase.
Differential Subordination for Certian Subclasses of -Valent Functions Assoicated with Generalized Linear Operator
Authors: El-Ashwah R. M. , Aouf M. K. , El-Deeb S. M.
Published: March 2013

By making use of the differential subordination analytic functions, we investigate inclusion relationships among certain classes of analytic and -valent functions defined by generalized linear operator.
Capturing and Reproducing Spatial Audio Based on a Circular Microphone Array
Authors: Alexandridis Anastasios , Griffin Anthony , Mouchtaris Athanasios
Published: March 2013

This paper proposes a real-time method for capturing and reproducing spatial audio based on a circular microphone array. Following a different approach than other recently proposed array-based methods for spatial audio, the proposed method estimates the directions of arrival of the active sound sources on a per time-frame basis and performs source separation with a fixed superdirective beamformer, which results in more accurate modelling and reproduction of the recorded acoustic environment. The separated source signals are downmixed into one monophonic audio signal, which, along with side information, is transmitted to the reproduction side. Reproduction is possible using either headphones or an arbitrary loudspeaker configuration. The method is compared with other recently proposed array-based spatial audio methods through a series of listening tests for both simulated and real microphone array recordings. Reproduction using both loudspeakers and headphones is considered in the listening tests. As the results indicate, the proposed method achieves excellent spatialization and sound quality.
Revision of the Messinian-Early Zanclean Sediments from ODP Hole 953C (Canary Island Archipelago, North-Eastern Atlantic): Biostratigraphy, Cyclostratigraphy, and Astronomical Tuning
Authors: Riforgiato Federica
Published: March 2013

A quantitative study was performed on calcareous plankton of the Messinian-early Zanclean succession recovered at ODP Leg 157 Hole 953C (Canary Island Archipelago, North-Eastern Atlantic). This revision allowed to recognize some events typically recorded in the Mediterranean region, highlighting affinities between the Mediterranean and North Atlantic Ocean, in the considered time interval. The presence of such events in an open-ocean succession provides the possibility to substantially improve the biostratigraphic resolution and supplies useful correlation tools between the Mediterranean and oceanic areas. Moreover, to unravel cyclical patterns of deposition and given that the investigated succession shows no evident lithological pattern, cyclostratigraphic analyses have been based on abundance fluctuations ofGlobigerinoides-Orbulinagroup, neogloboquadrinids, and warm-water versus cool-water species ratio. As a result, forty-three precession-controlled cycles have been recognized spanning from 6.457 Ma to 4.799 Ma.
New Strategies in the Treatment of Multiple Myeloma
Authors: Munshi Nikhil C. , Anderson Kenneth C.
Published: March 2013

Multiple myeloma is the second most common hematologic malignancy affecting terminally differentiated plasma cells. Although high-dose chemotherapy and autologous stem cell transplantation have improved survival in younger patients, the natural history of multiple myeloma has been changed with the availability of six new agents approved in the past 10 years (thalidomide, bortezomib, lenalidomide, liposomal doxorubicin, carfilzomib, and pomalidomide). Despite this significant improvement in the overall outcome, multiple myeloma remains incurable in the majority of patients, prompting a continued search for additional therapeutic options. Extensive molecular and genomic characterization of multiple myeloma cells in their bone marrow milieu, which affects myeloma cell growth and survival, has provided a number of novel drugable targets and pathways. Perturbation of protein catabolism at multiple levels has become an important target in multiple myeloma. Similarly, improvements in monoclonal antibody generation and vaccine development, along with identification of a number of cell surface and cellular targets, have led to the development of various strategies, including antibodies and antibody–drug conjugates that are under investigation preclinically and in early clinical studies. We propose that eventually, molecularly informed multiagent combination therapies will be required to eliminate the multiple myeloma cell clone for long-term disease control. Clin Cancer Res; 19(13); 3337–44. ©2013 AACR.
Neoadjuvant Chemotherapy with or without Zoledronic Acid in Early Breast Cancer—A Randomized Biomarker Pilot Study
Authors: Winter Matthew C. , Wilson Caroline , Syddall Stuart P. , Cross Simon S. , Evans Alyson , Ingram Christine E. , Jolley Ingrid J. , Hatton Matthew Q. , Freeman Jennifer V. , Mori Stefano , Holen Ingunn , Coleman Robert E.
Published: March 2013

Purpose: To investigate the short-term biologic effects of neoadjuvant chemotherapy +/− zoledronic acid (ZOL) in invasive breast cancer.

