bluuebunny/crossref_metadata_2025 huggingface dataset:
DIABETIC AUTONOMIC NEUROPATHY DETECTION BY HEART-RATE VARIABILITY POWER-SPECTRAL ANALYSIS
Authors: DESAI KAMALAKAR , GHISTA DHANJOO N. , EL MUGAMEX ISSAM JAHA , ACHARYA U. RAJENDRA , TOWSEY MICHAEL , ALI SULTAN ABDUL , SAEED MOHAMMED , FIKRI M. AMIN
Published: September 2011

Heart rate is a non-stationary signal and provides a powerful interplay between the sympathetic and parasympathetic nervous systems. The heart rate variation signal can reveal disorders associated with how these nervous systems regulate the heart rate, and hence may contain indicators of this disease state, or warnings about impending or future cardiac diseases. These indicators may be present at all times or may occur at random during certain intervals in the time scale. It is difficult and time consuming to pinpoint these abnormalities in a huge cardiac data set. Heart rate variability (HRV) constitutes a tool for assessing the activities of the autonomic nervous system (ANS). In this work, we have proposed a computer based analytical system to determine the HRV, and analyzed it to obtain HRV Power-spectrum for normal, diabetes and diabetes with neuropathy subjects in deep breathing, standing and supine position. We have then designated indices based on the HRV power-spectra power values and frequency shift of these peaks from their normal frequency values. We have shown the efficacy and sensitivity of these indices, to differentiate between normals, diabetics and diabetics with ischemic heart disease. Thus we have demonstrated how effectively these HRV power-spectral indices can enable diagnosis of diabetic autonomic neuropathy. Finally, we have composed an integrated index made up of these power-spectral indices, to facilitate distinguishing and diagnosing diabetic autonomic neuropathy in terms of just one index or number.
ID1 inhibits USF2 and blocks TGF-β-induced apoptosis in mesangial cells
Authors: Sato Alex Yuri Simões , Antonioli Eliane , Tambellini Rodrigo , Campos Alexandre Holthausen
Published: September 2011

Mesangial cells (MC) play an essential role in normal function of the glomerulus. Phenotypic changes in MC lead to the development of glomerular diseases such as diabetic nephropathy and glomerulosclerosis. The late phase of diabetic glomerulopathy is characterized by MC death and fibrosis. Current data highlight the transforming growth factor (TGF)-β as a trigger of the pathological changes observed in MC, including death by apoptosis. However, the mechanisms and mediators involved in this process are still poorly understood. Identification of novel elements involved in MC death may provide a better understanding of the pathophysiology of glomerular diseases. Here, we show that bone morphogenetic proteins (BMPs; known antagonists of the profibrotic effects of TGF-β in the kidney) strongly induce inhibitor of DNA binding (ID1) mRNA transcription and protein expression in human MC. ID genes have been implicated in cell survival control and are constitutively expressed in MC. We show that BMPs and ID1 exert an anti-apoptotic effect in MC by inhibition of USF2 transcriptional activity. On the other hand, TGF-β upregulates USF2, increasing BAX (proapoptotic gene) levels and apoptosis rates. Taken together, our results point to a novel molecular pathway that modulates MC apoptosis, which is potentially involved in the pathogenesis of glomerular diseases.
Acute unilateral ischemic renal injury induces progressive renal inflammation, lipid accumulation, histone modification, and “end-stage” kidney disease
Authors: Zager Richard A. , Johnson Ali C. M. , Becker Kirsten
Published: September 2011

There is an emerging concept in clinical nephrology that acute kidney injury (AKI) can initiate chronic kidney disease (CKD). However, potential mechanisms by which this may occur remain elusive. Hence, this study tested the hypotheses that 1) AKI triggers progressive activation of selected proinflammatory genes, 2) there is a relative failure of compensatory anti-inflammatory gene expression, 3) proinflammatory lipid accumulation occurs, 4) these changes correspond with “gene-activating” histone acetylation, and 5) in concert, progressive renal disease results. CD-1 mice were subjected to 30 min of unilateral renal ischemia. Assessments were made 1 day, 1 wk, or 3 wk later. Results were contrasted to those observed in uninjured contralateral kidneys or in kidneys from normal mice. Progressive renal injury occurred throughout the 3-wk postischemic period, as denoted by stepwise increases in neutrophil gelatinase-associated lipocalin gene induction and ongoing histologic damage. By 3 wk postischemia, progressive renal disease was observed (massive tubular dropout; 2/3rds reduction in renal weight). These changes corresponded with progressive increases in proinflammatory cytokine/chemokine gene expression (MCP-1, TNF-α, TGF-β1), a relative failure of anti-inflammatory enzyme/cytokine (heme oxygenase-1; IL-10) upregulation, and progressive renal lipid (cholesterol/triglyceride) loading. Stepwise increases in collagen III mRNA and collagen deposition (Sirius red staining) indicated a progressive profibrotic response. Postischemic dexamethasone treatment significantly preserved renal mass, indicating functional significance of the observed proinflammatory state. Progressive gene-activating H3 acetylation was observed by ELISA, rising from 5% at baseline to 75% at 3 wk. This was confirmed by chromatin immunoprecipitation assay of target genes. In sum, these results provide experimental support for the clinical concept that AKI can trigger CKD, this is partially mediated by progressive postischemic inflammation, ongoing lipid accumulation results (potentially evoking “lipotoxicity”), and increasing histone acetylation at proinflammatory/profibrotic genes may contribute to this self-sustaining injury-promoting state.
Trial-by-trial analysis of intermanual transfer during visuomotor adaptation
Authors: Taylor Jordan A. , Wojaczynski Greg J. , Ivry Richard B.
Published: September 2011

