bluuebunny/crossref_metadata_2025 huggingface dataset:
Are there adverse consequences of quizzing during informed consent for HIV research?
Authors: Sugarman J , Corneli A , Donnell D , Liu T Y , Rose S , Celentano D , Jackson B , Aramrattana A , Wei L , Shao Y , Liping F , Baoling R , Dye B , Metzger D
Published: June 2011

Introduction

While quizzing during informed consent for research to ensure understanding has become commonplace, it is unclear whether the quizzing itself is problematic for potential participants. In this study, we address this issue in a multinational HIV prevention research trial enrolling injection drug users in China and Thailand.

Methods

Enrolment procedures included an informed consent comprehension quiz. An informed consent survey followed.

Results

525 participants completed the informed consent survey (Heng County, China=255, Xinjiang, China=229, Chiang Mai, Thailand=41). Mean age was 33 and mean educational level was 8 yrs. While quizzing was felt to be a good way to determine if a person understands the nature of clinical trial participation (97%) and participants did not generally find the quiz to be problematic, minorities of respondents felt pressured (6%); anxious (5%); bored (5%); minded (5%); and did not find the questions easy (13%). In multivariate analysis, lower educational level was associated with not minding the quizzing (6–10 yrs vs 0–5 yrs: OR=0.27, p=0.03; more than 11 yrs vs 0–5 yrs: OR=0.18, p=0.03). There were also site differences (Heng County vs Xinjiang) in feeling anxious (OR=0.07; p=<0.01), not minding (OR=0.26; p=0.03), being bored (OR=0.25; p=0.01) and not finding the questions easy (OR=0.10; p=<0.01).

Conclusions

Quizzing during the informed consent process can be problematic for a minority of participants. These problems may be associated with the setting in which research takes place and educational level. Further research is needed to develop, test and implement alternative methods of ensuring comprehension of informed consent.

Trial Registration

clinicaltrials.gov numberNCT00270257.
TIME-DEPENDENT WORMHOLE SOLUTIONS OF f(R) THEORY OF GRAVITY AND ENERGY CONDITIONS
Authors: SAIEDI H. , NASR ESFAHANI B.
Published: June 2011

In this work, we construct time-dependent wormhole solutions in the context of f(R) theory of gravity. The background matter is considered to be traceless. By considering specific shape function and power-law expansion, exact solutions for f(R) are found. The null and the weak energy conditions (NEC and WEC) are checked for wormhole solutions. It is shown that the matter threading the wormhole spacetimes with either accelerated expansion or decelerated expansion satisfies the NEC and WEC.
WIGGLY STRING SOLUTIONS IN KERR–NEWMAN BLACK HOLE
Authors: SUZUKI HIROMI
Published: June 2011

Previously we investigated the cosmic wiggly strings in (3+1)-dimensional Schwarzschild, Reissner–Nordström and Kerr black holes. As an extension, the solutions in (3+1)-dimensional axially symmetric charged rotating black hole are investigated. The solution for the wiggly string exhibits open strings lying along the circular orbit in the equatorial plane outside horizon.
PROBABILITY DENSITY FUNCTION CONTROL OF QUANTUM SYSTEMS
Authors: XING YI-FAN , WU JUN
Published: June 2011

This paper proposes a new method of controlling quantum systems via probability density function (PDF) control. Based on the quantum model from the PDF perspective, two specific control algorithms are proposed for the general case and limited input energy, respectively. Unlike traditional quantum control methods, this method directly controls the probability distribution of the quantum state. It provides an alternative method for quantum control engineering.
CALCULATION OF ISODOSE CURVES FOR CCA AND CCB CONCAVE EYE APPLICATORS
Authors: MOWLAVI ALI ASGHAR , YAZDANI MAJED
Published: June 2011

BEBIG Ruthenium-106 ophthalmic plaques have been used for treatment of uveal melanoma, retinoblastoma, melanoma of the iris and other special applications for more than 30 years. The plaques consist of a thin film of Ru-106, a beta emitter encapsulated in pure silver. Simulations of small concave applicators CCA and CCB, manufactured by Bebig, were performed using Monte Carlo MCNP4C code which allows for description of the applicator (geometry and materials) in detail. Electrons are emitted from the 106 Ru nuclei isotropically with initial energy randomly sampled from the corresponding Fermi spectra and with initial positions uniformly distributed on the radioactive layer. In this work, relative doses were calculated in soft tissue phantom near the active layer. Isodose curves for CCA and CCB eye applicators were determined. Our calculated data agrees well with the measured phantom data reported in literature.
COMPARISON OF THREE EQUATIONS OF STATE FOR TRANSITION METALS
Authors: TIAN RONGGANG , SUN JIUXUN , YU FEI , YANG WEI , XUE XINYING
Published: June 2011

A modified generalized Morse (mGM) equation of state (EOS) is proposed that can incorporate the cohesive energy data correctly. It is compared with a four-parameter modified Rose EOS (MR EOS) which is proposed by following the Rose's approach and the Vinet EOS. The MR, mGM and Vinet EOSs are applied to five transition metals to fit all experimental compression data available. The results show that for all pressure ranges the mGM EOS gives the best fitting results. From the comparison of variation of pressure and energy versus compression ratio between MR and mGM EOS, it is clear that the pressure and energy of the MR EOS oscillate both in the neighborhood of (V/V0) ≈ 0.005 and in the range (V/V0) > 1. Such oscillations are physically incorrect, and the tendency of the mGM EOS are physically correct both in the neighborhood of (V/V0) ≈ 0.005 and in the range (V/V0) > 1. Generally speaking, the mGM EOS has evident advantage among the three EOSs, and the MR EOS's practical applications are seriously limited because of the physically incorrect oscillations.
ON THE INFLUENCES OF DEFENSIVE VOLATILES OF PLANTS IN TRITROPHIC INTERACTIONS
Authors: FERGOLA P. , WANG WENDI
Published: June 2011