Experimental Design: Forty patients were randomized to receive a single 4 mg infusion of ZOL 24 hours after the first cycle of FE100C chemotherapy, or chemotherapy alone. Randomization was stratified for tumor stage, ER, HER2, and menopausal status. All patients had repeat breast core biopsy at day 5 (D5) ± day 21 (D21). Effects on apoptotic index, proliferation (Ki67), growth index, surrogate serum markers of angiogenesis (VEGF), and serum reproductive hormones within the TGFβ family (activin-A, TGFβ1, inhibin-A, and follistatin) were evaluated and compared.

Results: Baseline clinicopathologic characteristics were well balanced. Cell growth index (increased apoptosis and reduced proliferation) fell at D5 in both groups but recovered more rapidly with chemotherapy + ZOL compared with chemotherapy alone by D21 (P = 0.006). At D5, a greater reduction in serum VEGF occurred with chemotherapy + ZOL compared with chemotherapy: median percentage change −23.8% [interquartile range (IQR): −32.9 to −15.8] versus −8.4% (IQR: −27.3 to +8.9; P = 0.02), but these effects were lost by D21. Postmenopausal women showed a decrease in follistatin levels from baseline in the chemotherapy + ZOL group at D5 and D21, compared with chemotherapy alone (Pinteraction = 0.051).

Conclusions: In this pilot study, short-term changes in biomarkers suggest potentially relevant interactions between tumor biology, chemotherapy, modification of the bone microenvironment, and the endocrine status of the host. Larger studies with more frequent dosing of zoledronic acid are needed to assess these complex interactions more thoroughly. Clin Cancer Res; 19(10); 2755–65. ©2013 AACR.
Epidemiology of Hereditary Ataxias in Spain: Hospital Discharge Registry and Population-Based Mortality Study
Authors: Alonso Verónica , Villaverde-Hueso Ana , Hens Manuel J. , Morales-Piga Antonio , Abaitua Ignacio , Posada de la Paz Manuel
Published: March 2013

Background: Hereditary ataxias (HA) comprise a group of genetically heterogeneous rare diseases. As important public health problems to be monitored, this study analyses the morbimortality of HA in Spain. Methods: Data were extracted from the national death index (1981-2008), using the International Classification of Diseases (ICD) 9th revision code 334 until 1998, and 10th revision code G11 from 1999 onwards. ICD-9 codes were then selected from the national discharge dataset (1998-2007). Age-adjusted morbidity and mortality rates were obtained by gender and 5-year period. Results: Of the 610 HA deaths from 1981 to 2008, 277 corresponded to Friedreich's ataxia (45.4%) and 333 (54.6%) to other and unspecified ataxias (non-Friedreich group). Both groups showed an increase in mortality trend, which was more pronounced in males from 1985-1989 to 1990-1994. Geographical distribution of mortality revealed higher risk for males, mainly in the north of Spain. A total of 5,341 HA hospitalisations were identified from 1998 to 2007. The average annual age-adjusted hospitalisation rate was 1.19 per 100,000 population, with a rising trend. Conclusion: This increase in morbidity and mortality, coupled with the slight interprovincial differences, indicate that more attention should be paid to these rare diseases by public authorities and society alike.
One-Year Surveillance of ESKAPE Pathogens in an Intensive Care Unit of Monterrey, Mexico
Authors: Llaca-Díaz Jorge Martín , Mendoza-Olazarán Soraya , Camacho-Ortiz Adrian , Flores Samantha , Garza-González Elvira
Published: March 2013