Studies of intermanual transfer have been used to probe representations formed during skill acquisition. We employ a new method that provides a continuous assay of intermanual transfer, intermixing right- and left-hand trials while limiting visual feedback to right-hand movements. We manipulated the degree of awareness of the visuomotor rotation, introducing a 22.5° perturbation in either an abrupt single step or gradually in ∼1° increments every 10 trials. Intermanual transfer was observed with the direction of left-hand movements shifting in the opposite direction of the rotation over the course of training. The transfer on left-hand trials was less than that observed in the right hand. Moreover, the magnitude of transfer was larger in our mixed-limb design compared with the standard blocked design in which transfer is only probed at the end of training. Transfer was similar in the abrupt and gradual groups, suggesting that awareness of the perturbation has little effect on intermanual transfer. In a final experiment, participants were provided with a strategy to offset an abrupt rotation, a method that has been shown to increase error over the course of training due to the operation of sensorimotor adaptation. This deterioration was also observed on left-hand probe trials, providing further support that awareness has little effect on intermanual transfer. These results indicate that intermanual transfer is not dependent on the implementation of cognitively assisted strategies that participants might adopt when they become aware that the visuomotor mapping has been perturbed. Rather, the results indicate that the information available to processes involved in adaptation entails some degree of effector independence.
Design Considerations for Autocalibrations of Wide-BandΔΣFractional-NPLL Synthesizers
Authors: Shin Jaewook , Shin Hyunchol
Published: September 2011

Autocalibration of VCO frequency and loop gain is an essential process in PLL frequency synthesizers. In a wide tuning-range fractional-NPLL frequency synthesizer, high-speed and high-precision automatic calibration is especially important for shortening the lock time and improving the phase noise. This paper reviews the design issues of the PLL auto-calibration and discusses on the limitations of the previous techniques. A very simple and efficient auto-calibration method based on a high-speed frequency-to-digital converter (FDC) is proposed and verified through simulations. The proposed method is highly suited for a very wide-bandΔΣfractional-NPLL.
Design of a Two-Element Antenna Array Using Substrate Integrated Waveguide Technique
Authors: Sellal Kheireddine , Talbi Larbi
Published: September 2011

The design of a two-element antenna array using the substrate integrated waveguide (SIW) technique and operating at 10 GHz is presented. The proposed antenna array consists of two SIW phase shifter sections with two SIW slot antennas. The phase shifting is achieved by changing the position of two inductive posts inserted inside each element of the array. Numerical simulations and experimental measurements have been carried out for three differential phases between the two antenna array elements, namely, 0°, 22.5°, and 67.5°. A prototype for each differential phase has been fabricated and measured. Results have shown a fairly good agreement between theory and experiments. In fact, a reflection coefficient of better than 20 dB has been achieved around 10 GHZ. The E-plane radiation pattern has shown a beam scan between 5° and 18° and demonstrated the feasibility of designing an SIW antenna phased array.
Preirradiation Graft Polymerization of Styrene in a Poly(tetrafluoroethylene) Film Investigated by Time-Resolved Small-Angle Neutron Scattering
Authors: Iwase Hiroki , Sawada Shin-ichi , Yamaki Tetsuya , Maekawa Yasunari , Koizumi Satoshi
Published: September 2011

Preirradiation graft polymerization of styrene in a poly(tetrafluoroethylene) (PTFE) film was examined by time-resolved small-angle neutron scattering (SANS). A crosslinked PTFE film, thickness of which is about 50 μm, was irradiated byγ-ray and immersed in a mixed solvent of styrene monomer and toluene. SANS elucidated that graft polymerization proceeds by two reaction processes (I) and (II). In process (I) at  min, graft polymerization occurs at an interface between crystalline and amorphous PTFE domains and the grafted polystyrene segregates from PTFE, forming a thin layer with a sharp interface. In process (II) at  min, grafted PS layer starts to bridge between crystalline domains. At the end of process (II), 40% of total crystalline PTFE domain is covered by the grafted PS chains.
Synthesis and Characterization ofSb2S3Nanorods via Complex Decomposition Approach
Authors: Alemi Abdolali , Hanifehpour Younes , Joo Sang Woo
Published: September 2011

Based on the complex decomposition approach, a simple hydrothermal method has been developed for the synthesizing of Sb2S3nanorods with high yield in 24 h at150∘C. The powder X-ray diffraction pattern shows the Sb2S3crystals belong to the orthorhombic phase with calculated lattice parametersa=1.120 nm,b=1.128 nm, andc=0.383 nm. The quantification of energy dispersive X-ray spectrometric analysis peaks give an atomic ratio of 2 : 3 for Sb : S. TEM and SEM studies reveal that the appearance of the as-prepared Sb2S3is rod-like which is composed of nanorods with the typical width of 30–160 nm and length of up to 6 μm. High-resolution transmission electron microscopic (HRTEM) studies reveal that the Sb2S3is oriented in the [10-1] growth direction. The band gap calculated from the absorption spectra is found to be 3.29 ev, indicating a considerable blue shift relative to the bulk. The formation mechanism of Sb2S3nanostructures is proposed.
Synthesis, Characterization and Catalytic Performance ofH3SiW12O40/SiO2Prepared by Sol-Gel Technique
Authors: Isahak W. N. R. W. , Ismail M. , Nordin N. M. , Jahim J. M. , Yarmo M. A.
Published: September 2011