Some mathematical models are suggested to describe the tritrofic interactions among plants, herbivores and their carnivorous enemies attracted by defensive volatiles of plants. For the interactions of Volterra type, it is proved that the threshold value for the persistence of herbivore and carnivore populations is not affected by the chemical attractions. Furthermore, the attraction to carnivores is beneficial to reduce the density of herbivores and increase the density of plants. If the interaction of plants and herbivores takes the Leslie type, the model admits the fold bifurcation that induces bistable positive equilibria. Numerical computations indicate that the response time of carnivores to defensive volatiles of plants induces periodic cycles and irregular fluctuations.
ON MINKOWSKI MEASURABILITY
Authors: MENDIVIL F. , SAUNDERS J. C.
Published: June 2011

Two "pathological" properties of Minkowski content are that countable sets can have positive content (unlike Hausdorff measures) and the property of a set being Minkowski measurable is quite rare. In this paper, we explore both of these issues.

In particular, for each d ∈ (0,2) we give an explicit construction of a countable Minkowski measurable subset of ℝ2 of Minkowski dimension d and arbitrary positive Minkowski content. We also indicate how this construction can be extended to ℝn, to construct a countable subset with arbitrary positive Minkowski content of any dimension in (0, n). Furthermore, we give an example of a strictly increasing C1 function which takes a Minkowski measurable subset of [0,1] onto a set which is not Minkowski measurable but of the same dimension.
Insider Trading in Hong Kong: Tests of Stock Returns and Trading Frequency
Authors: Firth Michael , Leung T. Y. , Rui Oliver M.
Published: June 2011

The main purpose of this paper is to examine the legal insider trading activities by directors of companies listed on the Hong Kong Exchange over the period 1993 to 1999. One characteristic of insider trading in Hong Kong is the high frequency of transactions and the large amounts of money involved. Inside purchases appear to signal and correct undervaluation and inside sales appear to signal and correct overvaluation. In contrast to research from Britain and the United States, insider sales are more informative than purchases. On average, insiders earn HK$91,297 per trade, while outsiders who mimic insiders' transactions earn minimal returns. Many firms suffer from infrequent trading and our results are consistent with directors engaging in inside transactions so as to help create a market for the shares. In additional tests, we find that the frequency of insider trading is a function of information asymmetry.
ON NON-ERGODIC PHASES IN MINORITY GAMES
Authors: DE MARTINO ANDREA , GALLA TOBIAS
Published: June 2011

In the first part of this review, we survey the known analytic results regarding the non-ergodic phase of standard Minority Games. Such phases are characterized by the fact that, at odds with ergodic regimes, the steady state properties of the game (e.g. the volatility) depend both on the initial conditions chosen for the agents' learning process as well as on the learning rate. Secondly, we present a discussion of the effects of finite-memory learning, which lifts the non-ergodicity, in the context of spherical Minority Games.
Zip14 is a complex broad-scope metal-ion transporter whose functional properties support roles in the cellular uptake of zinc and nontransferrin-bound iron
Authors: Pinilla-Tenas Jorge J. , Sparkman Brian K. , Shawki Ali , Illing Anthony C. , Mitchell Colin J. , Zhao Ningning , Liuzzi Juan P. , Cousins Robert J. , Knutson Mitchell D. , Mackenzie Bryan
Published: June 2011

Recent studies have shown that overexpression of the transmembrane protein Zrt- and Irt-like protein 14 (Zip14) stimulates the cellular uptake of zinc and nontransferrin-bound iron (NTBI). Here, we directly tested the hypothesis that Zip14 transports free zinc, iron, and other metal ions by using the Xenopus laevis oocyte heterologous expression system, and use of this approach also allowed us to characterize the functional properties of Zip14. Expression of mouse Zip14 in RNA-injected oocytes stimulated the uptake of 55Fe in the presence of l-ascorbate but not nitrilotriacetic acid, indicating that Zip14 is an iron transporter specific for ferrous ion (Fe2+) over ferric ion (Fe3+). Zip14-mediated 55Fe2+ uptake was saturable ( K0.5 ≈ 2 μM), temperature-dependent (apparent activation energy, Ea = 15 kcal/mol), pH-sensitive, Ca2+-dependent, and inhibited by Co2+, Mn2+, and Zn2+. HCO3− stimulated 55Fe2+ transport. These properties are in close agreement with those of NTBI uptake in the perfused rat liver and in isolated hepatocytes reported in the literature. Zip14 also mediated the uptake of 109Cd2+, 54Mn2+, and 65Zn2+ but not 64Cu (I or II). 65Zn2+ uptake also was saturable ( K0.5 ≈ 2 μM) but, notably, the metal-ion inhibition profile and Ca2+ dependence of Zn2+ transport differed from those of Fe2+ transport, and we propose a model to account for these observations. Our data reveal that Zip14 is a complex, broad-scope metal-ion transporter. Whereas zinc appears to be a preferred substrate under normal conditions, we found that Zip14 is capable of mediating cellular uptake of NTBI characteristic of iron-overload conditions.
Neural and hormonal control of food hoarding
Authors: Bartness Timothy J. , Keen-Rhinehart E. , Dailey M. J. , Teubner B. J.
Published: June 2011

