bluuebunny/crossref_metadata_2025 huggingface dataset:
Uterine artery occlusion and myomectomy for treatment of pregnant women with uterine leiomyomas who are undergoing cesarean section
Authors: Lin Jui‐Yu , Lee Wen‐Ling , Wang Peng‐Hui , Lai Man‐Jung , Chang Wen‐Hsun , Liu Wei‐Min
Published: March 2010

Aim:  To evaluate the efficacy of uterine artery occlusion and myomectomy (UAO+M) for pregnant women with uterine leiomyomas who are undergoing cesarean section (CS).

Methods:  Seventy‐two women with uterine leiomyomas undergoing CS for obstetrical reasons were enrolled into this case–control study. Thirty‐six patients underwent UAO+M during CS (UAO+M group), and 36 received CS alone (Control group). The UAO+M procedure was performed immediately after closure of the uterine incision wound. The outcome was measured by comparing surgical techniques, and future surgical intervention (myomectomy, uterine vessel occlusion or hysterectomy) for symptomatic leiomyoma.

Results:  The average follow‐up time was 63 months. General characteristics of the patients were similar in both groups. There were no statistical differences in intraoperative blood loss, postoperative recovery, complications, or wound pain between the two groups. The operative time was significantly longer in the UAO+M group compared with that in the Control group, but the further surgical intervention rate was significantly lower in the UAO+M group than in the Control group (2.8% vs 41.7%, P < 0.001). Seven patients (19%) in the UAO+M group and five (14%) in the Control group had a repeat CS during the follow‐up period.

Conclusion:  UAO+M could be considered for treating pregnant women with uterine leiomyomas who are undergoing CS, compared with observation, as this procedure can minimize the necessity for future surgery, with increased operative time for the UAO+M procedure, but without increased surgical morbidity.
The prostate cancer gene 3 (PCA3) urine test in men with previous negative biopsies: does free‐to‐total prostate‐specific antigen ratio influence the performance of the PCA3 score in predicting positive biopsies?
Authors: Ploussard Guillaume , Haese Alexander , Van Poppel Hendrik , Marberger Michael , Stenzl Arnulf , Mulders Peter F.A. , Huland Hartwig , Bastien Laurence , Abbou Clèment‐Claude , Remzi Mesut , Tinzl Martina , Feyerabend Susan , Stillebroer Alexander B. , Van Gils Martijn P.M.Q. , Schalken Jack A. , De La Taille Alexandre
Published: March 2010

Study Type – Diagnosis (exploratory cohort) Level of Evidence 2b

OBJECTIVE

To determine the performance characteristics of the prostate cancer gene 3 (PCA3) score on the outcome of biopsy relative to different ranges of free‐to‐total prostate‐specific antigen (PSA) ratio (f/tPSA) in men with a previous negative biopsy and a PSA level of 2.5–10 ng/mL, as urine tests like PCA3 are currently under investigation in order to improve prostate cancer diagnosis and to decrease the rate of unnecessary rebiopsies.

PATIENTS AND METHODS

Data from the previous prospective European multicentre study were reviewed. Only patients with a PSA level of 2.5–10 ng/mL were included in the present study. In all, 301 patients had complete data. The diagnostic accuracy of the PCA3 score for predicting a positive biopsy outcome was studied using sensitivity, specificity, negative and positive predictive values. The PCA3 performance was evaluated relative to three different subgroups of f/tPSA, as follows: >20% (group 1), 10–20% (group 2) and <10% (group 3).

RESULTS

The prostate cancer detection rates were 18.8%, 23.9% and 34.8% in groups 1, 2 and 3, respectively. The area under the receiver operating characteristic curve of the PCA3 score, total PSA and f/tPSA was 0.688, 0.553 and 0.571, respectively. The percentage of men with positive biopsies was 30.6%, 37.0% and 44.4% in those with a PCA3 score of >30, vs 10.3%, 15.5% and 28.6% when the PCA3 score was <30, in groups 1, 2 and 3, respectively. The difference was significant only in groups 1 and 2. In men with a f/tPSA of ≤10% the difference in detection rates relative to the PCA3 score was not statistically significant regardless of which PCA3 threshold was used. A high PCA3 score was significantly associated with age, clinical T2 stage and positive biopsy (P < 0.001, 0.013 and <0.001, respectively). In bivariate analysis accounting for the PCA3 score and the f/tPSA, a PCA3 score of >30 was a significant independent predictor of positive biopsies (odds ratio 3.01; 95% confidence interval 1.74–5.23; P < 0.001).

CONCLUSIONS

PCA3 remained a better predictor of prostate cancer than f/tPSA. In men with a f/tPSA of >10%, the use of the PCA3 score was highly correlated with the risk of having cancer on re‐biopsy, and could prevent unnecessary prostate biopsies if the value is low.
POSSIBILITY OF DYING AS A UNIFIED EXPLANATION OF WHY WE DISCOUNT THE FUTURE, GET WEAKER WITH AGE, AND DISPLAY RISK‐AVERSION
Authors: CHOWDHRY BHAGWAN
Published: March 2010