Background: Bacterial species from the ESKAPE group (i.e. Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) are frequently resistant to antibiotics. The purpose of this study was to monitor the incidence of ESKAPE pathogens at the intensive care unit (ICU) of a tertiary care hospital in Monterrey, Mexico. Methods: All clinically relevant organisms isolated from June 2011 to June 2012 were included. Identification and susceptibility testing was performed using panels from Sensititre. Resistance to oxacillin, for S. aureus, and the production of extended spectrum β-lactamases (ESBLs), for K. pneumonia, were determined as defined by the Clinical Laboratory Standards Institute. Also, the presence of vanA and vanB genes was determined in E. faecium vancomycin (VAN)-resistant isolates. Results: The majority of pathogens (64.5%) isolated in the ICU unit were from the ESKAPE group. The organisms most frequently isolated were A. baumannii (15.8%) and P. aeruginosa (14.3%). A high resistance to carbapenems was detected for A. baumannii (75.3%) while 62% of S. aureus isolates were confirmed to be methicillin resistant. Of the K. pneumoniae isolates, 36.9% were ESBL producers. We detected three E. faecium VAN-resistant isolates, all of which contained the vanA gene. Conclusion: The presence of the ESKAPE group of pathogens is a major problem in the ICU setting. The results of this study support the implementation of special antimicrobial strategies to specifically target these microorganisms.
Comparative Efficacy of Sunitinib versus Sorafenib as First-Line Treatment for Patients with Metastatic Renal Cell Carcinoma
Authors: Park Seong Joon , Lee Jae-Lyun , Park Inkeun , Park Kwonoh , Ahn Yongcheol , Ahn Jin-Hee , Lee Dae-Ho , Ahn Shin , Song Cheryn , Hong Jun Hyuk , Kim Choung-Soo , Ahn Hanjong
Published: March 2013

Background: This study investigated the efficacy and toxicity of sorafenib and sunitinib as primary treatment for patients with metastatic renal cell carcinoma (mRCC). Methods: We identified 49 and 220 patients treated with sorafenib and sunitinib, respectively, as first-line therapy in the Asan Medical Centre from April 2005 to March 2011. Results: Disease control rates of 71 and 74% were achieved with sorafenib and sunitinib, respectively (p = 0.687). After a median follow-up of 27.6 months, progression-free survival (PFS) and overall survival (OS) were not significantly different between the sorafenib and the sunitinib group (PFS 8.6 vs. 9.9 months, respectively, p = 0.948, and OS 25.7 vs. 22.6 months, p = 0.774). Patients treated with sorafenib required dose reduction due to toxicities less frequently than those treated with sunitinib (37 vs. 54%, p = 0.034). Haematological toxicity of grade 3 or 4 was more common in the sunitinib group than in the sorafenib group (45 vs. 4%, p < 0.001). Multivariate analysis showed old age, Heng's risk group, and bone and liver metastases, but not the type of vascular endothelial growth factor tyrosine kinase inhibitor, were independent prognostic factors affecting OS. Conclusion: The results of this study indicate that sorafenib has comparable efficacy to sunitinib in the treatment of mRCC patients and fewer and less severe toxicities, but the number of patients included in the study was small.
Pathological Characteristics, Biochemical Recurrence and Functional Outcome in Radical Prostatectomy Patients on Statin Therapy
Authors: Kontraros M. , Varkarakis I. , Ntoumas K. , Deliveliotis C.
Published: March 2013

Introduction: We assessed the pathological characteristics of the radical prostatectomy specimen, the rate of biochemical failure and the functional outcome after surgery, in terms of incontinence and erectile dysfunction rate, in patients on statin medication. Materials and Methods: A total of 588 patients with a mean age 65.2 years (SD = 5.7 years) participated in the study. All patients were contacted and interviewed. Results: Users who had been on statin medication for more than 2 years had lower levels of preoperative serum PSA (p = 0.034), a 2.76 times greater likelihood of being staged as pT3a to pT3b rather than pT2a to pT2c, and a 5.39 times greater likelihood of having a postoperative Gleason score equal to seven or more. Positive surgical margins and urinary incontinence were not significantly associated with statin use. The probability of erectile dysfunction was significantly greater for statin users. Conclusion: Statin medication was associated with a statistically significantly lower PSA value and an increased rate of high Gleason score and pathologic stage in patients receiving medication for more than 2 years. Statins were found to be an independent predictor of recurrence. Lastly, statin users were more likely to present with preoperative and postoperative erectile dysfunction.
The Role of Transarterial Embolization in the Management of Hematuria Secondary to Congenital Renal Arteriovenous Malformations
Authors: Zhang Bo , Jiang Zai-Bo , Huang Ming-Sheng , Zhu Kang-Shun , Guan Shou-Hai , Shan Hong
Published: March 2013