Many animals hoard food, including humans, but despite its pervasiveness, little is known about the physiological mechanisms underlying this appetitive behavior. We summarize studies of food hoarding in humans and rodents with an emphasis on mechanistic laboratory studies of species where this behavior importantly impacts their energy balance (hamsters), but include laboratory rat studies although their wild counterparts do not hoard food. The photoperiod and cold can affect food hoarding, but food availability is the most significant environmental factor affecting food hoarding. Food-deprived/restricted hamsters and humans exhibit large increases in food hoarding compared with their fed counterparts, both doing so without overeating. Some of the peripheral and central peptides involved in food intake also affect food hoarding, although many have not been tested. Ad libitum-fed hamsters given systemic injections of ghrelin, the peripheral orexigenic hormone that increases with fasting, mimics food deprivation-induced increases in food hoarding. Neuropeptide Y or agouti-related protein, brain peptides stimulated by ghrelin, given centrally to ad libitum-fed hamsters, duplicates the early and prolonged postfood deprivation increases in food hoarding, whereas central melanocortin receptor agonism tends to inhibit food deprivation and ghrelin stimulation of hoarding. Central or peripheral leptin injection or peripheral cholecystokinin-33, known satiety peptides, inhibit food hoarding. Food hoarding markedly increases with pregnancy and lactation. Because fasted and/or obese humans hoard more food in general, and more high-density/high-fat foods specifically, than nonfasted and/or nonobese humans, understanding the mechanisms underlying food hoarding could provide another target for behavioral/pharmacological approaches to curb obesity.
Estrogen regulation of the dopamine-activated GIRK channel in pituitary lactotrophs: implications for regulation of prolactin release during the estrous cycle
Authors: Christensen Heather R. , Zeng Qinghua , Murawsky Michael K. , Gregerson Karen A.
Published: June 2011

Prolactin (PRL), synthesized and secreted from lactotrophs of the anterior pituitary gland, is tonically inhibited by hypothalamic dopamine (DA) throughout the female reproductive (estrous) cycle. Our laboratory has shown that DA hyperpolarizes these cells by activating G protein-coupled inwardly rectifying K+(GIRK) channels; however, this response is only observed on proestrus. While the cellular mechanisms that allow for functional expression of this unique DA-signaling pathway are unclear, we hypothesized that activation of the DA-GIRK effector pathway is due to the rise in circulating estrogen (E2) during the preceding day of diestrus. Thus, we examined the effects of E2on primary lactotrophs isolated from female rats. Treatment with a physiological concentration of E2(40–80 pg/ml, in vivo or in vitro) induced a proestrous phenotype in diestrous lactotrophs. These cells exhibited a DA-induced membrane hyperpolarization, as well as a secretory rebound of PRL following DA withdrawal (characteristic of proestrous cells). Internal dialysis of GTPγS demonstrated that E2exposure enabled functional expression of GIRK channels, and this regulation by E2did not involve the D2R. The effect of E2was blocked by the receptor antagonist, ICI 182,780, and by the protein synthesis inhibitor, cycloheximide. Single-cell analysis revealed increased mRNA expression of GIRK channel subunits in E2-treated lactotrophs. While E2is known to have multiple actions on the lactotroph, the present findings illuminate a novel action of E2in lactotrophs—regulation of the expression of a DA effector, the GIRK channel.
pH-dependent regulation of the α-subunit of H+-K+-ATPase (HKα2)
Authors: Codina Juan , Opyd Timothy S. , Powell Zachary B. , Furdui Cristina M. , Petrovic Snezana , Penn Raymond B. , DuBose Thomas D.
Published: June 2011

The H+-K+-ATPase α-subunit (HKα2) participates importantly in systemic acid-base homeostasis and defends against metabolic acidosis. We have previously shown that HKα2plasma membrane expression is regulated by PKA (Codina J, Liu J, Bleyer AJ, Penn RB, DuBose TD Jr. J Am Soc Nephrol 17: 1833–1840, 2006) and in a separate study demonstrated that genetic ablation of the proton-sensing Gs-coupled receptor GPR4 results in spontaneous metabolic acidosis (Sun X, Yang LV, Tiegs BC, Arend LJ, McGraw DW, Penn RB, Petrovic S. J Am Soc Nephrol 21: 1745–1755, 2010). In the present study, we investigated the ability of chronic acidosis and GPR4 to regulate HKα2expression in HEK-293 cells. Chronic acidosis was modeled in vitro by using multiple methods: reducing media pH by adjusting bicarbonate concentration, adding HCl, or by increasing the ambient concentration of CO2. PKA activity and HKα2protein were monitored by immunoblot analysis, and HKα2mRNA, by real-time PCR. Chronic acidosis did not alter the expression of HKα2mRNA; however, PKA activity and HKα2protein abundance increased when media pH decreased from 7.4 to 6.8. Furthermore, this increase was independent of the method used to create chronic acidosis. Heterologous expression of GPR4 was sufficient to increase both basal and acid-stimulated PKA activity and similarly increase basal and acid-stimulated HKα2expression. Collectively, these results suggest that chronic acidosis and GPR4 increase HKα2protein by increasing PKA activity without altering HKα2mRNA abundance, implicating a regulatory role of pH-activated GPR4 in homeostatic regulation of HKα2and acid-base balance.
Between-subject variance in the magnitude of corticomuscular coherence during tonic isometric contraction of the tibialis anterior muscle in healthy young adults
Authors: Ushiyama Junichi , Suzuki Tatsuya , Masakado Yoshihisa , Hase Kimitaka , Kimura Akio , Liu Meigen , Ushiba Junichi
Published: June 2011