The purpose of this work is to study the synthesis, characterization, and catalytic performance of two types of solid heteropoly acid catalysts, namely, silicotungstic acid bulk (STAB) and STA-silica sol-gel (STA-SG) compared with sulfuric acid. From the XPS analyses, there was a significant formation of W-O-Si, W-O-W, and Si-O-Si bonding in STA-SG compared to that in STAB. The main spectra of O1s (90.74%, 531.5 eV) followed by other O1s peak (9.26%, 532.8 eV) were due to the presence of W-O-W and W-O-Si bonds, respectively. The STA-SG catalyst was found to be the more environmentally benign solid acid catalyst for the esterification reaction between oleic acid and glycerol due to its lower toxicity supported by silica via sol-gel technique. In addition, the ease of separation for STA-SG catalyst was attributed to its insoluble state in the product phase. The esterification products were then analysed by FTIR and HPLC. Both the H2SO4and the STAB gave high conversion of 100% and 98% but at a lower selectivity of GME with 81.6% and 89.9%, respectively. On the contrary, the STA-SG enabled a conversion of 94% but with a significantly higher GME selectivity of 95%, rendering it the more efficient solid acid catalyst.
Anemia in Children with Down Syndrome
Authors: Tenenbaum Ariel , Malkiel Sarah , Wexler Isaiah D. , Levy-Khademi Floris , Revel-Vilk Shoshana , Stepensky Polina
Published: September 2011

Background. Iron deficiency anemia impacts on cognitive development. The objective of this study was to determine the prevalence of anemia and iron deficiency in children with Down syndrome and identify risk factors for anemia.Methods. We conducted a prolective cross-sectional study of children attending a multidisciplinary Down syndrome medical center. One hundred and forty nine children with Down syndrome aged 0–20 years were enrolled in the study. Information obtained included a medical history, physical and developmental examination, nutritional assessment, and the results of blood tests.Results. Of the patients studied, 8.1% were found to have anemia. Among the 38 children who had iron studies, 50.0% had iron deficiency. In a multivariate analysis, Arab ethnicity and low weight for age were significantly associated with anemia. Gender, height, the presence of an eating disorder, and congenital heart disease were not risk factors for anemia.Conclusions. Children with Down syndrome are at risk for anemia and iron deficiency similar to the general population. Children with Down syndrome should be monitored for anemia and iron deficiency so that prompt intervention can be initiated.
Addition of Aripiprazole to the Clozapine May Be Useful in Reducing Anxiety in Treatment-Resistant Schizophrenia
Authors: Chanachev Aleksandar , Ansermot Nicolas , Crettol Wavre Séverine , Nowotka Ute , Stamatopoulou Maria-Eleni , Conus Philippe , Eap Chin B.
Published: September 2011

There exist many case reports and studies on the antipsychotic augmentation by aripirazole in partial responders to clozapine, the most seem to be finding a slight difference in the PANSS and CGI scores after the aripirazole addition. The results of our report are compatible with those of other studies but, we have found a considerable antianxiety action in both of the cases. The 5HT1A agonism of aripirazole could be hypothesized as mechanism contributing to this effect.
Subcapsular Orchiectomy in the Primary Therapy of Patients with Bone Metastasis in Advanced Prostate Cancer: An Anachronistic Intervention?
Authors: Rud Oleg , Peter Julia , Kheyri Reza , Gilfrich Christian , Ahmed Ali M. , Boeckmann Wieland , Fabricius Paul G. , May Matthias
Published: September 2011

Background. The therapeutic impact of palliative androgen deprivation in metastatic prostate cancer is indisputable. Bilateral orchiectomy represents the traditional method of AD but was reduced during the last years in favor for treatment with LHRH analogues. Due to limited economic resources of the health care system, the economically priced definite surgical castration might experience a renaissance.Methods. In this single-center retrospective study, 83 consecutive patients with osseous metastasized prostate cancer were evaluated, who had primarily been treated by subcapsular bilateral orchiectomy. Response to therapy, time until therapy failure, overall survival time, psychological disorders due to loss of organ, and disease-associated and postoperative surgical complications were recorded. The median followup was 35 months (IQR: 26–46).Results. Patients' mean age at surgery was 72.1 (54–91) years. Six patients (7.2%) displayed immediate tumor progression after orchiectomy. Median time of tumor remission and overall survival time were 29 and 36 months, respectively. 14% of the study group showed minor postoperative complications. No psychological problems occurred following bilateral orchiectomy.Conclusion. Due to an effective and persistent oncological effectiveness, less morbidity, and absence of psychological implications, bilateral subcapsular orchiectomy seems to be a practicable and advisable alternative in the first-line therapy of metastasized PCa.
AgBr-Coupled TiO2: A Visible Heterostructured Photocatalyst for Degrading Dye Pollutants
Authors: Liu Jianjun , Yu Yingchun , Liu Zhixin , Zuo Shengli , Li Baoshan
Published: September 2011