Objective: To evaluate the efficacy and safety of transarterial embolization (TAE) in the management of hematuria secondary to congenital renal arteriovenous malformations (AVM). Patients and Methods: Between May 2007 and February 2012, 6 patients with congenital AVM treated with TAE were analyzed retrospectively, followed by a brief review of TAE in the treatment of congenital AVM. Clinical records with respect to general conditions, location, embolic materials, complications and overall outcome were collected from the original hospital charts and outpatient medical records. Results: Three patients with AVM were confirmed by contrast-enhanced CT scans, and the other 3 patients were detected by renal angiography. TAE was performed with steel coils in 2 patients and n-butyl-2-cyanoacrylate (NBCA) in 4 patients. After a mean follow-up of 22 months, no serious adverse effects were observed in all patients. There were no complaints of hematuria at the end of the follow-up period. Conclusion: For unexplained massive hematuria, congenital renal AVM needs to be considered as a differential diagnosis. Selective renal angiography and embolization should be recommended as the first choice to treat massive hematuria secondary to congenital renal AVM.
The Giant Leap and Small Steps to Better Reperfusion in ST-Segment Elevation Myocardial Infarction Patients
Authors: Brekke Magne
Published: March 2013

No abstract available
Association of Calcium, Phosphate and Parathyroid Hormone with Renal Allograft Function: A Retrospective Cohort Study
Authors: Hiemstra Thomas F. , Brown Adam J.D. , Chaudhry Afzal N. , Walsh Michael
Published: March 2013

Background: Significant variations in postoperative levels of parathyroid hormone (PTH), calcium and phosphate exist after renal transplantation, but whether they affect allograft function is unknown. We investigated the association between early post-transplant levels of PTH, calcium and phosphate and graft function. Methods: We performed a single-centre cohort study of renal transplant recipients from Addenbrooke's Hospital, Cambridge, between April 1997 and March 2007, evaluating the association between plasma calcium, phosphate and PTH 1 month after transplantation and change in epidermal growth factor receptor (eGFR) in the first 12 months after transplantation (estimated using the Modification of Diet in Renal Disease Study equation). Differences in eGFR between 26 and 52 weeks after transplantation were computed using mixed effects linear regression models for repeated measures of eGFR, while adjusting for sociodemographic and biochemical variables. Results: Three hundred and forty-three patients were eligible for study. The mean age (standard deviation) at transplant was 43 years (13 years). Between 30 and 90 days after transplantation, the median (25th-75th percentile) eGFR was 33 (26-50) ml/min/1.73 m2, the mean calcium level was 2.4 (0.17) mmol/l and the mean phosphate level was 0.78 (0.23) mmol/l. There was a significant interaction between calcium and phosphate levels (p = 0.006). In patients with low levels of phosphate, higher levels of calcium were associated with declining eGFR over time. However, in patients with a high phosphate level, higher calcium was associated with improved eGFR. Conclusions: Higher serum calcium in patients with low serum phosphate after transplantation is associated with a decline in graft function during the first year after transplantation. Disorders of mineral metabolism after transplant may represent an important therapeutic target to preserve allograft function.
The Malnutrition-Inflammation-Depression-Arteriosclerosis Complex Is Associated with an Increased Risk of Cardiovascular Disease and All-Cause Death in Chronic Hemodialysis Patients
Authors: Choi Myung-Jin , Seo Jang-Won , Yoon Jong-Woo , Lee Sang-Kyu , Kim Soo-Jin , Lee Young-Ki , Noh Jung-Woo , Koo Ja-Ryong
Published: March 2013

Background: In chronic hemodialysis patients, malnutrition, inflammation, depression and arteriosclerosis are pathogenetically associated suggesting the presence of malnutrition-inflammation-depression-arteriosclerosis (MIDA) complex acting as a risk factor for cardiovascular disease (CVD). Methods: Nutritional status was assessed by serum albumin, subjective global assessment and normalized protein catabolic rate (nPCR). Inflammation was assessed by serum high-sensitivity C-reactive protein (hsCRP). Depression was assessed with the Beck Depression Inventory and DSM-IV criteria. The severity of arteriosclerosis was measured by pulse wave velocity (PWV). Results: Among 81 hemodialysis patients, 44 (54.3%) had malnutrition (albumin <4.0 mg/dl with subjective global assessment score <6 and/or nPCR <1.0) and 39 (48.1%) had inflammation (hsCRP >1 mg/l). The prevalence of depression was 50.6% (n = 41). Fifty-nine (73.8%) had arteriosclerosis (measured PWV > expected PWV based on age/blood pressure/gender adjustment). The severity of the all four individual MIDA components correlated well with each other. The average number of the MIDA complication (MIDA score) was 2.27 ± 1.33. -During the 5-year follow-up, 40 cases of CVD and 26 cases of all-cause death occurred. In Cox analysis adjusted for -previous CVD, age, diabetes, blood pressure, pulse pressure, intradialytic hypotension, B-type natriuretic peptide, -hemoglobin and hemodialysis incompliance, the MIDA score was an independent predictor of CVD and all-cause death: hazard ratio (95% confidence interval); 1.89 (1.13-3.17) and 3.48 (1.32-9.21) for an increase of 1 MIDA score. Conclusions: This study suggests the presence of MIDA complex, which is composed of malnutrition, inflammation, depression and arteriosclerosis. The MIDA complex syndrome was an independent risk factor for CVD and all-cause death in chronic hemodialysis patients.
CXCR7/CXCR4/CXCL12 Axis Regulates the Proliferation, Migration, Survival and Tube Formation of Choroid-Retinal Endothelial Cells
Authors: Jin Jing , Zhao Wen-cheng , Yuan Fei
Published: March 2013