Oscillatory activity of the sensorimotor cortex has been reported to show coherence with muscle activity in the 15- to 35-Hz frequency band (β-band) during weak to moderate intensity of isometric contraction. The present study examined the variance of the magnitude of the corticomuscular coherence across a large number of subjects. We quantified the coherence between EEG over the sensorimotor cortex and rectified electromyogram (EMG) from the tibialis anterior muscle during tonic isometric contraction at 30% of maximal effort in 100 healthy young individuals. We estimated the maximal peak of EEG-EMG coherence (Cohmax) and the ratio of the sum of the autopower spectral density function within the β-band to that of all frequency ranges for both EEG (EEGβ-PSD) and EMG (EMGβ-PSD) signals. The frequency histogram of Cohmax across all subjects showed a broad bell-shaped continuous distribution (range, 0.048–0.816). When the coherence was thresholded at the estimated significance level of P < 0.05 (0.114), 46 out of 100 subjects showed significant EEG-EMG coherence. Cohmax occurred within the β-band in the majority of subjects who showed significant EEG-EMG coherence ( n = 43). Furthermore, Cohmax showed significant positive correlations with both EEGβ-PSD ( r = 0.575, P < 0.001) and EMGβ-PSD ( r = 0.606, P < 0.001). These data suggest that even during simple tonic isometric contraction, the strength of oscillatory coupling between the sensorimotor cortex and spinal motoneurons varies among individuals and is a contributory factor determining muscle activation patterns such as the degree of grouped discharge in muscle activity within the β-band for each subject.
Cross talk in implicit assignment of error information during bimanual visuomotor learning
Authors: Kasuga Shoko , Nozaki Daichi
Published: June 2011

When a neural movement controller, called an “internal model,” is adapted to a novel environment, the movement error needs to be appropriately associated with the controller. However, their association is not necessarily guaranteed for bimanual movements in which two controllers—one for each hand—result in two movement errors. Considering the implicit nature of the adaptation process, the movement error of one hand can be erroneously associated with the controller of the other hand. Here, we investigated this credit-assignment problem in bimanual movement by having participants perform bimanual, symmetric back-and-forth movements while displaying the position of the right hand only with a cursor. In the training session, the cursor position was gradually rotated clockwise, such that the participants were unaware of the rotation. The movement of the right hand gradually rotated counterclockwise as a consequence of adaptation. Although the participants knew that the cursor reflected the movement of the right hand, such gradual adaptation was also observed for the invisible left hand, especially when the cursor was presented on the left side of the display. Thus the movement error of the right hand was implicitly assigned to the left-hand controller. Such cross talk in credit assignment might influence motor adaptation performance, even when two cursors are presented; the adaptation was impaired when the rotations imposed on the cursors were opposite compared with when they were in the same direction. These results indicate the inherent presence of cross talk in the process of associating action with consequence in bimanual movement.
Rheumatoid Arthritis-Associated Interstitial Lung Disease: Diagnostic Dilemma
Authors: Hamblin Mark J. , Horton Maureen R.
Published: June 2011

Interstitial lung disease (ILD) is an increasingly recognized complication of rheumatoid arthritis (RA) contributing to significantly increased morbidity and mortality. Diagnosis can be challenging since patients are unlikely to report dyspnea due to an overall decrease in physical activity with advanced arthritic symptoms. Additionally, infections, drug toxicity, and environmental toxins can mimic ILD, creating significant diagnostic dilemmas for the clinician. In this paper we will explore an effective clinical algorithm for the diagnosis of RA-ILD. We will also discuss features of drug-related toxicities, infections, and environmental toxins that comprise the main entities in the differential diagnosis of RA-ILD. Finally, we will explore the known and experimental treatment options that may have some benefit in the treatment of RA-ILD.
Tumor Microenvironment–Derived Proteins Dominate the Plasma Proteome Response during Breast Cancer Induction and Progression
Authors: Pitteri Sharon J. , Kelly-Spratt Karen S. , Gurley Kay E. , Kennedy Jacob , Buson Tina Busald , Chin Alice , Wang Hong , Zhang Qing , Wong Chee-Hong , Chodosh Lewis A. , Nelson Peter S. , Hanash Samir M. , Kemp Christopher J.
Published: June 2011

