bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of Racial and Ethnic Disparities in Surgical Care
Authors: Ayanian John Z.
Published: January 2008

Racial and ethnic disparities are a pervasive and persistent problem in health care. This article has three main objectives: 1) To highlight key studies related to racial disparities in cardiovascular care and outcomes; 2) To explore determinants of disparities specifically related to access to renal transplantation as a model for understanding racial disparities in greater depth; and 3) To present promising approaches to eliminate racial disparities in care. Performance reports of the quality of medical and surgical care by race and ethnicity will be a crucial and expanding tool as more organizations ascertain complete data on their patients’ race, ethnicity, language, and socioeconomic characteristics. Efforts to improve the quality of care and health outcomes of underserved racial and ethnic groups will also require effective coordination of care, patient‐centered communication, and constructive engagement with communities to eliminate disparities in health care and health.
Digital document and interpretation: re-thinking “text” and scholarship in electronic settings
Authors: Gradmann Stefan , Meister Jan Christoph
Published: January 2008

The contribution starts from outlining the evolution of the scholarly production flow from the print based paradigm to the digital age and in this context it explores the opposition of digital versus analog representation modes. It then develops on the triple paradigm shift caused by genuine digital publishing and its specific consequences for the social sciences and humanities (SSH) which in turn results in re-constituting basic scholarly notions such as ‘text’ and ‘document’. The paper concludes with discussing the specific value that could be added in systematically using digital text resources as a basis for scholarly work and also states some of the necessary conditions for such a ‘digital turn’ to be successful in the SSH.
Growth factor contents of autologous human sera prepared by different production methods and their biological effects on chondrocytes
Authors: Tanaka Yoko , Ogasawara Toru , Asawa Yukiyo , Yamaoka Hisayo , Nishizawa Satoru , Mori Yoshiyuki , Takato Tsuyoshi , Hoshi Kazuto
Published: January 2008

To discuss the autologous serum production for cartilage tissue engineering, we compared three kinds of sera: whole blood‐derived serum (WBS), platelet‐containing plasma‐derived serum (PCS), and plasma‐derived serum (PDS), on the growth factor contents and their biological effects on human auricular chondrocytes. EGF, VEGF and PDGF levels were highest in WBS, while PCS and PDS followed WBS. The proliferation effects of WBS were the most pronounced, followed by that of PCS, both of which realized a 1000‐fold‐increase in chondrocyte numbers at the third passage, whereas PDS reached it after passage 4. No significant differences were observed in histology or cartilaginous matrix measurements of tissue‐engineered cartilage produced from chondrocytes cultured under different serum conditions. WBS would be clinically useful because of its potent proliferation effects, while PCS, which possibly saves the red cell concentrate, may be an option in cases where there are elevated risks of blood loss.
From Landlords to Software Engineers: Migration and Urbanization among Tamil Brahmans
Authors: Fuller C. J. , Narasimhan Haripriya
Published: January 2008

In south India's rapidly expanding information technology (IT) industry, the small, traditional elite of Tamil Brahmans is disproportionately well represented. Actually, no figures to confirm this assertion exist, but all the circumstantial evidence suggests that it is true, especially among the IT professionals and software engineers employed by the leading software and services companies in Chennai (Madras).1Since the nineteenth century, Tamil Brahmans have successfully entered several new fields of modern professional employment, particularly administration, law, and teaching, but also engineering, banking, and accountancy. Hence the movement into IT, despite some novel features, has clear precedents. All these professional fields require academic qualifications, mostly at a higher level, and the Brahmans' success is seemingly explained by their standards of modern education, which reflect their caste traditions of learning.2
“Interpreters of Occident to the Awakening Orient”: The Jewish Public Health Nurse in Mandate Palestine
Authors: Hirsch Dafna
Published: January 2008

Recent scholarship on Zionism has shown Orientalism to be a pregnant concept through which to study the formation of Jewish society and culture in Palestine and later Israel. As this body of scholarship suggests, Zionist self-perception as an outpost of Western civilization in the Orient has played a fundamental role in shaping both Zionism's relations to the Palestinians and to its “internal Others”—mizrahi, literally, Oriental Jews. Indeed, it was Zioinist Orientalism which created themizrahicategory in the first place, turning heterogeneous Asian, North African, and Palestine's Sephardic Jewish communities into a single, supposedly coherent group in need of modernization and civilization, against which the ‘westernness’ of EuropeanashkenaziJews was repeatedly asserted. What these studies often overlook is that the Zionist ‘civilizing mission’ was initially directed at (east) European Jews. Thus, for many of the “culture builders” who during the mandate years operated in theyishuv—the Jewish community of Palestine—Jewish westernness was deemed a project, something yet to be achieved.
Question: How Have Middle East Scholars Contributed to the Broader Field of Gender and Women's Studies?
Authors: MOGHADAM VALENTINE M.
Published: January 2008

In August 2001, a conference on the state of Middle East women's studies took place at the Rockefeller Foundation Center in Bellagio, Italy. Apart from the gorgeous surroundings, the conference was memorable for the breadth and scope of the high-quality papers presented by scholars teaching in the United States, Europe, the Middle East, and North Africa. Many participants were active in the Association for Middle East Women's Studies. Some went on to establish the Journal of Middle East Women's Studies, Hawwa, and Brill's women and Islam monograph series. Most of us also publish in disciplinary journals and present papers at a variety of conferences.
SEASONALITY OF MARRIAGES IN SARDINIAN PASTORAL AND AGRICULTURAL COMMUNITIES IN THE NINETEENTH CENTURY
Authors: SANNA EMANUELE , DANUBIO MARIA ENRICA
Published: January 2008