I formulate a simple and parsimonious evolutionary model that shows that because most species face a possibility of dying because of external factors, called extrinsic mortality in the biology literature, it can simultaneously explain (a) why we discount the future, (b) get weaker with age, and (c) display risk‐aversion. The paper suggests that testable restrictions—across species, across time, or across genders—among time preference, aging, and risk‐aversion could be analyzed in a simple framework (JEL A10, D90).
THE IMPACT OF IMMIGRATION ON CHILD HEALTH: EXPERIMENTAL EVIDENCE FROM A MIGRATION LOTTERY PROGRAM
Authors: STILLMAN STEVEN , GIBSON JOHN , MCKENZIE DAVID
Published: March 2010

This paper uses a unique survey designed by the authors to compare migrant children who enter New Zealand through a random ballot with children in the home country of Tonga whose families were unsuccessful participants in the same ballots. We find that migration increases height and reduces stunting of infants and toddlers, but also increases BMI and obesity among 3‐ to 5‐yr‐olds. These impacts are quite large even though the average migrant household has been in New Zealand for less than 1 yr. Additional results suggest that these impacts occur because of dietary change rather than direct income effects.(JELJ61, I12, F22)
Three‐month‐olds show a negativity bias in their social evaluations
Authors: Kiley Hamlin J. , Wynn Karen , Bloom Paul
Published: March 2010

Previous research has shown that 6‐month‐olds evaluate others on the basis of their social behaviors – they are attracted to prosocial individuals, and avoid antisocial individuals (Hamlin, Wynn & Bloom, 2007). The current studies investigate these capacities prior to 6 months of age. Results from two experiments indicate that even 3‐month‐old infants evaluate others based on their social behavior towards third parties, and that negative social information is developmentally privileged.
Facial expressions modulate the ontogenetic trajectory of gaze‐following among monkeys
Authors: Teufel Christoph , Gutmann Anke , Pirow Ralph , Fischer Julia
Published: March 2010

Gaze‐following, the tendency to direct one’s attention to locations looked at by others, is a crucial aspect of social cognition in human and nonhuman primates. Whereas the development of gaze‐following has been intensely studied in human infants, its early ontogeny in nonhuman primates has received little attention. Combining longitudinal and cross‐sectional observational data from Barbary macaques at ‘La Forêt des Singes’, we show here that gaze‐following among conspecifics develops within the first year of life with a rapid increase between 5 and 6 months, reaching adult levels at 1 year. Sex, rank, and relatedness of the animal whose gaze the subject followed did not affect gaze‐following rates. Interestingly, however, the behavior was enhanced in all age classes if a gaze‐cue was accompanied by a facial expression. Furthermore, the effect of facial expressions had a modulatory influence on the ontogenetic trajectory of gaze‐following, suggesting that it is of functional significance in the development of the behavior. Follow‐up analyses revealed that one specific facial expression that is given in response to social interactions between third parties was particularly efficient in eliciting gaze‐following responses, indicating the importance of cues that are able to guide the acquisition of social information. Taken together, these results suggest that the development and the operation of gaze‐following are tuned to the social and physical characteristics of a species’ environment.
Reservation Wages, Labour Market Participation and Health
Authors: Brown Sarah , Roberts Jennifer , Taylor Karl
Published: March 2010

The concept of the reservation wage has played an important role in labour market theory, particularly in models of job search, labour supply and labour market participation. We focus on the determinants of reservation wages, with a particular focus on health, which has attracted very little attention despite its importance from a policy perspective. Using UK data we estimate an endogenous switching model which predicts reservation wages for the unemployed and market wages for the employed. Our results have important policy implications since they suggest that poor health is a major cause of economic inactivity.
BEYOND SECULARISM? TOWARDS A POST‐SECULAR POLITICAL THEOLOGY
Authors: SIGURDSON OLA
Published: March 2010

In this article I analyse some of the reasons for a recent, resurgent interest in religion and theology by political philosophers and relate this interest to an inherent instability in modernity itself. In the first part I describe the landscape of current political philosophy with a particular emphasis on radical philosophers. In the second part I describe how the liberal distinction between religion and politics generates a theological instability due to the effective disappearance of the social embodiment of religion within modernity. In the third part I draw some conclusions regarding the challenges the new post‐secular condition presents to theology.
EROS AND/AS DESIRE—A THEOLOGICAL AFFIRMATION: PAUL TILLICH READ IN THE LIGHT OF JEAN‐LUC MARION'S THE EROTIC PHENOMENON
Authors: HENRIKSEN JAN‐OLAV
Published: March 2010

The article interprets Tillich's varied elaborations on different aspects of eros, mainly in his Systematic Theology, by reading them in the light of Jean‐Luc Marion's phenomenological description of eros in its various aspects in The Erotic Phenomenon. The erotic in Tillich not only has to do with sex and desire, but also with his commitment to a realistic approach to what it means to be human, to human culture, and to confronting false and estranging interpretations of basic human phenomena. What seems to be missing in Tillich, however, is a more comprehensive treatment of eros/desire that would make possible an understanding of the phenomenological (and consequently existential) fullness of this phenomenon. I suggest that this can be achieved by reading Tillich by way of Marion's phenomenological analysis. This also has the virtue of overcoming the all‐too abstract character of Tillich's reasoning without at the same time dismissing Tillich's treatment of eros. I will also draw out some implications for how one might deal with eros and desire in the emerging discussion in present systematic theology.
In Defense of Old Industrial Spaces: Manufacturing, Creativity and Innovation in Williamsburg, Brooklyn
Authors: CURRAN WINIFRED
Published: March 2010

This article argues that the flexibility, creativity, and innovation deemed to be hallmarks of the new ‘creative’ economy are also present in more traditional manufacturing enclaves. Here I use examples drawn from New York City, perhaps the quintessential global city, to demonstrate that our understanding of creativity and innovation needs to recognize a broader spectrum of economic activity encompassing both new and traditional manufacturing. This case study is an attempt to expand the heteronomy of current urban policy that promotes gentrification and the wooing of the ‘creative class’ as the only method of urban development.