Tumor development relies upon essential contributions from the tumor microenvironment and host immune alterations. These contributions may inform the plasma proteome in a manner that could be exploited for cancer diagnosis and prognosis. In this study, we employed a systems biology approach to characterize the plasma proteome response in the inducible HER2/neu mouse model of breast cancer during tumor induction, progression, and regression. Mass spectrometry data derived from approximately 1.6 million spectra identified protein networks involved in wound healing, microenvironment, and metabolism that coordinately changed during tumor development. The observed alterations developed prior to cancer detection, increased progressively with tumor growth and reverted toward baseline with tumor regression. Gene expression and immunohistochemical analyses suggested that the cancer-associated plasma proteome was derived from transcriptional responses in the noncancerous host tissues as well as the developing tumor. The proteomic signature was distinct from a nonspecific response to inflammation. Overall, the developing tumor simultaneously engaged a number of innate physiologic processes, including wound repair, immune response, coagulation and complement cascades, tissue remodeling, and metabolic homeostasis that were all detectable in plasma. Our findings offer an integrated view of tumor development relevant to plasma-based strategies to detect and diagnose cancer. Cancer Res; 71(15); 5090–100. ©2011 AACR.
Expression of Amphiregulin and EGFRvIII Affect Outcome of Patients with Squamous Cell Carcinoma of the Head and Neck Receiving Cetuximab–Docetaxel Treatment
Authors: Tinhofer Ingeborg , Klinghammer Konrad , Weichert Wilko , Knödler Maren , Stenzinger Albrecht , Gauler Thomas , Budach Volker , Keilholz Ulrich
Published: June 2011

Purpose: Constitutive activation of epidermal growth factor receptor (EGFR) as a result of gene amplification, mutation, or overexpression of its ligands has been associated with response to EGFR targeting strategies. The role of these molecular mechanisms for the responsiveness of squamous cell carcinoma of the head and neck (SCCHN) to cetuximab-containing regimens remains unknown.

Experimental Design: Tumor biopsies from 47 patients, enrolled in a single-arm phase II multicenter study for second-line treatment of recurrent or metastatic SCCHN with cetuximab and docetaxel, were analyzed by immunohistochemistry for expression of EGFR, its deletion variant III (EGFRvIII) and its ligand amphiregulin (AREG). The relation between expression levels and disease control rate (DCR) was evaluated by logistic regression. Association between expression levels, progression-free survival (PFS), and overall survival (OS) was determined by Kaplan–Meier analysis, log-rank test, and uni- and multivariate Cox regression analysis.

Results: High expression of EGFR, EGFRvIII, and AREG was detected in 73%, 17%, and 45% of SCCHN cases, respectively. Expression levels of EGFR had no impact on PFS or OS. High expression levels of EGFRvIII were significantly associated with reduced DCR and shortened PFS (HR: 3.3, P = 0.005) but not with OS. Patients with high AREG expression in tumor cells had significantly shortened OS (HR: 2.2, P = 0.002) and PFS (HR 2.2, P = 0.019) compared with patients with low expression score. Multivariate Cox analysis revealed an independent association of AREG and EGFRvIII with PFS but only AREG was an independent prognosticator of OS.

Conclusions: High EGFRvIII and AREG expression levels identify SCCHN patients who are less likely to benefit from combination treatment with cetuximab and docetaxel. Clin Cancer Res; 17(15); 5197–204. ©2011 AACR.
Targeting GPCR-Mediated p70S6K Activity May Improve Head and Neck Cancer Response to Cetuximab
Authors: Bhola Neil E. , Thomas Sufi M. , Freilino Maria , Joyce Sonali , Sahu Anirban , Maxwell Jessica , Argiris Athanassios , Seethala Raja , Grandis Jennifer R.
Published: June 2011

Purpose: Epidermal growth factor receptor (EGFR) overexpression is correlated with decreased survival in head and neck cancer (HNC) where the addition of EGFR inhibition to standard chemoradiation approaches has improved treatment responses. However, the basis for the limited efficacy of EGFR inhibitors in HNC is incompletely understood. G-protein–coupled receptors (GPCR) have been shown to be overexpressed in HNC where GPCR activation induces HNC growth via both EGFR-dependent and -independent pathways. We hypothesized that targeting GPCR-induced EGFR-independent signaling would improve the efficacy of EGFR inhibition.

Experimental Design: Using a high-throughput phosphoproteome array, we identified proteins that were phosphorylated in HNC cells where EGFR expression was downmodulated by RNA interference (RNAi) in the presence or absence of a GPCR ligand. We confirmed the findings from the array by Western blotting followed by in vitro and in vivo phenotypic assays.

Results: p70S6K phosphorylation was elevated approximately sixfold in EGFR siRNA-transfected cells treated with a GPCR ligand. In addition to RNAi-mediated EGFR downmodulation, GPCR-mediated phosphorylation of p70S6K was modestly increased by EGFR inhibitor cetuximab approved by the Food and Drug Administration. Biopsies from cetuximab-treated patients also displayed increased phospho-p70S6K staining compared with pretreatment biopsies. HNC cells were growth inhibited by both genetic and pharmacologic p70S6K targeting strategies. Furthermore, p70S6K targeting in combination with cetuximab resulted in enhanced antitumor effects in both in vitro and in vivo HNC models.