The study of marriage seasonality of populations with different socioeconomic backgrounds may contribute to the better understanding their reproductive behaviours. This study analyses the monthly distribution of marriages in the 19th century in four agricultural villages and four pastoral villages on the island of Sardinia (Italy). The data were derived from 7340 marriage acts (3571 for the four agricultural villages and 3769 for the four pastoral villages). The aim is to ascertain whether the Sardinian agricultural and pastoral communities followed the matrimonial models reported for contemporary Italy and Europe and whether there was a change in the monthly distribution of marriages between the two halves of the 19th century. The results suggest that the marriage seasonality of the Sardinian farmers and shepherds was very similar to the patterns shown in the 19th century by Italian and European agricultural and pastoral communities. The Sardinian farmers preferred to marry in autumn–winter, while the Sardinian shepherds had a very high concentration of marriages in summer–autumn. Both communities avoided marriages in the Advent and Easter periods and in the month of May (dedicated to the Virgin Mary), and the farmers also in August (also dedicated to the Virgin Mary). Despite a certain seasonal stability, there was a significant change in the monthly distribution of marriages between the two halves of the 19th century in both the agricultural and pastoral communities, probably due to a series of laws that transformed the centuries-old socioeconomic system of Sardinia in the second half of the century.
Multi-jurisdictional investigation of interactive fountain-associated cryptosporidiosis and salmonellosis outbreaks
Authors: KIRIAN M. L. , MEREGILLANO G. , GENNETTE D. , WEINTRAUB J. M.
Published: January 2008

Interactive water fountains are established sources of gastrointestinal infections yet most health codes fail to regulate their design and operation. This report describes multi-agency, concurrent interactive fountain-associated cryptosporidiosis and salmonellosis outbreak investigations and highlights the need for the adoption of appropriate regulations for interactive fountains.
Perturbed Identity Matrices Have High Rank: Proof and Applications
Authors: ALON NOGA
Published: January 2008

We describe a lower bound for the rank of any real matrix in which all diagonal entries are significantly larger in absolute value than all other entries, and discuss several applications of this result to the study of problems in Geometry, Coding Theory, Extremal Finite Set Theory and Probability. This is partly a survey, containing a unified approach for proving various known results, but it contains several new results as well.
Self-Efficacy, Interest, and Task Performance
Authors: Niemivirta Markku , Tapola Anna
Published: January 2008

Abstract. The aim of this study was to examine how possible changes in self-efficacy and interest during a task relate to each other and whether such changes independently predict overall task performance. To achieve this, the participants, one hundred ninth-grade students, were repetitively asked to rate their efficacy judgments and interest while they were working on a complex problem-solving task. The results from a series of latent growth curve models showed a significant overall increase in students' self-efficacy during the task. Changes in interest and self-efficacy were positively correlated, and, after controlling for the effects of prior mathematics achievement, both the initial level of self-efficacy and the rate of change in interest independently predicted final task performance.
Emotionales Erleben von Lehrkräften beim Unterrichten
Authors: Frenzel Anne C. , Götz Thomas
Published: January 2008

Zusammenfassung. Ziel dieser Studie war es, das Ausmaß an Variabilität des Erlebens von Freude, Angst und Ärger bei Lehrkräften zu ermitteln, das auf ihre Persönlichkeit, das Unterrichtsfach (hier: Mathematik vs. Physik) und die jeweils unterrichtete Klasse zurückzuführen ist. Zudem wurde der Einfluss von Person- und Kontextmerkmalen auf das emotionale Erleben beim Unterrichten untersucht. 59 Gymnasiallehrkräfte (9 weiblich) gaben anhand von einem Fragebogen sowie einem Tagebuch Auskunft über ihre Unterrichtsemotionen in jeweils vier ihrer Klassen (zwei Mathematik-, zwei Physikklassen). Mehrebenenanalytische Varianzanalysen zeigten, dass insbesondere Angst, aber auch Freude, stärker person- und weniger kontextspezifisch sind, während Ärger in gleichen Teilen von der Lehrerpersönlichkeit wie von der jeweils unterrichteten Klasse abhängt. Eine Fachspezifität unterrichtsbezogener Emotionen ließ sich bei Kontrolle der Klassenspezifität nicht nachweisen. Mehrebenen-Regressionen lieferten Hinweise darauf, dass das emotionale Erleben der Lehrkräfte von ihren Kontrollüberzeugungen, aber auch von der Größe der Klassen und vom in den jeweiligen Stunden vorherrschenden Verständnis-, Motivations- und Disziplinniveau abhängt. Die Bedeutsamkeit der Befunde für die Unterrichtspraxis wird diskutiert.
Leseverständnis ohne Lesen?
Authors: Rost Detlef H. , Sparfeldt Jörn R.
Published: January 2008