Souplesse, créativité et innovation, censées être les traits distinctifs de la nouvelle économie ‘créative’, existent également dans des enclaves industrielles plus traditionnelles. Des exemples sont tirés de la ville de New‐York, sans doute la ville planétaire par excellence, afin de démontrer que notre compréhension de la créativité et de l’innovation a besoin d’étendre son spectre de l’activitééconomique afin d’englober des fabrications tant nouvelles que traditionnelles. Cette étude de cas tente d’accroître l’hétéronomie de la politique urbaine actuelle, laquelle encourage la gentrification et la séduction de la ‘classe créative’ comme unique méthode de développement urbain.
Genomic conflict in scale insects: the causes and consequences of bizarre genetic systems
Authors: Ross Laura , Pen Ido , Shuker David M.
Published: March 2010

It is now clear that mechanisms of sex determination are extraordinarily labile, with considerable variation across all taxonomic levels. This variation is often expressed through differences in the genetic system (XX‐XY, XX‐XO, haplodiploidy, and so on). Why there is so much variation in such a seemingly fundamental process has attracted much attention, with recent ideas concentrating on the possible role of genomic conflicts of interest. Here we consider the role of inter‐ and intra‐genomic conflicts in one large insect taxon: the scale insects. Scale insects exhibit a dizzying array of genetic systems, and their biology promotes conflicts of interest over transmission and sex ratio between male‐ and female‐expressed genes, parental‐ and offspring‐expressed genes (both examples of intra‐genomic conflict) and between scale insects and their endosymbionts (inter‐genomic conflict). We first review the wide range of genetic systems found in scale insects and the possible evolutionary transitions between them. We then outline the theoretical opportunities for genomic conflicts in this group and how these might influence sex determination and sex ratio. We then consider the evidence for these conflicts in the evolution of sex determination in scale insects. Importantly, the evolution of novel genetic systems in scale insects has itself helped create new conflicts of interest, for instance over sex ratio. As a result, a major obstacle to our understanding of the role of conflict in the evolution of sex‐determination and genetic systems will be the difficulty in identifying the direction of causal relationships. We conclude by outlining possible experimental and comparative approaches to test more effectively how important genomic conflicts have been.
Relationships between carbonyl sulfide (COS) and CO2 during leaf gas exchange
Authors: Stimler Keren , Montzka Stephen A. , Berry Joseph A. , Rudich Yinon , Yakir Dan
Published: March 2010

Commentary p 783
Practical Applicability and Limitations of the Elastic Modulus Degradation Technique for Damage Measurements in Ductile Metals
Authors: Bonora N. , Ruggiero A. , Gentile D. , De Meo S.
Published: March 2010

Abstract:  The use of damage models require a number of material parameters the identification of which should be made, when possible, based on direct measures of the damage that develops in the material. Among the possible experimental techniques to measure the occurrence of ductile damage in metals, the measure of the damage through the degradation of the material Young’s modulus has been indicated as one of the more effective technique and used by several authors. In this paper, this technique is critically reviewed highlighting the number of issues that may affect the measure of damage. In particular, the attention is focused in the case where damage process initiates at the onset necking and develops in the post‐necking regime where stress, strain and damage are no longer uniform in the gauged section. Since geometry variations alter the reference base length for both stress and strain definition, a procedure based on the use of finite element simulation is proposed in order to account for this effect on the measure of the stiffness loss. The procedure has been applied to two class of metals: a high strength steel and high purity copper.
Asymmetrical Bending Model for NiTi Shape Memory Wires: Numerical Simulations and Experimental Analysis
Authors: De la Flor S. , Urbina C. , Ferrando F.
Published: March 2010

Abstract:  A detailed numerical and experimental study of a NiTi Shape Memory Alloy (SMA) wire subjected to bending is presented in order to provide a complete characterisation of the material under this load case. The beam model presented is based on the classic Euler‐Bernoulli theory and uses De la Flor one‐dimensional constitutive equations modified to take into account different material responses to tension and compression as well as the different elastic properties of austenite and martensite. All the necessary experimental techniques were designed to determine the bending behaviour of NiTi SMA wire over the entire range of transformation temperatures. These experimental bending results were then compared with the numerical results. The numerical model proposed agrees quantitatively and qualitatively with the experimental bending results obtained for NiTi wire, representing an effective tool for the analysis of one‐dimensional structural devices. A comparison of the numerical results that assume symmetrical behaviour between tension and compression with the results that assume asymmetrical behaviour has shown that the tension/compression asymmetry is more pronounced in the martensitic range and has little influence on the response of the SMA wire subjected to bending at temperatures above Af. These results are analyzed and discussed.
A Photoelastic Study of T‐stress in Centrally Cracked Brazilian Disc Specimen Under Mode II Loading
Authors: Zakeri M. , Ayatollahi M. R. , Guagliano M.
Published: March 2010