Conclusions: These results indicate that increased phosphorylation of p70S6K in cetuximab-treated patients may be due to increased GPCR signaling. Therefore, the addition of p70S6K targeting strategies may improve treatment responses to EGFR inhibition. Clin Cancer Res; 17(15); 4996–5004. ©2011 AACR.
The ‘Centre Effect’ in Nephrology: What Do Differences between Nephrology Centres Tell Us about Clinical Performance in Patient Management?
Authors: Hodsman Alexandra , Ben-Shlomo Yoav , Roderick Paul , Tomson Charles R.V.
Published: June 2011

Improving the quality of care provided by nephrology centres to patients with kidney disease requires a clear understanding of how to compare performance after adjustment for case mix, combined with a detailed understanding of the structure and processes that are associated with the achievement of good clinical results. In this review, we discuss how to measure quality of care (using process or outcome measures), how to take case mix into account, how best to display comparisons between nephrology centres, and how to study the causes of real variations in quality between centres. This is a narrative review; we include examples from other fields in which the centre effect has been studied, including education.
Factors That Influence the Decision to Perform a Karyotype in Suspected Disorders of Sex Development: Lessons from the Scottish Genital Anomaly Network Register
Authors: Rodie M. , McGowan R. , Mayo A. , Midgley P. , Driver C.P. , Kinney M. , Young D. , Ahmed S.F.
Published: June 2011

Background: Although a karyotype represents the first objective evidence of investigating a case of suspected disorder of sex development (DSD), the factors that influence the clinician’s decision to initiate investigations are unclear. Methods: Cases of suspected DSD in Scotland were identified through the Scottish Genital Anomaly Network (SGAN) Register. The timing as well as other factors that influence the decision to perform a karyotype were subsequently studied. Results: Out of the 572 cases on the register, 383 (67%) were classified as having a non-specific disorder of under-masculinisation. In 463 (81%) cases, the sex of rearing was male, in 71 (12%) female, and in 38 (7%) cases data regarding sex of rearing were unavailable. A karyotype was reported to have been performed in 153/572 (27%) cases. Infants in Scotland with suspected DSD are more likely to have a karyotype performed in the presence of a low external masculinisation score, bilateral impalpable testes, proximal hypospadias, or associated malformations. Discussion: These data represent the first attempt at benchmarking the decision to check a karyotype and investigate infants with suspected DSD. Whilst this decision may be related to the complexity of the genital anomaly, there are other factors that may influence this decision, and these require further exploration through more rigorous systems for data collection.
Uninephrectomy of Diabetic OVE26 Mice Greatly Accelerates Albuminuria, Fibrosis, Inflammatory Cell Infiltration and Changes in Gene Expression
Authors: Zheng Shirong , Huang Yun , Yang Lu , Chen Teresa , Xu Jianxiang , Epstein Paul N.
Published: June 2011

Background/Aims: OVE26 (OVE) mice provide a valuable model of advanced diabetic nephropathy (DN), but they take 8 months to develop moderate interstitial fibrosis and reduced glomerular filtration rate (GFR). The aim of this project was to produce a more rapid and advanced model of DN. Methods: Uninephrectomy was applied to OVE and FVB mice at 2 months of age. Albuminuria, GFR, glomerulosclerosis, interstitial fibrosis, gene expression and monocyte infiltration were evaluated as a function of diabetes and uninephrectomy. Results: Albuminuria, monocyte infiltration, mesangial matrix expansion and renal fibrosis were greatly accelerated in uninephrectomized mice. DN was more advanced 10 weeks after uninephrectomy than in untreated OVE mice at 8 months of age. Uninephrectomy had almost no effect on these characteristics in non-diabetic mice. Microarray studies indicated that the accelerated fibrosis and cell infiltration in nephrectomized OVE mice were accompanied by corresponding gene expression changes in canonical pathways for fibrosis and inflammation. Conclusion: Uninephrectomy greatly accelerates all features of diabetic renal damage. This procedure provides a 10-week period after surgery to examine very large changes in the pathology of DN. The model may be particularly useful for testing new therapies and for analysis of the progression of albuminuria and fibrosis in DN.
Smoking Is a Risk Factor for Graft Failure and Mortality after Renal Transplantation
Authors: Agarwal Pramod K. , Hellemons Merel E. , Zelle Dorien M. , van Ree Rutger M. , van den Born Jacob , Homan van der Heide Jaap J. , Gans Rijk O.B. , van Son Willem J. , Navis Gerjan , Bakker Stephan J.L.
Published: June 2011

Background: Smoking in renal transplant recipients (RTR) is an acknowledged cardiovascular risk factor. It is, however, unclear whether smoking also increases the risk of graft failure (GF). Method: In this study, we prospectively assessed the association of current smoking versus past and never smoking with GF and mortality in 604 RTR (age 51.5 ± 12.1 years, 55% male). Results: At inclusion, 133 (22%) were current smokers, 255 (42%) were past smokers and 216 (36%) never smoked. During follow-up of 5.3 (4.7–5.7) years, 41 (7%) RTR experienced GF and 95 RTR (16%) died. Current smoking RTR had higher risk for GF compared to never smoking RTR (hazard ratio, HR = 3.3, 95% CI 1.5–7.1, p = 0.002). Past smoking RTR had similar risk of GF as never smoking RTR (HR = 1.1, 95% CI 0.5–2.6, p = 0.7). Current smoking RTR and past smoking RTR were at higher risk for death than never smoking RTR (HR = 2.1, 95% CI 1.1–3.8, p = 0.016, and HR = 2.4, 95% CI 1.4–4.0, p = 0.001, respectively). Conclusion: Smoking after renal transplantation is associated with risk for GF and mortality. Since past smoking is a risk factor for mortality but not for GF, smoking cessation may be beneficial to RTR in delaying GF in long term.
Semiotic Layering through Gesture and Intonation
Authors: Mendoza-Denton Norma , Jannedy Stefanie
Published: June 2011