Zusammenfassung. Wiederholt wurden Zweifel an der Konstruktvalidität von multiple-choice-Leseverständnistestaufgaben geäußert. Diese bestehen üblicherweise aus den drei Teilen “Text”, “Fragen” und “Antworten”. In drei aufeinander aufbauenden Feldexperimenten (N1 = 371, N2 = 349, N3 = 402) bearbeiteten Schüler der 7. bis 9. Klassenstufe verschiedene Leseverständnistestversionen, in denen sukzessive zentrale Komponenten eliminiert wurden: “Original”, “ohne Text”, “ohne Fragen”, “ohne Text und ohne Fragen”. Mit abnehmendem Informationsgehalt wurden die Aufgaben erwartungsgemäß schwieriger. Jedoch lösten die Schüler in den Versionen “Original”, “ohne Text” und “ohne Fragen” deutlich und in der Version “ohne Text und ohne Fragen” teilweise mehr Aufgaben “richtig”, als bei reinem Raten zu erwarten wäre. Dies kann in den Versionen, in denen kein Text vorgegeben wurde, nicht auf “Lesen” zurückgeführt werden. Verbale Intelligenz erwies sich als bedeutsamer Prädiktor der Leseverständnistestleistung. Die Relevanz der Befunde für eine konstruktvalide Leseverständnisdiagnostik wird diskutiert.
Reconstructed historical land cover and biophysical parameters for studies of land‐atmosphere interactions within the eastern United States
Authors: Steyaert Louis T. , Knox Robert G.
Published: January 2008

Over the past 350 years, the eastern half of the United States experienced extensive land cover changes. These began with land clearing in the 1600s, continued with widespread deforestation, wetland drainage, and intensive land use by 1920, and then evolved to the present‐day landscape of forest regrowth, intensive agriculture, urban expansion, and landscape fragmentation. Such changes alter biophysical properties that are key determinants of land‐atmosphere interactions (water, energy, and carbon exchanges). To understand the potential implications of these land use transformations, we developed and analyzed 20‐km land cover and biophysical parameter data sets for the eastern United States at 1650, 1850, 1920, and 1992 time slices. Our approach combined potential vegetation, county‐level census data, soils data, resource statistics, a Landsat‐derived land cover classification, and published historical information on land cover and land use. We reconstructed land use intensity maps for each time slice and characterized the land cover condition. We combined these land use data with a mutually consistent set of biophysical parameter classes, to characterize the historical diversity and distribution of land surface properties. Time series maps of land surface albedo, leaf area index, a deciduousness index, canopy height, surface roughness, and potential saturated soils in 1650, 1850, 1920, and 1992 illustrate the profound effects of land use change on biophysical properties of the land surface. Although much of the eastern forest has returned, the average biophysical parameters for recent landscapes remain markedly different from those of earlier periods. Understanding the consequences of these historical changes will require land‐atmosphere interactions modeling experiments.
Distinguishing high‐alumina mare basalts using Clementine UVVIS and Lunar Prospector GRS data: Mare Moscoviense and Mare Nectaris
Authors: Kramer Georgiana Y. , Jolliff Bradley L. , Neal Clive R.
Published: January 2008

High‐alumina (HA) mare basalts are a unique group of the lunar sample collection. Sample geochemistry indicates that these basalts are derived from sources composed of late‐stage cumulates from the Lunar Magma Ocean (LMO). Their aluminous nature suggests their sources contained significant plagioclase, which has implications regarding the efficiency of plagioclase separation from earlier forming, mafic cumulates in the LMO to form the anorthositic lunar crust, and hence the heterogeneity of the lunar mantle. The Apollo and Luna missions sampled HA basalts from four different locations that are separated by 80 equatorial degrees (∼2400 km). Radiometric age dating of these samples demonstrates aluminous basaltic volcanism spanned over 1 billion years, suggesting HA basalts may be more prevalent on the Moon than implied by the sample population. Knowing their global occurrence would ultimately enhance our understanding of lunar evolution. Aluminous mare basalts occupy a unique location in Th‐FeO compositional space that suggests they can be identified using global remote‐sensing data of the Moon. We present our approach for distinguishing exposures of HA basalts using Clementine ultraviolet‐visible‐infrared (UVVIS) and Lunar Prospector Gamma Ray Spectrometer (LP‐GRS) data with constraints based on the FeO, TiO2, and Th abundances of Apollo and Luna HA samples. We identified 34 regions of interest (ROIs) where HA basalts could be a prominent component of the lunar surface. By analyzing the rims and proximal ejecta from small impacts (0.4–4 km in diameter) into the mare surface we characterized compositionally distinct basaltic units that make up the mare and thus determined which units represent HA basalt lavas. The results were used to generate maps that depict discrete mare units and classify their general basalt type. Here we focus on two ROIs: Mare Moscoviense and Mare Nectaris. Mare Moscoviense is composed of four basaltic units, two of which are HA candidates. Clementine UVVIS data of Mare Nectaris show evidence of up to three mare basalt units. One is the remnants of a mid‐Ti unit that capped earlier low‐Ti flows. The majority of the basin is filled by a compositionally indistinguishable low‐Fe, low‐Ti basalt. However, spectral profiles suggest there are two units. Regardless, the units both fit the criteria for a HA basalt.
Early anthropogenic CH4 emissions and the variation of CH4 and 13CH4 over the last millennium
Authors: Houweling S. , van der Werf G. R. , Klein Goldewijk K. , Röckmann T. , Aben I.
Published: January 2008