A series of AgBr/TiO2visible photocatalysts with heterojunction structure was synthesized using Ti(OC4H9)4, KBr, and AgNO3as precursors. The phase composition, particle morphology and size, microstructures, and absorbance of these photocatalysts were characterized by X-ray diffraction, transmission electron microscope (TEM), high-resolution TEM, and UV-vis spectra. It was found that the coupled AgBr/TiO2was an effective photocatalyst to degrade the methylene blue under visible light irradiation, compared with the other noncoupled photocatalysts of AgBr, AgBr/P25, and P25. The photocatalytic activities of AgBr/TiO2increase first and then decrease with increasing the mass ratio ofmAgNO3/mTiO2and the photocatalyst with the mass ratio of 3.35 has the highest photocatalytic activity. The results showed that the coupled photocatalyst has the particle size of about 15 nm with homogeneous dispersion and has the strongest absorption in whole UV-vis light region (250∼800 nm) originated from the synergetic effect of heterostructured AgBr/TiO2. The coupled AgBr/TiO2photocatalyst can keep stable photocatalytic activity after five-circle runs.
The Ant GenusSphinctomyrmexMayr (Hymenoptera, Formicidae, Cerapachyinae) in the Neotropical Region, with the Description of Two New Species
Authors: Feitosa Rodrigo M. , Brandão Carlos Roberto F. , Fernández Fernando , Delabie Jacques C. H.
Published: September 2011

The ant genusSphinctomyrmexhas been represented in the Neotropical Region until now by a single species,S. stali, known only from sparse localities in southeastern Brazil. Two new neotropical species are herein described,S. marcoyisp. n. andS. schoerederisp. n. from workers collected in the Brazilian Amazon and Atlantic Forest, respectively. New records forSphinctomyrmex staliare presented, and the species is redescribed together with discussions on its high morphological variation and the identity of its type specimen. A key for the neotropicalSphinctomyrmexworkers, images of all species presently known, and a distribution map are supplied.
Synthesis of ZnO Nanoparticles to Fabricate a Mask-Free Thin-Film Transistor by Inkjet Printing
Authors: Liu Chao-Te , Lee Wen-Hsi , Shih Tsu-Lang
Published: September 2011

We report a low-cost, mask-free, reduced material wastage, deposited technology using transparent, directly printable, air-stable semiconductor slurries and dielectric solutions. We have demonstrate an emerging process for fabricating printable transistors with ZnO nanoparticles as the active channel and poly(4-vinylphenol) (PVP) matrix as the gate dielectric, respectively, and the inkjet-printed ZnO TFTs have shown to exhibit the carrier mobility of 0.69 cm2/Vs and the threshold voltage of 25.5 V. We suggest that the printable materials and the printing technology enable the use of all-printed low-cost flexible displays and other transparent electronic applications.
Freestanding Ge/GeO2 Core‐Shell Nanocrystals with Varying Sizes and Shell Thicknesses: Microstructure and Photoluminescence Studies
Authors: Giri P. K. , Dhara Soumen
Published: September 2011

Freestanding Ge/GeO2 core‐shell nanocrystals (NCs) with varying sizes and shell thicknesses were synthesized by a ball milling method. The core‐shell NCs consist of single crystalline Ge core and crystalline GeO2 shell. With increasing milling time, sizes of the NCs decrease while GeO2 shell layer thicknesses increase. After 30 hours of milling, size of the core‐shell NCs goes down to 11 nm. Analysis of high‐resolution transmission electron microscope images revealed the presence of strain in the NCs and lattice distortion/dislocations in the Ge core near the interface of Ge core and GeO2 shell. This induced a strong phonon localization effect as evident from Raman studies and leads to enhanced radiative recombination, resulting in intense photoluminescence. Strong photoluminescence peaks in the visible and UV region were observed from all the samples and are attributed to Ge/GeO2 interface defect states. Optical Raman scattering studies confirm the formation of strained Ge/GeO2 core‐shell NCs with varying thicknesses.
A Novel Kinase Inhibitor, INCB28060, Blocks c-MET–Dependent Signaling, Neoplastic Activities, and Cross-Talk with EGFR and HER-3
Authors: Liu Xiangdong , Wang Qian , Yang Gengjie , Marando Cindy , Koblish Holly K. , Hall Leslie M. , Fridman Jordan S. , Behshad Elham , Wynn Richard , Li Yu , Boer Jason , Diamond Sharon , He Chunhong , Xu Meizhong , Zhuo Jincong , Yao Wenqing , Newton Robert C. , Scherle Peggy A.
Published: September 2011

Purpose: The c-MET receptor tyrosine kinase plays important roles in the formation, progression, and dissemination of human cancer and presents an attractive therapeutic target. This study describes the preclinical characterization of INCB28060, a novel inhibitor of c-MET kinase.

Experimental Design: Studies were conducted using a series of in vitro and in vivo biochemical and biological experiments.

Results: INCB28060 exhibits picomolar enzymatic potency and is highly specific for c-MET with more than 10,000-fold selectivity over a large panel of human kinases. This inhibitor potently blocks c-MET phosphorylation and activation of its key downstream effectors in c-MET–dependent tumor cell lines. As a result, INCB28060 potently inhibits c-MET–dependent tumor cell proliferation and migration and effectively induces apoptosis in vitro. Oral dosing of INCB28060 results in time- and dose-dependent inhibition of c-MET phosphorylation and tumor growth in c-MET–driven mouse tumor models, and the inhibitor is well tolerated at doses that achieve complete tumor inhibition. In a further exploration of potential interactions between c-MET and other signaling pathways, we found that activated c-MET positively regulates the activity of epidermal growth factor receptors (EGFR) and HER-3, as well as expression of their ligands. These effects are reversed with INCB28060 treatment. Finally, we confirmed that circulating hepatocyte growth factor levels are significantly elevated in patients with various cancers.