Face-to-face communication is multimodal. In face-to-face interaction scholars can observe the interplay of several “semiotic layers,” modalities of information such as syntax, discourse structure, gesture, and intonation. The authors explore the role of gesture in structuring and aligning information in spoken discourse through a study of (1) the complementary co-occurrence of gestural apices and intonational pitch accents and (2) the supplementary co-occurrence of metaphorical gestures and elements in discourse. In the naturally occurring political speech situation the authors examine, metaphorical spatialization through gesture is key in indexing contextual relationships among the speaker, the politicians or government, and other external forces. The use of gestures simultaneously aligns with intonation and metaphorically manipulates political entities in space. Discourse context and social meaning are thus constructed together through the spoken and gestural channels and are supported through fine-grained structural alignment between intonation and gesture.
Innovation, regional development and relations between high- and low-tech industries
Authors: Hansen Teis , Winther Lars
Published: June 2011

The current European policy agenda strongly accentuates the importance of research and development (R&D) as a driver of economic growth. The basic assumption is that high European wage levels make it unlikely that less research-intensive parts of the economy can withstand competition from low-wage countries with increasingly skilled labour forces. Thus, the inferior growth of the European Union (EU) in the 1990s compared with the USA has been explained by the latter’s higher rate of R&D investments. The paper challenges this rather simplistic view of innovation and examines the regional consequences of such policies. EU growth has caught up with that of the USA during recent years and low-tech industries continue to have considerable economic importance in Europe in terms of jobs and value added, especially outside the main growth regions, but also in the major urban regions. Empirical evidence from Denmark and the UK provided in the paper suggests that low- and high-tech industries are closely interconnected because low-tech firms play important roles both as partners in the innovation processes of high-tech firms and as buyers of high-tech products. Therefore, EU industrial policy is not appropriate because it overlooks the continuing significance of low-tech industries. Furthermore, the rather uniform focus on R&D is associated with a strong emphasis on large city-regions where research-intensive industries are concentrated and, thus, increasing regional inequality in Europe is being produced.
Comparison of methods for improved RNA extraction from blood for early detection of Classical swine fever virus by real-time reverse transcription polymerase chain reaction
Authors: Das Amaresh , Beckham Tammy R. , McIntosh Michael T.
Published: June 2011

Classical swine fever (CSF) is a highly contagious disease of pigs. Early detection of the Classical swine fever virus (CSFV) in infected animals and routine surveillance is important for a rapid response and control of an outbreak of CSF. The current study investigated whole blood as a clinical specimen for the detection of CSFV by real-time reverse transcription polymerase chain reaction (real-time RT-PCR) in experimentally infected pigs. The virus was detectable in pre-clinical animals in whole blood and in different fractions of blood, including white blood cells, red blood cells (RBC), and serum. Based on an in-vitro binding assay, CSFV is retained in the RBC fraction. Naturally occurring PCR inhibitors of whole blood were shown to inhibit detection, and several commercial RNA extraction kits failed to remove these inhibitors. The commercial blood RNA extraction protocols were modified to achieve optimized single tube and high-throughput 96-well plate RNA extraction that efficiently removed PCR inhibitors from whole blood and enhanced detection of CSFV in experimentally inoculated pigs. This enabled detection 1–2 days earlier than observed using unmodified RNA extraction protocols. The results show effective use of whole blood as a clinical specimen for diagnosis and surveillance of CSF in pre-clinical animals.
Parental Experiences of Information Within Pediatric Oncology
Authors: Ringnér Anders , Jansson Lilian , Graneheim Ulla H.
Published: June 2011

Parents of children with cancer use information to create knowledge about their child’s disease. Information can help parents reduce chaos and create a feeling of control, but there are often obstacles to its acquisition, which has been described as similar to learning a new language. The purpose of this study was to describe parents’ experiences of acquiring and using information to create knowledge about their child’s cancer during the course of the illness. The authors used qualitative content analysis on data from focus groups and individual interviews with 14 parents of children with cancer. Two themes were constructed: (a) feeling acknowledged as a person of significance included feeling safe and secure in spite of uncertainty, having one’s hopes supported, and getting relief from other families’ experiences; (b) feeling like an unwelcome guest included feeling abandoned at important milestones, feeling forced to nag for information, and feeling burdened by the obligation to inform others. Parents may need extra attention at important milestones such as treatment cessation, with information meetings grounded in the parents’ own needs.
Toward Caring for Oneself in a Life of Intense Ups and Downs
Authors: Veseth Marius , Binder Per-Einar , Borg Marit , Davidson Larry
Published: June 2011

In this article, we discuss processes of recovery in bipolar disorder. We utilized a hermeneutical-phenomenological approach developed within a reflexive-collaborative framework to examine what individuals do to promote improvement and positive change in their own lives. The study was designed and carried out in collaboration with an expert-by-experience group of 12 coresearchers with firsthand experiences of mental distress and recovery. In-depth interviews were conducted with 13 participants who acknowledged having lived and dealt with a bipolar disorder. Four core themes were drawn from our analysis: (a) handling ambivalence about letting go of manic states; (b) finding something to hang on to when the world is spinning around; (c) becoming aware of signals from self and others; and (d) finding ways of caring for oneself. Interrelationships between the four themes, along with limitations, strengths, and implications of the study are discussed.
StoryCorps’ Memory Loss Initiative: Enhancing personhood for storytellers with memory loss
Authors: Savundranayagam Marie Y. , Dilley Lorna J. , Basting Anne
Published: June 2011