This study presents a new hypothesis to explain the observed variation of CH4 and δ13C‐CH4 over the last millennium. It was originally proposed that the observed minimum of δ13C‐CH4 prior to the start of industrialization is caused by a large shift in biomass burning emissions between 1400 and 1700 A.D. According to our new hypothesis, however, the δ13C‐CH4 minimum is the first sign of the global rise of anthropogenic CH4 emissions. The main idea is that emissions of isotopically depleted CH4, from, for example, rice cultivation, domestic ruminants, and waste treatment started increasing earlier than the isotopically enriched emissions from fossil fuel, which started with the start of industrialization. However, because the observed increase of atmospheric methane only started around 1750 A.D., these preindustrial anthropogenic emissions must have been accompanied by a net reduction of natural CH4 sources during the Little Ice Age (LIA) compensating for the increase of anthropogenic emissions during that period. Results of transient box model simulations for the last millennium show that under the new hypothesis a close agreement can be obtained between model and measurements. Prior to 1400 A.D., low emissions from anthropogenic biomass burning require a sizable contribution of methane emissions from vegetation to explain the observed high level of δ13C‐CH4. During the Little Ice Age, a larger than expected reduction of natural sources is needed, which calls for further verification using a more sophisticated modeling approach and additional constraints from ice core measurements.
Predictability of the Indian Ocean sea surface temperature anomalies in the GFDL coupled model
Authors: Song Qian , Vecchi Gabriel A. , Rosati Anthony J.
Published: January 2008

We explore the predictability of the sea surface temperature anomalies associated with the Indian Ocean Dipole/Zonal Mode (IODZM) at a three‐season lead, within the Geophysical Fluid Dynamics Laboratory (GFDL) coupled general circulation model (CGCM). In both control simulations and retrospective forecasts of the 1990's in the CGCM, we find that the occurrence of some IODZM events is preconditioned by oceanic conditions and potentially predictable three seasons in advance, while other IODZM events appear to be triggered by weather noise and have low predictability. The results highlight the necessity for future studies to distinguish periods when the IODZM is more or less predictable and search for its precursory pattern in the ocean.
First results of a ULF wave injected on open field lines by Space Plasma Exploration by Active Radar (SPEAR)
Authors: Clausen L. B. N. , Yeoman T. K. , Wright D. M. , Robinson T. R. , Dhillon R. S. , Gane S. C.
Published: January 2008

We present strong evidence that on 23 February 2007 between 2230 and 2330 UT the Space Plasma Exploration by Active Radar (SPEAR) system successfully modified the ionospheric electron density inside the northern polar cap. The modulated modification led to the generation of a small‐scale ultralow frequency (ULF) wave on open field lines which was detected by ground‐based magnetometers in the vicinity of the radar. It was not registered by magnetometer stations elsewhere inside the northern polar cap or at lower latitudes. The solar wind conditions are investigated, and although wave activity at the modulation frequency is present, it is shown that the local ULF wave is unlikely to originate from that activity.
Automatic reconstruction of fault networks from seismicity catalogs: Three‐dimensional optimal anisotropic dynamic clustering
Authors: Ouillon G. , Ducorbier C. , Sornette D.
Published: January 2008

We propose a new pattern recognition method that is able to reconstruct the three‐dimensional structure of the active part of a fault network using the spatial location of earthquakes. The method is a generalization of the so‐called dynamic clustering (or k means) method, that partitions a set of data points into clusters, using a global minimization criterion of the variance of the hypocenters locations about their center of mass. The new method improves on the original k means method by taking into account the full spatial covariance tensor of each cluster in order to partition the data set into fault‐like, anisotropic clusters. Given a catalog of seismic events, the output is the optimal set of plane segments that fits the spatial structure of the data. Each plane segment is fully characterized by its location, size, and orientation. The main tunable parameter is the accuracy of the earthquake locations, which fixes the resolution, i.e., the residual variance of the fit. The resolution determines the number of fault segments needed to describe the earthquake catalog: the better the resolution, the finer the structure of the reconstructed fault segments. The algorithm successfully reconstructs the fault segments of synthetic earthquake catalogs. Applied to the real catalog constituted of a subset of the aftershock sequence of the 28 June 1992 Landers earthquake in southern California, the reconstructed plane segments fully agree with faults already known on geological maps or with blind faults that appear quite obvious in longer‐term catalogs. Future improvements of the method are discussed, as well as its potential use in the multiscale study of the inner structure of fault zones.
Shear wave splitting and mantle flow associated with the deflected Pacific slab beneath northeast Asia
Authors: Liu Kelly H. , Gao Stephen S. , Gao Yuan , Wu Jing
Published: January 2008