Conclusions: Activated c-MET has pleiotropic effects on multiple cancer-promoting signaling pathways and may play a critical role in driving tumor cell growth and survival. INCB28060 is a potent and selective c-MET kinase inhibitor that may have therapeutic potential in cancer treatment. Clin Cancer Res; 17(22); 7127–38. ©2011 AACR.
Telomerase Peptide Vaccination in NSCLC: A Phase II Trial in Stage III Patients Vaccinated after Chemoradiotherapy and an 8-Year Update on a Phase I/II Trial
Authors: Brunsvig Paal Fr. , Kyte Jon Amund , Kersten Christian , Sundstrøm Stein , Møller Mona , Nyakas Marta , Hansen Gaute L. , Gaudernack Gustav , Aamdal Steinar
Published: September 2011

Purpose: We report two clinical trials in non–small cell lung cancer (NSCLC) patients evaluating immune response, toxicity, and clinical outcome after vaccination with the telomerase peptide GV1001: a phase II trial (CTN-2006) in patients vaccinated after chemoradiotherapy and an 8-year update on a previously reported phase I/II trial (CTN-2000).

Experimental Design: CTN-2006: 23 inoperable stage III patients received radiotherapy (2 Gy × 30) and weekly docetaxel (20 mg/m2), followed by GV1001 vaccination. CTN-2000: 26 patients were vaccinated with two telomerase peptides (GV1001 and I540). The immune responses were evaluated by T-cell proliferation and cytokine assays.

Results: CTN-2006 trial: a GV1001-specific immune response developed in 16/20 evaluable patients. Long-term immunomonitoring showed persisting responses in 13 subjects. Serious adverse events were not observed. Immune responders recorded a median PFS of 371 days, compared with 182 days for nonresponders (P = 0.20). CTN-2000 trial update: 13/24 evaluable subjects developed a GV1001 response. The immune responders achieved increased survival compared with nonresponders (median 19 months vs. 3.5 months; P < 0.001). Follow-up of four long-time survivors showed that they all harbored durable GV1001-specific T-cell memory responses and IFNγhigh/IL-10low/IL-4low cytokine profiles. Two patients are free of disease after 108 and 93 months, respectively.

Conclusions: Vaccination with GV1001 is well tolerated, immunizes the majority of NSCLC patients and establishes durable T-cell memory. The considerable immune response rate and low toxicity in the phase II trial support the concept of combining chemoradiotherapy with vaccination. The survival advantage observed for immune responders warrants a randomized trial. Clin Cancer Res; 17(21); 6847–57. ©2011 AACR.
Clinical Implementation of Comprehensive Strategies to Characterize Cancer Genomes: Opportunities and Challenges
Authors: MacConaill Laura E. , Van Hummelen Paul , Meyerson Matthew , Hahn William C.
Published: September 2011

An increasing number of anticancer therapeutic agents target specific mutant proteins that are expressed by many different tumor types. Recent evidence suggests that the selection of patients whose tumors harbor specific genetic alterations identifies the subset of patients who are most likely to benefit from the use of such agents. As the number of genetic alterations that provide diagnostic and/or therapeutic information increases, the comprehensive characterization of cancer genomes will be necessary to understand the spectrum of distinct genomic alterations in cancer, to identify patients who are likely to respond to particular therapies, and to facilitate the selection of treatment modalities. Rapid developments in new technologies for genomic analysis now provide the means to perform comprehensive analyses of cancer genomes. In this article, we review the current state of cancer genome analysis and discuss the challenges and opportunities necessary to implement these technologies in a clinical setting.

Significance: Rapid advances in sequencing technologies now make it possible to contemplate the use of genome scale interrogation in clinical samples, which is likely to accelerate efforts to match treatments to patients. However, major challenges in technology, clinical trial design, legal and social implications, healthcare information technology, and insurance and reimbursement remain. Identifying and addressing these challenges will facilitate the implementation of personalized cancer medicine. Cancer Discovery; 1(4): 297–311. ©2011 AACR.
The Potential Benefits of BIM in the Further Pursuit of Biomarker Discovery in Cancer Therapeutics
Authors: Yoshida Takeshi , Haura Eric B.
Published: September 2011

In this issue of Cancer Discovery, Faber and colleagues demonstrate that the basal expression of BIM is positively correlated with the amount of apoptosis induced by the corresponding tyrosine kinase inhibitor treatment within the same subtype of several oncogene-addicted cancer cell types. Their results suggest that pre-treatment assessment of BIM levels can identify patients who would benefit from molecularly targeted therapies even after biomarker-based patient selection. Cancer Discovery; 1(4); 289–90. ©2011 AACR.