StoryCorps’ Memory Loss Initiative was designed to gather oral histories of people with memory loss. This study investigated the StoryCorps interview experience for storytellers who self identify with early stage memory loss and the persons who interviewed them. StoryCorps interviews took place in Milwaukee, Chicago, and New York. Follow-up interviews were conducted with 42 persons with memory loss, along with 27 family members who participated in the StoryCorps interviews. Results revealed that the StoryCorps experience was a meaningful activity that allowed participants to acknowledge the beauty of the present moment, to reflect and engage in meaningful conversations, to re-affirm both the selfhood of individuals with memory loss and their relationships with family members, and to and be a part of national history while leaving a legacy for future generations within families. The findings are discussed within the context of personhood enhancing strategies for persons with memory loss.
Circulating endothelial progenitor cells in women with gestational alterations of glucose tolerance
Authors: Penno Giuseppe , Pucci Laura , Lucchesi Daniela , Lencioni Cristina , Iorio Maria Carla , Vanacore Renato , Storti Eugenia , Resi Veronica , Di Cianni Graziano , Del Prato Stefano
Published: June 2011

Endothelial progenitor cells (EPCs) play a role in angiogenesis during pregnancy. The aim of this study was to evaluate circulating EPCs in pregnant women with gestational alterations of glucose tolerance. Glucose tolerance, insulin sensitivity and β-cell function were derived from oral glucose tolerance tests in 23 women with normal glucose tolerance (NGT), 18 with gestational impaired glucose tolerance (GIGT) and 24 with gestational diabetes mellitus (GDM). Circulating cells expressing CD34 in combination with CD133, kinase insert domain receptor (KDR) or both were quantified by flow cytometry. Women with GIGT and GDM had lower CD34+KDR+ and CD34+CD133 +KDR+ cells at 27±3.2 weeks’ gestation compared with NGT (ANOVA p<0.02 for both). CD34+KDR+ and CD34+CD133+KDR+ cells were inversely correlated with the area-under-the-glucose-curve ( p<0.005, for both) and positively to insulin secretion-sensitivity index ( p<0.05, for both). Alterations of glucose tolerance during pregnancy are associated with a decrease in EPCs. Hyperglycaemia might exert a direct effect on depletion of EPCs.
Taking More, Now
Authors: Otto A. Ross , Markman Arthur B. , Love Bradley C.
Published: June 2011

Impulsivity is a stable personality trait associated with myopic choice behavior that favors immediate rewards over larger, delayed rewards and is often characterized as maladaptive inside and outside of the laboratory. An alternative view suggests that the consequences of trait impulsivity depend on the nature of the task environment. On this view, the optimal level of impulsivity varies across task payoff structures. This hypothesis is tested in two dynamic decision-making tasks that differ in the relative payoffs of delayed and immediate rewards. In a task that favors delayed rewards to immediate rewards, high-impulsive participants perform worse than low-impulsive participants. In contrast, in a task that favors immediate rewards over delayed rewards, high-impulsive participants outperform low-impulsive participants. These results suggest a more nuanced conceptualization of trait impulsivity as it applies to rewards-related decision making that may help explain the variability observed in this trait across individuals.
Cross-docking centre operation optimization using simulation-based genetic algorithm
Authors: Wu Y , Dong M , Yang D
Published: June 2011

The operational improvement of cross-docking centres in the literature involves job scheduling, layout design and dock assignment. The mentioned research is mainly concerned with makespan, number of tardy jobs or travel distance. However, these measures may not fully represent the main advantages of cross-docking operations. Little has been done to optimize the major performance measures of a cross-docking centre, which substantiates the main advantages of cross-docking technology. In this paper, inventory holding cost, transportation cost and backorder penalty cost are aggregated into total cost and a solution framework has been developed by integrating simulation, genetic algorithm (GA) and smart computing budget allocation (SCBA) for a comprehensive total cost minimization problem. This problem has huge search space even for medium-sized problem scenarios. To address this difficulty, the framework employs simulation to estimate the total cost, GA to search for better design and SCBA to efficiently allocate the simulation budget. Numerical experiments show that the proposed framework operates effectively in cases of different problem scales.
Late effects among pediatric patients followed for nearly 4 decades after transplantation for severe aplastic anemia
Authors: Sanders Jean E. , Woolfrey Ann E. , Carpenter Paul A. , Storer Barry E. , Hoffmeister Paul A. , Deeg H. Joachim , Flowers Mary E. D. , Storb Rainer F.
Published: June 2011

Aplastic anemia (AA), a potentially fatal disease, may be cured with marrow transplantation. Survival in pediatric patients has been excellent early after transplantation, but only limited data are available regarding late effects. This study evaluates late effects among 152 patients followed 1-38 years (median, 21.8 years). Transplantation-preparative regimes were mostly cyclophosphamide with or without antithymocyte globulin. Survival at 30 years for the acquired AA patients is 82%, and for the Fanconi anemia patients it is 58% (P = .01). Multivariate analysis demonstrated that chronic GVHD (P = .02) and Fanconi anemia (P = .03) negatively impacted survival. Two Fanconi patients and 18 acquired AA patients developed a malignancy that was fatal for 4. There was an increased incidence of thyroid function test abnormalities among those who received total body irradiation. Cyclophosphamide recipients demonstrated normal growth, basically normal development, and pregnancies with mostly normal offspring. Quality-of-life studies in adult survivors of this pediatric transplantation cohort indicated that patients were comparable with control patients except for difficulty with health and life insurance. These data indicate that the majority of long-term survivors after transplantation for AA during childhood can have a normal productive life.