A total of 361 SKS and five local S wave splitting measurements obtained at global and regional seismic network stations in NE China and Mongolia are used to infer the characteristics of mantle fabrics beneath northeast Asia. Fast polarization directions at most of the stations in the western part of the study area are found to be consistent with the strike of local geological features. The dominant fast directions at the eastern part, beneath which seismic tomography and receiver function studies revealed a deflected slab in the mantle transition zone (MTZ), are about 100° from north, which are almost exactly the same as the motion direction of the Eurasian plate relative to the Pacific plate, and are independent of the direction of local geological features. The splitting times at those stations are about 1 s which correspond to a layer of about 150 km thickness with a 3% anisotropy. The shear wave splitting observations, complemented by the well‐established observation that most of the eastern part of the study area is underlain by a lithosphere thinned by delamination in the Paleozoic era, can be best explained by the preferred alignment of metastable olivine associated with the subduction of the deflected Pacific slab in the MTZ, or by back‐arc asthenospheric flow in the mantle wedge above the slab.
Self‐potential signals induced by periodic pumping tests
Authors: Maineult Alexis , Strobach Elmar , Renner Jörg
Published: January 2008

We measured the variations of the self‐potential (SP) during periodic pumping tests performed at a test site located near a freshwater reservoir (Kemnader See, Bochum, Germany). Successions of injection and production intervals were applied in a borehole penetrating a jointed sandstone aquifer. We report the SP observations for tests with periods ranging between 10 and 60 min and flow rates between 10 and 25 L min−1. The SP responses at the surface exhibit the imposed period but are not truly harmonic contrary to the hydraulic pressure and SP measured in monitoring wells. In the grassy zone around the injection well, the amplitude of the SP signals decreases with distance from the injection well (around one order of magnitude at 10 m) in rough agreement with predictions for radial flow in a homogeneous medium around an infinite source. The shape of the SP responses also evolves with distance. Fourier spectral analysis reveals that the surface signals generally contain two main components at the main period and at half the period with the relative weight of the subperiodic components increasing with distance. Furthermore, the characteristics of the SP responses depend on whether the boreholes are left open or closed by packers. The comparison between surface and borehole measurements suggests that nonlinear phenomena are acting, probably related to the saturation and desaturation processes occurring in the vadose zone.
Evidence for major environmental perturbation prior to and during the Toarcian (Early Jurassic) oceanic anoxic event from the Lusitanian Basin, Portugal
Authors: Suan Guillaume , Mattioli Emanuela , Pittet Bernard , Mailliot Samuel , Lécuyer Christophe
Published: January 2008

The timing and causal relationships between the pronounced negative C isotope excursion and paleoenvironmental perturbations associated with the Toarcian oceanic anoxic event (Early Jurassic) remain unclear, particularly because biotic crises and carbonate production decrease appear to have been initiated earlier than the main C isotope anomaly. Here we present a new quantification of Late Pliensbachian–Early Toarcian calcareous nannofossils abundance and size from the Peniche reference section (Portugal) together with O and C isotope records of well‐preserved brachiopod shells from the same section. The brachiopod shell δ13C curve parallels that of bulk carbonate and records two pronounced negative isotopic excursions, close to the Pliensbachian‐Toarcian boundary (∼−2‰) and during the Toarcian oceanic anoxic event (∼−3.5‰). Our results indicate that both C isotope negative excursions were characteristic of benthic and shallow‐water environments, suggesting that these two carbon cycle perturbations affected all epioceanic reservoirs. Coeval shifts toward lower values of brachiopod oxygen isotope compositions and closely correlated northward migrations of Mediterranean ammonite fauna suggest that both events coincided with major rises in seawater temperatures, probably as a result of increased CO2 levels and enhanced greenhouse conditions. CO2‐induced changes in seawater chemistry likely affected the calcification potential of both neritic and pelagic systems, as evidenced by synchronous drops of platform‐derived carbonate accumulation and drastic reductions in size (>3 μm) of the main pelagic carbonate producer Schizosphaerella. We suggest that the Early Toarcian paleoenvironmental crisis occurred in two distinct episodes that were most likely related to two successive phases of intense volcanic degassing in the Karoo‐Ferrar province.
β1‐ and β2‐adrenoceptor responses in cardiomyocytes derived from human embryonic stem cells: comparison with failing and non‐failing adult human heart
Authors: Brito‐Martins M , Harding S E , Ali N N
Published: January 2008

Background and purpose:

Characterization of human embryonic stem cell‐derived cardiomyocytes (hESC‐CM) in relation to adult myocytes is essential for their future use in transplantation or as a model system. The β‐adrenoceptor pathways, which are known to be effective early in hESC‐CM development, are of major importance because of their control of rate and force of beating, arrhythmia generation and apoptosis/necrosis. We have therefore performed detailed pharmacological analysis of the β‐adrenoceptor responses in developing hESC‐CM.

Experimental approach:

hESC‐CMs were differentiated from H7 ESCs and studied up to 79 days of differentiation. Rate of beating and time course of contraction and relaxation were measured in superfused preparations.

Key results:

Responses to the mixed β1‐ and β2‐adrenoceptor agonist isoprenaline were evident from day 10 to day 79. Stability of the responses during an application, for repeated applications on the same experimental day and over the time of development, was determined. Concentrations for half‐maximal response (12.9 nM) were similar to those from adult human heart, but closer to those obtained from failing rather than normal ventricle. Acceleration of both contraction and relaxation was quantitatively similar to that in adult ventricular myocytes, as was sensitivity to muscarinic inhibition. Use of specific antagonists showed that both β1‐ and β2‐adrenoceptors contributed to contractile responses, as seen with adult myocytes.

Conclusions and implications:

These data show the compatibility of hESC‐CM with adult human myocardium in terms of β‐adrenoceptor response. The experiments described here also confirm the utility of the hESC‐CM preparation for detailed pharmacological analysis.