Abstract:  In the traditional formulation of the stress field near a crack tip, the presence of the T‐stress is generally considered only under mode I or mixed mode I and II conditions. In this paper its presence in almost pure Mode II is experimentally investigated by mean of photoelasticity and its effects on the isochromatic fringe patterns are discussed. The test specimens are Brazilian discs containing sharp central cracks. After crack generation, all residual stresses are removed with thermal treatment of the specimens. Then, a compressive load is applied in a specific angle to induce mode II deformation. The observed isochromatic fringes show very good consistency with theoretical predictions. Experimental results indicate that this specimen has a negative T‐stress in mode II condition. The results calculated for KII and T from photoelastic experiments agree well with numerical results available from finite element method.
Dynamic Mechanical Analysis of Hybrid Fibre/Glass Microspheres Composites
Authors: Ferreira J. A. M. , Capela C. , Costa J. D.
Published: March 2010

Abstract:  This article presents the results obtained in a current study of the viscous properties on hybrid short fibre/hollow glass microspheres composites fabricated with epoxy binder. The effect of the filler volume fraction and of the fibre reinforcement on the dynamic stiffness modulus, damping coefficient and glass transition temperature was studied. These properties were determined using dynamic mechanical analysis (DMA) in three points bending mode. The specimens were cut from plates produced by vacuum resin transfer moulding with microspheres weight contents up to 17%. Net resin exhibits storage modulus significantly higher than the 2% in weight of microspheres foam, while negligible effect was observed on the maximum loss modulus, maximum damping coefficient and glass transition temperature. The increase in filler volume fraction tends to decrease significantly storage and loss modulus at stable regions and the maximum damping coefficient, while glass transition temperature is only marginally affected. The addition of low contents of short fibre increases significantly storage modulus, particularly for carbon fibre, while maximum loss modulus does not exhibit a well‐defined tendency. Important reduction in the maximum damping coefficient was observed by the addition of both fibre reinforcements.
A Methodology for Accurately Measuring Mechanical Properties on the Micro‐Scale
Authors: Banks‐Sills L. , Shklovsky J. , Krylov S. , Bruck H. A. , Fourman V. , Eliasi R. , Ashkenazi D.
Published: March 2010

Abstract:  A methodology has been developed for accurately measuring the mechanical properties of materials used on the micro‐scale. The direct tension test method using a dog bone‐type specimen has been employed, as it is the most effective and straightforward method to obtain results including a full stress–strain curve. The goal of this investigation was to develop a universal, yet simple and reliable, methodology to be used for accurate characterisation of mechanical properties for a wide variety of materials. Specimens from single crystal silicon were fabricated using photolithography by means of deep reactive ion etching. This material was chosen as it is expected that on both the micro‐ and macro‐scales, Young's modulus will have the same value. Hence, the accuracy of the methodology may be unambiguously examined. The test set‐up includes a small test machine containing a load cell whose maximum capacity is 5 N and is capable of direct gripping and displacement control. The specimens were found to have a trapezoidal cross‐section that was accurately measured using a scanning electron microscope. The strains were obtained by means of digital image correlation using images obtained via optical microscopy. The quantities measured include Young's modulus E, the fracture strength σf and the fracture strain εf. The average value of E obtained in the micro‐tests agrees well with the reference value obtained on the macro‐scale.
Using a systems viability approach to evaluate integrated conservation and development projects: assessing the impact of the North Rupununi Adaptive Management Process, Guyana
Authors: MISTRY JAYALAXSHMI , BERARDI ANDREA , SIMPSON MATTHEW , DAVIS ODACY , HAYNES LAKERAM
Published: March 2010

Integrated conservation and development projects (ICDPs) are common place in the field of biodiversity conservation. However, there is little evidence in the wider literature on the successes of these projects, with failure attributed to a range of factors, including a bias on either conservation or development, weak assumptions and limited monitoring and evaluation. In this paper, we evaluate an ICDP in the North Rupununi district of Guyana. Using a systems viability approach, we show how assessing the project and the nested systems within which it is operating reveals numerous human and institutional capacity issues which could have been managed better if highlighted at the project development stage. We conclude with the proposal that a systems viability approach to ICDP development, monitoring and evaluation encourages greater learning and adaptive management processes for increasing the long‐term impact of ICDPs.
Amenities and disamenities: a hedonic analysis of the heterogeneous urban landscape in Shenzhen (China)
Authors: CHEN WENDY Y , JIM C Y
Published: March 2010

Landscape amenities and disamenities are important factors for households in making residence decision. This study presents a hedonic analysis of the amenity and disamenity effects arising from the heterogeneous urban landscape in a Chinese city. The sample is composed of 358 apartment characteristics and transaction data collected directly from home owners in the central built‐up area of Shenzhen. Four types of urban landscapes were included, namely urban parks, residential gardens, Shenzhen Bay, and urban villages. We applied a three‐dimensional model (availability, accessibility, and visibility) to estimate the amenity–disamenity effects of these urban landscape features. The results indicated that residential gardens were the most attractive landscape (an average increase of 17.2% of housing price) and urban villages had disamenity effects (a decrease of 3.72% for visibility and 2.5% for availability). The visibility of landscape was more valued than the accessibility. The lower weight accorded to the availability variable suggested: both benefits and possible negative impacts related to urban parks and Shenzhen Bay could be embodied in home buyers' behaviour; and the unavoidability of urban villages. The findings could provide insights to the location and design of residential areas vis‐à‐vis amenity–disamenity landscape features in Chinese cities that are rapidly expanding and redeveloping.
The xanthine derivative KMUP‐1 inhibits models of pulmonary artery hypertension via increased NO and cGMP‐dependent inhibition of RhoA/Rho kinase
Authors: Chung Hui‐Hsuan , Dai Zen‐Kong , Wu Bin‐Nan , Yeh Jwu‐Lai , Chai Chee‐Yin , Chu Koung‐Shing , Liu Chung‐Pin , Chen Ing‐Jun
Published: March 2010