Commentary on Faber et al., p. 352.
Calling 911 in Response to Stroke: No Change following a Four-Year Educational Campaign
Authors: Mikulík R. , Goldemund D. , Reif M. , Brichta J. , Neumann J. , Jarkovský J. , Krýza J.
Published: September 2011

Background: Public awareness campaigns are conducted to increase stroke awareness, yet evidence of their long-term effectiveness is limited. Since 2006, the Czech Stroke Society has conducted an educational campaign throughout the Czech Republic (CR) to increase awareness about stroke. This report evaluates the effectiveness of this campaign by comparing the results of a nationwide survey on stroke awareness in 2009 with the results from 2005. Methods: In 2009, a nationwide survey was conducted throughout the CR using the same methodology as in 2005 and employing a 3-stage random sampling method (area, household, and household member sampling). Participants >40 years of age were personally interviewed via a structured questionnaire concerning their knowledge and ability to correctly respond to stroke as assessed by the validated Stroke Action Test (STAT). The primary outcome measure was the difference in a STAT score >50% (i.e. respondents chose to call 911 for >50% of stroke symptoms) between 2005 and 2009. Campaign intensity was characterized by a systematic search for media messages about stroke in the CR. Results: A total of 601 interviews were obtained (90% response rate) in 2009 (592 people were interviewed in 2005). A STAT score >50% was achieved by 18% of the respondents both in 2005 and 2009 (p = 0.89). There was no increase in the knowledge of risk factors or warning signs between 2005 and 2009. Respondents who noticed the campaign (19%) had better STAT scores than respondents who did not (25 vs. 17%; p = 0.038). A systematic search revealed that the campaign had reasonable intensity because there were 978 media reports about stroke between 2006 and 2008. Conclusions: A medium-intensity educational campaign, based on donated advertising media, failed to increase stroke awareness. However, if the campaign had reached more people, it might have been effective. Therefore, in the future, paid advertising media should accompany free media, although such approach would require a substantially larger budget. Awareness campaigns should be constantly evaluated for their effectiveness to develop more successful strategies.
The Correlates and Course of Depression in Patients with Lacunar Stroke: Results from the Secondary Prevention of Small Subcortical Strokes (SPS3) Study
Authors: White Carole L. , McClure Leslie A. , Wallace Patricia M. , Braimah Janet , Liskay Alice , Roldan Ana , Benavente Oscar R. ,   for the SPS3 Investigators
Published: September 2011

Background: Little is known about post-stroke depression in patients with lacunar stroke due to cerebral small vessel disease. Our objectives were to describe the prevalence of depression, its correlates and to examine the course of depression over time in a cohort of patients with lacunar stroke, the majority of whom had mild functional disability. Methods: Depression was determined in participants in the international Secondary Prevention of Small Subcortical Strokes (SPS3) trial which is testing antiplatelet therapies and targets of blood pressure control in patients with lacunar strokes and assessing stroke recurrence and cognitive decline. Depression was evaluated using the Patient Health Questionnaire. Multivariable logistic regression models were fitted to examine the relationship between the covariates of interest and depression. Generalized estimating equations were used to examine the likelihood of depression over time, while accounting for the multiple measurements within each subject. Results: The prevalence of depression in 2,477 participants at approximately 4 months after stroke was 19%. Older age (OR 0.97; 95% CI 0.96–0.99), male gender (OR 0.62; 95% CI 0.48–0.80) and less cognitive impairment (OR 0.99; 95% CI 0.98–1.00) were independently associated with a lower risk of depression. Functional disability (OR 1.8; 95% CI 1.3–2.4), living with a spouse/family (OR 1.6; 95% CI 1.1–2.3) and risk factors for stroke (OR 1.2; 95% CI 1.0–1.3) were each independently associated with a higher risk of depression. Longitudinal modeling indicated that the likelihood of depression decreased by 1.12 times (95% CI 1.06–1.17) for each 1-year increase in time. Conclusions: One fifth of those in the SPS3 trial cohort reported depression that is sustained over time. Although this is lower than the prevalence reported for stroke in general, these results underscore the importance of early screening for post-stroke depression, treatment and follow-up to minimize the negative consequences associated with depression.
The Novel Potent Multidrug Resistance Inhibitors N,N-bis(cyclohexanol)amine Aryl Esters Are Devoid of Vascular Effects
Authors: Saponara Simona , Gorelli Beatrice , Tzankova Virginia , Martelli Cecilia , Teodori Elisabetta , Sgaragli Giampietro , Fusi Fabio
Published: September 2011

The aim of this study was to investigate the effects of the four isomers (3a, 3b, 3c and 3d) of a novel multidrug resistance-reverting agent – 3,4,5-trimethoxybenzoic acid 4-(methyl-{4-[3-(3,4,5-trimethoxyphenyl)acryloyloxy]cyclohexyl}amino)cyclohexyl ester – on vascular functions in vitro. A comparison of their mechanical and electrophysiological actions in rat aorta rings and single rat tail artery myocytes, respectively, was performed. In rat aorta rings, 3a–d antagonized both 60 mmol/l K+- and phenylephrine-induced contraction in a concentration-dependent manner, with maximal relaxation values averaging 50% of controls, 3d being the most effective of the series. The vasorelaxing effect was similar either in presence or absence of intact endothelium. In rat tail artery myocytes, out of the four isomers, only 3a consistently inhibited Ba2+ current through Cav1.2 channels. Our results provide functional evidence that 3a–d are weak vasorelaxing agents, although at concentrations much higher than those effective for multidrug resistance reversion in cancer cells.
Will Amazonia Dry Out? Magnitude and Causes of Change from IPCC Climate Model Projections
Authors: Cook Brian , Zeng Ning , Yoon Jin-Ho
Published: September 2011