British Journal of Pharmacology (2008) 153, 751–759; doi:10.1038/sj.bjp.0707619; published online 14 January 2008
C3a Receptor Modulation of Granulocyte Infiltration after Murine Focal Cerebral Ischemia is Reperfusion Dependent
Authors: Ducruet Andrew F , Hassid Benjamin G , Mack William J , Sosunov Sergei A , Otten Marc L , Fusco David J , Hickman Zachary L , Kim Grace H , Komotar Ricardo J , Mocco J , Connolly E Sander
Published: January 2008

The complement anaphylatoxin C3a contributes to injury after cerebral ischemia in mice. This study assesses the effect of C3a receptor antagonist (C3aRA) on leukocyte infiltration into the ischemic zone. Transient or permanent middle cerebral artery occlusion (MCAO) was induced in wild-type C57BI/6 mice. Intraperitoneal C3aRA or vehicle was administered 45 mins before or 1 h after occlusion. Twenty-four hours after occlusion, we harvested brain tissue and purified inflammatory cells using flow cytometry. Soluble intercellular adhesion molecule (ICAM)-1 protein levels were assessed using enzyme-linked immunosorbent assays, and ICAM-1 and C3a receptor (C3aR) expression was confirmed via immunohistochemistry. In the transient MCAO model, animals receiving C3aRA showed smaller strokes, less upregulation of C3aR-positive granulocytes, and less ICAM-1 protein on endothelial cells than vehicle-treated animals; no significant differences in other inflammatory cell populations were observed. C3a receptor antagonist-treated and vehicle-treated animals showed no differences in stroke volume or inflammatory cell populations after permanent MCAO. These data suggest that blocking the binding of C3a to C3aR modulates tissue injury in reperfused stroke by inhibiting the recruitment of neutrophils to the ischemic zone. It further establishes antagonism of the C3a anaphylatoxin as a promising strategy for ameliorating injury after ischemia/reperfusion.
Democratising Science? The Politics of Promoting Biomedicine in Singapore's Developmental State
Authors: Holden Kerry , Demeritt David
Published: January 2008

Drawing on Jasanoff's concept of coproduction [2004 States of Knowledge: The Co-production of Science and Social Order (Routledge, London) and Ong's notion of ‘graduated’ sovereignty [2000 Theory, Culture and Society17(4) 55–75], we analyse Singapore's promotion of the biomedical industry. To secure its place in the knowledge-based economy, Singapore's developmental state is determined to change the mind-set of its population and inculcate the individual creativity and entrepreneurialism needed for scientific innovation. It is also rolling out an internationally accepted framework of bioethics regulation. We explore the liberal values implicit in these two projects for promoting biomedicine and their implications both for the civic norms of Singapore's developmental state and for the wider relationships between science and liberal democracy.
Development of SCAR markers linked to zt-2, one of the genes controlling absence of tannins in faba bean
Authors: Gutierrez Natalia , Avila C. M. , Moreno M. T. , Torres A. M.
Published: January 2008

Faba beans (Vicia faba L.) have a great potential as a protein-rich fodder crop, but anti-nutritional factors such as condensed tannins reduce the biological value of their protein. Tannins can be removed from seeds by any of the two complementary genes, zt-1 and zt-2, which also determine white-flowered plants. The less common gene, zt-2, is also associated with increased protein levels and energy values and reduced fibre content of the seeds. To identify a cost-effective marker linked to zt-2, we analysed a segregating F2 population derived from the cross between the coloured flower and high tannin content genotype Vf6 and a zt-2 line. By using Bulked Segregant Analysis (BSA), five RAPD markers linked in coupling and repulsion phase to zt-2 were identified and their conversion into Sequence Characterised Amplified Regions (SCARs) was attempted. Amplification of the SCARS was more consistent, although the initial polymorphism was lost. Restriction digestion of SCAR SCAD16589 with AluI (SCAD16-A), Bsp120I (SCAD16-B) and HinfI (SCAD16-H) revealed clear differences due to the amplification of different loci. The consensus sequence of these CAPs (Cleavage Amplification Polymorphisms) markers allowed discrimination of three bands from which two new forward SCAR primers were developed based on specific sequences from zero tannin and high tannin content genotypes. To improve the efficiency of the marker screening, a multiplex PCR was developed that allowed the simultaneous amplification of the SCAR with the same advantages as a codominant marker. Marker validation was carried out with a new F2 population segregating for flower colour and tannin content, underscoring the potential of these markers in breeding selection to introgress the zt-2 gene for the development of new tannin free faba bean cultivars.
Patched, the receptor of Hedgehog, is a lipoprotein receptor
Authors: Callejo Ainhoa , Culi Joaquim , Guerrero Isabel
Published: January 2008