Background and purpose:  KMUP‐1 is known to increase cGMP, enhance endothelial nitric oxide synthase (eNOS) and suppress Rho kinase (ROCK) expression in smooth muscle. Here, we investigated the mechanism of action of KMUP‐1 on acute and chronic pulmonary artery hypertension (PAH) in rats.

Experimental approach:  We measured pulmonary vascular contractility, wall thickening, eNOS immunostaining, expressions of ROCK II, RhoA activation, myosin phosphatase target subunit 1 (MYPT1) phosphorylation, eNOS, soluble guanylyl cyclase (sGC), protein kinase G (PKG) and phosphodiesterase 5A (PDE‐5A), blood oxygenation and cGMP/cAMP, and right ventricular hypertrophy (RVH) in rats.

Key results:  In rings of intact pulmonary artery (PA), KMUP‐1 relaxed the vasoconstriction induced by phenylephrine (10 µM) or the thromboxane A2‐mimetic U46619 (0.5 µM). In endothelium‐denuded PA rings, this relaxation was reduced. In acute PAH induced by U46619 (2.5 µg·kg−1·min−1, 30 min), KMUP‐1 relaxed vasoconstriction by enhancing levels of eNOS, sGC and PKG, suppressing those of PDE‐5A, RhoA/ROCK II activation and MYPT1 phosphorylation, and restoring oxygenation in blood and cGMP/cAMP in plasma. Incubating smooth muscle cells from PA (PASMCs) with KMUP‐1 inhibited thapsigargin‐induced Ca2+ efflux and angiotensin II‐induced Ca2+ influx. In chronic PAH model induced by monocrotaline, KMUP‐1 increased eNOS and reduced RhoA/ROCK II activation/expression, PA wall thickening, eNOS immunostaining and RVH. KMUP‐1 and sildenafil did not inhibit monocrotaline‐induced PDE‐5A expression.

Conclusion and implications:  KMUP‐1 decreased PAH by enhancing NO synthesis by eNOS, with consequent cGMP‐dependent inhibition of RhoA/ROCK II and Ca2+ desensitization in PASMCs. KMUP‐1 has the potential to reduce vascular resistance, remodelling and RVH in PAH.
A role for L‐α‐lysophosphatidylinositol and GPR55 in the modulation of migration, orientation and polarization of human breast cancer cells
Authors: Ford Lesley A , Roelofs Anke J , Anavi‐Goffer Sharon , Mowat Luisa , Simpson Daniel G , Irving Andrew J , Rogers Michael J , Rajnicek Ann M , Ross Ruth A
Published: March 2010

Background and purpose:  Increased circulating levels of L‐α‐lysophosphatidylinositol (LPI) are associated with cancer and LPI is a potent, ligand for the G‐protein‐coupled receptor GPR55. Here we have assessed the modulation of breast cancer cell migration, orientation and polarization by LPI and GPR55.

Experimental approach:  Quantitative RT‐PCR was used to measure GPR55 expression in breast cancer cell lines. Cell migration and invasion were measured using a Boyden chamber chemotaxis assay and Cultrex® invasion assay, respectively. Cell polarization and orientation in response to the microenvironment were measured using slides containing nanometric grooves.

Key results:  GPR55 expression was detected in the highly metastatic MDA‐MB‐231 breast cancer cell line. In these cells, LPI stimulated binding of [35S]GTPγS to cell membranes (pEC50 6.47 ± 0.45) and significantly enhanced cell chemotaxis towards serum. MCF‐7 cells expressed low levels of GPR55 and did not migrate or invade towards serum factors. When GPR55 was over‐expressed in MCF‐7 cells, serum induced a robust migratory and invasive response, which was further enhanced by LPI and prevented by siRNA to GPR55. The physical microenvironment has been identified as a key factor in determining breast tumour cell metastatic fate. LPI endowed MDA‐MB‐231 cells with the capacity to detect shallow (40 nm deep) grooved slides and induced marked cancer cell polarization on both flat and grooved surfaces.

Conclusions and implications:  LPI and GPR55 play a role in the modulation of migration, orientation and polarization of breast cancer cells in response to the tumour microenvironment.

This article is part of a themed issue on Cannabinoids. To view the editorial for this themed issue visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00831.x
GPR55‐dependent and ‐independent ion signalling in response to lysophosphatidylinositol in endothelial cells
Authors: Bondarenko Alexander , Waldeck‐Weiermair Markus , Naghdi Shamim , Poteser Michael , Malli Roland , Graier Wolfgang F
Published: March 2010

Background and purpose:  The glycerol‐based lysophospholipid lysophosphatidylinositol (LPI) is an endogenous agonist of the G‐protein‐coupled receptor 55 (GPR55) exhibiting cannabinoid receptor‐like properties in endothelial cells. To estimate the contribution of GPR55 to the physiological effects of LPI, the GPR55‐dependent and ‐independent electrical responses in this cell type were investigated.