The Amazon rain forest may undergo significant change in response to future climate change. To determine the likelihood and causes of such changes, the authors analyzed the output of 24 models from the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) and a dynamic vegetation model, Vegetation–Global–Atmosphere–Soil (VEGAS), driven by these climate output. Their results suggest that the core of the Amazon rain forest should remain largely stable because rainfall in the core of the basin is projected to increase in nearly all models. However, the periphery, notably the southern edge of Amazonia and farther south into central Brazil (SAB), is in danger of drying out, driven by two main processes. First, a decline in precipitation of 11% during the southern Amazonia’s dry season (May–September) reduces soil moisture. Two dynamical mechanisms may explain the forecast reduction in dry season rainfall: 1) a general subtropical drying under global warming when the dry season southern Amazon basin is under the control of subtropical high pressure and 2) a stronger north–south tropical Atlantic sea surface temperature gradient and, to a lesser degree, a warmer eastern equatorial Pacific. The drying corresponds to a lengthening of the dry season by approximately 10 days. The decline in soil moisture occurs despite an increase in precipitation during the wet season, because of nonlinear responses in hydrology associated with the decline in dry season precipitation, ecosystem dynamics, and an increase in evaporative demand due to the general warming. In terms of ecosystem response, higher maintenance cost and reduced productivity under warming may also have additional adverse impact. Although the IPCC models have substantial intermodel variation in precipitation change, these latter two hydroecological effects are highly robust because of the general warming simulated by all models. As a result, when forced by these climate projections, a dynamic vegetation model VEGAS projects an enhancement of fire risk by 20%–30% in the SAB region. Fire danger reaches its peak in Amazonia during the dry season, and this danger is expected to increase primarily because of the reduction in soil moisture and the decrease in dry season rainfall. VEGAS also projects a reduction of about 0.77 in leaf area index (LAI) over the SAB region. The vegetation response may be partially mediated by the CO2 fertilization effect, because a sensitivity experiment without CO2 fertilization shows a higher 0.89 decrease in LAI. Southern Amazonia is currently under intense human influence as a result of deforestation and land-use change. Should this direct human impact continue at present rates, added pressure to the region’s ecosystems from climate change may subject the region to profound changes in the twenty-first century.
An Investigation of a Commercial Aircraft Encounter with Severe Clear-Air Turbulence over Western Greenland
Authors: Sharman R. D. , Doyle J. D. , Shapiro M. A.
Published: September 2011

This study presents digital flight data recorder (DFDR) analyses and high-resolution numerical simulations relevant to a severe clear-air turbulence (CAT) encounter over western Greenland by a Boeing 777 aircraft at 10-km elevation at 1305 UTC 25 May 2010. The environmental flow was dominated by an extratropical cyclone to the southeast of the Greenland tip, resulting in easterly flow at all levels. The results of the analyses indicate that the CAT encounter was related to mountain-wave breaking on the western lee (downslope) of the Greenland plateau. The simulations were not of especially high resolution (5-km horizontal grid spacing) by today’s standards, yet the simulation results do produce large-amplitude lee waves and overturning in good agreement with the encounter location as indicated by the DFDR. The success of this and other simulations in reproducing mountain-wave turbulence (MWT) events suggests that operational implementation of high-resolution nonhydrostatic simulation models, possibly an ensemble of models, over MWT-prone areas could produce more reliable forecasts of MWT than are currently available using gravity-wave-drag or MWT-postprocessing algorithms derived from global weather prediction models of relatively coarse scale.
Reply
Authors: Cook Garry D. , Nicholls Michael J.
Published: September 2011

A reexamination of the wind hazard from tropical cyclones for the city of Darwin (Northern Territory), Australia, by Cook and Nicholls concluded that its wind hazard is substantially underestimated by its allocation to region C in the Australian wind code. This conclusion was dismissed by Harper et al. on the basis of interpretation of anemometer records and Dvorak central pressure estimates as well as criticism of the simple technique and data used to interpret historic records. Of the 44 years of historical anemometer records presented by Harper et al. for Darwin, however, only one record was for a direct hit by an intense tropical cyclone. The other records derive from distant and/or weak tropical cyclones, which are not applicable to understanding the wind hazard at long return periods. The Dvorak central pressure estimates from which Harper et al. conclude that Port Hedland (Western Australia), Australia, has a greater wind hazard than Darwin does, when back transformed to Dvorak current-intensity values and gust speeds, indicate the converse. The simple technique used to derive wind hazard from historical cyclone occurrence is defended in detail and shown to produce estimates of wind hazard that are close to those accepted for five locations on the hurricane-affected coastline of the U.S. mainland. Thus the criticisms by Harper et al. of Cook and Nicholl’s work are shown to be invalid and the original conclusion that Darwin’s wind hazard is substantially underestimated in the current Australian wind code is supported.
‘Neutrality: A really dead concept?’ A reprise
Authors: Agius Christine , Devine Karen
Published: September 2011

This article approaches ‘neutrality’ as an essentially contested concept and traces its meaning and purpose over centuries-long historical timelines and situated political, societal and security contexts. It distinguishes neutrality from other concepts such as ‘neutralization’ ‘non-belligerency’, ‘non-alignment’, ‘military non-alignment’, ‘military neutrality’ and ‘non-allied’. The article explains the politics of defining neutrality in the current European political and legal landscape and in the context of shifting definitions and practices of war, peace, security and state sovereignty. This episteme-based analysis focuses on changes to neutrality in accordance with the rise and fall of particular empires and international actors over time, and changes to its status linked to the development and reification of particular meta-theoretically-based subfields of International Relations and Political Science, setting the background to this special issue of Cooperation and Conflict. A renewed emphasis on the normative aspects of neutrality (i.e. the role of domestic values, politics, preferences, history and mass publics in foreign policy formulation) is achieved by employing a range of perspectives, characterized by increased pluralism in levels of analysis and theoretical approaches. Through this pluralism, authors engage with (1) the strategic and normative drivers underpinning the norm of neutrality, (2) the potential for neutrals to serve as norm entrepreneurs in the field of peace promotion, (3) the tenuous legal status of elites’ quasi-neutral foreign policy constructions underpinned by tensions between discourses and practices and (4) the discursive strategies underpinning the move from neutral states’ traditional forms of neutrality to what is termed ‘post-neutrality’ in the current politico-legal context.
Neutrals as brokers of peacebuilding ideas?
Authors: Goetschel Laurent
Published: September 2011