The Hedgehog (Hh) family of secreted signaling proteins has a broad variety of functions during metazoan development and implications in human disease. Despite Hh being modified by two lipophilic adducts, Hh migrates far from its site of synthesis and programs cellular outcomes depending on its local concentrations. Recently, lipoproteins were suggested to act as carriers to mediate Hh transport in
Drosophila
. Here, we examine the role of lipophorins (Lp), the
Drosophila
lipoproteins, in Hh signaling in the wing imaginal disk, a tissue that does not express Lp but obtains it through the hemolymph. We use the up-regulation of the Lp receptor 2 (LpR2), the main Lp receptor expressed in the imaginal disk cells, to increase Lp endocytosis and locally reduce the amount of available free extracellular Lp in the wing disk epithelium. Under this condition, secreted Hh is not stabilized in the extracellular matrix. We obtain similar results after a generalized knock-down of hemolymph Lp levels. These data suggest that Hh must be packaged with Lp in the producing cells for proper spreading. Interestingly, we also show that Patched (Ptc), the Hh receptor, is a lipoprotein receptor; Ptc actively internalizes Lp into the endocytic compartment in a Hh-independent manner and physically interacts with Lp. Ptc, as a lipoprotein receptor, can affect intracellular lipid homeostasis in imaginal disk cells. However, by using different Ptc mutants, we show that Lp internalization does not play a major role in Hh signal transduction but does in Hh gradient formation.
A human mutation in Phox2b causes lack of CO
2
chemosensitivity, fatal central apnea, and specific loss of parafacial neurons
Authors: Dubreuil Véronique , Ramanantsoa Nélina , Trochet Delphine , Vaubourg Vanessa , Amiel Jeanne , Gallego Jorge , Brunet Jean-François , Goridis Christo
Published: January 2008

Breathing is maintained and controlled by a network of neurons in the brainstem that generate respiratory rhythm and provide regulatory input. Central chemoreception, the mechanism for CO
2
detection that provides an essential stimulatory input, is thought to involve neurons located near the medullary surface, whose nature is controversial. Good candidates are serotonergic medullary neurons and glutamatergic neurons in the parafacial region. Here, we show that mice bearing a mutation in
Phox2b
that causes congenital central hypoventilation syndrome in humans breathe irregularly, do not respond to an increase in CO
2
, and die soon after birth from central apnea. They specifically lack Phox2b-expressing glutamatergic neurons located in the parafacial region, whereas other sites known or supposed to be involved in the control of breathing are anatomically normal. These data provide genetic evidence for the essential role of a specific population of medullary interneurons in driving proper breathing at birth and will be instrumental in understanding the etiopathology of congenital central hypoventilation syndrome.
mef2
activity levels differentially affect gene expression during
Drosophila
muscle development
Authors: Elgar Stuart J. , Han Jun , Taylor Michael V.
Published: January 2008

Cell differentiation is controlled by key transcription factors, and a major question is how they orchestrate cell-type-specific genetic programs. Muscle differentiation is a well studied paradigm in which the conserved Mef2 transcription factor plays a pivotal role. Recent genomic studies have identified a large number of
mef2
-regulated target genes with distinct temporal expression profiles during
Drosophila
myogenesis. However, the question remains as to how a single transcription factor can control such diverse patterns of gene expression. In this study we used a strategy combining genomics and developmental genetics to address this issue
in vivo
during
Drosophila
muscle development. We found that groups of
mef2
-regulated genes respond differently to changes in
mef2
activity levels: some require higher levels for their expression than others. Furthermore, this differential requirement correlates with when the gene is first expressed during the muscle differentiation program. Genes that require higher levels are activated later. These results implicate
mef2
in the temporal regulation of muscle gene expression, and, consistent with this, we show that changes in
mef2
activity levels can alter the start of gene expression in a predictable manner. Together these results indicate that Mef2 is not an all-or-none regulator; rather, its action is more subtle, and levels of its activity are important in the differential expression of muscle genes. This suggests a route by which
mef2
can orchestrate the muscle differentiation program and contribute to the stringent regulation of gene expression during myogenesis.
Podocytes use FcRn to clear IgG from the glomerular basement membrane
Authors: Akilesh Shreeram , Huber Tobias B. , Wu Hui , Wang Gary , Hartleben Björn , Kopp Jeffrey B. , Miner Jeffrey H. , Roopenian Derry C. , Unanue Emil R. , Shaw Andrey S.
Published: January 2008

The glomerular filtration barrier prevents large serum proteins from being lost into the urine. It is not known, however, why the filter does not routinely clog with large proteins that enter the glomerular basement membrane (GBM). Here, we provide evidence that an active transport mechanism exists to remove immunoglobulins that accumulate at the filtration barrier. We found that FcRn, an IgG and albumin transport receptor, is expressed in podocytes and functions to internalize IgG from the GBM. Mice lacking FcRn accumulated IgG in the GBM as they aged, and tracer studies showed delayed clearance of IgG from the kidneys of FcRn-deficient mice. Supporting a role for this pathway in disease, saturating the clearance mechanism potentiated the pathogenicity of nephrotoxic sera. These studies support the idea that podocytes play an active role in removing proteins from the GBM and suggest that genetic or acquired impairment of the clearance machinery is likely to be a common mechanism promoting glomerular diseases.
Unmet Needs and Treatment Seeking in High Users of Mental Health Services: Role of Illness Perceptions
Authors: Broadbent Elizabeth , Kydd Robert , Sanders Deanna , Vanderpyl Jane
Published: January 2008

Objective: A small number of patients tend to use a disproportionately high amount of mental health services. Understanding the needs and behaviours of this group is important in order to improve patient management. Few studies have investigated the role that patients’ perceptions about their mental illness play in guiding coping responses and treatment seeking. The aim of the present study was to investigate how illness perceptions in high users of mental health services were related to unmet needs and treatment-seeking behaviours.