Experimental approach:  Applying small interference RNA‐mediated knock‐down and transient overexpression, GPR55‐dependent and ‐independent effects of LPI on cytosolic free Ca2+ concentration, membrane potential and transmembrane ion currents were studied in EA.hy296 cells.

Key results:  In a GPR55‐dependent, GDPβS and U73122‐sensitive manner, LPI induced rapid and transient intracellular Ca2+ release that was associated with activation of charybdotoxin–sensitive, large conductance, Ca2+‐activated, K+ channels (BKCa) and temporary membrane hyperpolarization. Following these initial electrical reactions, LPI elicited GPR55‐independent long‐lasting Na+ loading and a non‐selective inward current causing sustained membrane depolarization that depended on extracellular Ca2+ and Na+ and was partially inhibited by Ni2+ and La3+. This inward current was due to the activation of a voltage‐independent non‐selective cation current. The Ni2+ and La3+‐insensitive depolarization with LPI was prevented by inhibition of the Na/K‐ATPase by ouabain.

Conclusions and implications:  LPI elicited a biphasic response in endothelial cells of which the immediate Ca2+ signalling depends on GPR55 while the subsequent depolarization is due to Na+ loading via non‐selective cation channels and an inhibition of the Na/K‐ATPase. Thus, LPI is a potent signalling molecule that affects endothelial functions by modulating several cellular electrical responses that are only partially linked to GPR55.
ENaC‐mediated effects assessed by MRI in a rat model of hypertonic saline‐induced lung hydration
Authors: Blé F‐X , Cannet C , Collingwood S , Danahay H , Beckmann N
Published: March 2010

Background and purpose:  The epithelial sodium channel (ENaC) regulates airway mucosal hydration and mucus clearance. The lack of such regulation in cystic fibrosis patients leads to dessication of the airway lumen, resulting in mucostasis that establishes the environment for infections. Osmotic agents and negative ENaC regulators can be used to restore mucosal hydration. We aimed to assess whether: (i) osmotically driven fluid flux into the rat lung could be quantified in vivo by magnetic resonance imaging (MRI); and (ii) the MRI signals could be modulated through the regulation of ENaC function.

Experimental approach:  Lung images from spontaneously breathing rats were acquired following intra‐tracheal (i.t.) administration of physiological or hypertonic saline (HS). Compounds known to modulate the ENaC function were given i.t. prior to saline. Volumes of fluid signals were quantified on the images.

Key results:  A tonicity‐dependent increase in lung fluid was demonstrated following HS administration. Pretreatment with the ENaC blockers, amiloride or 552‐02, resulted in an enhancement of HS‐induced lung fluid signals, which were detectable for up to 4 h, consistent with a role for ENaC in fluid clearance. Aprotinin, a serine protease inhibitor that attenuates ENaC function, likewise enhanced the HS‐induced increase in lung fluid signal, while α1‐anti‐trypsin was without significant effect.

Conclusions and implications:  Proton MRI provides a non‐invasive technique for studying modulators of lung fluid hydration in rat lung in vivo. The pharmacological sensitivity of MRI‐detected fluid signals is consistent with ENaC‐mediated fluid reabsorption after HS. This target‐related readout may be used to characterize new ENaC modulators.
Terrestrial Reserve Networks Do Not Adequately Represent Aquatic Ecosystems
Authors: HERBERT MATTHEW E. , MCINTYRE PETER B. , DORAN PATRICK J. , ALLAN J. DAVID , ABELL ROBIN
Published: March 2010

Abstract:  Protected areas are a cornerstone of conservation and have been designed largely around terrestrial features. Freshwater species and ecosystems are highly imperiled, but the effectiveness of existing protected areas in representing freshwater features is poorly known. Using the inland waters of Michigan as a test case, we quantified the coverage of four key freshwater features (wetlands, riparian zones, groundwater recharge, rare species) within conservation lands and compared these with representation of terrestrial features. Wetlands were included within protected areas more often than expected by chance, but riparian zones were underrepresented across all (GAP 1–3) protected lands, particularly for headwater streams and large rivers. Nevertheless, within strictly protected lands (GAP 1–2), riparian zones were highly represented because of the contribution of the national Wild and Scenic Rivers Program. Representation of areas of groundwater recharge was generally proportional to area of the reserve network within watersheds, although a recharge hotspot associated with some of Michigan's most valued rivers is almost entirely unprotected. Species representation in protected areas differed significantly among obligate aquatic, wetland, and terrestrial species, with representation generally highest for terrestrial species and lowest for aquatic species. Our results illustrate the need to further evaluate and address the representation of freshwater features within protected areas and the value of broadening gap analysis and other protected‐areas assessments to include key ecosystem processes that are requisite to long‐term conservation of species and ecosystems. We conclude that terrestrially oriented protected‐area networks provide a weak safety net for aquatic features, which means complementary planning and management for both freshwater and terrestrial conservation targets is needed.
Contrasting Colonist and Indigenous Impacts on Amazonian Forests
Authors: LU FLORA , GRAY CLARK , BILSBORROW RICHARD E. , MENA CARLOS F. , ERLIEN CHRISTINE M. , BREMNER JASON , BARBIERI ALISSON , WALSH STEPHEN J.
Published: March 2010