Background/Aims: Stromal cell-derived factor-1 (SDF-1) has been shown to mediate a broad range of biological processes via CXCR4, once regarded as its only receptor. CXCR7 is a recently identified receptor for SDF-1. This study aimed to investigate whether the CXCR7/CXCR4/SDF-1 axis is involved in choroidal neovascularization (CNV) formation in an in vitro hypoxic model. Methods: CXCR7 siRNA and/or CXCR4 siRNA was transfected into a hypoxic model of the choroid-retinal endothelial RF/6A cell line. CCK-8 analysis, transwell migration analysis, annexin V-FITC and propidium iodide staining, and Matrigel tube formation analysis were performed to investigate the role of CXCR4 and CXCR7 in SDF-1-induced proliferation, migration, survival and tube formation of RF/6A cells. Results: CXCR4, but not CXCR7, mediates SDF-1-induced RF/6A cell migration and proliferation under hypoxic conditions, whereas CXCR7 was exclusively involved in RF/6A cell survival. In addition, CXCR7 and CXCR4 acted together to regulate RF/6A cell tube formation. Conclusion: The CXCR7/CXCR4/SDF-1 axis plays an important role in the formation of CNV, and may become a novel target for the treatment of CNV-associated diseases.
Statin Use and Calcific Uremic Arteriolopathy: A Matched Case-Control Study
Authors: Nigwekar Sagar U. , Bhan Ishir , Turchin Alexander , Skentzos Stephen C. , Hajhosseiny Reza , Steele David , Nazarian Rosalynn M. , Wenger Julia , Parikh Samir , Karumanchi Ananth , Thadhani Ravi
Published: March 2013

Background: Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is characterized by vascular calcification, thrombosis and intense inflammation. Prior research has shown that statins have anticalcification, antithrombotic and antiinflammatory properties; however, the association between statin use and CUA has not been investigated. Methods: This matched case-control study included 62 adult maintenance hemodialysis (HD) patients with biopsy-confirmed CUA diagnosed between the years 2002 and 2011 (cases). All cases were hospitalized at the time of diagnosis. Controls (n = 124) were hospitalized maintenance HD patients without CUA (matched to cases by gender and timing of hospitalization). Univariate and multivariable logistic regression models were applied to compute odds ratio (OR) and 95% confidence intervals (CI) for CUA in statin users, and also to examine previously described associations. -Results: The mean age of cases was 58 years. Most were females (68%), and of white race (64%). Statin use was more common in controls than in cases (39 vs. 19%, p < 0.01). Statin use was associated with lower odds of CUA in unadjusted (OR 0.38, 95% CI 0.18-0.79) and adjusted (OR 0.20, 95% CI 0.05-0.88) analyses. Hypercalcemia (OR 2.25, 95% CI 1.14-4.43), hypoalbuminemia (OR 5.73, 95% CI 2.79-11.77), calcitriol use (OR 5.69, 95% CI 1.02-31.77) and warfarin use (OR 4.30, 95% CI 1.57-11.74) were positively associated with CUA in adjusted analyses whereas paricalcitol and doxercalciferol were not (OR 1.33, 95% CI 0.54-3.27). Conclusion: Statin use may be negatively associated with odds of CUA. Further large prospective studies with attention to potential confounders are needed to confirm these findings.