Method: A total of 203 high users of mental health services were interviewed using the Brief Illness Perception Questionnaire, the Camberwell Assessment of Need and the Drug Attitude Inventory, and were also asked to report the number of visits they had made to the general practitioner in the past year. District Health Board clinical staff completed the Camberwell Assessment of Need and the Global Assessment of Functioning for each user.

Results: More negative perceptions about mental illness were associated with higher ratings of unmet needs by both patients and staff. Negative perceptions were also related to poorer attitudes towards medication, and lower functioning. Perceptions about the personal ability to control the illness were consistently associated with better outcomes. Patients’ causal attributions could be categorized as social, psychological, biological and behavioural. More frequent visits to the general practitioner were associated with perceptions of more severe symptoms, greater concern and higher emotional responses to the illness, and psychosocial causal attributions.

Conclusion: Illness perceptions provide a framework to assess patients’ ideas about severe mental illness and a means by which to identify maladaptive beliefs. Interventions targeted at changing these beliefs may encourage better self-management.
Association Between Duration of Untreated Psychosis, Premorbid Functioning, and Cognitive Performance and the Outcome of First-Episode Schizophrenia in Japanese Patients: Prospective Study
Authors: Yamazawa Ryoko , Nemoto Takahiro , Kobayashi Hiroyuki , Chino Bun , Kashima Haruo , Mizuno Masafumi
Published: January 2008

Objective: The aim of the present study was to identify the relationship between duration of untreated psychosis (DUP), premorbid functioning, and cognitive dysfunction and the outcome of first-episode schizophrenia.

Method: Thirty-four neuroleptic-naïve patients who consulted hospitals in Tokyo and who were treated by psychiatrists for the first time were evaluated with regard to DUP, premorbid functioning, psychiatric symptoms, and global functioning. The neuropsychological test battery consisted of the Letter Cancellation Test, Trail-Making Test, Digit Span and Verbal Fluency Test. One year later, 24 of the subjects were reassessed for psychiatric symptoms, global functioning, and social functioning, and the relationships between DUP, premorbid functioning, and cognitive performance and the outcome was investigated.

Results: Short DUP, good premorbid functioning, and good Letter Cancellation Test, Digit Span and Verbal Fluency Test scores were significantly associated with good outcome.

Conclusions: The present results in a Japanese sample are consistent with previous international evidence that delay of initial treatment, premorbid functioning, and cognitive deficits are associated with outcome. A major limitation of the present study was the small size of the subject group. But because the subjects were relatively homogeneous and not influenced by psychoactive substances, the results reflect the essence of the disorder.
Social Distance and Perceived Dangerousness Across Four Diagnostic Categories of Mental Disorder
Authors: Marie Dannette , Miles Brad
Published: January 2008

Objectives: To examine whether laypersons make categorical distinctions between psychoses, neuroses, and addictive behaviours relative to desired social distance and whether degree of familiarity and perceived dangerousness influences social distance judgements.

Method: Two studies were undertaken using the mental health literacy framework. The first study involved surveying lay beliefs and perceptions of a mentally ill person who exhibited behavioural cues of one of the following: schizophrenia, depression, alcohol abuse, or substance dependence. The second study involved a partial replication and refinement of the first study to determine whether discriminate judgements across diagnostic categories were influenced by perceived dangerousness.

Results: Findings from study 1 indicated that laypersons do differentiate between psychological disorders and respond to them differently relative to social distance. Results from study 2 confirmed those of study 1 and in addition suggested that perceived dangerousness influences social distance, largely with respect to schizophrenia.

Conclusions: Laypersons make categorical distinctions between different types of disorders. Perceived dangerousness is more strongly associated with schizophrenia, than is warranted when considered against acts of violence and aggression committed by individuals with alcohol abuse and substance dependence problems.
Longevity mutation in SCH9 prevents recombination errors and premature genomic instability in a Werner/Bloom model system
Authors: Madia Federica , Gattazzo Cristina , Wei Min , Fabrizio Paola , Burhans William C. , Weinberger Martin , Galbani Abdoulaye , Smith Jesse R. , Nguyen Christopher , Huey Selina , Comai Lucio , Longo Valter D.
Published: January 2008

Werner and Bloom syndromes are human diseases characterized by premature age-related defects including elevated cancer incidence. Using a novel Saccharomyces cerevisiae model system for aging and cancer, we show that cells lacking the RecQ helicase SGS1 (WRN and BLM homologue) undergo premature age-related changes, including reduced life span under stress and calorie restriction (CR), G1 arrest defects, dedifferentiation, elevated recombination errors, and age-dependent increase in DNA mutations. Lack of SGS1 results in a 110-fold increase in gross chromosomal rearrangement frequency during aging of nondividing cells compared with that generated during the initial population expansion. This underscores the central role of aging in genomic instability. The deletion of SCH9 (homologous to AKT and S6K), but not CR, protects against the age-dependent defects in sgs1Δ by inhibiting error-prone recombination and preventing DNA damage and dedifferentiation. The conserved function of Akt/S6k homologues in lifespan regulation raises the possibility that modulation of the IGF-I–Akt–56K pathway can protect against premature aging syndromes in mammals.