Abstract:  To examine differences in land use and environmental impacts between colonist and indigenous populations in the northern Ecuadorian Amazon, we combined data from household surveys and remotely sensed imagery that was collected from 778 colonist households in 64 colonization sectors, and 499 households from five indigenous groups in 36 communities. Overall, measures of deforestation and forest fragmentation were significantly greater for colonists than indigenous peoples. On average, colonist households had approximately double the area in agriculture and cash crops and 5.5 times the area in pasture as indigenous households. Nevertheless, substantial variation in land‐use patterns existed among the five indigenous groups in measures such as cattle ownership and use of hired agricultural labor. These findings support the potential conservation value of indigenous lands while cautioning against uniform policies that homogenize indigenous ethnic groups.
Predictors of Lane‐Change Errors in Older Drivers
Authors: Munro Cynthia A. , Jefferys Joan , Gower Emily W. , Muñoz Beatriz E. , Lyketsos Constantine G. , Keay Lisa , Turano Kathleen A. , Bandeen‐Roche Karen , West Sheila K.
Published: March 2010

OBJECTIVES: To determine the factors that predict errors in executing proper lane changes among older drivers.

DESIGN:

Cross‐sectional analysis of data from a longitudinal study.

SETTING: Maryland's Eastern Shore.

PARTICIPANTS: One thousand eighty drivers aged 67 to 87 enrolled in the Salisbury Eye Evaluation Driving Study.

MEASUREMENTS: Tests of vision, cognition, health status, and self‐reported distress and a driving monitoring system in each participant's car, used to quantify lane‐change errors.

RESULTS: In regression models, measures of neither vision nor perceived stress were related to lane‐change errors after controlling for age, sex, race, and residence location. In contrast, cognitive variables, specifically performance on the Brief Test of Attention and the Beery‐Buktenicka Test of Visual‐Motor Integration, were related to lane‐change errors.

CONCLUSION: The current findings underscore the importance of specific cognitive skills, particularly auditory attention and visual perception, in the execution of driving maneuvers in older individuals.
Metabolic Syndrome and Risk of Dementia in Older Adults
Authors: Forti Paola , Pisacane Nicoletta , Rietti Elisa , Lucicesare Anna , Olivelli Valentina , Mariani Erminia , Mecocci Patrizia , Ravaglia Giovanni
Published: March 2010

OBJECTIVES: To investigate the association between metabolic syndrome (MetS; a clustering of cardiovascular risk factors including abdominal obesity, hypertension, dyslipidemia, and hyperglycemia, each of which has been individually associated with dementia) and incident dementia, Alzheimer's disease (AD), and vascular dementia (VaD) in older adults before and after the age of 75.

DESIGN: Prospective population‐based cohort.

SETTING: An Italian municipality.

PARTICIPANTS: A community‐based sample of 749 subjects aged 65 and older who, in 1999/2000, were free of cognitive impairment and, in 2003/04, underwent follow‐up for incident dementia.

MEASUREMENTS: The relationship between incident overall dementia, AD, and VaD and MetS. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. MetS was defined according to the National Cholesterol Education Program criteria.

RESULTS: Risk of overall dementia and its subtypes was not associated with MetS or any MetS component in participants younger than 75. In participants aged 75 and older, MetS was associated with a lower risk of AD (hazard ratio (HR)=0.33, 95% confidence interval (CI)=0.12–0.94) but not of VaD, and abdominal obesity was associated with a lower risk of overall dementia (HR=0.53, 95% CI=0.28–0.98).

CONCLUSION: MetS measured in late life is not associated with risk of dementia. After age 75, persons with MetS may even be at lower risk for AD.
Long‐Term Effectiveness of Screening for Hearing Loss: The Screening for Auditory Impairment—Which Hearing Assessment Test (SAI‐WHAT) Randomized Trial
Authors: Yueh Bevan , Collins Margaret P. , Souza Pamela E. , Boyko Edward J. , Loovis Carl F. , Heagerty Patrick J. , Liu Chuan‐Fen , Hedrick Susan C.
Published: March 2010

OBJECTIVES: To evaluate the effect of hearing screening on long‐term hearing outcomes in a general population of older veterans.

DESIGN: Hearing loss in the elderly is underdetected and undertreated. Routine hearing screening has been proposed, but it is not clear whether screening identifies patients who are sufficiently motivated to adhere to treatment. A four‐arm randomized clinical trial was conducted to compare three screening strategies with no screening in 2,305 older veterans seeking general medical care.

SETTING: Veterans Affairs Puget Sound Health Care System.

INTERVENTIONS: The screening strategies were a tone‐emitting otoscope, a widely used questionnaire about hearing handicap, and a combination of both tools.

MEASUREMENTS: Hearing aid use 1 year after screening.

RESULTS: Of participants who underwent screening with the tone‐emitting otoscope, questionnaire, and combined testing, 18.6%, 59.2%, and 63.6%, respectively, screened positive for hearing loss (P<.01 for test of equality across three arms). Patients proceeded to formal audiology evaluation 14.7%, 23.0%, and 26.6% of the time in the same screening arms, compared with 10.8% in the control arm (P<.01 for test of equality across four arms). Hearing aid use 1 year after screening was 6.3%, 4.1%, and 7.4% in the same arms, compared with 3.3% in the control arm (P<.01). Hearing aid users experienced significant improvements in hearing‐related function and communication ability.