Neutral and alliance-free states continue to exist. Even though neutrality has lost its realistic survival function, it continues to serve as provider of national identity for neutral states. This identity is rooted in neutrality’s idealistic function, according to which neutral states used to engage for humanitarian issues and the reduction of violence in international relations. The argument developed suggests an extension of this traditional role concept of neutral states: they should engage as promoters of ideas in international peacebuilding which are contested because they are perceived as a threat to national sovereignty, such as the responsibility to protect (R2P). While neutrality’s realistic functions make neutral states credible advocates of sovereignty and autonomy, its idealistic functions provide them with a track record in positive reforms in international relations. Acting as norm entrepreneurs, neutral states could reduce the contradiction between ‘prevention’ and ‘intervention’. Therefore, the key argument of this article focuses on the basis of neutrality’s conceptual roots, the conditions for success of political ideas and examples from recent peacebuilding practice.
Attitudes to childhood overweight and obesity: The limits of cultural explanations
Authors: Chakrabarti Suparna , Abbott Stephen
Published: September 2011

Objectives:

To explore attitudes to and beliefs about childhood overweight and obesity among Bangladeshi mothers and to check maternal perceptions of their children’s weight status.

Design:

Mixed methods cross-sectional study.

Setting:

A general practice in East London, UK.

Methods:

Qualitative interviews with 14 mothers; weighing and measuring 22 children.

Results:

Mothers were generally aware of broad health promotion messages about diet and exercise, but many tended to under-estimate their children’s weight status. Differences in view did not reflect in any simple way English language skills, and the range of views reflected those in the majority population.

Conclusion:

Health promotion initiatives should assess individual needs; membership of a Bangladeshi community does not necessarily predict knowledge, beliefs or behaviour, and assumptions that this community is different from others are misleading.
Saliva, Diagnostics, and Dentistry
Authors: Urdea M.S. , Neuwald P.D. , Greenberg B.L. , Glick M. , Galloway J. , Williams D. , Wong D.T.W.
Published: September 2011

Saliva, a scientific and clinical entity familiar to every oral health researcher and dental practitioner, has emerged as a translational and clinical commodity that has reached national visibility at the National Institutes of Health and the President’s Office of Science and Technology. “Detecting dozens of diseases in a sample of saliva” was issued by President Obama as one of the 14 Grand Challenges for biomedical research in the 21st Century ( National Economic Council, 2010 ). In addition, NIH’s 2011 Government Performance Report Act (GPRA) listed 10 initiatives in the high-risk long-term category ( Collins, 2011 ). The mandate is to determine the efficacy of using salivary diagnostics to monitor health and diagnose at least one systemic disease by 2013. The stage is set for the scientific community to capture these national and global opportunities to advance and substantiate the scientific foundation of salivary diagnostics to meet these goals. A specific calling is to the oral, dental, and craniofacial health community. Three areas will be highlighted in this paper: the concept of high-impact diagnostics, the role of dentists in diagnostics, and, finally, an infrastructure currently being developed in the United Kingdom—The UK Biobank—which will have an impact on the translational and clinical utilizations of saliva.
Scientific Frontiers
Authors: Baum B.J. , Yates J.R. , Srivastava S. , Wong D.T.W. , Melvin J.E.
Published: September 2011

Saliva, a biofluid historically well-studied biochemically and physiologically, has entered the post-genomic ‘omics’ era, where its proteomic, genomic, and microbiome constituents have been comprehensively deciphered. The translational path of these salivary constituents has begun toward a variety of personalized individual medical applications, including early detection of cancer. Salivary diagnostics is a late-comer, but it is catching up where dedicated resources, like the Salivaomics Knowledge Base (SKB), now have taken center stage in the dissemination of the diagnostic potentials of salivary biomarkers and other translational and clinical utilities.
Salivary Diagnostics and Its Impact in Dentistry, Research, Education, and the Professional Community
Authors: Slavkin H.C. , Fox C.H. , Meyer D.M.
Published: September 2011

Oral fluid-based (salivary) tests have the potential to create practical, point-of-care clinical instruments that are convenient, practical, and comfortable to use in dentistry and medicine. Currently, there are no simple, accurate, and inexpensive sampling, screening, or detection methods to support definitive diagnostic platforms across dental and medical disciplines. Though the benefits from advancing screening and detection technologies seem eminent, analytical, chemical, molecular, genetic, and protein markers are still under development. Clinical applications in patient care must be validated independently to ensure that they are clinically accurate, reliable, precise, and uniformly consistent for screening and detecting specific diseases or conditions. As technology designed to improve patient care through risk assessment, prevention, and disease management is transferred into clinical practice, dentistry may need to reassess its role in general health care.