CONCLUSION: In older veterans, screening for hearing loss led to significantly more hearing aid use. Screening with the tone‐emitting otoscope was more efficient. The results are most applicable to older populations with few cost barriers to hearing aids.
Trends in the Health Status of Older Koreans
Authors: Jang Soong‐Nang , Kim Dong‐Hyun
Published: March 2010

Several recent studies have suggested that mortality, disability, and self‐rated health in older Americans have improved in last decade, but data from rapidly aging Asians remain sparse, and it is unclear that improvement extends to various health outcomes among older Korean populations. Trends in mortality, morbidity, disability, health behavior, and self‐rated health in older Koreans were assessed. Data were obtained from the National Death Statistics (1983–2006) and three representative and repeated cross‐sectional nationwide surveys: the National Elderly Activity Status and Welfare Needs Survey, the National Long‐term Care Needs Survey, and the Korean National Health and Nutrition Examination Survey. All‐cause mortality and disability decreased rapidly among older Koreans over the survey years, although some dimensions of health, including mortality from cancer, ischemic heart disease, and diabetes mellitus, have continued to deteriorate during this same period. Data on self‐rated health have also confirmed this trend toward diminished health status. These results are not consistent with the theory of compression of morbidity. Given the complexity and controversies characterizing health changes in the older population, continuing examination of the latest information about various aspects of mortality, disability, morbidity, and health behavior is necessary for the development of future improvements in healthy life expectancies in older Koreans.
Testing a Primary and a Secondary Endpoint in a Group Sequential Design
Authors: Tamhane Ajit C. , Mehta Cyrus R. , Liu Lingyun
Published: March 2010

Summary We consider a clinical trial with a primary and a secondary endpoint where the secondary endpoint is tested only if the primary endpoint is significant. The trial uses a group sequential procedure with two stages. The familywise error rate (FWER) of falsely concluding significance on either endpoint is to be controlled at a nominal level α. The type I error rate for the primary endpoint is controlled by choosing any α‐level stopping boundary, e.g., the standard O'Brien–Fleming or the Pocock boundary. Given any particular α‐level boundary for the primary endpoint, we study the problem of determining the boundary for the secondary endpoint to control the FWER. We study this FWER analytically and numerically and find that it is maximized when the correlation coefficient ρ between the two endpoints equals 1. For the four combinations consisting of O'Brien–Fleming and Pocock boundaries for the primary and secondary endpoints, the critical constants required to control the FWER are computed for different values of ρ. An ad hoc boundary is proposed for the secondary endpoint to address a practical concern that may be at issue in some applications. Numerical studies indicate that the O'Brien–Fleming boundary for the primary endpoint and the Pocock boundary for the secondary endpoint generally gives the best primary as well as secondary power performance. The Pocock boundary may be replaced by the ad hoc boundary for the secondary endpoint with a very little loss of secondary power if the practical concern is at issue. A clinical trial example is given to illustrate the methods.
A Bayesian Approach to Dose–Response Assessment and Synergy and Its Application to In Vitro Dose–Response Studies
Authors: Hennessey Violeta G. , Rosner Gary L. , Bast Jr Robert C. , Chen Min‐Yu
Published: March 2010

SummaryIn this article, we propose a Bayesian approach to dose–response assessment and the assessment of synergy between two combined agents. We consider the case of an in vitro ovarian cancer research study aimed at investigating the antiproliferative activities of four agents, alone and paired, in two human ovarian cancer cell lines. In this article, independent dose–response experiments were repeated three times. Each experiment included replicates at investigated dose levels including control (no drug). We have developed a Bayesian hierarchical nonlinear regression model that accounts for variability between experiments, variability within experiments (i.e., replicates), and variability in the observed responses of the controls. We use Markov chain Monte Carlo to fit the model to the data and carry out posterior inference on quantities of interest (e.g., median inhibitory concentrationIC50). In addition, we have developed a method, based on Loewe additivity, that allows one to assess the presence of synergy with honest accounting of uncertainty. Extensive simulation studies show that our proposed approach is more reliable in declaring synergy compared to current standard analyses such as the median‐effect principle/combination index method (Chou and Talalay, 1984, Advances in Enzyme Regulation 22,27–55), which ignore important sources of variability and uncertainty.
Multiple Imputation Approaches for the Analysis of Dichotomized Responses in Longitudinal Studies with Missing Data
Authors: Lu Kaifeng , Jiang Liqiu , Tsiatis Anastasios A.
Published: March 2010

Summary Often a binary variable is generated by dichotomizing an underlying continuous variable measured at a specific time point according to a prespecified threshold value. In the event that the underlying continuous measurements are from a longitudinal study, one can use the repeated‐measures model to impute missing data on responder status as a result of subject dropout and apply the logistic regression model on the observed or otherwise imputed responder status. Standard Bayesian multiple imputation techniques (Rubin, 1987, in Multiple Imputation for Nonresponse in Surveys) that draw the parameters for the imputation model from the posterior distribution and construct the variance of parameter estimates for the analysis model as a combination of within‐ and between‐imputation variances are found to be conservative. The frequentist multiple imputation approach that fixes the parameters for the imputation model at the maximum likelihood estimates and construct the variance of parameter estimates for the analysis model using the results of Robins and Wang (2000, Biometrika 87, 113–124) is shown to be more efficient. We propose to apply (Kenward and Roger, 1997, Biometrics 53, 983–997) degrees of freedom to account for the uncertainty associated with variance–covariance parameter estimates for the repeated measures model.